Child health

Review Attention deficit hyperactivity disorder in adults: conceptual and clinical issues Julian N Trollor MJA 1999; 171: 421-425 Abstract - Introduction - Conceptual issues - Clinical assessment - Management - Monitoring progress - Conclusion - Acknowledgement - References - Authors' details - - More articles on Psychiatry Abstract Reports published over the past decade indicate that attention deficit hyperactivity disorder (ADHD) is a cause of significant psychological impairment in adults. The adulthood disorder occurs as a continuation of its childhood counterpart, with the full ADHD syndrome persisting into early adulthood in about a third of those with childhood ADHD. Despite advances in the understanding of the neurobiology of adult ADHD, the diagnosis is made clinically by establishing a retrospective childhood diagnosis, evaluating the current symptom profile and excluding alternative medical or psychiatric causes of symptoms. Adults with ADHD have high rates of comorbid psychiatric disorder and suffer significant relationship dysfunction, work and educational failure. There is emerging evidence for the effectiveness of specific treatments for adult ADHD, including stimulant medications and some antidepressants. Clinicians should be aware of this potentially treatable disorder in young adults presenting with psychological difficulties and a history of childhood ADHD symptoms. Introduction Attention deficit hyperactivity disorder (ADHD) is one of the most common disorders of childhood, affecting 3%-5% of school-age children.1 It was previously considered a diagnosis applicable only to children and adolescents, but studies of cohorts of ADHD children followed up prospectively have shown that the condition continues into adulthood in an appreciable proportion of patients.2-6 These studies have highlighted the poor psychosocial outcome of this patient population in adulthood, with high rates of educational failure, substance misuse disorders, personality disorders and other psychopathological disorders. Conceptual issues Definition The diagnosis of adult ADHD, as with most psychiatric disorders, is made on clinical grounds. Case identification is based on systematic assessment of symptom profile and exclusion of alternative psychiatric or medical causes. The Diagnostic and statistical manual of mental disorders, 4th edition1 (DSM-IV), reflects the recent conceptual shift in ADHD diagnosis by using wording applicable to adults as well as children (Box 1). Because some ADHD symptoms (eg, inattention, forgetfulness, motor restlessness) occur commonly in the community to a varying extent, it is difficult to decide where the boundary should be drawn between normal and pathological. This dilemma is partly answered in DSM-IV by allowing only those symptoms that are persistent and maladaptive to be counted toward diagnosis. In addition, impairment in at least two settings (eg, work, university, home or social life) is required before a diagnosis of ADHD can be made. Facility exists in DSM-IV for clinicians to specify "ADHD in partial remission" for patients in whom the full diagnostic criteria, although met in childhood, are no longer fulfilled. The clinical status of this less severely affected group awaits clarification. Relationship to childhood ADHD ADHD symptoms must have been present in childhood (although not necessarily recognised) for an adulthood diagnosis to be sustainable. Follow-up studies of childhood ADHD cohorts show considerable discrepancy in reported rates of retention of ADHD diagnosis by early adulthood. Such discrepancies are multifactorial and relate to different diagnostic and exclusion criteria used for study entry, variation in illness severity in original cohorts and differences in age at follow-up. Although up to two-thirds of patients may continue to have symptoms of ADHD as adults,4 only a third will satisfy full diagnostic criteria at age 18,2,3 with further age-dependent decline continuing into the mid 20s.5,6 Comorbidity in adult ADHD Rates of psychopathology among ADHD children in adulthood are high (2-2.5 times those of controls), with a particularly high risk for antisocial personality disorder (up to 10 times that of controls) and drug or alcohol misuse (4-5 times that of controls).4,7 ADHD adults have elevated rates of mood disorder (2-6 times),7,8 anxiety disorders (2-4 times),7,8 relationship dysfunction (2 times),7 and learning disorder7 compared with control populations. The high rate of comorbid psychopathology seen in adult ADHD may be in part a reflection of the impact of longstanding adaptive impairments on development, as well as shared familial, environmental and possibly genetic vulnerabilities. Theoretical and practical implications of comorbidity in adult ADHD have been reviewed in detail elsewhere.9 Pathophysiology Despite its proposed neurobiological basis and predominantly biological treatment, the precise pathophysiological mechanisms of adult ADHD remain obscure. A complete review of this area is beyond the scope of this article and has been provided elsewhere.10,11 Research has focused on a hypothesised functional deficit of monoamines, especially dopamine and noradrenaline. An understanding of the functional12 and structural13-15 neuroanatomy of ADHD is beginning to emerge, implicating dysfunctional prefrontal-striatal circuits in the pathogenesis of ADHD. Clinical assessment The need for a diagnostic hierarchy The key steps in the diagnostic assessment of adults presenting with possible ADHD are shown in the Figure. Many presenting for assessment readily identify with the symptoms of the disorder. However, up to half of those presenting to specialty clinics for assessment of possible ADHD do not have ADHD as the primary diagnosis.16 Thus, approach to this popular diagnosis demands a standardised and objective assessment. Nature and severity of current symptoms The symptoms of ADHD in adults are an extension of those seen in children. Patients may experience difficulty sustaining attention in a number of settings, particularly when performing demanding cognitive tasks. Hyperactivity manifests physically, but may also have a mental component (having accelerated or multiple simultaneous thoughts); however, hyperactivity is not essential for the diagnosis. Patients may manifest impulsive symptoms verbally (by making tactless comments or interrupting others), or may engage in impulsive high risk activities. Often patients have poor organisational skills and an exaggerated response to minor frustrations. A longitudinal assessment of the impact of symptoms should be consistent with impairment secondary to ADHD symptoms. Common experiences of the ADHD sufferer may include recurrent educational or occupational failure, relationship instability and poor ability to organise personal affairs. Establishing a retrospective childhood diagnosis of ADHD A sound retrospective diagnosis of probable ADHD in childhood should be considered as a central precursor to a diagnosis of ADHD in adulthood. A retrospective assessment of childhood symptoms should be made regardless of whether a past childhood diagnosis of ADHD has been made. A retrospective diagnosis is supported by consistent parental reports of symptoms of ADHD in one or more settings, as well as objective accounts of aberrant behaviour recorded in past school reports. Assessing other psychological and medical problems All patients should be asked about the presence of symptoms of common psychiatric and medical disorders (past and present) that can mimic ADHD (Box 2). This is particularly important when patients present for the first time at a relatively late age (eg, over 35 years). In some cases, diagnostic difficulty arises where superimposed symptoms of a second psychiatric disorder coexist with longstanding symptoms of ADHD. Chronic use of many illicit drugs (eg, cannabis, cocaine, amphetamines) and alcohol should be considered as a possible cause of the presenting cognitive and behavioural symptoms. Adult ADHD patients are at high risk of comorbid drug misuse and are more likely to report failed attempts to curtail their drug use.17,18 In patients in whom possible ADHD symptoms and drug misuse occur together, it is usually prudent to reassess for ADHD symptoms after treatment of the drug misuse. Recent (eg, within the past two or three months) or ongoing misuse of illicit substances is a relative contraindication to prescription of stimulant medication. A non-stimulant treatment may be offered to patients with significant ADHD symptoms who are unable to curtail illicit drug use. Adjunctive diagnostic tests Routine investigations: Routine blood tests (urea, electrolyte, creatinine levels, a full blood count, liver and thyroid function tests) are of use only when the presentation suggests an underlying medical disorder. Random urinary drug screening may be performed to monitor illicit drug use in selected patients. An electrocardiogram (EEG) is performed in older adults or those with a history or signs of cardiac disease, particularly when treatment with tricyclic antidepressants is being considered. Rating scales: Rating scales are a useful adjunct to clinical assessment, but do not provide a diagnostic test for adult ADHD. Scales have been developed for retrospective self-report of childhood symptoms (eg, Wender-Utah Rating Scale19) and retrospective parent report of childhood symptoms (eg, Conners Abbreviated Symptom Questionnaire20). Rating scales can also be used to evaluate the severity of current symptoms and to monitor treatment (eg, Patient's Behavior Checklist for ADHD Adults21). Neuropsychological testing: A range of neuropsychological deficits have been reported in children and adolescents with ADHD. Preliminary neuropsychological studies of adults22-27 have produced some conflicting findings, but, on the whole, are consistent with those in childhood, and provide some support for the validity of adult ADHD. The most commonly administered test in adults is a computerised test of sustained attention (Continuous Performance Task). At present, there is insufficient evidence to recommend detailed neuropsychological evaluation for ADHD adults on a routine basis. However, neuropsychological testing may be useful in patients in whom diagnosis is difficult, or when cognitive impairment secondary to another disorder is suspected (eg, those with previous head injury, alcohol-related cognitive deficits, or early dementias). Neurophysiological testing: Quantitative electroencephalograph (EEG) abnormalities, including decreased power of alpha and beta bandwidths in posterior leads and increased frontal theta, have been demonstrated in ADHD children and adolescents.28-30 Quantitative EEG findings have not yet been systematically studied in adults with ADHD and, at present, cannot be advocated for routine assessment. Studies of event-related potentials (ERPs) in children and adolescents with ADHD have found a number of abnormalities in the late positive potential (P3b) amplitude and latency,30-32 as well as abnormalities of the early negative potentials (N1 and N2).31,33,34 However, these findings are seen in a variety of other disorders (eg, autism, learning disability) and hence lack diagnostic specificity. There are few published studies of ERP findings in adults with ADHD, and thus at present their use is for research rather than diagnostic assessment. Functional neuroimaging: Positron emission tomography (PET) findings, including abnormality of glucose uptake in the premotor and frontal cortices12 and reduced [fluorine-18] fluorodopa ratios in the prefrontal cortex,35 support the hypothesis of prefrontal and dopaminergic deficits as central to the pathophysiology of adult ADHD, but do not have clinical application. Structural and functional neuroimaging studies may be appropriate in selected cases when another cause of cognitive and behavioural symptoms is suspected. Management Education Response to initial diagnosis is highly variable, with reactions ranging from relief at an explanation for the symptoms to grief over the "lost years" of the untreated disorder. Education regarding ADHD and its treatment is essential. Further information can be obtained by patients from popular books, ADHD support groups, and the Internet <http://www.nimh.nih.gov/publicat/adhdmenu.cfm> Pharmacotherapy There are only a few published reports examining the efficacy of pharmacotherapy for adult ADHD.36 Drug treatment is generally reserved for those with moderate or severe symptoms, or when more conservative measures have failed. Current evidence supports stimulant responsiveness across age groups,37 but there have only been six published double-blind placebo-controlled trials of psychostimulant use in adults. A review of these36 noted considerable variability in response rates to stimulants (range, 25%-78%; mean, 52%) and attributed this to multiple factors, including diagnostic and dose variation between studies. No convincing evidence has emerged that long term supervised prescription of stimulants leads to drug tolerance or misuse. Commonly used dose ranges for the two stimulants available in Australia are the same as those for ADHD children (0.3-1.0 mg/kg per day for methylphenidate, and 0.2-0.5 mg/kg per day for dextroamphetamine). The mechanisms of action of stimulant medication have been reviewed.38 Stimulants should not be taken together with other psychotropic drugs, unless recommended by an experienced clinician. Tricyclic antidepressants (TCAs) have been assessed as effective treatments for childhood and adolescent ADHD. Two studies of ADHD in adults39-40 support a role for desipramine, nortriptyline and imipramine at typical antidepressant dosages as second-line treatment for adult ADHD. However, initial treatment with TCAs should be considered in selected patients (those at risk of misuse of prescribed stimulants, and those with comorbid depression and anxiety). The newer antidepressants venlafaxine41-43 and bupropion44 have shown promise in open studies, but further evaluation is required. Serotonin reuptake inhibitors may be appropriate for those with comorbid anxiety, depression, obsessive-compulsive symptoms and severe impulsivity, but as yet there is no evidence of their value for the treatment of ADHD symptoms alone. The monoamine oxidase-B inhibitor L-deprenyl has been shown to reduce ADHD symptoms in a single trial in adults.45 Cognitive behavioural therapy Cognitive and behavioural strategies have yet to be systematically evaluated as independent treatments for adult ADHD. However, to overcome skill deficits commonly seen in ADHD, patients can be taught basic skills such as time management, organisational strategies, problem solving and anger management. Controversial treatments A number of controversial treatments are available for adult ADHD. Dietary supplementation, exclusion diets and herbal supplements have not been shown to be of benefit in adults. EEG biofeedback is an expensive treatment of growing popularity, but has yet to be properly evaluated. A case history of adult ADHD in a 22-year-old man is given in Box 3. Monitoring progress Patient response to treatment can be monitored at various levels: subjective feedback from patient and family; self- and observer-rating scales; educational progress; employer reports; and repeat neuropsychological assessment. No consensus guidelines exist regarding duration of treatment or adequate methods of monitoring progress. If stimulant treatment has been continued through late adolescence into adulthood, it is prudent to review the need for continuing treatment every 6-12 months. A medication-free period (eg, 4-6 weeks) may allow re-evaluation of symptom severity, thus helping to determine the need for ongoing treatment. For patients commencing stimulant medication for the first time as adults, there should be clear evidence of functional improvement over the first 3-6 months of treatment. Clear short-term functional improvement justifies continuing stimulant prescription over the next 12 months. Thereafter, a patient's progress should be reviewed as above. Those with persistence of the full adult ADHD profile may require medication until educational goals have been met, or until stable employment is obtained. This allows the patient to further develop the skills needed to compensate for persisting symptoms. A small group of patients with severe symptoms may require stimulant medication indefinitely. Conclusion There are published reports to support the continuation of ADHD into adulthood in about a third of patients with childhood ADHD. Symptoms of the disorder can be disabling, and considerable comorbid psychopathology may be present. With recognition and appropriate management of the disorder, considerable gains may be anticipated in most patients. As with any emergent condition, our current understanding of adult ADHD is incomplete, and limited published data are available. A systematic and evidence-based approach to diagnosis and management is therefore required, which should be revised as new developments occur. Acknowledgement The assistance of Professor Perminder Sachdev in reviewing a previous draft version of this article is gratefully acknowledged. References American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Association, 1994: 83-85. Gittleman R, Mannuzza S, Shenker R, Bonagura N. Hyperactive boys almost grown up: I. Psychiatric status. Arch Gen Psychiatry 1985; 42: 937-947. Mannuzza S, Klein RG, Bonagura N, et al. Hyperactive boys almost grown up: V. Replication of psychiatric status. Arch Gen Psychiatry 1991; 48: 77-83. Weiss G, Hechtman L, Milroy T, Perlman T. Psychiatric status of hyperactives as adults: a controlled prospective 15-year follow-up of 63 hyperactive children. J Am Acad Child Psychiatry 1985; 24: 211-220. Mannuzza S, Klein RG, Bessler A, et al. Adult outcome of hyperactive boys: educational achievement, occupational rank and psychiatric status. Arch Gen Psychiatry 1993; 50: 565-576. Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 1998; 155: 493-498. Biederman J, Faraone SV, Spencer T, et al. Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry 1993; 150: 1792-1798. Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety and other disorders. Am J Psychiatry 1991; 148: 564-577. Horning M. Addressing comorbidity in adults with Attention Deficit Hyperactivity Disorder. J Clin Psychiatry 1998; 59 [Suppl 7]: 69-75. Castellanos FX. Toward a pathophysiology of attention deficit hyperactivity disorder. Clin Paediatr 1997; 36: 381-393. Faraone SV, Biederman J. Neurobiology of Attention-Deficit Hyperactivity Disorder. Biol Psychiatry 1998; 44: 951-958. Zametkin AJ, Nordahl TE, Gross M, et al. Cerebral glucose metabolism in adults with hyperactivity of childhood onset. N Engl J Med 1990; 323: 1361-1366. Castellanos FX, Giedd JN, Eckburg P, et al. Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder. Am J Psychiatry 1994; 151: 1791-1796. Semrud-Clikeman M, Filipek PA, Biederman J, et al. Attention-deficit hyperactivity disorder: magnetic resonance imaging morphometric analysis of the corpus callosum. J Am Acad Child Adolesc Psychiatry 1994; 33: 875-881. Castellanos FX, Giedd JN, Marsh WL, et al. Quantitative brain magnetic resonance imaging in attention deficit hyperactivity disorder. Arch Gen Psychiatry 1996; 53: 607-616. Roy-Byrne P, Scheele L, Brinkley J, et al. Adult attention deficit hyperactivity disorder: assessment guidelines based on clinical presentation to a specialty clinic. Compr Psychiatry 1997; 38: 133-140. Goodwin DW, Schulsinger F, Hermansen L, et al. Alcoholism and the hyperactive child syndrome. J Nerv Ment Dis 1975; 160: 349-353. Carroll KM, Rounsaville BJ. History and significance of childhood attention deficit hyperactivity disorder in treatment-seeking cocaine abusers. Compr Psychiatry 1993; 34: 75-82. Ward MF, Wender PH, Reimherr FW. The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. Am J Psychiatry 1993; 150: 885-890. Goyette CH, Conners CK, Ulrich RF. Normative data on Revised Conners Parent and Teacher Rating Scales. J Abnorm Child Psychol 1978; 6: 221-236. Patient's Behaviour Checklist for ADHD Adults. In: Barkley RA, ed. Attention deficit hyperactivity disorder: a clinical workbook. New York: The Guilford Press, 1991: 43. Seidman LJ, Biederman J, Weber W, et al. Neuropsychological function in adults with attention deficit hyperactivity disorder. Biol Psychiatry 1998; 44: 260-268. Matochik JA, Rumsey JM, Zametkin AJ, et al. Neuropsychological correlates of familial attention deficit hyperactivity disorder in adults. Neuropsychiatry, Neuropsychol Behav Neurol 1996; 9: 186-191. Downey KK, Stelson FW, Pomerleau OF, Giordani B. Adult attention deficit hyperactivity disorder: psychological test profiles in a clinical population. J Nerv Ment Dis 1997; 185: 32-38. Lovejoy DW, Ball JD, Keats M, et al. Neuropsychological performance of adults with attention deficit hyperactivity disorder (ADHD): diagnostic classification estimates for measures of frontal lobe/executive functioning. J Int Neuropsychol Soc 1999; 5: 222-233. Corbett B, Stanczak DE. Neuropsychological performance of adults evidencing attention-deficit hyperactivity disorder. Arch Clin Neuropsychol 1999; 14: 373-387. Jenkins M, Cohen R, Malloy P, et al. Neuropsychological measures which discriminate among adults with residual symptoms of attention deficit disorder and other attentional complaints. Clin Neuropsychol 1998; 12: 74-83. Mann CA, Lubar JF, Zimmerman AW, et al. Quantitative analysis of EEG in boys with attention deficit hyperactivity disorder: a controlled study with clinical implications. Paediatr Neurol 1992; 8: 30-36. Chabot RJ, Merkin H, Wood LM. Sensitivity and specificity of QEEG in children with attentional deficits or specific developmental learning disorders. Clin Electroencephalogr 1996; 27: 26-34. Kuperman S, Johnson B, Arndt S, et al. Quantitative EEG differences in a nonclinical sample of children with ADHD and undifferentiated ADD. J Am Acad Child Adolesc Psychiatry 1996; 35: 1009-1017. Loiselle DL, Stamm JS, Maitinsky S, Whipple SC. Evoked potential and behavioral signs of attentive dysfunctions in hyperactive boys. Psychophysiology 1980; 17: 193-201. Holcomb PH, Ackerman PT, Dykman RA. Cognitive event-related potentials in children with attentional and reading deficits. Psychophysiology 1985; 22: 656-667. Satterfield JH, Schell AM, Nicholas T, Backs RW. Topographic study of auditory event-related potentials in normal boys and boys with attention deficit disorder with hyperactivity. Psychophysiology 1988; 25: 591-606. Klorman R, Brumaghim JT, Salzman LF, et al. Effects of methylphenidate on processing negativities in patients with attention-deficit hyperactivity disorder. Psychophysiology 1990; 27: 328-337. Ernst M, Zametkin AJ, Matochik JA, Cohen RM. Dopa decarboxylase activity in attention deficit hyperactivity disorder adults -- a [fluorine-18] fluorodopa positron emission tomographic study. J Neurosci 1998; 18: 5901-5907. Wilens TE, Biederman J, Spencer TJ, Prince J. Pharmacotherapy of adult attention deficit hyperactivity disorder: a review. J Clin Psychopharmacol 1995; 15: 270-279. Spencer T, Biederman J, Wilens T, et al. Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry 1996; 35: 409-432. Solanto M. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 1998; 94: 127-152. Wilens TE, Biederman J, Mick E, Spencer TJ. A systematic assessment of tricyclic antidepressants in the treatment of adult attention-deficit hyperactivity disorder. J Nerv Ment Dis 1995; 183: 48-50. Wilens TE, Biederman J, Prince J, et al. Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Am J Psychiatry 1996; 153: 1147-1153. Adler LA, Resnick S, Kunz M, Devinsky O. Open-label trial of venlafaxine in adults with attention deficit disorder. Psychopharmacol Bull 1995; 31: 785-788. Hedges D, Reimherr FW, Rodgers A, et al. An open trial of venlafaxine in adult patients with attention deficit hyperactivity disorder. Psychopharmacol Bull 1995; 31: 779-783. Findling RL, Schwartz MA, Flannery DL, Manos MJ. Venlafaxine in adults with attention-deficit hyperactivity disorder: an open clinical trial. J Clin Psychiatry 1996; 57: 184-189. Wender PH, Reimherr FW. Buproprion treatment of attention deficit hyperactivity disorder in adults. Am J Psychiatry 1990; 147: 1018-1020. Wood DR, Reimherr FW, Wender PH. The use of l-deprenyl in the treatment of attention deficit disorder, residual type (ADD, RT). Psychopharmacol Bull 1983; 19: 627-629. (Received 4 Feb, accepted for publication 20 Jul, 1999) Authors' details Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW. Julian N Trollor, MB BS, FRANZCP, Staff Specialist; and Conjoint Lecturer, School of Psychiatry, University of New South Wales. Reprints will not be available from the author. Correspondence: Dr J N Trollor, Neuropsychiatric Institute, McNevin Dickson Building, Prince of Wales Hospital, Randwick, NSW 2031. J. TrollorATunsw.edu.au 1: Summary of DSM-IV criteria for attention deficit hyperactivity disorder1 (all criteria from A to D must be met) A: Six or more symptoms of either Inattention or Hyperactivity-impulsivity present for at least six months to a degree that is maladaptive and inconsistent with developmental level. Inattention Often: fails to give close attention to details or makes careless mistakes in schoolwork, work or other activities has difficulty sustaining attention in tasks or play activities does not seem to listen when spoken to directly does not follow through on instructions and fails to finish schoolwork, chores or duties in the workplace has difficulty organising tasks and activities avoids, dislikes or is reluctant to engage in tasks that require sustained mental effort loses things necessary for tasks or activities easily distracted by extraneous stimuli forgetful in daily activities Hyperactivity-impulsivity Often: fidgets with hands, feet or squirms in seat leaves seat in classroom or other situations in which remaining seated is expected runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness) has difficulty playing or engaging in leisure activities quietly "on the go" or acts as if "driven by a motor" talks excessively blurts out answers before questions completed has difficulty awaiting turn interrupts or intrudes on others B: Some symptoms causing impairment were present before 7 years of age. C: Some impairment is present in two or more settings. D: Evidence of clinically significant impairment in social, academic or occupational functioning. Back to textBack to text 2: Differential diagnoses of adult attention deficit hyperactivity disorder Medical Past head injury or anoxia Sleep disorders (eg, sleep apnoea) Recent viral infection including HIV Long term medical illness (eg, renal or liver failure) Seizure disorder (eg, petit mal) Endocrine disorder (eg, hypothyroidism, hyperthyroidism, hypoglycaemia) Psychiatric Anxiety disorder Major depression Bipolar disorder (eg, chronic hypomania) Cyclothymia Antisocial and borderline personality disorders Effect of prescribed medications (eg, benzodiazepines, anticholinergic drugs, anticonvulsants) Other central nervous system disorder (eg, degenerative disorders) Substance misuse (alcohol, long term cocaine or amphetamine use, cannabis) Back to text Case history -- adult attention deficit hyperactivity disorder (ADHD) Presentation: A 22-year-old unemployed carpenter, referred by his general practitioner, reported difficulty concentrating when reading or listening to verbal instructions, and difficulty following through multistep tasks. He had lost numerous jobs because of poor organisational skills, failure to complete assigned tasks, and a tendency to become easily bored or frustrated in his work. He was disorganised in most aspects of managing his personal affairs. There was a history of experimenting with illicit substances, instability in interpersonal relationships, and low self-esteem. The patient's mother confirmed his account of untreated, moderately severe ADHD symptoms from school entry. Assessment: The patient was physically restless, easily distracted and verbally impulsive. There was no evidence of psychiatric or medical illness. Neuropsychological assessment revealed reduced arithmetic skills, reduced speed of information processing, impulsive responses and failure to maintain attention over time. A diagnosis of ADHD was made. Management: Combined psychological and pharmacological treatment was instituted. Over a series of 12 sessions, the patient was given information about ADHD, and participated in sessions to enhance organisational skills, impulse control and self-esteem. He was prescribed dextroamphetamine, 5 mg twice a day, and later the dose was increased to 5 mg three times a day. Both the patient and his family reported amelioration of his symptoms. He was able to successfully start a part-time job, and later returned to full-time employment as a carpenter. A trial without stimulant medication at 12 months led to appreciable exacerbation of symptoms, and dextroamphetamine was reinstituted. He has remained in stable employment over a follow-up period of 18 months and continues to take dextroamphetamine on work days only. Back to text

