Child health

To the Editor: Kawasaki disease (KD) is an acute vasculitis of unknown aetiology occurring mostly in infants and young children. KD is characterised by fever of more than 4 days’ duration; conjunctivitis; rash; cervical lymphadenopathy; erythema of the lips, oral mucosa, palms and soles; and oedema of the hands and feet.1 Coronary artery aneurysms develop in 15%–25% of untreated children,2 with attendant risk of ischaemic heart disease, myocardial infarction and sudden death.3,4 Treatment with intravenous immunoglobulin (IVIG) within the first 10 days reduces the incidence of aneurysm to less than 5%.4 A KD diagnosis is clinical, based on the recognition of a characteristic set of signs and symptoms.4 The 10%–45% of children who meet only some of the classical criteria are said to have “atypical” or “incomplete” KD. These children have a higher risk of coronary artery aneurysm than children with typical KD.4 Abdominal symptoms, including acute appendicitis and appendicular vasculitis, can occur before the development of classical features of KD.4,5 A 50% coronary artery aneurysm rate has been reported in children with KD and acute abdomen. It is still unclear whether this reflects a delay in diagnosis and treatment or is a marker of a more severe vasculitis involving the intestinal tract. A 3-year-old boy presented with a 2-week history of remittent, high-spiking fever (37.5–39.0° C; 2–3 spikes/day), right lower quadrant abdominal pain, and McBurney’s sign with rebound tenderness. Abdominal ultrasonography suggested a diagnosis of acute appendicitis with peritonitis. The postoperative diagnosis was appendicular vasculitis with peritoneal inflammation and serous secretion. Fever persisted despite treatment with intravenous cephalosporin. Several days later, the boy developed conjunctivitis, cracked lips, a raised erythrocyte sedimentation rate and C-reactive protein level, and thrombocytosis (715 × 109 platelets/L). KD was suspected, and an echocardiogram revealed two sacciform coronary artery aneurysms (diameters, 3.1 mm and 2.9 mm) in the proximal part of the common trunk. The child was given IVIG (2 g/kg) and oral acetylsalicylic acid (100 mg/kg per day in four divided doses). As the fever failed to resolve, the patient was given a second dose of IVIG,4 this time leading to a dramatic clinical improvement. Five days later, he developed oedema of the hands and periungual peeling of the fingers. His aspirin dose was reduced to 5 mg/kg/day. Follow-up echocardiograms at 3 months and 6 months demonstrated persistent coronary artery dilatation. Persistent fever with conjunctivitis and cracked lips should alert clinicians to the possibility of KD. At our patient’s age, acute appendicitis is rare, and other causes of abdominal pain must be excluded. In this case, the unusual postoperative course, with persistent fever even after antibiotic treatment, was another clue to establishing the correct diagnosis.

Maria Cristina Maggio · Andrea Liotta · Salvino M Vitaliti · Giovanni Corsello

To the Editor: With the ski season in Australia drawing to a close for another year, it is a good time to reflect on the injury prevention benefits of wearing helmets when skiing or snowboarding. Skiing falls can be fatal. Two people have died from head injuries on Australian skifields in recent years: a skier died after colliding with a tree branch on an intermediate run at Mt Buller, Victoria, in 2003; and in 2006, a novice snowboarder died after falls sustained while snowboarding at Thredbo, New South Wales.1 Neither person was wearing a helmet. In Australia in 2002–03, 3.5% of skiing-related hospital admissions and 6.2% of snowboarding-related admissions were due to intracranial injuries.2 During the 2004 and 2005 ski seasons we collected data on the use of helmets in snowboarders presenting to the Mt Buller Medical Centre. Of 494 snowboarders, 17.6% had been wearing helmets, and none had sustained a head injury. Of the nine patients with head injuries, none had been wearing helmets. These figures are similar to those reported in overseas studies, which have shown that wearing a helmet can reduce the snow-sport head injury rate by up to 60%.3,4 The use of helmets for snow sports makes intuitive and biological sense, as it does for cyclists, but, unfortunately, Australia is yet to issue a snow-sport helmet performance standard, as it does for bicycle helmets. Helmet use should be strongly recommended for all snowboarders and skiers. In particular, helmets should be made compulsory for children, who are more susceptible to head injury4 and who are often present at ski resorts in large organised school groups that could readily be made to comply. At present in Australia, helmet use is not compulsory for children attending skiing or snowboarding lessons