Julian N Trollor

Research Why do preterm infants die in the 1990s? Lex W Doyle, Sheryle Rogerson, Shu-Ling Chuang, Matthew James, Ellen D Bowman and Peter G Davis MJA 1999; 170: 528-532 Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - Articles on similar material Abstract Objectives: To describe the mortality rate for preterm infants (born 23-36 completed weeks' gestational age) and to determine the causes of death, focusing on avoidable causes. Design and setting: Prospective cohort study of preterm infants born at Royal Women's Hospital, Melbourne (a tertiary referral hospital with a neonatal intensive care unit and a special care nursery) from January 1994 to December 1996. Subjects: 2475 consecutive liveborn infants with gestational ages from 23 to 36 weeks. Main outcome measures: Mortality rate during the primary hospitalisation, and causes of death. Results: The total mortality rate was 4.8% (118/2475). The mortality rate declined with increasing maturity. The decrease in mortality was rapid between 23 and 28 weeks' gestational age, from 64.5% at 23 weeks to 4.0% at 28 weeks, then slower, falling to 0.4% at 36 weeks. Fifty of the 118 infants who died had lethal congenital anomalies. Lethal anomalies accounted for three-quarters of deaths in infants aged 28-36 weeks. The mortality rate in infants free of lethal anomalies was 2.8% (68/2425) and only 0.2% (4/1759) for infants aged 32-36 weeks. In the 68 infants without lethal anomalies who died, few obvious preventable causes were identified. Conclusions: Mortality rates fell rapidly between 23 and 28 weeks' gestational age. Survival rates for preterm infants born after 31 weeks' gestational age approached the survival rates of term infants. Lethal congenital anomalies were the most common cause of death; preventable causes of death were rare. Introduction The survival rate for very preterm infants (born at 23-27 weeks' gestational age) has improved dramatically with advances in perinatal care,1 particularly efforts to reduce neonatal respiratory distress syndrome (hyaline membrane disease), such as administering corticosteroids to the mother before delivery,2 administering exogenous surfactant to preterm infants,3 and assisted ventilation.4 However, mortality rates and causes of death for more mature but still preterm infants (28-36 weeks' gestational age) have received little attention, especially since the advent of exogenous surfactant in Australia in 1991. As hyaline membrane disease has diminished as a cause of death of preterm infants, other causes of death, some of which may be preventable, have assumed more prominence. The aim of this study of preterm infants 23-36 weeks' gestational age born in 1994-1996 in a hospital with neonatal intensive care facilities was to describe the variation with gestational age in the mortality rate and the causes of death, focusing on avoidable causes. Methods Setting This was a prospective cohort study of consecutive livebirths between 23 and 36 completed weeks of gestational age in the Royal Women's Hospital, Melbourne, over the three years from 1 January 1994 to 31 December 1996. Data collection Data have been collected prospectively since 1977 on all infants admitted to the neonatal intensive care unit (NICU), all infants of birthweight below 1500 g, and all infants below 32 weeks' gestational age, whether admitted to the NICU or not. Data on infants 32 to 36 weeks were collected from the special care nursery (SCN) admissions book, and the hospital's main computer database was checked to obtain data on those not admitted to either the NICU or SCN. Data collected included gestational age, birthweight, and mortality during the primary hospitalisation, whether during the neonatal period (first 28 days after birth) or later. Data were included for infants transferred from our hospital to another. Gestational age in completed weeks was assigned according to the first antenatal ultrasound scan, or maternal dates if no ultrasound report was available. Birthweight ratio was calculated by dividing the infant's birthweight by the expected gender-specific median birthweight for that gestational age.5 Causes of death For infants who died, the major causes of death were determined after the regular monthly clinicopathological conference at which the deaths of all livebirths within the hospital were discussed, and which was chaired by one of the authors ( LW D), who retained all records from the meeting. Causes of death included lethal congenital anomalies, complications of prematurity, perinatal asphyxia, or sepsis (Box 1). Preventable causes of death For each infant who died, avoidable factors included whether antenatal corticosteroids or surfactant had been given to infants who died from respiratory causes, whether intramuscular vitamin K had been given to those who died from pulmonary haemorrhage, whether appropriate anti-infective therapies were given to those who died from infection, and whether antenatal corticosteroids had been given to those who died from cerebroventricular haemorrhage or cystic periventricular leukomalacia. Data analysis Mortality data for preterm births at the Royal Women's Hospital were compared with published data for livebirths in Victoria in 1994,7 1995,8 and 1996,9 and for admissions to neonatal intensive care units in Australia and New Zealand in 1994.10Data were edited and analysed with SPSS for Windows.11 Dichotomous variables were contrasted by 2 analysis, and continuous variables were compared by Mann-Whitney U test,12 as most data were skewed. Results Causes of death There were 2475 infants of 23-36 weeks' gestational age born during the study period, of whom 118 died (4.8%). The mortality rate diminished rapidly between 23 and 28 weeks' gestational age (from 64.5% at 23 weeks to 4.0% at 28 weeks), then more slowly, to reach 0.4% at 36 weeks (Box 2). The autopsy rate in the infants who died was 51.8% (59/114), with no data on autopsies for four infants who died after transfer to other hospitals. Fifty infants died of lethal anomalies, all but two within 28 days of birth (Box 3). Lethal anomalies accounted for 11 of 67 deaths (16.4%) in infants born at 23-27 weeks' gestational age, 16 of 24 deaths (66.7%) in infants born at 28-31 weeks' gestational age, and 23 of 27 deaths (85.2%) in those born at 32-36 weeks' gestational age. Sixty-eight infants died who were without lethal anomalies: 2.8% of the 2425 livebirths, but only 0.2% of infants of 32-36 weeks' gestational age (4/1759) (Box 4). Sixty-one died within 28 days of birth and seven (10.3%) died later during the primary hospitalisation. In the Australian and New Zealand Neonatal Network, 35 of 256 deaths (13.7%) of infants of less than 32 weeks' gestational age without lethal anomalies died during the primary hospitalisation but after 28 days of age.10 Preventable causes of death Respiratory problems: The mothers of 23 of the 30 infants who died from HMD or BPD had received antenatal corticosteroids. In the remaining seven cases, the gestational ages were 23 or 24 weeks. In six cases there was not enough time to give corticosteroids, five mothers presenting in advanced preterm labour and one with eclampsia. In the seventh case, the gestational age was 23 weeks and before birth the infant was considered incapable of surviving, yet was given full intensive care postnatally. All 30 infants who died from HMD or BPD received exogenous surfactant after birth. The one infant who died from pulmonary haemorrhage without HMD received antenatal corticosteroids and did not have respiratory distress after birth and therefore did not re- ceive exogenous surfactant; the fatal pulmonary haemorrhage occurred at three days of age. The two infants who had HMD and pulmonary haemorrhage also received antenatal corticosteroids. All three infants who died from pulmonary haemorrhage had received intramuscular vitamin K at birth. None had clinical signs of heart failure or a patent ductus arteriosus before the haemorrhage. None had clinical indications for an echocardiogram, hence subclinical cardiac dysfunction cannot be excluded. Considering the 12 infants in the gestational age range 28-36 weeks who died without lethal anomalies, six died from sepsis, two from asphyxia, two from BPD, one from pulmonary haemorrhage, and one from SIDS. None died acutely from HMD. Infections: In the 22 infants who died from sepsis without NEC, there were only two in whom the management might have been different. In one infant of 30 weeks' gestational age the mother ignored the antenatal signs of sepsis for several days before presenting to hospital and delivering a moribund infant who died at 11 hours of age from E. coli pneumonia, despite full treatment, including appropriate antibiotics. In the other infant, of 33 weeks' gestation, who died of herpes simplex, the clinical presentation was that of sepsis several days before death, but, in the absence of other features of herpes in the mother or infant, no antiviral therapy was given. CVH and CPVL: Antenatal corticosteroids were given to the mothers of all nine infants in whom CVH or CPVL were major contributing causes of death. In addition to the five infants in whom CVH was a major cause of death, another 12 infants who died had a grade 3 or 4 CVH that was thought not to contribute substantially to their deaths. Comparison with regional outcomes The neonatal survival rate for infants of 24-31 weeks' gestational age at our hospital was similar to that reported in regional data from Victoria for the same three years7-9 (Box 5). In livebirths of less than 2500 g birthweight in Victoria in 1994-1996, 377 infants died within 28 days; 33.4% with lethal anomalies (compared with 44.0% in our hospital cohort; 2 = 3.7, not significant) and 5.6% died from infections (compared with 24.8% in our hospital; 2 = 32.9, P < 0.0001). The neonatal mortality rate in livebirths free of lethal malformations with birthweights greater than 2499 g was 0.45 per 1000 (81/178834) in Victoria in 1994-1996,7-9 compared with 2.27 per 1000 (4/1735) in infants of 32-36 weeks' gestational age in our hospital. The survival rate to hospital discharge in 1994 for infants free of lethal malformations cared for in neonatal nurseries at 23-31 weeks' gestational age was higher in our hospital than in reported data from the Australian and New Zealand Neonatal Network (Box 6). Discussion Comparing our data with regional data in Australia is difficult. States and territories provide data to the Australian Institute of Health and Welfare (AIHW), which then produces an annual report.13 However, the denominator in the AIHW report is predominantly determined by birthweight; gestational age is reported for confinements (ie, mothers), or for births, but not for all livebirths. Regional reports from Victoria provide data for births, including stillbirths and livebirths, by gestational age, but in two-week intervals, and only up to 31 weeks' gestational age.7-9 Moreover, the numerator in both of these regional data sets is usually limited to the neonatal period, rather than the primary hospitalisation. The Australian and New Zealand Neonatal Network collects data from all the Australian and New Zealand Neonatal Intensive Care Units.10 In this data set, the denominator is limited to admissions to neonatal units, eliminating livebirths who die outside the neonatal unit, and hence augmenting the reported survival rates. Moreover, this data set is limited to infants up to 31 weeks' gestation and excludes those with lethal malformations. The numerator, however, includes deaths in the neonatal period and those beyond 28 days of age that occur during the primary hospitalisation. Comparing data on cause of death is also difficult. Most government data collection sources, such as those in Victoria7-9 and other States, rely on confidential reports. They may not obtain enough data to classify the cause of death, and rarely can they confirm the gestational age. The final report includes an individual infant under only one cause of death, even though there may be several equally contributing causes of death, such as the common combination of HMD and airleak, which caused 25% of deaths from non-lethal causes in our study. Our system of clinicopathological conferences for each death, although not perfect, provided more detailed information about causes of death. As regional data sources do not provide complete data on deaths during the primary hospitalisation at all gestational ages, we cannot compare survival rates for preterm infants (32-36 weeks) with those of term infants (37-42 weeks). However, we have calculated rates of neonatal survival in Victoria for livebirths free of lethal malformations with birthweight greater than 2499 g, assuming that the results would be similar for infants of 37-42 weeks' gestation. In our hospital, the neonatal survival rate for infants of 32-36 weeks' gestational age (99.77%) approached the neonatal survival rate expected of term infants in Victoria (99.95%). The commonest causes of death were lethal anomalies, sepsis, and HMD. Deaths from lethal anomalies are over-represented in our hospital compared with Victoria as a whole as most have been diagnosed antenatally, and, in many cases, the mother has been transferred before birth from another hospital for management because of the fetal anomaly. The death rate from infection is higher in our hospital than for Victoria, but this is probably because infants in our hospital live longer, and hence acquire infections, rather than dying soon after birth from other problems related to prematurity. E. coli and Group B streptococci remain the chief cause of septic deaths, particularly soon after birth, consistent with the observations of Isaacs et al.14 Staphylococcus species are an increasingly frequent cause of late infections,15 and of late deaths in our study. HMD remains a leading cause of death for very preterm infants despite the fact that most mothers receive antenatal corticosteroid therapy and all infants receive exogenous surfactant. Improvements in exogenous surfactant offer hope of reducing mortality further, but other antenatal interventions, such as thyrotropin stimulating hormone,16 have been disappointing in large randomised controlled trials. HMD did not cause any deaths in our hospital in more mature preterm infants (28-36 weeks). Within the infants who died from HMD, the observation that those who also had an airleak were not as growth restricted as those who had no airleak might reflect some structural change within the lung or with use of pulmonary surfactant that is associated with growth restriction. The problem of extreme intrauterine growth restriction is highlighted by the deaths from pulmonary haemorrhage in three infants, all with birthweight ratios below 0.55. The pulmonary haemorrhage was not caused by failure to give intramuscular vitamin K at birth.17 The mechanism for fatal pulmonary haemorrhage is unclear, but may represent acute left heart failure, contributed to by a patent ductus arteriosus. The association of pulmonary haemorrhage and fetal growth restriction is well known and may be related to histological changes in the ductus arteriosus in growth-restricted fetuses.18 Pulmonary haemorrhage is also seen more frequently with exogenous surfactant therapy,19 which was given to two of the three infants in our study who died of pulmonary haemorrhage. Preventing prematurity, an obvious solution to the problem of higher death rates in preterm infants, remains an elusive goal. In all infants who died, few obvious preventable factors, apart from avoiding preterm birth, were evident. The Annual Report from the Victorian Consultative Council on Obstetric and Paediatric Mortality and Morbidity consistently identifies more avoidable factors in stillbirths than neonatal deaths.7-9 In summary, mortality rates fell sharply between 23 and 28 weeks' gestational age, and few infants of more than 28 weeks' gestational age without lethal anomalies died. Survival rates for preterm infants of more than 31 weeks' gestational age approached the survival rates expected of term infants. There were few obvious avoidable factors in the deaths of any of the infants who died, either in the very preterm infants of 23-27 weeks' gestational age, or the more numerous preterm infants of 28-36 weeks' gestational age. References The Victorian Infant Collaborative Study Group. Outcome at 2 years of children 23-27 weeks' gestation born in Victoria in 1991-92. J Paediatr Child Health 1997; 33: 161-165. Crowley P. Corticosteroids before preterm delivery (Cochrane Review). In: The Cochrane Library, Issue 2. Oxford: Update Software, 1998. [Updated quarterly.] Soll RF. Natural surfactant extract vs synthetic surfactant in the treatment of established respiratory distress syndrome (Cochrane Review). In: The Cochrane Library, Issue 2. Oxford: Update Software, 1998. [Updated quarterly.] Doyle LW, Davis P, Dharmalingam A, Bowman E. Assisted ventilation and survival of extremely low birthweight infants. J Paediatr Child Health 1996; 32:138-142. Beeby PJ, Bhutap (sic) T, Taylor LK. New South Wales population-based birthweight percentile charts. J Paediatr Child Health 1996; 32: 512-518. Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline- membrane disease: bronchopulmonary dysplasia. N Engl J Med 1967; 276: 357-368. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual report for the year 1994. Melbourne: Department of Human Services, 1995. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual Report for the Year 1995: Incorporating the 34th Survey of Perinatal Deaths in Victoria. Melbourne: Department of Human Services, 1996. <http://hna.ffh.vic.gov.au/phb/hce/peri/ob95/index.htm> Accessed 11 May 1999. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Annual report for the year 1996. Melbourne: Department of Human Services, 1997. <http://hna.ffh.vic.gov.au/phb/hce/peri/rep_96/contents.htm> Accessed 11 May 1999. Donoghue DA. Australian and New Zealand Neonatal Network, 1994. Sydney: AIHW National Perinatal Statistics Unit, 1996. [Neonatal Network Series no. 1.] SPSS for Windows version 6.1 [computer program]. Chicago: SPSS Inc, 1994. Moses LE, Emerson JD, Hosseini H. Analyzing data from ordered categories. N Engl J Med 1984; 311: 442-448. Lancaster P, Huang J, Lin M. Australia's mothers and babies 1993. Sydney: AIHW National Perinatal Statistics Unit, 1996. [Perinatal Statistics Series No. 3.] Isaacs D, Barfield C, Clothier T, et al. Early-onset group B streptococcal infections in Aboriginal and non- Aboriginal infants. Med J Aust 1995; 163: 302-306. Isaacs D, Barfield C, Clothier T, et al. Late-onset infections of infants in neonatal units. J Paediatr Child Health 1996; 32:158-161. Actobat Study Group. Australian collaborative trial of antenatal thyrotropin-releasing hormone (ACTOBAT) for prevention of neonatal respiratory disease. Lancet 1995; 345: 877-882. Loughnan PM, McDougall PN, Balvin H, et al. Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1. J Paediatr Child Health 1996; 32: 268-269. Ibara S, Tokunaga M, Ikenoue T, et al. Histologic observation of the ductus arteriosus in premature infants with intrauterine growth retardation. J Perinatol 1994; 14: 411-416. Raju TN, Langenberg P. Pulmonary hemorrhage and exogenous surfactant therapy: a metaanalysis. J Pediatr 1996; 123: 603-610. (Received 29 Jun 1998, accepted 25 Mar 1999) Authors' details Division of Paediatrics, The Royal Women's Hospital, Melbourne, VIC. Lex W Doyle, MD, MSc, FRACP, Paediatrician, and Associate Professor, Department of Obstetrics and Gynaecology, University of Melbourne; Sheryle Rogerson, MB BS, Paediatric Fellow; Shu-Ling Chuang, MB BCh, MRCP, Paediatric Fellow; Matthew James, MB ChB, MRCP, Paediatric Fellow; Ellen D Bowman, MB BS, FRACP, Paediatrician; Peter G Davis, MD, BS, FRACP, Paediatrician. Reprints will not be available from the authors. Correspondence: Associate Professor Lex Doyle, Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC 3052. Email: l.doyle@obgyn-rwh.unimelb.edu.au ©MJA 1999 Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1999 Medical Journal of Australia. 1: Causes of death defined Lethal congenital anomalies: Any infants with major malformations that were considered untreatable or who died despite attempts at surgical correction, and infants with untreatable inborn errors of metabolism, chromosomal abnormalities, or overwhelming congenital infection acquired early in pregnancy. Complications of prematurity: Hyaline membrane disease (HMD), with or without an airleak: clinical signs of respiratory distress in the first days after birth, supported by radiological and/or autopsy evidence. Airleak comprised any air not confined to normal airspaces, such as pulmonary interstitial emphysema or pneumothorax. Bronchopulmonary dysplasia (BPD): respiratory distress beyond four weeks of age requiring oxygen therapy, and radiographic changes typical of bronchopulmonary dysplasia,6 or a pathological diagnosis of bronchopulmonary dysplasia at autopsy. Necrotising enterocolitis (NEC): confirmed by definite radiological, operative, or autopsy evidence. Cerebroventricular haemorrhage (CVH): included any evidence of haemorrhage of any degree identified by ultrasound examination or autopsy. Cerebroventricular haemorrhage was considered a substantial contributor to death when knowledge of an intracerebral haemorrhage (grade 4) led to withdrawal of intensive care and the infant subsequently died. Cystic periventricular leukomalacia (CPVL): included any cystic degeneration within the cerebral cortex. Cystic periventricular leukomalacia was considered the cause of death when it was severe enough to lead to the withdrawal of intensive care. Ultrasound scanning was routine within the first three days after birth, at the end of the first week, then monthly until discharge as a minimum. Pulmonary haemorrhage was diagnosed in infants with frothy, blood-stained tracheal fluid and clinical deterioration in respiratory function, or at autopsy. Perinatal asphyxia: Infants who were liveborn but failed to respond adequately to resuscitation at birth. Neonatal sepsis: Infants who died with clinical signs of sepsis supported by positive blood or cerebrospinal fluid (CSF) culture, but also included the occasional infant in whom sepsis was considered likely, but in whom blood or CSF cultures were sterile because of prior treatment with antibiotics, most commonly via the mother before birth. Pneumonia was diagnosed in infants with respiratory distress, signs of sepsis and a chest x-ray consistent with pneumonia, or at autopsy. Back to textBack to textBack to text 4: Causes of death in 68 preterm infants without lethal anomalies born at Royal Women's Hospital, Melbourne, January 1994-December 1996Median gestationalMedianMajorNumberage in weeksbirthweightcause*(%)(range)(range)Not offered intensive care7 (10.3%)23 (23-23)580 (545-725)Perinatal asphyxia5 (7.6%)26 (24-28.5)725 (630-1322)Sepsis27 (39.7%)25 (23-26)751 (606-896)NEC5 (7.4%)24 (23-29.5)756 (610-916)HMD23 (33.8%)24 (23-26)600 (522-750)HMD with airleak17 (25.0%)24 (23-25.5)670 (561-853)HMD without airleak6 (8.8%)25.5 (23-27) 509 (371-582)BPD7 (10.3%)26 (24-28)711 (640-751)CPVL4 (5.9%)25 (24-27)765 (568-858)Pulmonary haemorrhage3 (4.4%)27 (27-30)¶390 (315-756)¶Other**5 (7.4%)Total6825 (23-27)721 (590-856)MedianMedian days ofMajorbirthweight ratioage at deathcause*(range)(range)Not offered intensive care1.03 (0.94-1.23)1 (1-1)Perinatal asphyxia0.96 (0.83-1.13)1 (1-1)Sepsis1.00 (0.90-1.09)8 (1-15)NEC1.02 (0.68-1.16)14 (10-22.5)HMD0.92 (0.82-1.07)2 (1-4)HMD with airleak0.99 (0.89-1.13)2 (1-3.5)HMD without airleak0.66 (0.36-0.92)1.5 (1-5)BPH0.80 (0.66-0.92)38 (19-141)CPVL0.82 (0.76-1.13)49 (22-55)Pulmonary haemorrhage0.37 (0.30-0.54)¶5 (3-5)¶Other**Total0.95 (0.82-1.07)* Some infants had more than one major cause of death. Range = interquartile range. BPD = bronchopulmonary dysplasia Includes five infants who died with NEC. Six also had HMD, two had both HMD and CVH, and two had CVH. CPVL = cystic periventricular leukomalacia Three infants also had CVH and two had pulmonary haemorrhage. CVH = cerebroventricular haemorrhage¶ Range = complete range. HMD = Hyaline membrane disease** Two with cardiomyopathy following twin-twin transfusion syndrome, one spontaneous gut perforation, one neuroblastoma, one sudden infant death syndrome. NEC = necrotising enterocolitisInfants not offered intensive care were significantly less mature than those who died after intensive care (median gestational age 23, interquartile range 23-23 v. median gestational age 25, interquartile range 24-27; z = 3.0, P < 0.01). Excluding those with lethal anomalies and those not offered intensive care, children dying with HMD were less mature than those dying without HMD (median gestational age 24, interquartile range 23-26 v. median gestational age 26, interquartile range 24-28; z = 2.9, P < 0.01) and lighter at birth (median birthweight 600 g, interquartile range 522-750 g v. median birthweight 758 g, interquartile range 683-888 g; z = 3.0, P < 0.01), but had similar birthweight ratios (median 0.92, interquartile range 0.82-1.07 v. median 0.96, interquartile range 0.81-1.05, not significant). Within the group of infants who died of HMD, those who also had airleak were not significantly different in maturity, but were significantly heavier (z = 2.7, P < 0.01) and had higher birthweight ratios (z = 2.5, P < 0.02). The three infants who died of pulmonary haemorrhage were particularly growth restricted, with birthweight ratios of 0.30, 0.37, and 0.54, respectively; their median birthweight ratio of 0.37 was substantially below that of the infants who died of other causes (median birthweight ratio 0.96, interquartile range 0.85-1.07; z = 2.8, P < 0.01). Most infants who died did so soon after birth, except those who died of sepsis, BPD, or CPVL. Infants who died of sepsis were generally quite immature and small at birth, but were not particularly growth restricted. In infants without NEC who died of sepsis, the infectious organisms were Escherichia coli (8), Group B streptococci (3), Staphylococcus aureus(5), S epidermidis (1), Haemophilus influenzae (1), Klebsiella and Pseudomonas spp. combined (1), Streptococcus viridans (1), Candida albicans (1) and herpes simplex (1). E. coli and Group B streptococci were the predominant organisms causing early infections, and Staphylococcus species, later infections. Back to textBack to textBack to text

Lex W Doyle · Sheryle Rogerson · Shu-Ling Chuang · Matthew James · Ellen D Bowman · Peter G Davis

Viewpoint Rethinking the early childcare agenda Who should be caring for very young children? Peter S Cook MJA 1999; 170: 29-31 Introduction - High-quality childcare - Evidence of undesirable outcomes - Being with mother - Many mothers want to care for their own children - A rethink is needed - Acknowledgement - References - Authors' details - - More articles on Paediatrics Introduction In Western societies, mothers often seek paid employment because of societal or economic pressures or a desire to continue a career, and place their infants in childcare centres. There is a perception that trained carers can rear children as well as, or perhaps better than, the mothers themselves.1 The Australian Child Care Task Force2 has recommended subsidised expansion of the "childcare industry", saying that all families should have access to affordable, high quality childcare by trained, professional carers. "Childcare" in this article refers to institutional day centre care, but in research studies it may variously mean any regular non-maternal care or non-parental care. Theoretically, children can spend as many hours in childcare by the age of five as they will spend in school over the next 12 years.3 I argue here that for children up to 2½ to 3 years of age, and particularly during infancy, this agenda of subsidised, universally available, high quality professional childcare is misconceived, and a rethink is needed. Evidence suggests that this agenda: Is unrealistic (eg, high quality childcare for all is not affordable); Overlooks accumulating evidence of risks of undesirable outcomes sometimes associated with early childcare; Is contrary to much expert opinion about what is likely to be best for infants; Is contrary to the desire of many working mothers to care for their own children, if they could afford it; and Relies partly on the now-discredited ideology of cultural determinism. High-quality childcare for all is unrealisable Morgan concluded that "Affordable care is low-quality care" and the "difficulties and cost of providing good quality care, with its highly involved and trained staff, small group size, caregiver stability and low infant to caregiver ratios, should surely demonstrate how 'affordable, universally available, good-quality, easily accessible childcare' . . . is a chimaera, unrealisable in the real world."1Australian standards require one carer for five infants under two, which professionals consider inadequate.1,4,5 Moreover, although Australian governments subsidise 60% of childcare costs,2 Loane found "mediocrity more prevalent than excellence",4 reporting that an assessment of half of Australia's 2400 childcare centres showed 13% failed the national accreditation3 and 40% achieved only the minimal standard, with frequent inadequacies in areas such as child management, safety, health, and nutrition.4 Evidence of undesirable outcomes, sometimes independent of quality Evidence about the effects of childcare, beneficial or harmful, is incomplete and sometimes contradictory. Research into outcomes (whether by standardised tests, or behavioural or socioemotional ratings) is inherently complex, with imperfect instruments, and many confounding variables. Longitudinal studies, showing longer term outcomes, require dedication, expertise, time and money. The interpretation of outcome studies has been hotly debated.6-9 While many infants in childcare apparently thrive, Morgan has reviewed the "mounting evidence of adverse side-effects",1 and some of the evidence pointing to risks is outlined here. Not surprisingly, children in childcare have an increased risk of infectious diseases,10 but the psychological effects are of most concern, as the foundations of the human mind and emotional development are laid in these early years.11 An enduring aspect of the child's world is the parent-child relationship, and one central feature of this relationship is the infant-mother attachment. As mammals, secure attachments between infants and their mothers (and/or effective surrogate mothers) have been vital for our species' survival.7,8,12 Research shows that the security or insecurity of this attachment provides the foundation upon which subsequent relations with adults and peers are built.12 According to Rutter, moderate but significant associations have been found between insecure attachment and various forms of psychopathology both in childhood and adult life.13 To settle some controversies, a multicentre, longitudinal US childcare study is currently investigating the influence and interactions of selected variables on childcare outcomes. These variables include child's sex and temperament, mother's psychological adjustment and sensitivity in the home and at play, and type of childcare, age of child at entry, amount and stability of childcare, and childcare quality assessed for the individual child. This study has established that the security of infant-to-mother attachment can be reliably and validly assessed at 15 months of age.14 Some findings associated with increased risk are shown in the Box. While some of these differences were modest or small, they were consistent in direction. Further analysis through the course of this major study may illuminate the longer-term significance of these findings. Meanwhile, although earlier research had limitations (eg, sample bias and lack of standardised measures of childcare quality), a meta-analysis17 of the 101 childcare outcome studies from many countries published in peer-reviewed journals between 1957 and 1995 found robust evidence of adverse outcomes associated with non-maternal care in the areas of children's infant-mother attachment security, their socioemotional development (including increased anger, anxiety, and hostility in boys, and overdependency, anxiety, and depression in girls), and in their behaviour (including hyperactivity, aggression and non-compliance). They found no support for the belief that high quality day care is an acceptable substitute for parental care. Statistical analysis of group findings can obscure individual reactions. Harsman18 studied 26 infants before they commenced Swedish quality long daycare centre at ages ranging from 6 to 12 months. She followed them through five months in childcare, comparing them with 26 controls (matched pairwise for age, sex and socioeconomic background) cared for by their mothers. Although many infants adjusted easily to childcare, at one stage 11 of the children were assessed as "sad and depressed" in the childcare situation. By the end of the study, the childcare group showed significantly lower scores than the mother-care group in the hearing, speech, and personal-social subscales of the Griffiths' Mental Development Scale.18 Space precludes discussion of the adverse effects on parents, but many mothers in two-income families are overloaded and "stressed-out".1,2 Being with mother is likely to be best This childcare agenda, in disregarding the child's age, is contrary to much expert professional opinion that, ideally, it is likely to be best for very young children to be mostly with their mothers. Of 904 professional members of the World Association for Infant Psychiatry and Allied Disciplines from 56 countries, 402 responded anonymously to a survey asking what kinds of care, at various ages up to 36 months, they considered likely, ideally, to be best from the infants' viewpoint.19 A majority of the respondents believed that it is "very important" for infants "to have their mothers available to them through most of each 24 hours" for more than one year, and to be cared for "principally by mother" until over two years. Only 11% selected full-day group care as the best option for children aged up to 30 months. The author concluded: "The findings show that the polled professionals consider that the development and well-being of children under 3 would be served best by patterns of care that are diametrically opposed to those politicians promise, policy-makers aspire to provide and parents strive to find".19 Many mothers want to care for their own children According to extensive surveys of mothers seeking or using childcare in order to work, many mothers would prefer to care for their young children at home if they could afford to do so.1,20,21 Moreover, in 1993, 65% of Australians reportedly thought it preferable that mothers of preschool children should not take paid employment outside the home.22 Yet when, as in Australia, taxation systems largely disregard childrearing costs23 and favour two-income families, the latter can outbid single-income families in acquiring homes. Prices rise to the level the market will bear and, to compete, more mothers seek paid employment and childcare.1,24 Childcare subsidies aggravate this vicious circle, unless balanced by equal help to home-caring parents through "family-friendly" taxation policies.23,25 A rethink is needed This childcare agenda relies partly on the now-discredited ideology of cultural determinism,26-28 which taught that human nature is culturally determined by social conditioning, denying evolutionary and biological influences. Yet the needs of infants and their mothers, as mothers, are based in our genes and cannot be refashioned to suit ideologies. We need social patterns of support for parenting which respect the human givens, recognising that we each have a pedigree of mothers who, overall (through millions of years), were selected for success in all the essential processes of primate mothering -- including childbirth, breastfeeding, and bonding/attachment, as well as the carrying and rearing of a baby girl who would grow up to do likewise -- not in isolation but within a related social group.8,29,30 Research increasingly illuminates the long-term significance of optimal early maternal nurture for healthy cognitive, emotional and physical development.11,31-35 The precautionary principle -- primum non nocere -- is fundamental in healthcare. Large-scale institutional, long-daycare rearing of babies and very young children by professionals offering no continuing relationship with them is without successful precedent in the history of our species. When the evidence and professional opinion agree that mothers are the best people to care for their young children, it seems neither wise nor cost-effective15 for governments to spend large sums of money subsidising childcare for mothers who would prefer to be helped to care for their infants themselves. Perhaps "How can we provide quality childcare for everybody?2" asks the wrong question. Taking into account the biologically determined needs of young human beings and their mothers, we should be asking "How -- in our detribalised societies -- can we best help and support those parents who wish to do a mutually satisfying job of mothering and fathering their infants and young children without jeopardising their own futures?". Some proposals have been offered,1,8,20,23,30,36 and I suggest that if some of the resources directed towards providing childcare were creatively redirected to supporting high quality parenting we would be more likely to achieve our real goal of enhancing the well-being of mothers, young children, and society. Acknowledgement I am indebted to Professor Jay Belsky, Distinguished Professor of Human Development and Family Studies at Pennsylvania State University, for his generous willingness to communicate with me, but responsibility for the text is mine. References Morgan P. Who needs parents? The effects of childcare and early education on children in Britain and the USA. London: Institute of Economic Affairs, 1996: 1-15, 48-58, 90-98, 114-118. Economic Planning Advisory Commission Child Care Task Force. Future child care provision in Australia. Canberra: AGPS, 1996: xv, xvi, 16, 37. National Childcare Accreditation Council. Putting children first: quality improvement and accreditation system handbook. Sydney: National Childcare Accreditation Council, 1993. Loane S. Who cares? guilt, hope and the child care debate. Melbourne: Reed, 1997: 120-152. Hope D. Spare the non-maternal care and nurture the child. The Australian 1998 4 June. Belsky J. Consequences of child care for children's development: a deconstructionist view. In: Booth A, editor. Child care in the 1990s: trends and consequences. New Jersey: Lawrence Erlbaum, 1992: 83-94. Karen R. Becoming attached: unfolding the mystery of the infant-mother bond and its impact on later life. New York: Warner, 1994. Cook PS. Early child care -- infants and nations at risk. Melbourne: News Weekly Books, 1997: 26-31, 76-89, 154-158, 182-190. Ochiltree G. Effects of child care on young children: forty years of research. Melbourne: Australian Institute of Family Studies, 1994. (Early childhood study paper No. 5.) Ferson MJ. Control of infections in child care. Med J Aust 1994; 161: 615-618. Cockburn F. The minds of our children: sensory input and the development of the human infant brain and mind. The British Association of Perinatal Medicine Founder's Lecture. Proceedings of the XVth Congress of Perinatal Medicine; Sep 1996; Glasgow. London: Parthenon, 1997: 53-60. Belsky J, Cassidy J. Attachment: theory and evidence. In: Rutter M, Hay D, editors. Development through life: a handbook for clinicians. Oxford: Blackwell Scientific Publications, 1994: 373-402. Rutter M. Clinical implications of attachment concepts: retrospect and prospect. J Child Psychol Psychiatry 1995; 36: 549-571. National Institute of Child Health and Human Development. Early Child Care Research Network. The effects of infant child care in infant-mother attachment security: results of the NICHD study of early child care. Child Dev 1997; 68: 860-879. Belsky J. Early childcare, parenting, and the parent-child relationship. Invited testimony delivered to the US Senate Subcommittee on Children and Families, 23 Jan 1998. National Institute of Child Health and Human Development. Early Child Care Research Network. Mother-child interaction and cognitive outcomes associated with early child care: results of the NICHD study up to 36 months. Bethesda, Maryland: NICHD, April 1997. Violato C, Russell C. A meta-analysis of the published research on the effects of non-maternal care on child development. In: Violato C, Genuis M, Paolucci E, editors. The changing family and child development. London: Ashgate. In press. Harsman I. Dagliga separationer och tidig daghemsstart. (Daily separations and early entry into day care). Stockholm: HLS Forlag, 1994 (ISBN 91-7656-334-0). Leach P. Infant care from infants' viewpoint: the views of some professionals. Early Dev Parent 1997; 6: 47-58. Leach P. Children first: what society must do -- and is not doing -- for children today. Harmondsworth, Middlesex: Penguin, 1994: 68-102: 240-265. Vandenheuvel A. Mothers with young children: should they work? Do they want to work? Family Matters 1991; 30: 47-49. (Melbourne: The Australian Institute of Family Studies.) Evans MDR. Norms on women's employment over the life course: Australia 1989-1993. Worldwide Attitudes, International Social Science Survey, Australia, ISSN 1323-9589, Canberra: Research School of Social Sciences, Australian National University, 1995. Sullivan L. Tax injustice: keeping the family cap-in-hand. Sydney: Centre for Independent Studies, 1998. (Issue analysis No. 3.) Ochiltree G, Edgar D. Today's child care, tomorrow's children. Melbourne: Australian Institute of Family Studies, 1995. (Early childhood study paper No. 7.) Casey DJ. Economic justice for the family. The Australian Family 1996; 17(3): 11-17. (Melbourne: The Australian Family Association.) Freeman D. The debate at heart is about evolution. In: Fairburn M, Oliver WH, editors. The certainty of doubt: Tributes to Peter Munz. Wellington: Victoria University Press, 1996. Freeman D. Margaret Mead and the heretic: the making and unmaking of an anthropological myth (Foreword). Melbourne: Penguin, 1996: vi-xiv. Freeman D. The fateful hoaxing of Margaret Mead: an historical analysis of her Samoan researches. Boulder, Colo: Westview, 1998. Werner EE. Infants around the world: cross-cultural studies of psychomotor development from birth to two years. J Cross-Cult Psychol 1972; 3: 111-134. Cook PS. Childrearing, culture and mental health: exploring an ethological-evolutionary perspective in child psychiatry and preventive mental health, with particular reference to two contrasting approaches to early childrearing. Med J Aust 1978; Spec Suppl 2: 3-14. Lucas A, Morley R, Cole TJ, et al. Breast milk and subsequent intelligence quotient in children born pre-term. Lancet 1992; 339: 261-264. Prescott JW. Affectional bonding for the prevention of violent behaviors: neurobiological, psychological, and religious/spiritual determinants. In: Hertzberg AJ, et al, editors. Violent behavior, Vol 1: Assessment and intervention. New York: PMA Publishing, 1990: 110-142. Prescott JW. The origins of human love and violence. J Prenat Perinat Psychol 1996; 10(3): 143-188. Higley JD, Thompson WW, Champouz M, et al. Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in Rhesus monkeys (Macaca mulatta). Arch Gen Psychiatry 1993; 50: 615-623. Meaney MJ, Bhatnagan S, Dioria J, et al. Molecular basis for the development of individual differences in the hypothalamic-pituitary-adrenal stress response. Cell Mol Neurobiol 1993; 13: 321-347. Cook PS. Antenatal education for parenthood, as an aspect of preventive psychiatry: some suggestions for programme content and objectives. Med J Aust 1970; 1: 676-681. For comment see Slack-Smith et al's Letter to the Editor 2 August 1999 Authors' details 62 Greycliffe Street, Queenscliff, NSW 2096. Peter S Cook, FRANZCP, MRCPsych, Child Psychiatrist (retired). Reprints: Dr P S Cook, c/o PO Box 84, Repton, NSW 2454. Email: pcookATmidcoast.com.au ©MJA 1999 © 1999 Medical Journal of Australia. Some findings of a major longitudinal childcare study in the United States Analysis of children aged 15 months found:14,15 Quality of care was important, assessed, not globally, but by how sensitive, responsive, affectionate and (cognitively) stimulating the carers were in the individual carer-child relationship. Children in lower quality childcare risked adverse outcomes.15 Evidence for whether quality childcare compensated for lower quality maternal care was mixed, but the less time children of insensitive mothers spent apart from them in childcare the more likely they were to be securely attached. Regardless of childcare quality and other variables, boys in more than 30 hours of non-maternal care per week had an increased risk of insecure attachment. Infants whose mothers rated in the lowest 25% for "sensitivity" (summarising extensive observational assessments) had an increased risk of insecure attachment if they had over 10 hours' non-maternal care per week. Childcare of low quality, or instability (more than one change of arrangement), each independently increased an infant's risk of insecurity. Separate risk factors appeared to be cumulative in their effects. Analysis of children aged 36 months found:16 Family and child characteristics were major influences in predicting outcomes, both in mother-child relationships and in cognitive and language areas. Childcare variables had smaller, but consistent, additional effects on mother-child relationships. Poorer-quality childcare had adverse influences, and more hours in non-maternal care (mean weekly hours recorded across 0-6, 0-15, 0-24, and 0-36 months) were associated with less sensitive and engaged mother-child interactions across the first three years, and with the child showing less affection towards the mother at 24 and 36 months. Back to text

Peter S Cook

Medical Research Perspectives The TVW Telethon Institute for Child Health Research The birth and growth of a research institute Fiona Stanley Diverse research workers, variously funded by public and private sources, were drawn together to create an Institute and an opportunity to work together on the complex problems in child health. MJA 1998; 169: 630-633 Introduction - Research origins - Rationale for a multidisciplinary institute for child health research - Growth - Successes - Threats - References - Author's details - - More articles on Aboriginal health Introduction In 1967 two men shared a game of golf and a vision for research to improve child health. Sir James Cruthers, then Managing Director of Channel 7 (TVW, Perth), suggested to Jim Clarkson, then the Chief Executive Officer of the Princess Margaret Hospital for Children (PMH) in Perth, the concept of a "Telethon" to raise money from the community for research at PMH. The Telethon became an annual event and in the first year raised funds for the PMH Children's Medical Research Foundation, which funded two small hospital research groups: a clinical immunology research unit founded by Dr Keven Turner, an immunologist from Adelaide, and a clinical nutrition research group established by Dr Michael Gracey, a paediatric gastroenterologist from Melbourne with a special interest in Aboriginal children and their health. From these beginnings, the TVW Telethon has gone on to fund a range of medical research in Western Australia, ultimately providing the essential infrastructural finance for the Institute for Child Health Research, established in 1990 and now a vigorous multidisciplinary research centre employing nearly 200 people. The Institute's name acknowledges not only this beginning but the continuing support from the TVW Telethon. Sir James Cruthers has only recently stepped down from the Institute's Board of Directors. Research origins The first two research groups funded by the Telethon were based at PMH. In the 1970s, the immunology group was beavering away, almost in isolation, in the neglected area of mucosal immunology, looking particularly at the developing respiratory tree and what role the immune system might play in allergy and asthma. This area of immunology and cell biology has now become of global importance in attempts to explain the epidemic of asthma and allergy sweeping the Western world. The work of Patrick Holt was particularly important at the time and has continued to be pre-eminent in the study of the development of allergic sensitisation and asthma.1,2Meanwhile, I had been fortunate enough to be awarded a National Health and Medical Research Council (NHMRC) overseas training fellowship in epidemiology at London University and at the National Institutes of Health, USA. When I returned to Perth in 1977, I used the $4000 setting-up grant in the last year of my fellowship to establish the Western Australian Cerebral Palsy Register (the only other registers at that time were in Sweden and Denmark) and the first congenital malformations register in Australia (funded by the Commonwealth Government in the wake of the Agent Orange scare). Then, as Senior Medical Officer in Child Health for the Health Department of Western Australia, I and my colleagues developed statewide links with midwives and child health nurses which laid the foundations for the Maternal and Child Health Research Data Base. This population-based, record-linked database has become the best in Australia (and probably the world) and now underpins much of the epidemiological work of the Institute.3 They were great days, as there was so little going on in maternal and child health epidemiology in Australia and we felt like pioneers! In 1980 these databases moved with me into a new NHMRC Unit of Epidemiology and Preventive Medicine at the Queen Elizabeth II Medical Centre, and spawned a range of epidemiological studies describing maternal and child health in WA and testing a range of hypotheses, focusing on birth defects, cerebral palsy and low birth weight. Telethon grants in the 1980s funded the Cerebral Palsy Register for nearly 10 years and a case-control study of dietary folate and neural tube defects as well.4,5 We commenced our work in indigenous maternal and child health and employed Aboriginal health workers in research before others had considered it important. The resulting partnerships with Aboriginal communities have grown even stronger since the Institute was established. Towards the middle of the 1980s I sensed that only by collaborating with basic scientists were epidemiologists ever going to get at biological mechanisms, properly elucidate causal pathways and be able to develop effective preventive strategies. Telethon funds appeared less secure at this time as they were being given away to other causes. I discussed these problems with Professor Lou Landau, who in 1984 had just accepted the Chair in Paediatrics in Perth, and we began to think of setting up an institute of child health research at the Children's Hospital, taking those with NHMRC funding with us, trying to get some additional funds for infrastructure and solving complex diseases! We both thought it a wonderful idea and invited Sir Gus Nossal across from Melbourne to address the hospital on "The birth of a research institute" -- this inspiring lecture was given in 1985 and aroused interest among local people in the concept. By this time Dr Wayne Thomas (from the Walter and Eliza Hall Institute in Melbourne), Dr Geoff Stewart (from the United Kingdom) and Dr Ursula Kees (from Switzerland) had all joined the Clinical Immunology Research Unit at Princess Margaret Hospital, and most of them now had "secure" NHMRC funding. Ursula Kees' group worked closely with the oncologists in the hospital, particularly Dr Michael Willoughby, the head of the oncology unit, who was determined that the Children's Cancer and Leukaemia Foundation would provide some secure funding for her laboratory in the new Institute. He could see this was crucial to the success of better identification of childhood cancers, investigating aetiology and discovering new therapies. Were we mad? We planned to set up a world-class institute in an isolated city in the biggest but most deserted State in Australia, in the middle of the crisis over business and political corruption known as "WA Inc" and as a recession was in full swing. We invited a group of Australia's leading researchers to Perth in 1986 and asked them to interview all of the researchers in child health and make an assessment. Despite the difficulties, the committee felt we had the right ingredients and encouraged us to go ahead. With the support of the Princess Margaret Hospital Board, and particularly of Professor Lou Landau, the proposal was developed further. In 1989, encouraged by Sir Gus Nossal, I applied for and was appointed Director of the new Institute. In 1990 we moved into our building -- the old School of Nursing at PMH, which was renovated with donations from the WA Lotteries Commission and the Incorporated Body of PMH. The support from other groups like the Variety Club of WA and the community has been the most crucial aspect of our success in this whole venture. Rationale for a multidisciplinary institute for child health research The problems in child health are now complex -- epitomised by diseases such as asthma, birth defects and other developmental problems, cancers and psychosocial problems. These stem from a complicated series of interactions between genes and environment, with variable causal pathways demanding complex solutions for their management or prevention. Our thinking was that if we brought together scientists from different disciplines under one roof we might be able to unravel the causes more successfully than working away separately in our little research areas. The aims of the Institute were to describe the burden of diseases in children and families in WA, to seek causal pathways using all types of scientific methods, and then to apply any knowledge to prevent disease in the community or to improve treatment at the bedside. We started as 90 scientists in four separate groups in 1989, with little infrastructure support, although our research grants from the NHMRC and other local foundations were adequate. Cell Biology, Molecular Biology and Cancer and Leukaemia moved in under the direction of Patrick Holt, Wayne Thomas and Ursula Kees, respectively, from the old PMH Children's Medical Research Foundation. My group from the NHMRC Unit moved to form the Division of Epidemiology and Biostatistics. Research in all these groups has blossomed at the Institute. Ursula Kees' group is making a seminal contribution on the role of homeobox gene malfunction in childhood leukaemia and has, in close collaboration with the PMH Oncology Unit and the international Children's Cancer Group, made significant contributions to the use of genetic markers to determine the prognosis and treatment for children.6,7Wayne Thomas's group is best known for its detailed work on the structure and immunology of house dust mite allergens, and a molecular approach to developing new types of immunotherapy8,9and the development of a candidate vaccine for all types of Haemophilus influenzae based on a conserved outer membrane protein.10 Patrick Holt's group has continued to describe the immunological mechanisms which operate during the development of tolerance to inhaled antigens,11,12 which are of extreme interest to both fundamental immunologists and allergists alike. Growth 1992 was the year of recruitment! We conducted an international search for a top biostatistician, which paid off with the recruitment of Dr Paul Burton, who became the Institute's senior biostatistician, and his wife, Dr Jenny Kurinczuk, an outstanding perinatal epidemiologist with a special interest in reproductive issues. Dr Burton conducted theoretical biostatistical research in a range of analytical problems (such as the analysis of complex interacting data sets and new methods of randomised trials), supported much of the biostatistical needs of the Institute and of our collaborators and spearheaded our new endeavours in genetic epidemiology. Within two years he became head of our new Division of Biostatistics and Genetic Epidemiology. Also in 1992 we sought an outstanding clinical researcher to establish a new Division of Clinical Sciences, with the brief of not only doing research in the Institute bridging the basic and clinical sciences, but also being a role model and stimulus for clinical research on the PMH campus. Dr Peter Sly was lured from Melbourne by offering him "fame and poverty" (he still has the letter) and he has continued to be a great success, collaborating with many groups in the Institute, the hospital and with fetal physiologists and respiratory researchers locally and internationally. In that year as well we were extremely fortunate in convincing the Health Department of Western Australia to second to us two outstanding clinical psychologists, Dr Steve Zubrick and Sven Silburn, whose research has underpinned the State Policy on Youth Suicide and other strategies in child and adolescent mental health. Dr Zubrick became head of the new Division of Psychosocial Research, with Silburn his very able deputy. The arrival of Australia's first MacFarlane Burnet Fellow, Professor Colin Sanderson, whose work on interleukin-5 was recognised internationally, created our last new division (Molecular Immunology) in 1994. This was an important bit of the jigsaw in our multidisciplinary attack on the complex disease of asthma. Dr Dierdre Coomb also arrived and established a laboratory specialising in the extracellular matrix, adhesion molecules and the mechanisms of inflammation, metastasis and haematopoiesis. As I look back now, some of our recruitment was part of a grand plan and some, as you would understand if you were in such an isolated and remote community, was opportunistic. Whatever the reason, the resulting mix has worked, as shown by our growth (from less than 50 to nearly 130 research staff in eight years), the way that many groups are collaborating in the Institute and the output to meet our goals. Successes A major reason for our success in fundraising from the local business community was that our research was focused on health problems that were well known as major burdens to the community -- asthma, adolescent suicide, birth defects, cerebral palsy, cancers and Aboriginal health. Another major factor was that we have had significant success in translating results into action (see Box); examples include the research on folate and spina bifida, reducing suicidal behaviours, improving outcome following bone marrow transplants in children with leukaemia, influencing the uptake of Haemophilus influenzae type b vaccination (which virtually eradicated the disease) and establishing a successful maternal and child health program for Aboriginal families in Kalgoorlie. Most of these are national and international issues and our Institute is increasingly being seen as a source of information for government and a model of success in multidisciplinary research and in translating research into policy. So, eight years on, have we been successful? How do you measure success in a multidisciplinary Institute? At the end of the first year of operation (June 1991) the Institute had $1.4 million in peer-reviewed grants, with a total operating revenue of $3 million (which included ongoing refurbishment costs). By the close of 1997 the Institute had gained $5.9 million in grants (including $2.5 million in NHMRC funding) and a total operating revenue of $8.3 million. You cannot force groups of different disciplines such as immunology and epidemiology and biostatistics to work together; all you can do is recruit thoughtful and good scientists and put them next to each other and hope that they talk! I remember two episodes vividly -- Patrick Holt saying "we have a great hypothesis we have developed in the lab and we need you epidemiologists to test it out for us"; this spawned our multidisciplinary asthma cohort study with Patrick Holt, Paul Burton, Peter Sly, Anne Read and myself testing the hypothesis that early and repeated infections may influence the immune response away from allergy and reduce the risk of asthma. The other episode was Colin Sanderson (head of Molecular Immunology) commenting that one of the best people in the Institute was Steve Zubrick, the head of Psychosocial Research -- given the usual contempt in which psychologists are held by "serious" scientists, this was great praise indeed! Bridges being developed between groups enhance the chances of collaboration. Threats With all this success and delight that we have survived our birth, with the new joint Commonwealth and State government $22.5 million building program heading for an early 2000 completion date, with such community support and government acceptance of our role, why am I concerned for our future? Our vulnerability now relates mainly to research funding and the support for our next generation -- our current students and postdoctoral staff. We are finding that research funding is much better in other countries and in other States and that we cannot offer our senior and rising bright young minds incentives to stay with us or even to stay in full time research. Some are off to overseas positions or into the private sector or into academic jobs with all the toil of teaching but at least some security. Our most recent sadness was that Paul Burton and Jenny Kurinczuk have been head-hunted back to the UK to tenured, well paid (at least double the NHMRC salaries they are currently receiving) academic positions at the University of Leicester. We will miss them greatly, but we can take some pride in having provided an environment for these two outstanding young people to develop their research careers to this level. Our policy of establishing an Institute by asking successful scientists to join us and bring their own salaries (usually NHMRC funded) was our only way of getting things going, but is not the way we can continue. It ensured that we only had peer-reviewed science in the Institute and meant that we could spend our precious and scarce resources on infrastructure and not research salaries. This ensured our survival, but it is not good policy in the longer term. The NHMRC roulette is not conducive to recruiting the brightest and the best. The Board needed little convincing to realise that such vulnerability is unacceptable and we are now looking at ways of securing our best people. Independent institutes are disadvantaged compared with universities because they do not receive direct infrastructure support from the Department of Employment, Education and Youth Affairs. Our Institute cannot match this year's increases in academic salaries as the NHMRC decided not to fund such an increase for research for its grant holders. Yet young scientists cannot be expected to work for low wages when salaries in other similar countries are much higher. We continue to lobby at Federal and State level, and wonder why, with our successes in improving child health, excellent research and scholarship, we are so undervalued in this country. Private funding alone is not the answer. I salute the likes of the visionary Sir James Cruthers and all the past, current and future corporate and private sponsors of research in Australia: what you could now do for us is to become advocates to convince governments to join with you in investing in our brightest and our best. Any less and our capacity to do research and benefit from it will be limited. References Holt PG, Yabuhara A, Prescott S, et al. Allergen recognition in the origin of asthma. Ciba Found Symp 1997; 206: 35-49. Holt PG, Macaubas C. Development of long-term tolerance versus sensitisation to environmental allergens during the perinatal period. Curr Opin Immunol 1997; 9: 782-787. Stanley FJ, Croft ML, Gibbins J, Read AW. A population database for maternal and child health research in Western Australia using record linkage. Paed Perinat Epidem 1994; 8: 433-447. Stanley FJ, Watson L. Methodology of a cerebral palsy register. The Western Australian experience. Neuroepidemiology 1985; 4: 146-160. Bower C, Stanley FJ. Dietary folate as a risk factor for neural-tube defects: evidence from a case-control study in Western Australia. Med J Aust 1989; 150: 613-619. Kees UR, Burton PR, Lu C, Baker DL. Homozygous deletion of the p16/MTS1 gene in pediatric acute lymphoblastic leukemia is associated with unfavorable clinical outcome. Blood 1997; 89: 4161-4166. Salvati PD, Ranford PR, Ford J, Kees UR. HOX11 expression in pediatric acute lymphoblastic leukemia is associated with T-cell phenotype. Oncogene 1995; 11: 1333-1338. Thomas WR, Smith W. House dust mite allergens. Allergy 1998; 53: 821-832. Thomas WR, Smith W, Hales BJ. House dust mite allergen characterisation: implications for T-cell responses and immunotherapy. Intern Arch Allergy Immunol 1998; 115: 9-14. Thomas WR, Flack FS, Callow MG, Chua KY. A high-molecular-weight outer membrane protein that is a potential target for protective immunity to type b and untypeable Haemophilus influenzae. J Infect Dis 1992; 165 Suppl 1: S75-S76. Stumbles PA, Thomas JA, Pimm CL, et al. Resting respiratory tract dendritic cells preferentially stimulate Th2 responses and require obligatory cytokine signals for induction of Th1 immunity. J Exp Med 1998. In press. McMenamin C, Pimm C, McKersey M, Holt PG. Regulation of IgE responses to inhaled antigen in mice by antigen-specific gamma delta T cells. Science 1994; 265(5180): 1869-1871. Author's details TVW Telethon Institute for Child Health Research, Perth, WA. Fiona Stanley, AC, MD, FAFPHM, FRACP, Director, and Variety Club Professor of Paediatrics, The University of Western Australia. Reprints: Professor Fiona Stanley, TVW Telethon Institute for Child Health Research, PO Box 855, West Perth, WA 6872. Email: infoATichr.uwa.edu.au URL: http://www.ichr.uwa.edu.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> Milestones for the TVW Telethon Institute for Child Health Research Year Corporate history Research highlights 1985–1990 Planning for an Institute: including international review Cloning of house dust mite allergens (Wayne Thomas et al, from 1988) 1989 Professor Fiona Stanley appointed Director 5 year NHMRC project awarded to Epidemiology division 1990 Institute opened with a Board of Directors and Scientific Advisory Committee and the following research divisions: Cell Biology (Patrick Holt), Molecular Biology (Wayne Thomas), Epidemiology (Fiona Stanley), Leukaemia and Cancer (Ursula Kees) Cloning of outer membrane protein of all types H influenzae (vaccine candidate) (Wayne Thomas et al) 1991 Affiliation with The University of Western Australia Commonwealth grant to complete laboratories Psychosocial Research (Stephen Zubrick) Clinical Sciences (Peter Sly) Folate confirmed to prevent neural tube defects (Carol Bower and Fiona Stanley) 1992 Affiliation with Princess Margaret Hospital for Children Senior Biostatistician appointed (Paul Burton) Launch of Hib vaccination program World first folate and NTD prevention project launched 1993 New Board and other committees: Intellectual Property, Finance, Fundraising Molecular Immunology (Colin Sanderson) Cell Adhesion Laboratory (Dierdre Coombe) WA Child Health Survey commenced 1994 Biostatistics and Computing (Paul Burton) becomes a division Epidemiology Division now headed by Carol Bower Immune deviation by g/d T cells (Christine McMenamin and Patrick Holt) 1995 Administration and Corporate Services established (Robert Ginbey) State Government pledge for new building "Give every Child a Chance" fundraising campaign ($10 800 000 pledged) International review Child Health Survey Vol 1 (Stephen Zubrick and Sven Silburn) HOX 11 deregulation in T cell leukaemias (Patricia Salvati and Ursula Kees) 1996 Consolidation of infrastructure (UWA, HDWA) New approach to Commonwealth Government for building grant First NHMRC Program for Public Health (Maternal and Child Health) Child Health Survey Vol 2 (Stephen Zubrick and Sven Silburn) Only one case of Hib meningitis reported (after vaccination program) Aboriginal maternal and child health research project in Goldfields becomes a government-funded health service 1997 Joint announcement of Capital Works Grant totalling $22 500 000 from State and Commonwealth Governments Child Health Survey Vol 3 (Stephen Zubrick and Sven Silburn) First reduction in rate of NTD (from average of 2 to 1.2 per 1000) 1998 Commence new building program in September Persistence of fetal Th2 immune responses in atopic versus non-atopic individuals (Susan Prescott and Patrick Holt) 2000 New building complete Second international review

Fiona Stanley

Consumers & Healthcare Children with severe disabilities: options for residential care Is living under the same roof necessary for a nurturing family relationship? Kevin J Bain MJA 1998; 169: 598-600 Introduction - References - Authors' details - - More articles on Paediatrics Introduction In the past 10 years, professional and government opinion has changed about where children with severe disabilities and high support needs should live. Previously, families were encouraged to place these children in an institution and to "forget" them. Then, in the late 1980s, the process of closing large institutions began in most Australian States, and "permanency planning" (Box 1) gained professional favour, although not always practical government support. The objective now is for children with severe disabilities to live with a family -- preferably their birth family but, failing that, an adoptive or foster family. But is this enthusiasm for virtually all children with disabilities to live with a family unrealistic or doctrinaire? Are other options worthwhile? What are the important considerations for public policy? 1: Permanency planning Permanency planning (which also informs policy in the child protection field1) is based on the view that a long-term day-to-day relationship between the growing child and at least one continuous caregiver is necessary in any model of care. It arose from the concern that children in foster care drift, with a loss of contact with natural parents and negative emotional and social consequences for the child as placements break down and foster agency staff move on.2 The philosophy is also not comfortable with rostered staff models ("group homes"). Specific aims of permanency planning are:3 To identify and provide the financial and other supports needed by the birth family to enable the child to stay at home, at least until legal adulthood; For children who have previously been relinquished or placed in institutions, to pursue permanent reunification with the natural family as the most desirable option; and If parents request an out-of-home placement, to pursue adoption or long-term placement with a foster family, preferably on an "open" basis so that the birth parents continue with an informal parenting role. What impact can a child with a severe disability have on a family? A child with a severe disability invariably leads to great personal and financial stress in the home.4-6 While some children have a need for intensive medical and therapeutic support or continuous care, others have long-term behavioural patterns that include regular violence to themselves or others, chewing or breaking furniture and house fittings, screeching or being noisy at all hours, ingesting inedibles, smearing faeces, or absconding. Despite therapeutic or behavioural interventions there may be very slow development, or regression.7 While "in-home support" will cater for the needs and preferences of many parents, the sometimes severe restrictions on the family's life choices will not be acceptable to all, particularly if the burden of care is offloaded onto other family members. Can society regard a solution as satisfactory when chronic stress is hidden in the private domain? For example, a Queensland agency which implemented faithfully the total movement of children with high medical and physical support needs back into birth family settings after a period of institutionalisation reported that the outcome was often "harsh".8 While families were reported happy to have their children home, the care required was stressful, demanding, labour-intensive, constant, costly, tiring and mostly unacknowledged. Other reported impacts on the family included:8 Very little social life; Reduced time and energy for other family members; Expectations on other children to share physical and emotional caring; Restrictions on types of family activities (eg, camping); Very little time off and few holidays; Reduced career opportunities; Working part rather than full time or not being able to work at all; Coping alone when carers were sick or on leave; Extra demands of school holidays; Physical and emotional tiredness; and Feelings of low self esteem and worth. Instead of an exclusive focus on what is believed best for the child, there needs to be an acknowledgement of the wider impact on the family. An analysis of the impact of deinstitutionalisation on families in the United States pointed out that the disabled child's right "to live in the least restrictive environment" is only a half-statement of the issue: The right to live in the least restrictive environment should apply to family members as well as to handicapped individuals. Thus [the] concept of least restriction should be considered in light of the needs of each family member. Placing many severely handicapped children and youth in the least restrictive environment of their families results in their family being required to live in a highly restrictive manner.9 Additionally, the 1993 Australian Bureau of Statistics survey of carers found that, while many resident carers of people with severe or profound handicaps have been brought closer to the person being cared for, a quarter feel that this role has put a greater strain on the relationship.1 The presumption that family care is superior care may not be true: there is clear potential for destructive and perhaps abusive relationships. More financial and other support for the family, while helpful, is not always a complete solution. A NSW survey of 171 families of children under seven years with disabilities and high support needs found that 25% had either sought alternative residential care for their child or considered it might become necessary, particularly if the mother, as main carer, was unable to continue, or the child became larger and harder to manage.10 The degree to which these circumstances can be avoided by more and better services may be limited. For the 6% who had already sought care, family survival -- physically, socially and emotionally -- was at stake. However, the push from Australian governments to keep the child at home is strong, and out-of-home placement is usually difficult to access. Because urgent cases move to the top of the queue, anecdotal reports are that a cat-and-mouse game ensues as parents are required to demonstrate their trauma. The game-playing to access accommodation services may also involve giving up the child to the State as a ward, manufacturing a situation of homelessness, or following the child protection route (ie, abuse or threatened abuse of the child). Should foster care be the only alternative to living at home? In the past, foster care arrangements were generally admitted to be difficult to establish and maintain for children with autism, severe disabilities and certain types of challenging behaviour.11 Is the current enthusiasm for foster care evidence-based or cost-based? Evidence cited to support foster care as the universal solution12-16 generally comprises case reports of its success in sustaining arrangements rather than achieving measured improvements for the child. In fact, one of the few longitudinal studies (a three-year study of 148 children in the United States) suggested that the developmental opportunities claimed for specialised foster care were unlikely to be realised for children at the lower levels of intellectual functioning.17 Furthermore, low levels of attachment behaviour, often associated with severe intellectual disability or the autistic spectrum diagnosis, are likely to jeopardise foster care.17 Yet, these children are generally the target group for foster care programs in Australia. Lower cost to government is also cited as a major advantage of substitute family care over rostered staff arrangements. However, children with high support needs may be expensive to support irrespective of setting. In the Victorian alternative care program (Family Options), the level of annual caregiver payments starts at $4160 and rises to between $10 886 and $22 144 for children with very high needs, with additional discretionary payments of up to $10 000 per annum, and possibly extra money for home modifications.18 This compares to a benchmark of $47 000 in annual operating costs to support a high-needs person in a small group home (Ms Diana Heggie, General Manager, Operations and Residential Services Development, Spastic Society of Victoria, personal communication). These financial disbursement policies also lead to tensions. Birth families often report that financial support available to foster carers to look after severely disabled children is not available to their parents to do the same. Providers report that clients who may be able to avoid a crisis if supported modestly at an earlier stage end up as genuine emergencies. In practice, foster care may be distorted to resemble a rostered staff situation to maintain the placement, with a large number of volunteer carers and parenting shared between different families at different sites. The operational needs of care for some children are going to involve many rostered carers however the model is labelled. The view of many parents, advocacy groups, academics, foster agencies and child welfare practitioners is that the pendulum has swung too far in reducing access to other options, such as group homes (see Box 2). 2: Where do children with severe disabilities live now? In 1993, an estimated 63500 Australian children in the 5-14 years age group had a severe or profound handicap (meaning they always or sometimes need personal assistance or supervision with activities of daily living - self-care, mobility or verbal communication).1 There are no official figures for Australia on how many of these children are cared for at home. Figures for New South Wales suggest that it is the overwhelming majority, and that families who seek alternative care usually do so when the child reaches adolescence.10Similarly, the number of formal requests to State disability services departments for out-of-home placements is not generally available. However, the main agency in South Australia experienced a 300% increase in these requests in the five years to 1994, with 28 children listed as needing alternative accommodation urgently.19 When it is acknowledged that remaining at home is not viable, government departments in most Australian States pursue "specialised" foster care as the preferred option. (NSW is a notable exception, with group homes and large institutions more common.) Tasmania focuses on in-home support. In South Australia and Queensland, planners claim the emphasis on foster care and in-home support is highly successful. However, in Western Australia and Victoria, children either unsuited or unable to be matched to foster carers remain for years in respite houses or residential units attached to hospitals. Should we retain non-family options? The disfavour towards non-family models of residential care comes from the days when children with disabilities lived in large institutions, and their families were encouraged to forget them. Institutions are well on the way out in Australia, and planners adopt a strong "gatekeeping" role to minimise any divergence from the two approved models -- birth or substitute family. A 1993 US study found that families who placed their child in a residential facility were much more likely to continue a high level of contact with their child than did previous generations, including visits to the residential facility, visits by the child to the family home, phone calls, and involvement in the child's individualised habilitation plan.20The authors hypothesised that, because families are no longer likely to place their children at birth, they develop attachment, which buffers against non-involvement during subsequent placement. Tangible benefits for other family members occurred after placement in a residential facility, including better relationships with other children, more normal social life and more employment and educational opportunities.20,21 While today's parents want community living for their children with disabilities, those seeking out-of-home placement may see a group home with rostered staff as an attractive option. It has the potential to provide long-term security, trained staff, and greater authority to birth parents to influence decisions about the child's welfare than does foster care. Rostered staff carers can resist "burnout", and often develop a familiarity and attachment to the child, even when it is not strongly returned. A situation in which the child lives in a rostered staff home but has regular visits to and from the birth family, which is also heavily involved in the child's educational and medical issues, behavioural plans, and personal development, is desired by some parents and already exists in Australia, albeit in a policy "twilight zone". This approach can allow important objectives of permanency planning to be achieved, if high levels of family involvement are encouraged. Permanency planning in Australia needs to drop slogans appropriate to a different time and accommodate subtlety, an openness to evolution and changing values and preferences. Incorporating "best practice" into policy With the current redevelopment of accommodation services in most Australian States, a participatory and transparent evaluation process is needed. Planners and providers should continuously share the results of the implementation process with the families they serve, other professionals and service providers. Although the policy of integrating people with disabilities into the community is widely supported, there is still little knowledge of how it can be achieved when disabilities are severe. Independent evaluations of successful foster care and rostered staff programs are needed, with results made available to all. These should examine the priorities not just of planners (minimal placement breakdowns, placement avoidance, and service cost reduction), but also of families (family satisfaction, strengthening of birth family links, and quality of care). It is doubtful whether this will happen without changed reporting arrangements, because of political sensitivities and organisational rivalries derived from the contracting-out process. A recent House of Representatives Committee heard many negative stories about contracting-out of welfare services, including reduced sharing of professional knowledge, lack of contract management expertise, blurred lines of accountability, contract clauses which prohibit public comment, and unwieldy and inconsistent performance standards.22 It recommended that the responsibility for setting standards and measuring performance of the welfare sector be assumed by the Australian Institute of Health and Welfare (AIHW, a statutory authority established in 1987 as an independent health and welfare statistics and information agency). The committee also recommended service-specific advisory committees to facilitate the effective flow of information from States to the AIHW. The technical expertise and independence which the AIHW brings to the evaluation process can only help in establishing a firmer knowledge base for policy development in this important and under-researched area. References Australian Institute of Health and Welfare. Australia's welfare 1997. Canberra: AGPS, 1997: 206, 329, 307. Taylor SJ, Lakin KC, Hill BK. Permanency planning for children and youth: out of home placement decisions. Except Child 1989; 55: 541-549. Center for Human Policy (Syracuse University). Introducing a statement in support of families and their children. <http://soeweb.syr.edu/thechp/fsbintro.htm> Sighted 3 Nov 1998. Casey S. Barriers to women returning to the paid workforce when they have a child with a disability. Melbourne: Association For Children With A Disability, 1998. Birenbaum A, Cohen HJ. On the importance of helping families: policy implications from a national study. Ment Retard 1993; 31: 67-74. Schofield HL, Murphy B, Nankervis J, et al. Family carers: women and men, adult offspring, partners, and parents. J Fam Stud 1997; 3: 149-168. Moore TG. Promoting the healthy functioning of young children with developmental disabilities, and their families. Fam Matters 1996; 44: 20-25. Fleming R. Post-institutionalisation -- policy and services. Proceedings of the Australian Cerebral Palsy Association National Conference, Brisbane, 1998: 97-99. Turnbull AP, Brotherson MJ, Summers JA. The impact of deinstitutionalisation on families: a family systems approach. Paper presented at the Working Conference on Deinstitutionalization and the Education of Handicapped Children. Minneapolis, 1982. Llewellyn G, Dunn P, Fante M, et al. Families with young children with disabilities and high support needs. Sydney: University Of Sydney Family Support and Services Project, 1996: 3. Department of Human Services (Victoria). Family options policies and procedures manual interim guidelines. Melbourne: DHS, 1997. Macaskill C. It's a bonus. Adoption fostering (Barnado's United Kingdom) 1988; 12: 24-28. Elliot B, Young M. Melanie's program evaluation final report. Sydney: Centacare Catholic Community Services, 1993. Provencale G. Characteristics of a successful community living program and support service. Melbourne: Yungaburra Foundation, 1988. Shoultz B, O'Connor S, Hulgin K, Newman P. Permanency planning in Michigan: from philosophy to reality. Syracuse, NY: Center on Human Policy, Syracuse University, 1994. Center on Human Policy, Syracuse University. Families for all children. <http://soeweb.syr.edu/thechp/bullfams.htm#tab> Sighted 3 Nov 1998. Borthwick-Duffy S, Widaman K, Little TD, Eyman RK. Foster family care for persons with mental retardation. Washington DC: American Association for Mental Retardation 1992. Monograph 17. Napthine D. Letter to the Association for Children with a Disability from the Minister for Youth and Community Services, Victoria, 5 September 1997. Kelly F, Clark J, McEntee P, Dench S. Factors contributing to the relinquishment of children with intellectual disability. Social policy reports and proceedings no. 123. Sydney: Social Policy Research Centre, University of New South Wales, 1995: 77-87. Blacher J, Baker BL. Family involvement in residential treatment of children with retardation: is there evidence of detachment? J Child Psychol Psychiatry 1994; 35: 505-520. Blacher J. Placement and its consequences for families of children who have mental retardation. In: Blacher J , editor. When there's no place like home: options for children living apart from their natural families. Baltimore: Paul H Brookes, 1994: 213-243. House of Representatives Standing Committee on Family and Community Affairs. What price competition? A report on the competitive tendering of welfare service delivery. Canberra: AGPS, 1998. Authors' details Melbourne, Vic. Kevin J Bain, Travelling Fellow, Rosemary F Dybwad International Fellowship Trust, former Board member of Victorian intellectual disability advocacy bodies, and parent of an 11-year-old boy living in a respite house. Reprints: Mr K J Bain, 9 Caroline Street, East Hawthorn, VIC 3123. Email: kevinbainATyahoo.com.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Kevin J Bain

Paediatric rotavirus gastroenteritis: where to now in prevention and treatment? While we await a preventive vaccine, we should concentrate on appropriate management, which means avoiding medications and giving dilute fluids to counter dehydration MJA 1998; 169: 241-242 Rotavirus is a major cause of gastroenteritis affecting young children worldwide. In this issue of the Journal, Carlin and colleagues present data which suggest that, of the approximately 20 000 children under five years admitted to hospital with acute gastroenteritis in Australia annually (a rate of 15/1000 per year), rotavirus is responsible in 50%.1 This accords with a recent New South Wales study suggesting that 56% of hospitalisations for acute gastroenteritis in this age group could be attributed to rotavirus.2The virus was first identified in 1973 by Bishop and coworkers at the Royal Children's Hospital, Melbourne, when they used electron microscopy to examine duodenal biopsies from infants admitted to hospital with severe acute non-bacterial gastroenteritis.3 Since that time, rotavirus has also been shown to be a cause of acute gastroenteritis in the young of a wide range of wild and domestic mammals. The virus, a member of the family Reoviridae, can be classified into serogroups A-G, and most human infections are caused by serogroup A. Routine diagnosis is based on rapid detection of group A antigen in faeces, generally by latex agglutination or enzyme immunoassay. In temperate climates, rotavirus infection occurs all year round, with very pronounced annual winter-spring peaks in incidence. The major epitope associated with a protective immune response is the viral outer capsid glycoprotein VP7. In mammalian rotavirus strains, monoclonal antibodies can be used to differentiate this protein into 10 serotypes, of which four, G1 to G4, are responsible for most cases of severe disease in young children. The rotavirus genome comprises 11 segments of double-stranded RNA, which readily allows genetic reassortment when coinfection is induced in vitro with strains of differing serotypes from one or more species.4 Approaches to vaccine development have concentrated on G1 rhesus strains, strains of human neonatal origin and tetravalent rhesus-human reassortants expressing G1-G4 serotypes. Large-scale clinical trials to date have shown advantages in the tetravalent vaccine candidates in protective efficacy,4 and it is likely that an oral tetravalent rhesus-human reassortant rotavirus vaccine will be approved in Australia in the next 1-2 years. Randomised controlled trials of this vaccine given as three oral doses between six weeks and six months of age were conducted among both urban and Native American populations in the United States, and in Finland. These trials showed protective efficacies of 49%-66% against any rotavirus gastroenteritis and 69%-100% against very severe infection.5-7 The vaccine was found to be relatively safe, with adverse reactions largely limited to fever and irritability after the first dose -- one-third of children had fever over 38oC, while 3% had fever over 39oC.8 Another approach to preventing rotavirus gastroenteritis is passive immunisation -- giving oral preparations containing high-titre rotavirus antibodies derived from the colostrum of immunised cows. One study showed a marked reduction in the incidence of hospital-acquired rotavirus infection when hospitalised children were given a hyperimmune bovine colostrum preparation,9 and further trials are under way to assess the value of community use. Use of either active or passive immunisation may be of particular value in children aged under three years attending long- daycare, as rotavirus infection in this group causes substantial morbidity and family disruption.10 Although preventing rotavirus gastroenteritis has obvious appeal, our medium-term focus will continue to be on managing children with acute gastroenteritis. Carlin et al note substantial differences in hospital admission rates between Australian States and raise the possibility that there are variations in hospital admission policies or practices.1 Other local data have shown that most children admitted to two NSW children's hospitals have only a minor degree of dehydration.11,12 In an editorial comment on one of these NSW studies, Barnes indicated "continuing concern as to why so many mildly dehydrated children are admitted to Australian hospitals and why so many of them receive intravenous therapy".13 We have limited information on the management of gastroenteritis in the community and in hospital emergency departments. Most of the data are based on extrapolation from children who have been admitted to hospital. Preadmission management is suboptimal -- antibiotics, antiemetics or antidiarrhoeals are prescribed for more than 20%.11,12 The use of oral rehydration solution in the community is low, although most children are offered appropriately diluted clear fluids.11,12 While hospitalised children with gastroenteritis may not accurately reflect treatment practices in the community, there remains a disparity between management guidelines14 and actual practice. Treatment of gastroenteritis in the community should include continued breastfeeding in infants or increased fluids in older children. Either oral rehydration solution or appropriately diluted fluids are acceptable. Children should be allowed to return to their usual diet if they are hungry. Regular review of the child's progress, with particular focus on fluid balance, should be regarded as good clinical practice and not as overservicing. By contrast, medications are rarely required, may be harmful and should be avoided. Undiluted cordial, fruit juice or carbonated drinks (such as flat lemonade) are hyperosmolar solutions and pose the danger of exacerbating the diarrhoea. The prospect that a future rotavirus vaccine, if widely used, will have a major beneficial impact is exciting. Coupled with this is the need to deliver more effective clinical management of acute gastroenteritis in the community. Mark J Ferson Director, Public Health Unit, South Eastern Sydney Area Health Service and Staff Specialist in Public Health, Sydney Children's Hospital, Sydney, NSW Richard Henry John Beveridge Professor, School of Paediatrics, Sydney Children's Hospital and University of New South Wales, Sydney, NSW Carlin JB, Chondros P, Masendycz P, et al. Rotavirus infection and rates of hospitalisation for acute gastroenteritis in young children in Australia, 1993-1996. Med J Aust 1998; 169: 252-256. Ferson MJ. Hospitalisations for rotavirus gastroenteritis among children under five years of age in New South Wales. Med J Aust 1996; 164: 273-276. Bishop RF, Davidson GP, Holmes IH, Ruck BT. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet 1973; ii: 1281-1283. Kapikian AZ, Hoshino Y, Chanock RM, Perez-Schael I. Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant vaccine In: Chiba S, Estes MK, Nakata S, Calisher CH, editors. Viral gastroenteritis. Vienna: Springer-Verlag, 1996: 163-175. Rennels MB, Glass RI, Dennehy PH, et al. Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines -- report of the National Multicenter Trial. Pediatrics 1996; 97: 7-13. Toensuu J, Koskenniemi E, Pang X-L, Vesikari T. Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Lancet 1997; 350: 1205-1209. Santosham M, Moulton LH, Reid R, et al. Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations. J Pediatr 1997; 131: 632-638. Joensuu J, Koskenniemi E, Vesikari T. Symptoms associated with rhesus-human reassortant rotavirus vaccine in infants. Pediatr Infect Dis J 1998; 17: 334-340. Davidson GP, Whyte PBD, Daniels E, et al. Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet 1989; ii: 709-712. Ferson MJ, Stringfellow S, McPhie K, et al. A longitudinal study of rotavirus infection in child-care centres. J Paediatr Child Health 1997; 33: 157-160. Loughlin EV, Notaras E, McCullough C, et al. Home-based management of children hospitalized with acute gastroenteritis. J Paediatr Child Health 1995; 31: 189-191. Elliott EJ, Backhouse JA, Leach JW. Pre-admission management of acute gastroenteritis. J Paediatr Child Health 1996; 32: 18-21. Barnes GL. Oral rehydration solutions in gastroenteritis before and after admission to hospital. J Paediatr Child Health 1996; 32: 16-17. Gastroenteritis. A guide for parents and caregivers. Sydney: Australian Gastroenterology Institute, 1996. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Mark J Ferson · Richard Henry

Rotavirus infection and rates of hospitalisation for acute gastroenteritis in young children in Australia, 1993-1996 John B Carlin, Patty Chondros, Paul Masendycz, Helen Bugg, Ruth F Bishop and Graeme L Barnes For editorial comment, see Ferson MJA 1998; 169: 252-256 Abstract - Introduction - Methods - Results - Discussion - Acknowledgments - References - Authors' details - Figure 1 - Figure 2 - - - ©MJA1998 Abstract Objective: To determine rates of hospitalisation of young children for acute gastroenteritis in Australia, and to estimate the proportion of these admissions caused by rotavirus infection. Design: Analysis of hospital admission records, and parallel, prospectively collected data on rotavirus-positive admissions. Setting: Hospitals admitting young children in all Australian States and Territories in 1993-1996. Patients: All children under five years admitted to hospital for acute gastroenteritis (International Classification of Diseases, ninth revision principal diagnosis codes 003.0, 004.0-009.3 and 558.9). Main outcome measures: Rate of hospital admission per 1000 children per year by State, and the proportion of admissions caused by rotavirus infection. Results: There were almost 20 000 hospital admissions annually in Australia for acute gastroenteritis in children under five years, at an average rate of 15/1000. An estimated 50% of these were attributable to rotavirus infection, implying a rate of hospitalisation for rotavirus-related gastroenteritis of 7.5/1000/year. Among children under two years this rate was 11.6/1000. Rotavirus incidence rates generally followed a typical seasonal pattern in temperate regions of the country, with sharp peaks in mid to late winter. Rates of hospitalisation varied markedly, even between States with apparently similar patterns of disease, while the incidence in the Northern Territory was 3-5 times higher than other States. Conclusions: Rotavirus-related gastroenteritis is a major cause of hospital admissions in young children, and large savings to the healthcare system are possible if it can be prevented at reasonable cost. Variation in treatment practices between States may be worth studying in greater detail as another source of potential savings. MJA 1998; 169: 252-256 Introduction Rotavirus is a major cause of severe gastroenteritis in young children. Although discovered only 25 years ago,1 the role of this virus in the huge burden of diarrhoeal disease in developing countries was recognised quickly, and in 1985 it was estimated to be responsible for 870 000 deaths annually.2 In developed countries, mortality from gastroenteritis is low, but many studies have documented the large burden of morbidity caused by rotavirus.3-7Precise estimates of rotavirus-related morbidity are difficult to obtain from routine hospital data because stool samples for microbiological testing are not obtained from all children admitted to hospital with diarrhoea. Even when testing is performed, the findings may not be recorded or coded in the medical record. There was no specific category in the International Classification of Diseases, ninth revision (ICD-9-CM) for rotavirus diarrhoea until 1993, and since then the specified code (008.61) has not been used consistently. However, many studies have shown that at least 30% of hospital admissions for acute gastroenteritis in young children are the result of rotavirus infection and, further, that the incidence of rotavirus infection has a distinctive cyclical pattern with a peak in winter (this is unique to rotavirus among all major pathogens associated with gastroenteritis).3,4,6,8-10 While other Australian studies have examined aspects of rotavirus gastroenteritis,5,11 there are no national population-based estimates of the incidence of hospital admission for acute gastroenteritis in young children. Such estimates are important in assessing preventive measures, and in evaluating the cost-effectiveness of rotavirus vaccines currently under development.12,13 We aimed to provide the first national data on rates of hospitalisation of young children for acute gastroenteritis in Australia, and to estimate the proportion of these admissions that could be ascribed to rotavirus infection. Our results will be used in a later study to estimate the cost-effectiveness of rotavirus vaccination. Methods State and Territory health departments provided computer files with unidentified records for the years 1993 through 1996 of all hospital admissions of children under the age of five with a principal diagnosis in the medical record of acute gastroenteritis. In our analysis, we combined data from the Australian Capital Territory with those from New South Wales. Acute gastroenteritis was identified as ICD-9-CM codes in the range 003-009 (covering infectious gastroenteritis of various known and unknown origins) or code 558.9 ("other and unspecified noninfectious gastroenteritis"). This last code was included for consistency with other studies in the expectation that it might comprise a substantial number of cases of infectious gastroenteritis. Similar files of admission records were obtained from participating paediatric hospitals in each of the States (see Box 1). Records from the Royal Children's Hospital (RCH), Melbourne, and Princess Margaret Hospital (PMH), Perth, also included an identifying hospital record number. 1: Participating hospitals Royal Children's Hospital, Melbourne (VIC) Princess Margaret Hospital, Perth (WA) Women's and Children's Hospital, Adelaide (SA) Alice Springs Hospital (NT) Royal Darwin Hospital (NT) Royal Hobart Hospital (TAS) Sydney Children's Hospital (formerly Prince of Wales Children's Hospital) (NSW) New Children's Hospital, Sydney (Royal Alexandra Hospital for Children) (NSW) Westmead Hospital, Sydney (NSW) Royal Brisbane Hospital (QLD) Microbiology departments at participating hospitals were asked to forward all rotavirus-positive faecal specimens obtained from children under five years who were admitted for acute gastroenteritis to laboratories at RCH, where rotavirus infection was confirmed by enzyme immunoassay.14 All participating hospitals provided specimens over the entire study period, except that Westmead Hospital participated in the study for the first two years only, and was replaced by Sydney Children's Hospital in 1995. Seasonal, temporal, and geographic variation in strains of rotaviruses will be reported elsewhere. We estimated the proportion of gastroenteritis admissions that were caused by rotavirus infection both by direct and indirect means. The direct method involved a linked analysis of admissions and rotavirus data. Admission and laboratory records from RCH (Melbourne) and PMH (Perth) were linked by means of hospital unit record number and date of admission/date of specimen, thus identifying the proportion of admissions that we could directly confirm as involving rotavirus infection. This analysis was supplemented with information from each hospital's pathology records, as it became clear that not every rotavirus-positive specimen was being sent on to our laboratory (usually owing to insufficient size of samples). Further, it was possible to omit patients for whom no faecal test was performed, to give a more appropriate denominator for estimating the fraction admitted because of rotavirus infection (calculated as rotavirus fraction = number of admissions with positive rotavirus test result/number of admissions with faecal specimen tested). The indirect statistical estimation of the rotavirus fraction and the rationale behind this method are described in Box 2. The study was approved by ethics committees in each of the participating hospitals. 2: Statistical estimation of the rotavirus fraction We assumed (i) that rotavirus is the only major cause of childhood gastroenteritis admissions that shows significant seasonal variation; and (ii) that the total number of admissions due to rotavirus in a State is a constant multiple of the number seen in our participating hospital(s). Thus, total admissions per month were expressed as the sum of a constant number (representing non-rotavirus causes) and varying numbers of rotavirus admissions. The resulting linear regression model for the number of admissions in a State in each month was used to estimate the rotavirus fraction (the proportion of hospital admissions for acute gastroenteritis resulting from rotavirus infection). This is shown mathematically below, where: Ni = number of acute gastroenteritis admissions in the State in month i; ni = number of "rotavirus-positive" admissions in the State's participating (index) hospital(s); = monthly number of admissions statewide not caused by rotavirus; and = scaling factor relating the number of "rotavirus-positive" admissions in the State to that in the index hospital(s). The regression model (in which i = random error) is: Ni = + ni + i , which leads to: We followed earlier practice4,5 and used ordinary least squares to estimate , despite the fact that the model does not fit the usual assumptions of linear regression (in particular, the variance of i cannot be expected to be constant). As the assumption that there is perfect correlation between rotavirus incidence recorded at the index hospital and total rotavirus numbers at all hospitals in the State is inevitably untrue, there will be an underestimation of in this model, and consequently some underestimation of the rotavirus fraction. On the other hand, if the assumption that rotavirus is the only agent responsible for seasonal variation is wrong, then the estimation may be biased in either direction. The estimate is also potentially subject to other biases relating to the completeness and regularity of coverage of the contributed rotavirus samples. These biases are likely to outweigh random error, so that conventional confidence intervals would not provide a reliable indicator of uncertainty. Results Total numbers and estimated rates of acute gastroenteritis admissions are shown in Box 3. Of all admissions, 65.7% involved children under the age of two years, with approximately equal numbers in each of the first two years of life, and declining numbers in each of the subsequent three years to age five. The age breakdown was similar in all States except the Northern Territory, where a substantially larger proportion were aged under two (86.1%). Length of stay was also considerably longer in the Northern Territory. There were slightly more boys than girls (53.1% overall), consistent across all States. Of all admissions, 29.4% were coded 558.9, although this proportion declined sharply over the four years of the study as coding practices apparently changed. 3: Acute gastroenteritis in children aged less than five years, 1993-1996. Number and rate of hospital admissions, rate ratio relative to the Victorian rate, and average length of stay (95% confidence intervals in parentheses) State or TerritoryAverage annual admissionsAnnual rate per 1000 children under 5 yearsRate ratio relative to VictoriaAnnual rate per 1000 children under 1 yearAnnual rate per 1000 children aged 1-2 yearsAverage length of stay Victoria29159.2 (9.0-9.3)1.00 14.6 (14.1-15.1)14.4 (13.9-14.8) 1.93 days (1.90-1.96) Tasmania3199.3 (8.8-9.8) 1.01 (0.96-1.07) 15.0 (13.6-16.4) 15.1 (13.7-16.6) 1.79 days (1.71-1.87) Western Australia178614.2 (13.9-14.5) 1.55 (1.51-1.60) 25.3 (24.3-26.2) 24.9 (24.0-25.9) 3.13 days (3.03-3.23) Queensland377316.0 (15.7-16.2) 1.74 (1.70-1.79) 24.0 (23.3-24.7) 26.4 (25.6-27.1) 2.15 days (2.11-2.18) New South Wales*786617.1 (16.9-17.3) 1.87 (1.83-1.91) 25.5 (25.0-26.0) 27.5 (27.0-28.1) 2.11 days (2.09-2.13) South Australia189519.2 (18.8-19.7) 2.10 (2.04-2.16) 32.0 (30.7-33.2) 30.7 (29.5-31.9) 2.09 days (2.03-2.15) Northern Territory85449.8 (48.2-51.4) 5.44 (5.24-5.65) 106.2 (101.0-111.3) 108.1 (102.9-113.3) 9.18 days (8.88-9.47) Total1940815.0 (14.9-15.1) 23.9 (23.6-24.2) 25.0 (24.7-25.3) * Including Australian Capital Territory. Box 4 shows the temporal pattern of all admissions and of rotavirus admissions in index hospitals in the five largest States and the Northern Territory. The seasonal peaks in the eastern States (New South Wales, Victoria, Queensland, and South Australia) were generally coincident and occurred regularly in the colder months from July to September (except for the unusual final year in South Australia). In contrast, the weaker and less regular peaks in Western Australia occurred earlier than in the eastern States, and there was no discernible seasonal pattern in the Northern Territory. Even where the seasonal pattern was less distinct, the peaks in statewide admissions were reflected in peaks in the numbers of rotavirus- positive specimens. 4: Monthly incidence of hospital admission for acute gastroenteritis in children under five years of age in Australian mainland States and the Northern Territory, 1993-96 (solid line) and number of rotavirus-positive specimens received from participating hospitals in that State, rescaled from the hospital to the State level (dashed line), by the "regression method" For the data linkage method, among 1732 children admitted for whom a specimen was tested, we received 767 rotavirus-positive specimens from RCH (Melbourne) and found another 205 admissions with hospital records showing a positive rotavirus test, giving an estimated rotavirus fraction of 56%. The corresponding totals from PMH (Perth) were 1631, 626 and 161, respectively, giving a rotavirus fraction of 49%. Regression estimates of the rotavirus fraction ranged from a low of 22% for the Northern Territory (based on a total of 598 rotavirus-positive specimens) to a high of 41% for Victoria (984 specimens). When data from all States were combined, the correlation between rotavirus numbers and admissions increased, because a more accurate representation of the relationship between total admissions and rotavirus numbers in participating hospitals was obtained by pooling. The resulting estimated rotavirus fraction was 50% (based on 4634 specimens received). Separate estimates obtained for children aged under one year, one year to less than two years, and at least two years were 34%, 60% and 48%, respectively. Discussion This national four-year study has shown that there are almost 20 000 hospital admissions annually in Australia for acute gastroenteritis in children aged under five years -- an average rate of 15 per 1000, 50% of which appear to be attributable to rotavirus infection. The annual rate of hospitalisation for rotavirus-related gastroenteritis in children under five is therefore about 7.5 per 1000. Among children under two years, combining estimates for the two one-year age brackets, the corresponding rate is 11.6 per 1000, or just over one in every 100 children. Of the two methods we used to estimate the proportion of admissions that were caused by rotavirus, the method involving direct linkage of hospital admission records and stool specimen tests is likely to be the more accurate. Estimates of 56% (Melbourne) and 49% (Perth) were obtained for the two centres where it was available. These estimates may be too low, as enzyme immunoassay can fail to detect up to 10% of rotavirus-positive specimens.15 Conversely, they might be too high on a population-wide basis, as they were based on tertiary referral centres where the severity of admitted cases -- and therefore the likelihood of rotavirus involvement -- might be higher (although this was only weakly supported by our data on mean length of stay [LOS], which showed a small difference between RCH [mean LOS 1995-1996, 2.15 days] and the whole of Victoria [1.87 days], and no difference between PMH and WA averages [2.80 v. 2.85]). Our second method, based on a regression model, was subject to statistical fluctuations and assumptions that imply it might produce an underestimate of the rotavirus fraction (see Box name="box2"2). In particular, the coverage of rotavirus specimen collection varied between States and also, at times, within States. For example, only a relatively small number of specimens (457) were ascertained from New South Wales, implying that the rotavirus fraction for that State might be considerably underestimated. In fact, when the regression method was applied to the pooled national data, we found reasonable convergence between the two methods, and believe they both support the conclusion that 50% of all gastroenteritis admissions in this age group are due to rotavirus. A reasonable range of possible alternative estimates around this value would be from 40% to 60%. In other studies, estimates of the proportion of hospital admissions in children under five years attributable to rotavirus have ranged from around 30% to as high as 66%.3,4,6,8,9,16 United States studies from the Centers for Disease Control have estimated this proportion both by a simple "residual" method based on assuming that all diarrhoea admissions in the winter seasonal peaks are rotavirus-related,17 and a more direct method based on an eight-year series of children admitted to a Washington DC hospital.6 Both methods indicated that rotavirus was responsible for about one-third of admissions, and the corresponding annual rate of hospitalisation for rotavirus-related gastroenteritis in children under five years was 2.8 per 1000. In the United Kingdom, estimates have been based on laboratory surveillance and hospital discharge data, with a similar statistically based estimation procedure to ours.4 It was found that 43% of admissions in children under five years could be attributed to rotavirus, corresponding to 5.3 per 1000 admissions per year. A New South Wales study by Ferson also used a regression method, based on a larger sample of rotavirus surveillance data than ours, and estimated an annual rate of hospital admission of 8.7 per 1000.5 Using the 1993-1996 NSW hospital admission rates (Box name="box3"3), this corresponds to a rotavirus fraction of 51%, very consistent with our national estimate. Ferson's study found over twice the rate of rotavirus gastroenteritis in the second year of life compared with the first, a slightly greater difference than suggested by our data. The findings of both studies are consistent with a detailed investigation of children with gastroenteritis over 13 years at RCH Melbourne, which found that no pathogen could be identified in a substantially greater proportion of infants under six months than in older children.18 There were substantial differences in hospital admission rates between the States, with NSW, Queensland and South Australia having almost twice the rate of hospitalisation of Victoria. It seems very unlikely that these differences are the result of different disease patterns, especially as the seasonal patterns in these States were very similar. Nor are they likely to be explained by differences in coding, as our incidence figures are based on an inclusive selection of principal diagnosis ICD-9-CM codes. In particular, the inclusion of code 558.9 ("non-infectious gastroenteritis") identified a substantial number of apparently miscoded cases of viral diarrhoea, consistent with findings in other reports.4,5 The differences may reflect variations in patterns of primary care influencing the numbers of children who present to hospital emergency departments, and/or differences in hospital admission policies. The relative importance of each of these factors warrants further study, as it appears likely that substantial savings could be made if hospitalisation rates nationally could be reduced. There were no major seasonal differences in gastroenteritis incidence between States, except in the Northern Territory and Western Australia, where the relative importance of rotavirus in the gastroenteritis disease burden may be somewhat reduced. There is little evidence in our data of a progressive spread of the rotavirus epidemic across the country each year, in the manner that has been described in North America,19 apart from the fact that the annual peak of rotavirus activity in Western Australia appears generally to precede that in the eastern States. The Northern Territory was the most clearly distinct of all the regions, not only in its substantially higher hospital admission rate and lack of seasonal pattern, but also in the dramatically longer length of stay of patients. Average length of stay in this study (2.2 days, excluding the Northern Territory) was substantially shorter than that reported in the United States (3.9 days20), but very similar to British findings.4 Given the higher admission rates in Australia, shorter length of stay may reflect a less severe spectrum of illness, or possibly better management involving more widespread use of oral rehydration solution. Our results imply that 10 000 hospital admissions occur annually in Australia for rotavirus gastroenteritis. The direct cost of this hospital care is at least $12 million, based on an (Australian national diagnosis-related group-based) estimate of $1244 per admission,21 and may be as high as $15-$18 million (preliminary analysis, RCH [Melbourne] costing data). A successful rotavirus vaccine -- depending on its cost -- could result in substantial savings to the healthcare system. Acknowledgments The study was funded by the Public Health Research and Development Committee of the National Health and Medical Research Council. It would not have been possible without the generous cooperation of numerous individuals in all State and Territory health authorities, and in medical records and hospital information units at the participating hospitals, or without the participation and skilled assistance of the following microbiologists and paediatricians: G Davidson, P Goldwater, T Kok, A Lawrence, L Micken, S Weir (Adelaide); G Clift, J Erlich, J Hagger, R Matters, F Morey (Alice Springs); J Faogali, J Farrah, R Shepherd, M Witt (Brisbane); G Lum, A Lowe, A Ruben, B Way, K Withnall (Darwin); A Carmichael, A Claridge, K Dahlenburg, R Fang, R Tucker (Hobart); B Crawford, G Hogg, B Ross, R Schnagl, P Ward (Melbourne); B Dwyer, R Hill, A May, G O Connor, B Wild (Perth); P Amin, T Borg, A Cunningham, J MacRae, P McIntyre, C McIvor, K McPhie, J Mitchell, J Montgomery, G Sandico (Sydney). References Bishop RF, Davidson GP, Holmes IH, Ruck BJ. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet 1973; 2: 1281-1283. Bern C, Glass RI. Impact of diarrheal diseases worldwide. In: Kapikian AZ, editor. Viral infections of the gastrointestinal tract. New York: Marcel Dekker, 1994: 1-26. Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. J Infect Dis 1996; 174 (Suppl 1): S5-S11. Ryan MJ, Ramsay M, Brown D, et al. Hospital admissions attributable to rotavirus infection in England and Wales. J Infect Dis 1996; 174 (Suppl 1): S12-S18. Ferson MJ. Hospitalisations for rotavirus gastroenteritis among children under five years of age in New South Wales. Med J Aust 1996; 164: 273-277. Brandt CD, Kim HW, Rodriguez WJ, et al. Pediatric viral gastroenteritis during eight years of study. J Clin Microbiol 1983; 18: 71-78. Matson DO, Estes MK. Impact of rotavirus infection at a large pediatric hospital. J Infect Dis 1990; 162: 598-604. Konno T, Suzuki H, Imai A, et al. A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis. J Infect Dis 1978; 138: 569-576. Spence L, Singer O, Kibsey P, Fauvel M. Rotavirus infection in children with diarrhoea admitted to a general hospital in metro Toronto. Can J Pub Health 1985; 76: 17-20. Lewis HM, Parry JV, Davies HA, et al. A year's experience of the rotavirus syndrome and its association with respiratory illness. Arch Dis Child 1979; 54: 339-346. Liddle JLM, Burgess MA, Gilbert GL, et al. Rotavirus gastroenteritis: impact on young children, their families and the health care system. Med J Aust 1997; 167: 304-307. Smith JC, Haddix AC, Teutsch SM, Glass RI. Cost-effectiveness analysis of a rotavirus immunization program for the United States. Pediatrics 1995; 96: 609-615. Barnes GL, Lund JS, Adams L, et al. Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate. J Paediatr Child Health 1997; 33: 300-304. Coulson BS, Unicomb LE, Pitson GA, Bishop RF. Simple and specific enzyme immunoassay using monoclonal antibodies for serotyping human rotaviruses. J Clin Microbiol 1987; 25: 509-515. Husain M, Seth P, Broor S. Detection of group A rotavirus by reverse transcriptase and polymerase chain reaction in feces from children with acute gastroenteritis. Arch Virol 1995; 140: 1225-1233. Donelli G, Ruggeri FM, Tinari A, et al. A three-year diagnostic and epidemiological study on viral infantile diarrhoea in Rome. Epidemiol Infect 1988; 100: 311-320. Ho MS, Glass RI, Pinsky PF, Anderson LJ. Rotavirus as a cause of diarrheal morbidity and mortality in the United States. J Infect Dis 1988; 158: 1112-1116. Barnes GL, Uren E, Stevens KB, Bishop RF. Etiology of acute gastroenteritis in hospitalized children in Melbourne, Australia, from April 1980 to March 1993. J Clin Microbiol 1998; 36: 133-138. LeBaron CW, Lew J, Glass RI, et al. Annual rotavirus epidemic patterns in North America: Results of a 5-year retrospective survey of 88 centers in Canada, Mexico, and the United States. JAMA 1990; 264: 983-988. Jin S, Kilgore PE, Holman RC, et al. Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus. Pediatr Infect Dis J 1996; 15: 397-404. Australian casemix report: on hospital activity, 1995-96. Canberra: Department of Health and Family Services, 1997. (Received 30 Oct 1997, accepted 4 May 1998) Authors' details Clinical Epidemiology and Biostatistics Unit, Royal Children's Hospital, Melbourne, VIC. John B Carlin, BSc(Hons), PhD, Deputy Head, and Associate Professor, Department of Paediatrics, University of Melbourne; Patty Chondros, BSc(Hons), Research Assistant. Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne, VIC. Paul Masendycz, BAppSc, Research Assistant; Helen Bugg, BSc, Research Assistant; Ruth F Bishop, AO, DSc, PhD, Senior Principal Research Fellow (NHMRC, and Professor, Department of Paediatrics, University of Melbourne; Graeme L Barnes, MD, FRACP, Senior Gastroenterologist, and Associate Professor, Department of Paediatrics, University of Melbourne. Reprints: Associate Professor G L Barnes, Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, VIC 3052. E-mail: barnesgATcryptic.rch.unimelb.edu.au - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

John B Carlin · Patty Chondros · Paul Masendycz · Helen Bugg · Ruth F Bishop · Graeme L Barnes

Abstract Objective: To ascertain the effectiveness of a home vaccination service for children behind in their vaccination schedule. Design: Randomised controlled trial of nurse-administered vaccination at home. Children were allocated at random to the intervention or the control group before any contact with the parents was made. Setting: 10 council areas in north-west metropolitan Melbourne defined by 56 postcode zones. Six-week intervention period from November 1996. Participants: 405 children -- all those in the study area (n = 2610) 90 days late (age 9 months) for their third diphtheria-tetanus-pertussis/poliomyelitis/Haemophilus influenzae type B (DTP/OPV/Hib) vaccination, or 120 days late (age 16 months) for their measles-mumps-rubella (MMR) vaccination, according to the Australian Childhood Immunisation Register. Main outcome measures: Number of children completing DTP/OPV/Hib or MMR during the intervention period, and number up to date before intervention. Results: Verification of vaccination status with the parents revealed that 123 (60%) of the children in the intervention group and 113 (56%) of those in the control group were up to date with their vaccinations, leaving a study population of 81 (intervention group) and 88 (control group). Vaccination was achieved in 46 (57%) intervention children and 24 (27%) control children (risk ratio [RR], 2.08; 95% CI, 1.4-3.1; P < 0.001). For DTP/OPV/Hib, 18/32 (56%) intervention children and 12/36 (33%) control children were vaccinated (P = 0.06). For MMR, 28/49 (57%) and 12/52 (23%) children were vaccinated, respectively (P < 0.001). Home vaccinations were completed with 26 families (including five siblings). The average cost per child vaccinated as a result of the home program was $92.52. Conclusion: Home vaccination for children behind in their immunisation schedule is an effective, acceptable and relatively cheap method of completing recommended vaccinations. We recommend that a home vaccination program be widely implemented and made available, particularly for disadvantaged families. Introduction In Australia, incomplete immunisation of children under 2 years of age remains an important public health problem. Many children never complete their immunisation schedule or are many months overdue.1 Uptake rates are lowest for measles-mumps-rubella vaccination at age 12 months and the diphtheria-tetanus-pertussis booster at 18 months.1-3 Being late for a primary course is predictive of being late for or missing subsequent vaccinations.3,4Parents' beliefs about the seriousness of the vaccine-preventable illnesses and the safety and efficacy of vaccines are important predictors of vaccination uptake.5 However, there are other barriers to children being vaccinated -- frequent minor childhood illnesses, parental forgetfulness, and advice from health providers to delay vaccinations.6-10 A current strategy to overcome barriers to vaccination is to make vaccination more accessible, but parents are still required to bring their children to be vaccinated. For some families, however, it may be more effective to take the vaccination service to the child. We have explored (i) the effectiveness of offering a home vaccination service to children at greatest risk of not completing their immunisation schedule by age 2 years; and (ii) the usefulness of the Australian Childhood Immunisation Register (ACIR) for identifying these at-risk children. Method Participants The Australian Childhood Immunisation Register provided identifying information for children living in 10 local council areas in north-west metropolitan Melbourne (defined by 56 postcode zones) who were either born January 1996 and 90 days late for their third diphtheria-tetanus-pertussis/poliomyelitis/Haemophilus influenzae type B vaccination (DTP/OPV/Hib; 1st milestone), or born June 1995 and 120 days late for their measles-mumps-rubella vaccination (MMR; 2nd milestone). The intervention period comprised six weeks from November 1996. Making contact to verify vaccination status before randomisation would have in itself constituted an intervention. Therefore, before any contact was made with the parents, the children were allocated at random (by computer) to the intervention or the control group. Contact We made initial contact with the intervention group by letter, then by telephone one to three weeks later to verify vaccination status, to organise an appointment, and to administer a pre-vaccination health check as recommended by the National Health and Medical Research Council's Australian immunisation handbook.11 This health check was to ensure that the child did not require special medical attention and could be vaccinated at home. If no telephone contact could be made, two follow-up letters were sent. As local councils and maternal and child health nurses provide a substantial number of childhood vaccinations in Victoria and maintain vaccination records, we checked these (possible) providers for vaccination details if parents could not be contacted. Children were confirmed as either overdue for vaccination or up to date with vaccination if parents, the local council or the maternal and child health nurse provided a record of the vaccination. Intervention The study was approved by the Royal Children's Hospital Ethics in Human Research Committee. Parents signed a consent form to participate in the study and a standard State Government vaccination consent form. A nurse administered vaccination in the child's home at a time convenient to the parents. Siblings were also vaccinated if they were due for vaccination. The nurse providing the vaccination had completed a standard Victorian Government Department of Human Services immunisation course. A resuscitation kit (including adrenalin) was taken on each home visit, and the cold chain was maintained by transporting vaccines in a temperature-monitored car refrigerator. Before vaccination, the nurse administered a pre-vaccination health checklist11 to confirm the child's medical history, as obtained during the initial telephone contact, and to assess the child's health on the day of vaccination. Vaccines that were due were verified from the parent-held Child Health Record. The child's temperature was taken if he or she was hot or appeared unwell (a temperature > 38.58c precludes vaccination11). Paracetamol was offered to all children before vaccination. The nurse remained with the family for more than 20 minutes after vaccination. The visits included time for parents to complete questionnaires about immunisation service use, reasons for the delay in vaccination, education level, family size and whether the family had a Health Care Card. (A Health Care Card is a Federal Government card available to low income families, including those receiving government pensions, to obtain concessions for health and medical expenses; ie, it is an indicator of disadvantage or poverty.) Neither written consent nor sociodemographic information was obtained from parents who chose to have their child vaccinated by another provider, or whose child was up to date with immunisation, or who refused to take advantage of the home service. Follow-up of control children Two months after the intervention period, and based on updated information from the Australian Childhood Immunisation Register, we sent letters to parents of control children for whom neither the Register nor local councils had recorded a third DTP/OPV/Hib or an MMR vaccination. We followed the letters with a telephone call to verify vaccination status and to offer, in this case, vaccination at the Royal Children's Hospital. Parents of control children were also informed of local vaccination services offered by the maternal and child health nurse or of the schedules of mobile vaccination vans provided by local councils. No sociodemographic information was collected from the parents of control children. Cost analysis Costs included travel, estimated at $0.50 per kilometre, nursing time at $25 per hour, consumables (excluding vaccines) as charged by the Royal Children's Hospital and clerical work at $17 per hour for 18 days. Statistical analysis Sample size was estimated assuming that 35% of intervention children would accept vaccination and 6% of control children would be immunised. This would require 30 in each group, with a set at 0.05 and statistical power 80%. Statistical associations were assessed with chi-squared tests. Confidence intervals and risk ratios were calculated with the STATA program.12 Results Subjects There were 2610 children born in June 1995 or January 1996 in the study area and registered with the Australian Childhood Immunisation Register. Of these, 416 children (16%) were identified by the Register as overdue for their third DTP/OPV/Hib or MMR. The Figure shows the number of children on the Register meeting the study criteria, the number excluded and the vaccination status of the children in the intervention and control groups at the time of contact. On verification of vaccination status with parents, 123 (60%) of the intervention children and 113 (56%) of the control children were confirmed as being up to date with their immunisation schedule, and therefore were ineligible for the intervention, leaving 81 children in the intervention group and 88 control children. Those whose status could not be verified were assumed for analysis to be unvaccinated. In total, 2430 (93%) children were up to date with their vaccinations at the beginning of the study period: 1219 (95%; 95% confidence interval [CI], 93.6%-96.0%) 9-month-old children and 1211 (92%; 95% CI; 90.8%- 93.8%) 16-month-old children. Intervention Table 1 shows the number of children vaccinated during the intervention period. To estimate the effect of the intervention on uptake for the full cohort, the cohort was divided into two equal groups (n = 1305 each). The number of children immunised in the group with the intervention children increased from 1220 (93.5%) before intervention to 1266 (97%) after intervention. The group with the control children increased from 1210 (93%) to 1234 (95%). Using similar logic, but dividing for type of vaccine, in the group with intervention children the rate for 1st milestone vaccination increased to 98% and for 2nd milestone to 97%, whereas the rates for the group with control children increased to 96% and 94%, respectively. The mean (SD) age for DTP/ OPV/Hib vaccination for intervention and control children was 10 (0.2) months and 11.5 (0.3) months, respectively (which was significantly different; P < 0.001), compared with 7 (1.3) months for children having DTP vaccination before study commencement. The mean (SD) age for MMR vaccination for intervention and control children was 17.2 (0.1) months and 19 (0.3) months (P < 0.001), compared with 14 (1.7) months for those having MMR vaccination before study commencement. In the intervention group 26 children were immunised by the study nurse and 19 by their doctor or local council service. One child who had a severe egg allergy was vaccinated at the Royal Children's Hospital Immunisation Adverse Events Clinic. Ten children due for MMR were also given their 18-month DTP/Hib boosters and five siblings were brought up to date with their vaccination schedule. In all, 82 vaccines were administered to study children and siblings. On the day of vaccination 13 children had colds or were taking antibiotics; none had a fever. All were vaccinated as arranged. Two families refused the service because they were against immunisation and 22 families preferred to use their own doctor. As mentioned, 19 did so within the study period. One mother changed her mind about home vaccination because of concern about her child's egg intolerance. The child was vaccinated a month after the intervention by her doctor. Table 2 summarises the demographic information of those immunised at home and major reasons given by parents for delayed vaccinations. Costs The mean cost per child vaccinated in the intervention group was $92.52, and the mean cost per visit per vaccine was $52. These costs excluded cost of visits to the general practitioner by those being vaccinated by their own doctor. Fifty-one per cent of the cost was attributable to clerical time needed to verify vaccination status. Travel costs were 12% of total costs and 33% of nurses' costs. Discussion We have shown that offering home vaccination is an effective method of bringing children (and their siblings) up to date with their immunisation schedule. Importantly, we used information from a population-based register, and thus provided vaccinations for children in socially disadvantaged families. Such families have been identified previously by the Australian Bureau of Statistics13 and others14 as being most at risk of not completing the scheduled childhood immunisations. A major finding of this study was the unexpectedly high proportion of children already vaccinated at the commencement of the study. This proportion was substantially higher than expected from previous statewide estimates -- 95% v. 84% for 1st milestone vaccination and 92% v. 78% for 2nd milestone vaccination2 -- and exceptionally high given that our study was conducted in a socially disadvantaged area. Data for our study on children's vaccination status were from Australian Childhood Immunisation Register enrolments, which are derived from Medicare data and miss about 2% of children; however, this would have had a minimal impact on these vaccination estimates. It is also unlikely that substantial misclassification of vaccination status occurred. While we did not formally cross-check vaccination dates, when dates were obtained from two sources 85% matched. When dates differed it cannot be assumed that Register dates were correct. In some cases vaccinations reported to the Register by us were incorrectly recorded or missing. Thus, we found the usefulness of the Australian Childhood Immunisation Register as a source of accurate information to be limited. However, our study was undertaken in the first year of the Register's existence and it is expected that accuracy of the Register will improve. Limitations of this study arise from the need to randomise the population sample before verification of immunisation status. This has the potential to introduce bias because of the possibility of differences in response between the intervention and control groups. Another limitation was the number of children in each group with whom no contact was made. However, these limitations are unlikely to have caused substantial bias. In both groups a similar number of control (56%) and intervention children (60%) were excluded because they were up to date with vaccinations, and likewise the proportion of control (15%) and intervention children (14%) who could not be contacted to determine immunisation status was similar. There is also no reason to suppose that any differences in vaccination rates between these two uncontacted groups would be sufficient to bias the estimate of the intervention effect. Assuming that 50% of the children in each group who could not be contacted were vaccinated, the risk ratio for vaccination would be 1.67 (95% CI, 1.3-2.2; P < 0.001). Itinerancy is a risk factor for incomplete and late vaccination,3,15 making it not surprising that a considerable number considered overdue for vaccination could not be contacted. We have shown that those who can be contacted can be vaccinated. A similar program that accesses vaccination information at a local level may be more efficient at targeting families who move frequently. It is obvious that a home service will cost more than mass vaccination programs. The cost per vaccine, taking into account only nurses' time and travel costs, was about $23, which compares favourably with the £8 reported by an outreach program in the United Kingdom.16 The costs of the service would be reduced with improved accuracy of Australian Childhood Immunisation Register information (clerical costs would be reduced by 50%), by offering a local rather than a centralised service (travelling costs would be reduced by 30%), and by incorporating the vaccination service into a broader home visiting program to promote child health and support disadvantaged families in this endeavour. As indicated by many studies,17-22 a barrier to age-appropriate immunisation is often not parental unwillingness to have their child vaccinated, but immunisation providers failing to provide a service. About a third of the parents of children behind in their vaccinations reported having recently consulted a doctor. In almost all these cases the child could have been vaccinated at that time. To prevent diseases such as measles, immunisation rates need to exceed 95%.23 Even the high uptake rates found at the commencement of our study are below this level. Innovative and proactive methods are necessary to attain these high levels and have been found to be effective.15,24 Acknowledgements This study was funded by National Health and Medical Research Council (NHMRC) project grant number HS371. Lyndal Bond was funded by an NHMRC Scholarship. We would like to thank the research nurse (Michelle Wills), the Royal Children's Hospital Immunisation Adverse Events Clinic for providing a service for children in the intervention and control groups, and local council health departments for their cooperation. References Australian Bureau of Statistics. Children's immunisation Australia. Canberra: ABS, April 1995, 1996. (Catalogue No. 4352.0.) Lester R, Norris P. 1994/5 Pre-school immunisation coverage. Notifications for Victoria, July-September 1995. Health Protection Update (Public Health Division, Department of Human Services, VIC) 1995; 3: 10-13. Hanna CJ, Wakefield JE, Doolan CJ, Messner JL. Childhood immunisation factors associated with failure to complete the recommended schedule by two years of age. Aust J Public Health 1994; 18: 15-24. Li J, Taylor B. Factors affecting uptake of measles, mumps, and rubella immunisation. BMJ 1993; 307: 168-171. Peckham C, Bedford H, Senturia J, Ades A. The Peckham Report National Immunisation Study: factors influencing immunisation uptake in childhood. Horsham: Action Research For The Crippled Children, 1989. Jones K, Fasher B, Hanson R, et al. Immunisation status of casualty attenders: risk factors for non- compliance and attitudes to "on the spot" immunisation. J Paediatr Child Health 1992; 28: 451-454. Miles TA, Merrell WH. An outbreak of measles in the Hunter area of New South Wales. Aust J Public Health 1992; 16: 302-304. New SJ, Senior ML. "I don't believe in needles": qualitative aspects of a study into the uptake of infant immunisations in two English health authorities. Soc Sci Med 1991; 33: 509-518. Harding GC. How can the uptake of vaccines be increased? J Inst Health Educ 1984; 22: 5-11. Adjaye N. Measles immunisation: some factors affecting non-acceptance of vaccine. Public Health 1981; 95: 185-188. National Health and Medical Research Council. The Australian immunisation handbook. 6th ed. Canberra: AGPS, 1997. Stata Statistical Software [computer program], Release 5.0. College Station, Tex: Stata Corporation, 1997. Australian Bureau of Statistics. 1989-90 National Health Survey children's immunisation, Australia. Canberra: AGPS, 1992. Bazeley P, Kemp L. Childhood immunisation: the role of parents and service providers. A review of the literature. Canberra: National Immunisation Programme, Commonwealth Department of Human Services and Health, AGPS, 1994. Pearson M, Makowiecka K, Gregg J, et al. Primary immunisations in Liverpool II: is there a gap between consent and completion? Arch Dis Child 1993; 69: 115-119. Jefferson N, Sleight G, MacFarlane A. Immunisation of children by a nurse without a doctor present. BMJ 1987; 294: 423-424. MacIntyre R, Nolan T. Attitudes of Victorian vaccine providers to pertussis vaccine. Med J Aust 1994; 161: 295-299. Burgess MA. Pertussis vaccine -- time to stop the confusion. Med J Aust 1994; 161: 293-294. Begg NT, Nicholl A. Immunisation. BMJ 1994; 309: 1073-1075. Stevens D, Baker R, Hands S. Failure to immunise against whooping cough. Arch Dis Child 1986; 61: 382-387. Kinder J, Teare L, Rao M, et al. False contraindications to childhood immunisation. Br J Gen Pract 1992; 42: 160-161. Askew GL, Finelli L, DeGraaf J, et al. Beliefs and practices regarding childhood vaccination among urban pediatric providers in New Jersey. Pediatrics 1995; 96: 889-892. Nolan T. Measles -- eradication or procrastination? Med J Aust 1990; 152: 449-450. Birkhead GS, LeBaron CW, Parsons P, et al. The immunisation of children enrolled in the special supplemental food program for women, infants and children (WIC). JAMA 1995; 274: 312-316. (Received 29 Sep 1997, accepted 6 Apr 1998) Authors' details Clinical Epidemiology and Biostatistics Unit, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC. Lyndal M Bond, MA(ApplPsych), NHMRC Scholar. Terry M Nolan, PhD, FRACP, FAFPHM, Head, Clinical Epidemiology and Biostatistics Unit. Department of Human Services, Melbourne, VIC. Rosemary A Lester, MB BS, MPH, FAFPHM, Head, Infectious Diseases Unit. Reprints: Ms Lyndal Bond, Clinical Epidemiology and Biostatistics Unit, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, VIC 3052. E-mail: bondATcryptic.rch.unimelb.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Lyndal M Bond · Terry M Nolan · Rosemary A Lester

Abstract Objective: To describe the results of vaccinating children with a history of serious adverse reactions after vaccination or of egg allergy at a special clinic established for that purpose. Design: Retrospective case series. Patients: Children who attended the clinic between 1 August 1994 and 31 July 1996 after being referred by vaccine providers. Setting: A clinic conducted in the Emergency Department of The Canberra Hospital, Australian Capital Territory. Main outcome measures: Reasons for referral; vaccinations given; and subsequent adverse vaccination events. Results: 91 children received 155 vaccinations at the clinic, and only one serious event -- a hypotonic/hyporesponsive episode (HHE) after diphtheria-tetanus-whole-cell pertussis (DTPw), oral polio and Haemophilus influenzae type b vaccination -- was subsequently reported; this child recovered spontaneously. Fifty-three children referred because of a previous serious adverse vaccination event were revaccinated at the clinic with whole-cell pertussis vaccine (47), combined diphtheria and tetanus vaccine (4), tetanus toxoid (1), and typhoid vaccine (1). Three children (referred because of previous meningitis, subdural haemorrhage or parental suspicion of allergy to DTPw) received their first dose of pertussis vaccine at the clinic. The remaining 35 children had a history of egg allergy and were given measles-mumps-rubella vaccine. Conclusions: We successfully vaccinated children with histories of serious reactions to vaccination, including HHEs, convulsions, apnoea, high temperatures and persistent screaming, as well as those with egg allergy. We believe special clinics can improve vaccination coverage. Introduction In 1995, there were almost 10 000 reported cases of vaccine-preventable disease in Australia.1 In that same year, an Australian Bureau of Statistics survey found only 52% of children were fully vaccinated, and that advice against vaccination or concern about the side effects were among the main reasons for missing vaccination.2 Reactions do occur after vaccination, but these are usually mild. They are often caused by the whole-cell pertussis component.3 While it is rarely necessary to delay or avoid subsequent vaccinations in children who have had reactions4 if the reaction was serious, continuing vaccination can be a very difficult decision for both parents and vaccination providers. The Canberra Hospital (formerly Woden Valley Hospital) in the Australian Capital Territory services a population which includes approximately 22 000 children aged less than five years. In August 1994, a special clinic was established to provide vaccination under close medical supervision for children who had had a serious adverse event after a previous vaccination or who had a history of egg allergy (at one time considered a contraindication to measles-mumps-rubella vaccination). We report the results of vaccinations provided to children in the first two years of the clinic. Similar clinics have been established in the United Kingdom,5,6 but data from an Australian setting have not previously been published. Methods The clinic was conducted fortnightly (occasionally more frequently) in The Canberra Hospital's Emergency Department. We accepted children who met the national surveillance definition of a serious adverse event after vaccination (Box 1, below),7 except those who had had encephalopathy within seven days of vaccination or an immediate severe allergic or anaphylactic reaction, both of which contraindicate further vaccination.8 We also accepted children with egg allergy who required measles- mumps-rubella (MMR) vaccine. Local vaccination providers, including medical practitioners and community nurses, received a written protocol for referral of children and were asked to direct referrals through the Immunisation Coordinator at ACT Health & Community Services. Medical practitioners were also advised about the clinic through a seminar series and in bulletins from ACT Health & Community Services. We asked providers to establish the nature and severity of the reaction and not to refer children whose parents were merely anxious about vaccination. On referral, parents were provided with written information about the risks and benefits of vaccination and, if appropriate, an appointment was made with the clinic. Parents were advised to give children paracetamol (15 mg/kg) at 8:00 am on the day of the clinic and to attend at 8:50 am. A paediatrician examined each child before vaccination and discussed the relevant history with the parent; we did not confirm egg allergy by means of skin tests. For each child, the injection site, vaccine, batch number and any adverse event after vaccination at the clinic was recorded. Electronic images of these records were stored in the hospital database. Parents were advised that children should remain under observation at the clinic for two hours after vaccination, and were provided with an information sheet on paracetamol use after vaccination. They were urged to contact the clinic if any adverse event occurred after leaving the hospital, but were not otherwise routinely followed up. We used the national surveillance criteria (Box 1)7 to define serious events after vaccination at the clinic. The reason for each referral and, where applicable, vaccines associated with the previous adverse event were retrospectively recorded in a database. Data on vaccines given at the clinic, length of stay and subsequent adverse events were obtained retrospectively from hospital records. Any record of subsequent attendance at the hospital was also checked to identify adverse events after vaccination at the clinic (The Canberra Hospital is the only public hospital with paediatric services in the ACT). The two-year study period was from 1 August 1994 to 31 July 1996. Epi Info version 6.04 was used to analyse the data.9 Results Fifty-two clinics were conducted over the two years. No more than five children attended on any one day. Overall, 91 children received 155 vaccinations during 110 visits (eight children attended twice, three attended three times, and one attended six times). Reasons for attendance were a serious adverse vaccination event (53), egg allergy (35), seizure associated with meningitis (1), subdural haemorrhage in infancy (1), and possible allergy to diphtheria-tetanus-whole-cell pertussis (DTPw) vaccine on the basis of family history (1). The median age of all children attending the clinic at the first visit was 14 months (range, 2 months to 15 years). Of the 53 children attending because of a previous vaccination event, 21 (40%) were aged 3 to 8 months; those attending because of egg allergy were aged 10 months to 15 years, while the three remaining children were aged 2 to 5 months. The male:female ratio was 1.2:1. Five children were referred to the clinic but did not attend; three were subsequently vaccinated by their general practitioners and two -- one referred because of a previous adverse vaccination event and one because of egg allergy -- were lost to follow-up. Box 2 shows that, of the previous serious adverse vaccination events for which 53 children were referred, all but one occurred after DTPw vaccination, and persistent screaming (> 3 hours) was the most frequent reaction. For 29 of these children (55%) the adverse event occurred after the first dose of vaccine, for 15 (28%) after the second, for six (11%) after the third, and for three (6%) after the fourth. At the clinic, 47 of these children were revaccinated with one dose of whole-cell pertussis vaccine in the form of DTPw or monovalent pertussis, four received combined diphtheria and tetanus vaccine (CDT), one received tetanus toxoid, and one received typhoid vaccine. Haemophilus influenzae type b vaccine (Hib), oral polio vaccine (OPV), and MMR vaccines were also provided where appropriate. Three other children (referred because of previous meningitis, subdural haemorrhage or parental suspicion of allergy to DTPw) received their first dose of pertussis vaccine at the clinic. None of the 35 children referred because of egg allergy had experienced anaphylaxis after egg or were considered severely allergic; all were vaccinated at the clinic with MMR vaccine. During 110 visits, 88 children were observed for two hours, 16 for three hours, two for four hours and one for six hours (19 children were observed for longer than the stipulated period because of parental concern only). The three remaining children were observed for one hour (leaving at the request of their parents) and included two who received MMR and one (referred because of suspected allergy to DTPw) who received DTPw, OPV and Hib. No adverse events were recorded during the clinic observation period. No child vaccinated with MMR had any adverse event reported after discharge from the clinic. Similarly, no adverse events were reported after discharge for any of the 20 children referred because of persistent screaming; of these, 19 received one dose of a whole-cell pertussis vaccine at the clinic. The remaining child received CDT. One child aged six months had a serious adverse event (hypotonic-hyporesponsive episode [HHE]) eight hours after vaccination with DTPw, OPV and Hib at the clinic. This child had been referred because of similar episodes, once three hours after receiving the first course of DTPw, OPV and Hib, and then again six hours after receiving the second course. The episode, which occurred at home, lasted only a few minutes and the child recovered spontaneously; a doctor was not consulted. This child was subsequently vaccinated with MMR at 12 months and revaccinated with DTPw and Hib (fourth dose) at 18 months by the child's usual vaccine provider. The parent reported that the child had suffered no further episodes. Four other children who had previously had an HHE after DTPw vaccination were revaccinated with DTPw at the clinic and no further episodes were reported. The absence of further episodes was confirmed for three of these children when they made subsequent visits to the clinic; the parent of the fourth child was contacted and confirmed that no further episodes had occurred (vaccination was completed through the child's usual vaccine provider). Mild reactions were reported for two children vaccinated at the clinic. The first, aged two months, screamed persistently for an unspecified duration after receiving DTPw, OPV and Hib. The child had not been previously vaccinated and was attending because of a suspected allergy to DTPw. After assessment, the paediatrician did not consider the child's reaction severe enough to warrant supervision of subsequent vaccinations at the clinic and recommended routine vaccination by the child's usual vaccine provider. The second child, aged 16 months, had a high temperature (level unspecified) and local reaction after receiving DTPw (third dose) and Hib. Although this is considered a mild reaction, the parent did not consent to a further dose of DTPw. CDT was provided at a subsequent visit, without any reported reaction. Discussion We successfully vaccinated children with a history of serious reactions to vaccination, including HHEs, convulsions, apnoea, high temperatures and persistent screaming, as well as children with a history of egg allergy. HHEs are rare, but are known to occur after receipt of pertussis vaccines.3 They have previously been shown to have no neurological or long term sequelae on follow-up.10 One child vaccinated at the clinic with DTPw (third dose), OPV and Hib reportedly had an HHE (which we were not able to validate as it occurred after discharge from the clinic). As recovery from these episodes can be quick,10 it is often necessary to rely on a parent's description. This child, who had also had an HHE after each of the two previous DTPw vaccinations, received a fourth dose of DTPw from the child's usual vaccine provider, and the parent confirmed that no further HHE had occurred. We successfully revaccinated four other children who had had an HHE. We believe the results from our clinic support the National Health and Medical Research Council (NHMRC) recommendation that an HHE does not usually contraindicate further doses of pertussis vaccine.3We cannot discount the possibility that serious reactions occurred after vaccination at the clinic, but were not reported. However, as serious reactions had been reported previously for these children, and as they had attended the clinic and their parents had been encouraged to report any adverse event after discharge, we consider this unlikely. Only two children vaccinated with DTPw at the clinic experienced mild reactions (these would not contraindicate further doses of pertussis-containing vaccines).3,4 However, we had expected that more mild to moderate reactions would be reported. Deloria et al found that children who had had common reactions to pertussis vaccination (including a temperature of over 38¡C and swelling and redness at the injection site) were approximately 1.5 to 8 times more likely to experience the same reaction at a subsequent vaccination.11 After DTPw vaccination, about 50% of children will have swelling or redness at the injection site, 30% will have a high temperature and approximately 30% will be inconsolable or cry persistently.3 The small number of minor reactions detected in our study may reflect under-reporting after discharge, but may also be the result of prophylactic paracetamol use.3 We do not know the total number of ACT children who experienced a serious adverse vaccination event making them suitable for referral to the clinic. However, we do know that 36 618 doses of DTPw vaccine were given in the ACT during the period of our study (Julie Donda, ACT Health & Community Services, personal communication). The Australian immunisation handbook estimates that the rate for persistent screaming (> 3 hours) after DTPw vaccination is about 1/100 doses, while for HHEs and convulsions the rates are 1/300 to 1/30 000 doses, and about 1/1750 doses, respectively.3 In comparison, the referral rates for children attending our clinic were persistent screaming, 1/1800 doses; HHEs, about 1/7000 doses; and convulsions, about 1/12 000 doses. This suggests that referral rates were low, except, possibly, for HHE. Perhaps there is a need to raise awareness among vaccine providers and parents of both the existence of the clinic and of the importance of reporting serious adverse events. Hospital-based clinics such as ours provide an important service in addressing the immediate concerns of both parents and providers. We used whole-cell pertussis vaccine, but the recent introduction of acellular pertussis vaccine may further improve acceptability, particularly for parents who are not prepared to continue with DTPw vaccine. The use of acellular pertussis vaccines should reduce the incidence of mild to moderate reactions, but its impact on the incidence of serious reactions is not yet clear.12 Active follow-up after vaccination at the clinic is now being undertaken and we believe this should improve identification of delayed reactions and encourage completion of outstanding vaccinations. It is possible that detection of serious adverse events after vaccination at the clinic would be further improved by increasing the observation time if this is indicated by previous history. Over time, the clinic should provide reassurance to both parents and vaccine providers by practically demonstrating the safety of vaccines, but the service should be reserved for those most at need. Children with egg allergy and those with persistent screaming after vaccination made up over half of the patients attending the clinic, and all were successfully vaccinated. The NHMRC currently recommends that a paediatrician be consulted if there is genuine concern over possible egg allergy, with a view to vaccination under controlled conditions such as those in our clinic.3 What constitutes genuine concern is unclear, but we believe that only those with severe reactions considered appropriate by an experienced paediatrician, such as anaphylaxis to egg, should be referred to the clinic. Both parents and vaccine providers need to be reassured that most children with egg allergy, those who have screamed persistently after vaccination, and perhaps some others, can and should be vaccinated through their usual vaccine providers.3,13 We believe the clinic is an essential component of the ACT's immunisation program, improving vaccination coverage by vaccinating children who may otherwise remain unvaccinated or incompletely vaccinated, and by encouraging reporting of adverse vaccination events. Similar clinics for children with serious adverse reactions to vaccination and severe allergies, such as anaphylaxis to egg, should be encouraged in all States and Territories. We believe children with mild to moderate reactions (including persistent screaming) should be revaccinated through their usual vaccine provider. It is essential that all vaccine providers are well informed of the recommendations for vaccination, particularly with respect to contraindications.3 We should all endeavour to ensure that children are vaccinated in accordance with the recommended schedule. Acknowledgements We thank Yvonne Epping for her support and assistance as Immunisation Coordinator at ACT Health & Community Services; the staff of the Emergency Department at The Canberra Hospital who conducted the clinics; the vaccination providers for their cooperation in referring patients; and Dr Christine Roberts of the National Centre for Epidemiology and Population Health for her comments on the manuscript. The Master of Applied Epidemiology Program is funded by the Commonwealth Department of Health and Family Services. References Herceg A, Oliver G, Myint H, et al. Annual report of the National Notifiable Diseases Surveillance System, 1995. Commun Dis Intell 1996; 20: 440-464. Australian Bureau of Statistics. Children's immunisation. Australia April 1995. Canberra: ABS, 1996. (Catalogue No. 4352.0.) National Health and Medical Research Council. The Australian immunisation handbook. 6th ed. Canberra: AGPS, 1997. The Australian College of Paediatrics policy statement. Contraindications to immunization against pertussis. J Paediatr Child Health 1994; 30: 310-311. Ko MLB, Rao M, Teare L, et al. Outcome of referrals to a district immunisation advisory clinic. Commun Dis Rep 1995; 5: R146-R149. Newport MJ, Conway SP. Experience of a specialist service for advice on childhood immunisation. J Infect 1993; 26: 295-300. Curran M, Herceg A. Surveillance data in CDI. Commun Dis Intell 1997; 21: 8. National Health and Medical Research Council. The Australian immunisation procedures handbook. 5th ed. Canberra: AGPS, 1994. Dean AG, Dean JA, Coulombier D, et al. Epi Info [computer program]. Version 6. A word processing, database, and statistics program for epidemiology on microcomputers. Atlanta, Ga: Centers for Disease Control and Prevention, 1994. Barraff LJ, Shields WD, Beckwith L, et al. Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation. Pediatrics 1988; 81: 789-794. Deloria MA, Blackwelder WC, Decker MD, et al. Association of reactions after consecutive acellular or whole-cell pertussis vaccine immunizations. Pediatrics 1995; 96 (3 Suppl): 592-594. Decker MD, Edwards KM, Steinhoff MC, et al. Comparison of 13 acellular pertussis vaccines: adverse reactions. Pediatrics 1995; 96 (3 Suppl): 557-566. Aickin R, Hill D, Kemp A. Measles immunisation in children with allergy to egg. BMJ 1994; 309: 223-225. (Received 30 Oct 1997, accepted 21 Jan 1998) Authors' details National Centre for Disease Control, Commonwealth Department of Health and Family Services, and National Centre for Epidemiology and Population Health, Canberra, ACT. Ross M Andrews, MPH, DipAppSci(Env Health), Master of Applied Epidemiology Student; Ana Herceg, MB BS, MPH, Medical Epidemiologist. South Australian Health Commission, Adelaide, SA. Ann E Kempe, MSc(Hons), RN, Manager, South Australian Immunisation Unit. Emergency Department, The Canberra Hospital, ACT. Kam K Sinn, MB BS, FRACP, Paediatrician. Reprints will not be available from the authors. Correspondence: Mr R M Andrews, Department of Human Services, Level 17, 120 Spencer Street, Melbourne, VIC 3000. E-mail: ross.andrewsATdhs.vic.gov.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia ".

Ross M Andrews · Ann E Kempe · Kam K Sinn · Ana Herceg

Use of systematic reviews of randomised trials by Australian neonatologists and obstetricians Christopher F C Jordens, Penelope Hawe, Les M Irwig, David J Henderson-Smart, Margaret Ryan, Deborah A Donoghue, Roger G Gabb and Ian S Fraser MJA 1998; 168: 267-270 For editorial comment see Phillips Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1998 Abstract Objective: To determine what proportion of Australian neonatologists and obstetricians report using systematic reviews of randomised trials. Design: Cross-sectional survey using structured telephone interviews. Setting: Australian clinical practice in 1995. Participants: 103 of the 104 neonatologists in Australia (defined as clinicians holding a position in a neonatal intensive care unit); a random sample of 145 members of the Royal Australian College of Obstetricians and Gynaecologists currently practising in Australia. Main outcome measures: Information sources used in clinical practice; reported awareness of, access to and use of systematic reviews, and consequent practice changes. Results: Response rates were 95% (neonatologists) and 87% (obstetricians); 71 neonatologists (72%) and 55 obstetricians (44%) reported using systematic reviews, primarily for individual patient care. Databases of systematic reviews were used with a median frequency of once per month. Among neonatologists, systematic reviews were used more commonly by those who were familiar with computers, attended professional meetings, and had authored research papers. Among obstetricians, they were used more commonly by those who were familiar with computers, had less than 10 years' clinical experience, attended more deliveries, and were full-time staff specialists in public hospitals. Of neonatologists who reported using systematic reviews, 58% attributed some practice change to this use. For obstetricians, the corresponding figure was 80%. Conclusions: There is evidence that Australian neonatologists and obstetricians use systematic reviews and modify their practice accordingly. Dissemination efforts can benefit from knowledge of factors that predict use of systematic reviews. Introduction Randomised controlled trials are widely accepted as the best method of evaluating the effectiveness of medical interventions. However, their findings are slow to change medical opinion and practice.1,2 The communication of clinically important research findings is hampered by the volume and geometric growth of the medical literature.3 Reviews address this problem, but conventional review methodology is unscientific4,5 and open to selection biases inherent in the publication process.5,6 This has led to the development of systematic reviews. A properly conducted systematic review begins with an exhaustive search for published and unpublished randomised trials addressing a well defined research question. The second step is to identify trials of adequate quality to contribute to decision-making. The results of included trials are then pooled, or "meta-analysed", to arrive at a quantitative estimate of the benefits and harms of treatment. Systematic reviews published by the Cochrane Collaboration are also continuously updated by specialist review groups.7 Systematic reviews in pregnancy and childbirth have been available for some years. In 1988 a comprehensive trial register became commercially available in database form as the Oxford database of perinatal trials.8 Effective care in pregnancy and childbirth, 9 a textbook based on this research synthesis, was published the following year, with a guide for non- specialist readers.10 A companion textbook, Effective care of the newborn infant,11 appeared in 1992. From 1993, systematic reviews relating to pregnancy and childbirth were available electronically in the Cochrane pregnancy and childbirth database.12 All these reviews are currently being updated for The Cochrane library.13 These new publications represent prototypes for future publications in other fields of practice. However, their impact on clinical practice remains uncertain, despite several surveys to ascertain the extent of their dissemination and uptake.14-18 To make a practical difference, systematic reviews must be readily available to clinicians who are aware of them, who use them, and who implement their findings. To ascertain whether this is occurring in Australia, we conducted a survey of neonatologists and obstetricians with the aims: To gauge awareness of, access to, and use of the Oxford database, Cochrane database, and Effective care textbooks; To place these resources in the context of other information sources that inform practice in obstetrics and neonatology; and To ascertain how often and why these resources are consulted, predictors of their use, and whether their use has led to reported changes in clinical practice. Methods Participants Clinicians who held a position in one of Australia's 23 neonatal intensive care units were eligible for the survey. The Australian and New Zealand Neonatal Network (ANZNN), which covers all neonatologists, provided a current listing. The Royal Australian College of Obstetricians and Gynaecologists (RACOG) drew a simple random sample of 20% of Fellows from its membership. Those sampled were eligible if they were currently practising obstetrics. Any clinicians not currently practising in Australia, not on the telephone network, or who were involved in designing this survey, were ineligible. Eligible clinicians were sent an introductory letter, telephoned, and invited to schedule a confidential, 10-minute telephone interview about information sources used in clinical practice. Systematic reviews were not mentioned until the interview was under way. Interviews An existing interview schedule15,16 was modified in consultation with the ANZNN and the RACOG. Respondents were first asked to name the three main sources of information they used for keeping up with new developments in their field, and for dealing with uncertainty about a specific treatment decision. They were also asked which of the three information sources they considered the most important or useful for each task. Respondents were then asked about their access to and use of computers, and asked directly whether they had heard of, had access to, and used the Cochrane database, Oxford database, and Effective care of the newborn infant (neonatologists) or Effective care in pregnancy and childbirth (obstetricians). Those who reported using any of these resources were asked what a systematic review was, how often they consulted that resource, what they used it for, whether they thought using it had made any difference to their clinical practice and, if so, whether they could name a treatment policy they had altered in response to evidence from a systematic review. To count as users of systematic reviews, respondents had to mention randomised trials or meta-analysis in their description of a systematic review. The final questions sought demographic information on clinical experience, place of education, attendance at professional meetings, research publications, academic appointments, and qualifications. A research degree was defined as a doctorate, relevant master's degree, or bachelor's degree of science in medicine, held in addition to basic medical and specialty qualifications. Reports of authorship were verified by searching MEDLINE and by screening abstracts. For neonatologists it was noted whether they held full- or part-time positions, whether they worked in a hospital with an obstetric unit, whether they headed a neonatal unit, and in which unit they worked. For obstetricians, it was noted whether they held a position as a full-time staff specialist in a public hospital. They were asked how many deliveries they attended each year, and whether they worked at any hospital with an accredited RACOG training post. The interview schedule was modified after a pilot study with seven neonatologists in New Zealand. The main survey was conducted between August and December 1995, with ethics approval from the ANZNN, RACOG and the University of Sydney. All interviews were conducted by the first author (C F C J). Analysis Confidence intervals for the proportion of obstetricians who reported using systematic reviews were calculated with a finite population correction. Confidence intervals were not calculated for the corresponding proportion of neonatologists, as this was ascertained for all Australian neonatologists. Descriptive and c 2 analyses were conducted. Then, using a backwards stepwise modelling procedure, a multivariate logistic regression analysis was used to determine which study factors predicted the reported use of systematic reviews. With the neonatology data, this modelling procedure was repeated using binomial generalised estimating equations to adjust for clustering of respondents within neonatal units.19 Results Of 106 listed neonatologists, three were ineligible (one had retired, one was not practising in Australia, and one was involved in designing this survey). Of the 103 eligible clinicians remaining, 98 completed interviews (95% response). From a sample of 210 obstetricians, 65 were ineligible for the survey (51 no longer practised obstetrics, 13 were not practising in Australia, and one could not be located on the telephone network). Of 145 eligible obstetricians, 126 completed interviews (87% response). Respondent characteristics are shown in Box 1, with comparative data on computer use. For the purpose of keeping up with new clinical developments, respondents favoured journals, conferences and meetings, colleagues and MEDLINE (in that order) over systematic reviews. For the purpose of clinical problem-solving, colleagues, MEDLINE, journals, and other printed medical literature were favoured over systematic reviews as sources of information. Although the percentages favouring each source varied between the two specialties and according to whether the respondent was simply nominating the resource or nominating it as the most important resource, the rank order of the resources remained consistent. In each specialty, 21% of respondents mentioned systematic reviews without prompting from the interviewer when naming the information sources they used, or when describing their computer use. When questioned directly about systematic reviews, 71 neonatologists (72%) and 55 obstetricians (44%; 95% confidence interval, 36%-51%) reported using them in either electronic database or textbook form. The confidence interval indicates the reliability of the sample prevalence as an estimate of the population prevalence. The Figure shows reported levels of awareness of, access to and use of systematic reviews by specialty. Predictors of use of systematic reviews Results of the multivariate analysis are shown in Box 2. Among neonatologists, three factors significantly (P<0.05) and independently predicted use of systematic reviews: attendance at meetings of the Australian Perinatal Society, authorship of at least one research paper, and familiarity with computers (our index of this was use of a computer for word-processing). Results from cluster analysis agreed with those from logistic regression. Among obstetricians, four factors sig nificantly and independently predicted use of systematic reviews: familiarity with computers, mode of practice (full-time staff specialists were more likely to use systematic reviews than others), clinical experience (recent graduates were more likely to use systematic reviews), and number of deliveries per year (likelihood of using systematic reviews increased with this number). Descriptors of use of systematic reviews Both neonatologists and obstetricians reported using databases of systematic reviews with a median frequency of once per month. The main purpose for using systematic reviews (irrespective of their format) reported by respondents from both specialties was individual patient care. Systematic reviews were also said to be used for (in rank order of frequency of reporting) teaching, preparing a pre sentation, reviewing current management or developing evidence-based protocols or guidelines, settling disputes, background information, reviewing a topic, research, as a source of references, and patient information. Of the 71 neonatologists who reported using systematic reviews, 58% said that this had changed their clinical practice in some way, and 44% gave at least one example of a treatment policy they had altered in response to a systematic review. The most common examples were treatment of respiratory disorders, and use of steroids and indomethacin. Corresponding percentages for obstetricians who reported using systematic reviews were 80% (reported a change in practice) and 71% (gave at least one example). The most common example was use of steroids in management of preterm rupture of membranes. Discussion We found that 72% of neonatologists and 44% of obstetricians reported consulting systematic reviews, primarily for the purpose of individual patient care. Databases of systematic reviews were used at a median frequency of once per month. Systematic reviews were used more commonly by those who were familiar with computers in both specialties, by those who attended professional meetings and had authored research papers among neonatologists, and by those who had had less than 10 years' clinical experience, attended more deliveries, and who had a position as a full-time staff specialist among obstetricians. The findings of this survey are based on self-reporting. Although the survey was designed to minimise over-reporting, it was still subject to imprecision in respondents' recall about (for example) the frequency with which they used systematic reviews, and to difficulties in attributing practice changes to their use. Nevertheless, this was the first study of the use of systematic reviews by Australian clinicians, and the findings have immediate and practical relevance for organisations such as universities, government agencies and specialty colleges that are trying to improve access to the best available evidence and to promote its use.20-23 The association between use of systematic reviews and attendance at Australian Perinatal Society meetings among neonatologists could reflect greater receptiveness to innovations among clinicians who attend professional meetings. However, it also supports the perception (reported elsewhere13 ) that professional organisations play an important role in disseminating research findings. Future dissemination efforts could usefully concentrate on these organisations. In both specialties, familiarity with computers predicted use of systematic reviews. Better access to digital information technology and training in its use is therefore likely to enhance uptake of these reviews. This might include improved access to The Cochrane library and the Internet, and training workshops for searching specialist databases. The remaining predictors of use of systematic reviews, as well as the overall contrast between neonatology and obstetrics, suggest that specialists practising primarily in public hospitals are more likely to use systematic reviews than those working primarily in private practice. Special efforts are therefore needed to reach the latter. As systematic reviews do not appear to rank highly among the information sources used in clinical practice, it is important to stress their relative advantages. Uptake of this innovation appears more likely among recent graduates, with senior clinician researchers acting as "product champions".24 Although debate persists as to whether practising clinicians accept the innovations of evidence-based medicine,25 our survey found evidence that Australian neonatologists and obstetricians use systematic reviews, and appear to modify their practice accordingly. Efforts are needed to enhance the use of these reviews, and to conduct further evaluations of their influence on clinical practice. In attempting to improve practice standards, it is important to pursue methods which have been shown to be effective.26 Acknowledgements We would like to thank the many clinicians who gave up their time to participate in this survey. Infrastructure support for this project was provided by the Department of Public Health and Community Medicine at the University of Sydney. Special thanks are due to Petra Macaskill, who conducted the cluster analysis, and Jeanette Ward and Mary Osborne, from the Central Sydney Area Health Service Needs Assessment and Health Outcomes Unit, who provided helpful advice on survey procedures. References Antman EM, Lao J, Kupelnick B, et al. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts: treatments for myocardial infarction. JAMA 1992; 268: 240-248. Stross JK, Harlan WR. The dissemination of new medical information. JAMA 1979; 241: 2622-2624. Warren KS. From papyrus to parchment to paper to pixels: information technology and the future of biomedical publishing. In: Lock S, editor. The future of medical journals. London: BMJ, 1991: 127-146. Mulrow CD. The medical review article: state of the science. Ann Intern Med 1987; 106: 485-488. Light RJ, Pillemer DB. Summing up: the science of reviewing research. Cambridge: Harvard University Press, 1984. Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev 1992; 14: 154-176. Sackett DL. The Cochrane Collaboration. ACP J Club 1994; 120 Suppl 3: A-11. Chalmers I, editor. Oxford database of perinatal trials. Version 1.2, disk issue 7 (Spring). Oxford: Oxford University Press, 1992. Chalmers I, Enkin M, Keirse MJNC. Effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989. Enkin M, Keirse MJNC, Chalmers I. A guide to effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989. Sinclair JC, Bracken MB. Effective care of the newborn infant. Oxford: Oxford University Press, 1992. Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, editors. Cochrane pregnancy and childbirth database. Oxford: Update Software, 1993. The Cochrane Library [database on disk and CD-ROM]. The Cochrane Collaboration. Oxford: Update Software; 1996. Updated quarterly. Lomas J. Retailing research: increasing the role of evidence in clinical services for childbirth. Milbank Q 1993; 71: 439-475. Stocking B. Implementing the findings of effective care in pregnancy and childbirth in the United Kingdom. Milbank Q 1993; 71: 497-523. Paterson-Brown S, Fisk NM, Wyatt JC. Uptake of meta-analytical overviews of effective care in English obstetric units. Br J Obstet Gynaecol 1995; 102: 297-301. Paterson-Brown S, Wyatt JC, Fisk NM. Are clinicians interested in up to date reviews of effective care? BMJ 1993; 307: 1464. Hyde C. Who uses the Cochrane pregnancy and childbirth database? BMJ 1995; 310: 1140-1141. Zeger SL, Liang K-Y. Longtitudinal data analysis for discrete and continuous outcomes. Biometrics 1986; 42: 121-130. Rychetnik L. Evidence-based medicine in the GMP (Graduate Medical Program). Focus: graduate medical degree news and events. Sydney: 1995: 1-2. Liddle J, Williamson M, Irwig L. Method for evaluating research and guideline evidence. Sydney: NSW Department of Health, 1996. National Health and Medical Research Council. Clinical practice guidelines: the management of early breast cancer. Canberra: NHMRC, 1995. Commonwealth Department of Human Services and Health. Guidelines for the development and implementation of clinical practice guidelines. Canberra: the Department, 1995. Rogers EM. Diffusion of innovations. New York: MacMillan, 1983. Miles A, Bentley P, Polychronis A, Grey J. Evidence-based medicine: why all the fuss? J Evaluation Clin Pract 1997; 2: 83-85. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 1993; 342: 1317-1322. (Received 11 Jun, accepted 11 Sep, 1997) Authors' details University of Sydney, Sydney, NSW. Christopher F C Jordens, MPH, Postgraduate Student, Department of Public Health and Community Medicine; now Researcher, Centre for Values, Ethics and the Law in Medicine, Department of Surgery, University of Sydney; Penelope Hawe, MPH, Senior Lecturer, Department of Public Health and Community Medicine; Les M Irwig, FFPHM, PhD, Associate Professor, Department of Public Health and Community Medicine; David J Henderson-Smart, PhD, FRACP, Professor, and Director, NSW Centre for Perinatal Health Services Research, and Department of Neonatal Medicine, Royal Prince Alfred Hospital, Sydney, NSW; Deborah A Donoghue, RN, BSocSc, Senior Research Assistant, Australian Institute of Health and Welfare National Perinatal Statistics Unit; Ian S Fraser, MD, FRACOG, Professor in Reproductive Medicine, Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants. Royal Australian College of Obstetricians and Gynaecologists, Melbourne, VIC. Margaret Ryan, MSW, PhD, Research Officer. Centre for Professional Development, Victoria University of Technology, Melbourne, VIC. Roger G Gabb, PhD, Professor, and Director. Reprints: Mr C F C Jordens, Department of Surgery, Blackburn Building D06, University of Sydney, NSW 2006. E-mail: cjordens AT surgery.usyd.edu.au Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Penelope Hawe · Les M Irwig · David J Henderson-Smart · Margaret Ryan · Deborah A Donoghue

Position Statement Paediatric advanced life support The Australian Resuscitation Council Guidelines The Advanced Life Support Committee of the Australian Resuscitation Council MJA 1996; 165: 199-206 Basic cardiorespiratory resuscitation - Advanced life support - Techniques in paediatric advanced life support - Medications and fluids used in paediatric advanced life support - Management after resuscitation - Cessation of cardiopulmonary resuscitation - Contributors - References - Register to be notified of new articles by email - These guidelines by the Australian Resuscitation Council (ARC) provide brief step-by-step outlines of the management of common life-threatening emergencies in infants and children. The guidelines are similar, but not identical, to guidelines published by the American Heart Association 1 and the European Resuscitation Council. 2 An international liaison committee (including representation from the ARC) is attempting to resolve differences and will in due course publish common advisory statements. The current guidelines are specifically for advanced life support, but some essential techniques of basic life support are presented. Further details of basic life support for infants and children 3 and specific guidelines for resuscitation of asphyxiated newborn infants have been published. 4,5 Basic cardiorespiratory resuscitation Cardiorespiratory arrest should be suspected when the infant or child loses consciousness, appears pale or cyanosed, or is apnoeic or pulseless (see definitions in Box 1). Assess airway and breathing by observing movement of the chest and feeling for expired breath. Position the head and neck to maintain an open airway. Movement of the chest without expiration implies an obstructed airway. If the obstruction is not relieved by backward head tilt and chin lift or by forward jaw thrust, the pharynx should be inspected with a laryngoscope and cleared of any secretions, vomitus or blood with a sucker (Yankauer). Forceps (Magill) may be needed to extract a foreign body. If spontaneous ventilation is not immediately resumed, artificial ventilation is commenced with mouth-to-mask expired air, a self-inflating resuscitation bag or an oxygen-inflated bag and mask circuit. Supplemental 100% oxygen should be added. Insertion of an oropharyngeal airway (Guedel) may facilitate ventilation. Assess the circulation by palpating the carotid, brachial or femoral pulse. Commence external cardiac compression (ECC) if a pulse is not palpable or it is: < 80 beats per minute (bpm) in a newborn or infant; < 60 bpm in a small child; < 40 bpm in a large child. Precede ECC with 2-5 slow breaths to reinflate the lungs. The patient should be placed on a firm surface, and compression directed to the lower sternum to a depth approximating a third of the anteroposterior diameter of the chest, or at a depth of 2-3 cm and rate of 100/min for a newborn or infant; depth of 3-4 cm and rate of 100/min for a small child; depth of 4-5 cm and rate of 80-100/min for a large child. ECC for a newborn or infant can be performed with two fingers, although a better technique is to encircle the chest with both hands, compressing the sternum anteriorly with the thumbs while stabilising the vertebral column posteriorly with the fingers. The rescuer's hands must encircle the chest freely and not restrict chest expansion. ECC for a small child can be performed with the heel of one hand and, for a large child or teenager, with two hands. A cycle should be 50% chest compression and 50% relaxation. Combine ECC and assisted ventilation in an infant or small child in a ratio of 5 : 1. For a large child or teenager in whom a two-handed technique of ECC is required, a single rescuer may achieve better circulation and ventilation with a ratio of compression to ventilation of 15 : 2. If a mask is used, breaths should be delivered between successive compressions to allow adequate expansion of the lungs, but if an endotracheal tube is used coordination is less crucial as effective ventilation can be given against the resistance imposed by ECC. For the asphyxiated newborn, ECC should be at a rate of 120/minute and ventilation at 40-60/min (i.e., in a ratio of 3 : 1). 5,6 Advanced life support Advanced life support implies a patent airway by endotracheal intubation, mechanical ventilation with oxygen, the treatment of cardiac arrhythmias, the treatment of the cause of cardiorespiratory arrest and of complications arising from its management. When several rescuers are in attendance, tracheal intubation and ventilation, display of the electrocardiograph (ECG) and access to the circulation should be attempted simultaneously. Thereafter treatment should be guided by the cardiac rhythm (see Flowchart in Box 2). Tracheal intubation is the first priority. This establishes and maintains a patent airway, facilitates mechanical ventilation with 100% oxygen, minimises pulmonary aspiration, enables suctioning of the trachea and provides a route for the administration of selected drugs. If intubation cannot be accomplished easily, ventilate and oxygenate the patient using a mask before reattempting intubation. Assess the cardiac rhythm by displaying the ECG via chest leads or the defibrillator paddles. Proceed with drug therapy or immediate direct current (DC) shock (Box 2), while maintaining ECC and mechanical ventilation with supplemental 100% oxygen. Secure access to the circulation with a peripheral intravenous (IV) cannula. If cannulation is difficult, do not waste time (more than 90 seconds) with repeated unsuccessful attempts -- instead use the intraosseous (IO) route or the (less effective) respiratory tract via the endotracheal tube (ETT). 7 All drugs and resuscitative fluids may be given via the IO route but only adrenaline, atropine and lignocaine may be given via the ETT. Central venous cannulation of the subclavian or internal jugular veins should not be attempted initially as it wastes time and is potentially hazardous. However, cannulation of an external jugular or femoral vein may be easily accomplished. Surgical cutdown onto a vein may be required. Intracardiac injection should not be attempted unless all alternative methods of access to the circulation are impossible. The doses of drugs, DC shock and fluid therapy are based on body weight, which may be estimated according to age if the weight is unknown: Newborn: 3.5 kg 1 year: 10 kg 1-9 years: (age in years x 2) + 8 kg 10 years and over: age in years x 3.3 kg. Doses may also be prescribed on the basis of height. 8,9 Drug doses according to the 50th percentiles of weight and height for age are given in Box 3. Asystole or severe bradycardia If the cardiac rate is unresponsive to ventilation with 100% oxygen, asystole or pulseless severe bradycardia ( < 80 bpm in an infant, < 60 bpm in a small child, < 40 bpm in a large child or teenager) should be treated with adrenaline (10 µg/kg IV or IO, or 100 µg/kg via the ETT). The subsequent dose of adrenaline by any route is up to 100 µg/kg. If sinus rhythm cannot be restored, sodium bicarbonate (1 mmol/kg IV or IO) and/or atropine (20 µg/kg IV, IO or ETT), with additional doses of adrenaline, may be successful. If facilities are available, cardiac pacing (via the oesophageal, transcutaneous, transvenous or epicardial routes) may be effective. Ventricular fibrillation and pulseless ventricular tachycardia The only effective treatment of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) is DC shock. If the onset of VF is recent or is observed, a precordial thump may be given (although its efficacy has not been proven) and defibrillation should be attempted before any other treatment. The initial DC shock treatment of VF or pulseless VT is 2 J/kg, increasing to a maximum of 4 J/kg 10,11 in a series of three shocks. If sinus rhythm does not occur, give adrenaline (10 µg/kg IV or IO, or 100 µg/kg ETT) and a further three shocks of 4 J/kg. Persistent or refractory VF or VT may be treated with lignocaine (1 mg/kg IV, IO or ETT) followed by another series of up to three shocks of 4 J/kg. If the VF or VT remains refractory, alternative agents (bretylium tosylate 5 mg/kg, sodium bicarbonate 1 mmol/kg, magnesium sulfate 0.05-0.1 mmol/kg) may be tried, in combination with adrenaline (100 µg/kg IV, IO or ETT) and a series of three shocks of 4 J/kg. However, no drug has been conclusively proven to improve the efficacy of DC shock. Electromechanical dissociation (pulseless electrical activity) Electromechanical dissociation exists if pulses are absent despite relatively normal coordinated electrical activity on the ECG. It may be due to poor intrinsic myocardial contractility or secondary to a number of remediable causes, including hypoxaemia, hypovolaemia, severe acidosis, tension pneumothorax, pericardial tamponade, hyperkalaemia, hypocalcaemia, poisoning with a calcium channel blocker or hypothermia. It may also be due to massive pulmonary embolism. Treatment is with adrenaline, 10 µg/kg IV or IO or 100 µg/kg ETT initially, with subsequent doses up to 100 µg/kg by any route. If the electromechanical dissociation is persistent, consider hypovolaemia or severe acidosis and give a bolus of crystalloid or colloid fluid (20 mL/kg IV or IO) and/or sodium bicarbonate (1 mmol/kg). An underlying cause should be sought by clinical examination and investigations, including a chest x-ray, 12-lead ECG and echocardiograph if possible. Supraventricular tachycardia Supraventricular tachycardia (SVT) may cause severe hypotension or pulselessness. Synchronised DC shock (0.5-1 J/kg) should be given immediately to a pulseless patient. If blood pressure is adequate, vagal stimulation or drug therapy may be used. Adenosine is the drug of first choice. Alternatives are digoxin, a beta-blocker or a calcium channel blocker. Calcium channel blockers should not be used to treat SVT in infants because their negative inotropic effect may be fatal. Techniques in Paediatric advanced life support are given in Box 4. Medications and fluids used in paediatric advanced life support are summarised in Box 5. Management after resuscitation The cause of cardiorespiratory arrest should be sought and specifically treated. Complications of the resuscitation procedure should also be sought, especially if secondary deterioration occurs. This includes a chest x-ray to check the position of the endotracheal tube, to exclude pneumothorax, lung collapse or aspiration and to check the cardiac silhouette, and a blood sample for estimation of the haemoglobin level, pH, gas tensions and electrolyte and glucose concentrations. Supportive therapy should be provided until there is recovery of function of vital organs. This may include oxygen therapy, mechanical ventilation, inotropic infusion and renal support for several days or longer. Recovery in infants and children is usually slow because cardiorespiratory arrest is often secondary to prolonged global hypoxaemia and ischaemia with prior damage of other organs. Particular care should be taken to ensure adequate cerebral perfusion with well oxygenated blood and adequate blood pressure. Cessation of cardiopulmonary resuscitation The decision to cease cardiopulmonary resuscitation should be based on a number of factors, including the patient's pre-arrest condition, response to resuscitation, remediable factors, likely outcome and the opinions of experienced medical personnel. References Emergency Cardiac Care Committee and Subcommittees of the American Heart Association. Guidelines for cardiopulmonary resuscitation and emergency cardiac care. JAMA 1992; 268: 2171-2302. Paediatric Life Support Working Party of the European Resuscitation Council. Guidelines for paediatric life support. BMJ 1994; 308: 1349-1355. Manual Australian Resuscitation Council. Policy Statements. Policies 12.1-12.9, November 1995. (Located at the Royal Australasian College of Surgeons, Spring Street, Melbourne.) Emergency Cardiac Care Committee and Subcommittee of the American Heart Association. Guidelines for cardio resuscitation and emergency cardiac care. JAMA 1992; 268: 2276-2281. Roy RN, Betheras FR. The Melbourne chart -- a logical guide to neonatal resuscitation. Anaesth Intens Care 1990; 18: 348-357. The Advanced Life Support Committee of the Australian Resuscitation Council. Adult advanced life support. The Australian Resuscitation Council Guidelines. Med J Aust 1993; 159: 616-621. Tibballs J. Endotracheal and intraosseous drug administration for paediatric CPR. Aust Fam Physician 1992; 21: 1477-1480. Lubitz SL, Seidel JS, Chameides L, et al. A rapid method for estimating weight and resuscitation drug dosages from length in the pediatric age group. Ann Emerg Med 1988; 17: 576-581. Oakley P, Phillips B, Molyneux E, Mackway-Jones K. Updated standard reference chart. BMJ 1993; 306: 1613. Chameides L, Brown GE, Raye JR, et al. Guidelines for defibrillation in infants and children. Report of the American Heart Association Target Activity Group: cardiopulmonary resuscitation in the young. Circulation 1977; 56 (suppl): 502A-503A. Gutgesell HP, Tacker HA, Geddes LA, et al. Energy dose for ventricular defibrillation of children. Pediatrics 1976; 58: 898-901. Rogers FB. Technical note: a quick and simple method of obtaining venous access in traumatic exsanguination. J Trauma 1993; 34: 142-143. Hornchen U, Schuttler J, Stoeckel H, et al. Endobronchial instillation of epinephrine during cardiopulmonary resuscitation. Crit Care Med 1987; 15: 1037-1039. Jasani MS, Nadkarni VM, Finkelstein MS, et al. Effects of different techniques of endotracheal epinephrine administration in pediatric porcine hypoxic-hypercarbic cardiopulmonary arrest. Crit Care Med 1994; 22: 1174-1180. Patterson M, Boenning D, Klein B. High dose epinephrine in pediatric cardiopulmonary arrest (CPA). Pediatric Emerg Care 1994; 10: 310. Goetting MG, Paradis NA. High-dose epinephrine improves outcome from pediatric cardiac arrest. Ann Emerg Med 1991; 20: 22-26. Contributors This document was drafted and revised by Dr James Tibballs at the request of the Australian Resuscitation Council. Submissions were received from members of the Advanced Life Support Committee of the ARC and from Dr R Henning, Dr F Shann, Ms S Kinney (Melbourne); Dr A Duncan (Perth); Dr J McEniery, Dr G Delbridge, Dr B Lister (Brisbane); Dr B Wilkins, Dr R Choong, Dr B Duffy, Dr T Gratten-Smith, Dr I Alexander, Dr M Schindler, Dr J Gillis, Dr A O'Connell, Dr D Schell, Dr O Miller (Sydney); Dr S R Keeley, Dr A J Slater, Dr G M Shaw, Dr J Raftos (Adelaide); Dr E R Segedin (Auckland); Dr L Quan (Seattle); and Dr D Zideman (London). Members of the Advanced Life Support Committee: Dr M Allen (ARC South Australian Branch). Dr R A Capps (Australian Defence Force). A/Prof V Callanan (ARC Chairman; and Australian and New Zealand College of Anaesthetists). Ms J Dennett (Confederation of Australian Critical Care Nurses). Mr M Draheim (ARC Tasmanian Branch). Ms J Finn (Royal College of Nursing, Australia). Dr L Grigg (Cardiac Society of Australia and New Zealand; and National Heart Foundation). Mr A Hadj (Royal Australasian College of Surgeons). Mr J Hall (Institute of Ambulance Officers, Australia). Mr K Hambrecht (Co-opted member). Prof G A Harrison (Chairman, ARC Advanced life Support Committee; and Australian and New Zealand College of Anaesthetists). Dr I Jacobs (ARC Western Australian Branch). Mr O Juul (ARC New South Wales Branch). Mr S Leahy (Surf Lifesaving Association of Australia). Ms J Maclean (Royal Lifesaving Society, Australia). Dr P Morley (ARC Victorian Branch). Dr J O'Callaghan (Co-opted member). Dr A Phillips (Royal Australian College of General Practitioners). Mr C Smith (ARC Queensland Branch). Dr J Taylor (Co-opted member). Dr J Tibballs (Australian and New Zealand Intensive Care Society). Mrs E P Tyler (Australian Red Cross Society). Dr J Wassertheil (Australasian College for Emergency Medicine). Dr J Williamson (St John Ambulance Australia). No reprints will be available. Correspondence: Dr J Tibballs, Intensive Care Unit, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, VIC 3052. ©MJA 1996 Home |

For Debate Trauma in pregnancy and cerebral palsy: is there a link? The link between maternal trauma during pregnancy and cerebral palsy remains to be proven Marisa T Gilles, Eve Blair, Linda Watson, Nadia Badawi, Louisa Alessandri, Vivienne Dawes, Aileen J Plant and Fiona J Stanley MJA 1996; 164: 500-501 Introduction - Acknowledgements - References - Authors' details - - Articles on similar material Introduction Maternal trauma during pregnancy has been implicated in the aetiology of cerebral palsy in the surviving offspring.1,2 In 1991, a child with cerebral palsy received a settlement of three million dollars after it was alleged that the mother's negligent driving of a motor vehicle resulted in an accident which caused cerebral palsy in the child.1 The case rested on the testimony of an expert witness whose argument was based on a case series of six children with cerebral palsy born to mothers who had been involved in motor vehicle accidents. (Bergin AM, Stack JP, Stephenson JBP, King M. Cerebral palsy after motor accidents in pregnancy. Proceedings of the British Paediatric Neurology Association, Dublin, 1990 [unpublished data].) Possible mechanisms for the association between pregnancy trauma and cerebral palsy include reduced placental bloodflow, placental embolisation and placental abruption. To address the issue of trauma in pregnancy and subsequent cerebral palsy, we examined the Western Australian Cerebral Palsy Register3 (a subset of the Maternal and Child Health Research Database)4 which collects information on all children in the State who develop cerebral palsy (updated to the age of five years). We also examined the Hospital Morbidity Data System, which collects information on all acute hospital admissions. These two databases were selected in order to compare the rates of cerebral palsy in the offspring of women who, during their pregnancy, had trauma that required hospitalisation with the rates of cerebral palsy in the children of women who did not experience trauma. The Box outlines the methods and results of our study. Despite the fact that this was a population-based study over 11 years (1982-1992), the unadjusted relative risk of having a child with cerebral palsy after exposure to trauma was 1.4 (95% confidence interval, 0.34-5.77), which was not statistically significant. It was inappropriate to adjust for gestational age or low birth weight as they may have been factors in the aetiological pathway (e.g., trauma may induce a premature birth). Trauma occurs more commonly during the third trimester of pregnancy than at any other time in a woman's life.5 The incidence of trauma during pregnancy is reported to be about seven to eight per cent, but hospitalisation for trauma in pregnancy is rare. In the years of our study, only 0.3% of pregnant women were hospitalised. However, the severity of maternal trauma does not correlate well with the degree of fetal damage. Even minor trauma can cause fetal death and preterm labour,6-8 but few studies have considered the effect on long-term fetal outcome.2 Women who are not hospitalised (because of apparently minor trauma) may still have fetal compromise. In addition, women experiencing domestic violence may avoid medical attention, and hence such women may be under-represented in our study. Domestic violence during pregnancy, reported at rates between 8% and 17%, has been linked to fetal death, fetal distress and intrauterine growth retardation.9-11 The existence of one woman who was admitted to hospital for trauma at 28 weeks' gestation but had not been recorded as pregnant in the Hospital Morbidity Data System calls into question the validity of this data system in recording certain admission and discharge details relevant to our study. For example, in the presence of major trauma a pregnancy may be overlooked or not recorded, especially if the woman is in early pregnancy. This would lead to an underestimation of the number of women experiencing trauma during pregnancy who did not have a child with cerebral palsy, as only those women who were coded as being pregnant in the Hospital Morbidity Data System were included in the sample population. Our study has not resolved whether major trauma during pregnancy is associated with long term neurological problems in the child. In view of increasing litigation in this area, larger analytical studies into the outcomes following physical trauma during pregnancy are needed. This will best be achieved when better mechanisms for recording details of trauma during pregnancy, including domestic violence, are developed. Acknowledgements This study would not have been possible without the financial support of Healthway and PHRDC, who fund the Cerebral Palsy Register; data provided by the Health Department of WA; the expertise of Dr Richard Hockey, who carried out the linkage; and the editorial support generously supplied by Dr Ian Rouse and Dr Jennifer Kurinczuk. References Lynch v Lynch & Anor. Supreme Court of New South Wales (1991). Australian Tort Reports 81-117. Anquist KW, Parnes S, Cargill Y, Tawagi G. An unexpected fetal outcome following a severe maternal motor vehicle accident. Obstet Gynecol 1994; 84: 656-658. Stanley FJ, Watson L. Methodology of a cerebral palsy register. The Western Australian experience. Neuroepidemiology 1985; 4: 146-160. Stanley FJ, Croft ML, Gibbins J, Read AW. A population database for maternal and child health research in Western Australia using record linkage. Paediatr Perinat Epidemiol 1994; 8: 433-447. Patterson RM. Trauma in pregnancy. Clin Obstet Gynecol 1984; 27: 32-38. Williams JK, McClain L, Rosemurgy AS, Colorado NM. Evaluation of blunt abdominal trauma in the third trimester of pregnancy: Maternal and fetal considerations. Obstet Gynecol 1990; 75: 33-37. Farmer DL, Adzick S, Crombleholme WR, et al. Fetal trauma: relation to maternal injury. J Pediatr Surg 1990; 25: 711-714. Murdoch Eaton DG, Ahmed Y, Dubowitz LMS. Maternal trauma and cerebral lesions in preterm infants. Case reports. Br J Obstet Gynaecol 1991; 98: 1292-1294. Macfarlane J, Parker B, Soeken K, Bullock L. Assessing for abuse during pregnancy. Severity and frequency of injuries and associated entry into prenatal care. JAMA 1992; 267: 3176-3178. Dye TD, Tolliver NJ, Lee RV, Kenney CJ. Violence, pregnancy and birth outcome in Appalachia. Paediatr Perinat Epidemiol 1995; 9: 35-47. Webster J, Sweett S, Stolz TA. Domestic violence in pregnancy. A prevalence study. Med J Aust 1994; 161: 466-470. Stanley FJ, Watson L. Trends in perinatal mortality and cerebral palsy in Western Australia, 1967 to 1985. BMJ 1992; 304: 1658-1663. World Health Organization. International Classification of Diseases. 1975 revision, Vol 1. Geneva: Presses Centrales, 1977. Gee V. The 1991 Western Australian Birth Cohort. Statistical Series 34. Perth: Health Department of Western Australia, 1994: 5. Authors' details Health Statistics Branch, Health Department of Western Australia, Perth, WA. Marisa T Gilles, FAFPHM, Research Registrar; and Research Registrar, National Centre for Epidemiology and Population Health, Canberra. TVW Telethon Institute for Child Health Research, Perth, WA. Eve Blair, PhD, Senior Research Officer; Linda Watson, Research Assistant; Nadia Badawi, MSc, MRCPI, Paediatric Research Fellow; Louisa Alessandri, BSc(Hons), PhD, Research Officer; Fiona J Stanley, MD, FAFPHM, Professor of Paediatrics. Department of Public Health, The University of Western Australia, Perth, WA. Aileen J Plant, PhD, FAFPHM, Senior Lecturer. Women's Cancer Screening Service, Health Department of Western Australia, Perth, WA. Vivienne Dawes, FAFPHM, Medical Officer. No reprints will be available. Correspondence: Linda Watson, TVW Telethon Institute for Child Health Research, PO Box 855, West Perth, WA 6872. E-mail: Linda@ichr.uwa.edu.au Material trauma and cerebral palsy: a Western Australian population-based study, 1982-1992 Cerebral Palsy Register The study population was extracted from the Cerebral Palsy Register, a data subset of the Maternal and Child Health Research Database, and consisted of mothers of all children with cerebral palsy born between 1982 and 1992 inclusive, excluding those children who had a documented postnatal cause of cerebral palsy. A year-of-birth cohort of the Cerebral Palsy Register is only considered complete at the age of five years. Thus, by including the years 1990 to 1992 it is possible that as yet unregistered cases of cerebral palsy may have been misclassified as not having cerebral palsy. However, because cerebral palsy is rare (approximately 2 per 1000 live births),12 the effect of this error is very small. Hospital Morbidity Data System The sample population comprised all women between the ages of 14 to 50 with an ICD-9 external cause of injury (excluding poisons, drugs and medical misadventure)13 and the additional code for pregnancy in the Hospital Morbidity Data System. To validate the Hospital Morbidity Data System, a second method of identifying cases was used. The period of pregnancy was defined as the time between the second postmenstrual week and delivery, and the dates defining this period were identified for each pregnancy that resulted in a child with cerebral palsy. Database linkage Data from the Cerebral Palsy Register were linked with the births file, another subset of the Maternal and Child Health Research Database, to obtain identifying data for each mother in the study group, such as surname, maiden name, date of birth and address at the time of delivery. Using these identifying data, mothers were linked to the Hospital Morbidity Data System to determine exposure to trauma requiring hospitalisation during pregnancy. Statistical analysis Data were analysed using two-by-two contingency tables, and the relative risk was calculated with 95% confidence intervals. Results 529 children were born with cerebral palsy between 1982 and 1992, inclusive (extracted from the Cerebral Palsy Register). (See Box.) 770 pregnant women were hospitalised for trauma between 1982 and 1992 (extracted from the Hospital Morbidity Data System). The details of two of the mothers hospitalised for trauma during their pregnancy matched the details of two mothers of children with cerebral palsy. The incidence of cerebral palsy in children of women hospitalised for trauma during pregnancy was 2.6 per 1000 pregnant women. The incidence of cerebral palsy in children of women who did not experience trauma requiring hospitalisation during their pregnancy was 1.8 per 1000 pregnant women. A woman exposed to trauma requiring hospitalisation during pregnancy had 1.4 times the risk of having a child with cerebral palsy compared with a woman who had not had this experience (unadjusted relative risk, 1.4; 95% confidence interval, 0.34-5.77). The number of cases was small and this result was not statistically significant (Box). One mother who had a child with cerebral palsy and had been hospitalised for trauma during pregnancy was not recorded as being pregnant on the Hospital Morbidity Data System. Inclusion of this case in the two-by-two analysis increased the relative risk to 2.2 (95% confidence interval, 0.66-6.69), but only those women coded as being pregnant in the Hospital Morbidity Data System were included in the sample population (see text). Back to text

Marisa T Gilles · Eve Blair · Linda Watson · Nadia Badawi · Louisa Alessandri · Vivienne Dawes · Aileen J Plant · Fiona J Stanley

Passive smoking and respiratory function in very low birthweight children Lex W Doyle, Geoffrey W Ford, Anthony Olinsky, Annette M L Knoches and Catherine Callanan For editorial comment see Woodward & Jamrozik Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgement - References - Authors' details - ©MJA1997 Abstract Aim: To determine if an adverse relationship exists between passive smoking and respiratory function in very low birthweight (VLBW) children at 11 years of age. Setting: The Royal Women's Hospital, Melbourne. Patients: 154 consecutive surviving children of less than 1501 g birthweight born during the 18 months from 1 October 1980. Methods: Respiratory function of 120 of the 154 children (77.9%) at 11 years of age was measured. Exposure to passive smoking was established by history; no children were known to be actively smoking. The relationships between various respiratory function variables and the estimated number of cigarettes smoked by household members per day were analysed by linear regression. Results: Most respiratory function variables reflecting airflow were significantly diminished with increasing exposure to passive smoking. In addition, variables indicative of air-trapping rose significantly with increasing exposure to passive smoking. Conclusions: Passive smoking is associated with adverse respiratory function in surviving VLBW children at 11 years of age. Continued exposure to passive smoking, or active smoking, beyond 11 years may lead to further deterioration in respiratory function in these children. MJA 1996; 164: 266-269 Introduction Passive smoking is associated with several adverse health outcomes in children, including higher rates of asthma,1 and infections of the upper2 and lower3 respiratory tract. Further, respiratory function is reduced with passive smoking in children who have no lung disease,4 as well as those with lung diseases such as asthma5 and cystic fibrosis.6 To survive the neonatal period, many very low birthweight (VLBW) children (less than 1500 g at birth) require prolonged periods of assisted ventilation, and some may develop bronchopulmonary dysplasia (BPD) and suffer from ongoing respiratory problems as a consequence. We have previously reported the respiratory health to eight years of age of cohorts of children of birthweight 500-999 g (n = 83), 1000-1500 g (n = 114) and > > 2500 g (n = 51).7 Passive smoking was significantly related to the duration of hospitalisation for respiratory problems up to two years of age for all children in that study, but was not associated with changes in respiratory function at eight years of age. In contrast, in another recent cohort study of respiratory function at seven years of age in children of birthweight less than 2000 g Chan et al.8 reported reduced air-flow rates with maternal smoking, but not with smoking by other household members. Because the effects of passive smoking could increase with increasing duration of exposure, the aim of this study was to determine if an adverse relationship exists between passive smoking and respiratory function at 11 years of age in VLBW children. Methods We studied 154 consecutive surviving children of less than 1501 g birthweight born during the 18 months from 1 October 1980 at the Royal Women's Hospital, Melbourne, the largest of the three tertiary-level perinatal centres in Victoria. Details of the survival rate and early neonatal care of this cohort have been described.9,10 Bronchopulmonary dysplasia (BPD) was diagnosed in children who had required intermittent positive pressure ventilation in the neonatal period, who had respiratory distress and were still having oxygen therapy at 28 days of age, and who had an abnormal chest x-ray consistent with stage III or IV disease (as defined by Northway et al.11 ) at or after 28 days. A previous report of the respiratory function of this cohort at eight years of age7 included data for some children with birthweights of less than 1000 g born before 1 October 1980. We did not have the resources to measure respiratory function at 11 years of age of the children born before October 1980. Respiratory health was determined by history and examination, and measurement of respiratory function. Children who had required bronchodilators within the previous year for attacks of wheezing were considered to have asthma. Data on passive smoking were obtained by asking the parents about the daily consumption of cigarettes by members of the household. We did not distinguish between mothers and other smokers, or between smoking inside or outside the home. Some data on maternal smoking in pregnancy had been collected in the perinatal period, but were obtained for only one-third of mothers. Children were questioned about active smoking in their parents' absence. As some children had changed households in their lifetimes, we considered those who had lived in any household with smokers over the 11-year period to have been passively smoking during childhood. Two categories of social class were determined -- unskilled or unemployed, and other (professional, skilled or semi-skilled) -- based on the occupation of the family breadwinner. Respiratory function was measured in the Department of Thoracic Medicine at the Royal Children's Hospital, Melbourne, as described previously,7 by personnel blinded to the exposure of individual children to passive smoking. Maximum expiratory flow rates were recorded with a pneumotachograph (Fleisch No. 3, Switzerland) and plotted against volume by integrating flow on an X-Y recorder to obtain flow-volume loops. Maximum flow rates at 75% (VEmax75%), 50% (VEmax50%) and 25% (VEmax25%) of forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), were measured from the loops. Flow rates were corrected for body size by dividing by vital capacity (VC). Vital capacity, FVC and forced expiratory volume in one second (FEV1) were measured with a water-filled spirometer (Godart Expirograph, Bilthoven, Netherlands) in accordance with standard guidelines, and results at body temperature and pressure saturated with water vapour were expressed as a percentage of the predicted value for age, height and sex.12 Total lung capacity (TLC) and residual volume (RV) were measured in a body plethysmograph (Jaeger Bodyscreen 2, Wurzburg, Germany). Children were not subjected to bronchial provocation tests as these are poorly tolerated, and we were eager to maintain a high degree of cooperation with these and with future respiratory function tests. Not all children could complete all respiratory function tests, either because of poor cooperation, or unavailability or malfunction of equipment on the day of testing. Data were edited and analysed using SPSS.13 Dichotomous variables were contrasted by chi-squared analysis, and continuous variables by t test, or Mann-Whitney U test if the data were skewed. The dose-response relationship between the estimated daily number of cigarettes consumed by members of the household and various respiratory function variables was established by linear regression; linear and quadratic relationships were tested. Data were then analysed by linear regression to adjust for the potentially confounding variables of birthweight, gestational age, birthweight ratio (child's birthweight divided by median birthweight for gestational age14 ), sex, BPD, and asthma; all variables were entered simultaneously, even if they were not statistically significant. Durations of intermittent positive pressure ventilation and oxygen therapy were not included as they were strongly related to BPD. For all analyses, P values of less than 0.05 for any test were regarded as statistically significant. Results We measured the respiratory function of 120 of the 154 (77.9%) children at 11 years of age. Of the 34 children not tested, 15 lived in another State, four lived in another country, 10 refused the tests, three were lost to follow-up, and two were too disabled to complete the tests. There were no substantial differences in perinatal variables between children who did and did not have respiratory function tests at 11 years of age. Eighty of the 120 children (66.7%) had been exposed to passive smoking in the household. The only substantial differences in perinatal or subsequent variables between children who were and were not exposed to passive smoking were a significantly longer duration of oxygen therapy and a lower proportion of unskilled or unemployed families in the group not exposed (Table 1). For children exposed to passive smoking, the median number of cigarettes consumed in the household per day was 21 (interquartile range, 15-25). Of the 15 children tested who had developed BPD in the newborn period, three (20%) had asthma at 11 years of age; this proportion was similar for children with asthma at 11 who did not have BPD (22 of 105; 21%). For variables expressed as a percentage of predicted values (FEV1, FVC, RV, TLC), the means of the measured values were all close to their expected values of 100% (Table 2). For all respiratory function variables significantly associated with the dose of passive smoking, a quadratic relationship was more significant than a linear relationship (Table 2, Figures 1 and 2). Most respiratory function variables reflecting airflow (VEmax75%/VC, VEmax50%/VC, FEF25%-75%/VC, FEV1 and FEV1/FVC) were significantly diminished by increasing exposure to passive smoking (Table 2 [below], Figures 1a and 1b). In addition, RV, TLC and RV/TLC rose significantly (consistent with progressive air trapping) with increasing exposure to passive smoking (Table 2 [below], Figure 1c). One child was exposed to 115 cigarettes per day, and the next highest exposure was only 70 cigarettes per day. When the child exposed to 115 cigarettes per day was excluded, most of the statistically significant relationships disappeared, except for the increases in RV and RV/TLC (Figure 2). From the multiple linear regression analyses, some variables reflecting flow (VEmax75%/VC, VEmax50%/VC, VEmax25%/VC, FEF25%-75%/VC and FEV1/FVC) were significantly higher in girls. BPD was significantly associated with reductions in some variables reflecting air-flow (VEmax50%/VC, FEF25%-75%/VC, FEV1 and FEV1/FVC), as was asthma (with significant reductions in FEF25%-75%/VC, FEV1 and FEV1/FVC). FVC was significantly lower and VEmax25%/VC significantly higher with lower social class. Birthweight ratio, birthweight and gestational age were not significantly associated with any lung function variable. None of the statistical conclusions relating respiratory function variables with passive smoking were altered by adjusting for all potentially confounding variables, except that the reduction in VEmax50%/VC was no longer statistically significant. Discussion Passive smoking was associated with reduced airflow and air-trapping in VLBW children at 11 years of age, which is consistent with observations in non-preterm children free of lung disease.4 However, this finding was different from our observations of these children at eight years of age,7 when passive smoking was unassociated with any lung function variable. Chan et al.8 reported reduced flow rates with smoking by mothers in children of less than 2000 g birthweight at seven years of age, but they did not measure variables reflecting air-trapping. We did not distinguish between mothers and other smokers in the household. The association between passive smoking and adverse respiratory function in our VLBW children at 11, but not at eight, years of age suggests that the harmful effects of passive smoking take time to become obvious in VLBW children. Moreover, the adverse response seems to accelerate with increasing dose of passive smoking (Figures 1 and 2). We are concerned that continued exposure to passive smoking, or, even worse, active smoking, beyond 11 years will lead to not only further, but also to an accelerating rate of, deterioration in respiratory function. Our results should not be overinterpreted. They were not substantially altered by adjusting for potentially confounding perinatal or other variables, but we did not have data on a wide range of confounding variables. Moreover, they were heavily influenced by one child who lived in a household whose members consumed 115 cigarettes per day. Excluding this child from the analysis, the only remaining statistically significant associations indicated air-trapping with increasing exposure to passive smoking. However, we consider that this child's data should not be excluded just on the basis of heavier-than-average exposure to passive smoking. To remove any doubt about the association between passive smoking and adverse lung function in VLBW children, lung function could be measured in another cohort of VLBW children, or the same cohort when they are older. Parents of VLBW children, particularly those of children who have received assisted ventilation, frequently ask about long-term lung problems. Many variables, such as family history or duration of assisted ventilation and oxygen therapy, may be related to long-term lung problems, but most cannot be altered by the parents. Exposure to passive smoking is one variable associated with poorer respiratory function in VLBW children they can influence. Until there is evidence to the contrary, families of VLBW children should be encouraged to stop exposing their children to cigarette smoke in the household. As there appears to be a dose-response relationship, those who cannot stop smoking should at least reduce their children's exposure to passive smoking. Acknowledgement This study was supported in part by a grant from the Royal Women's Hospital-3AW Community Services Trust. References Landau L. Smoking and childhood asthma. Med J Aust 1991; 154: 715-716. Wright AL, Holberg C, Martinez FD, et al. Relationship of parental smoking to wheezing and nonwheezing lower respiratory tract illnesses in infancy. J Pediatr 1991; 118: 207-214. Etzel RA, Pattishall EN, Haley NJ, et al. Passive smoking and middle ear effusion among children in day care. Pediatrics 1992; 90: 228-232. Cook DG, Whincup PH, Papacosta O, et al. Relation of passive smoking as assessed by salivary cotinine concentration and questionnaire to spirometric indices in children. Thorax 1993; 48: 14-20. Chilmonczyk BA, Salmon LM, Megathlin KN, et al. Association between exposure to environmental tobacco smoke and exacerbations of asthma in children. N Engl J Med 1993; 328: 1665-1669. Smyth A, O'Hea U, Williams G, et al. Passive smoking and impaired lung function in cystic fibrosis. Arch Dis Child 1994; 71: 353-354. Kitchen WH, Olinsky A, Doyle LW, et al. Respiratory health and lung function in 8-year-old children of very low birth weight: a cohort study. Pediatrics 1992; 89: 1151-1158. Chan KN, Noble-Jamieson CM, Elliman A, et al. Lung function in children of low birth weight. Arch Dis Child 1989; 64: 1284-1293. Kitchen WH, Ford GW, Murton LJ, et al. Mortality and two year outcome of infants of birthweight 500-1500 g: relationship with neonatal cerebral ultrasound data. Aust Paediatr J 1985; 21: 253-259. Kitchen WH, Yu VYH, Lissenden JV, Bajuk B. Collaborative study of very-low-birthweight infants: techniques of perinatal care and mortality. Lancet 1982; i: 1 454-1457. Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Engl J Med 1967; 276: 357-368. Hibbert ME, Lanigan A, Landau LI, Phelan PD. Lung function values from a longitudinal study of healthy children and adolescents. Pediatr Pulmonol 1989; 7: 101-109. SPSS for Windows [computer program]. Version 6.1. Chicago, Ill: SPSS Inc, 1994. Kitchen WH, Robinson H, Dickinson AJ. Revised intrauterine growth curves for an Australian hospital population. Aust Paediatr J 1983; 19: 157-161. (Received 8 Jun, accepted 18 Nov 1995) Authors' details Division of Paediatrics, the Royal Women's Hospital, Melbourne, VIC. Lex W Doyle, MD, FRACP, Paediatrician; and Associate Professor, Departments of Obstetrics and Gynaecology, and Paediatrics, the University of Melbourne. Geoffrey W Ford, MB BS, FRACP, Paediatrician. Annette M L Knoches, MB BS, FRCP(C), Paediatrician. Catherine Callanan, RN, Research Nurse. Department of Thoracic Medicine, the Royal Children's Hospital, Melbourne, VIC. Anthony Olinsky, FRACP, Respiratory Physician. No reprints will be available. Correspondence: Associate Professor L W Doyle, Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC 3052. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Lex W Doyle · Geoffery W Ford · Anthony Olinsky · Catherine Callanan

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Susan M Sayers FRACP, DCH, AmBdNeonatPerinat · Jennifer R Powers BSc, AssocDipAppSc(Comp)

Hereditary pancreatitis causes severe early-onset pain and hospitalisation. In 15 Australian patients undergoing total pancreatectomy and islet auto transplantation (TPIAT), we observed a marked reduction in hospital admissions, inpatient days and emergency visits, complete analgesic cessation by 24 months and durable insulin independence in nearly half of the patients. These findings highlight TPIAT’s potential to improve quality of life and reduce healthcare burden. Our programme aims to build evidence to support public funding and ensure equitable access to this procedure.

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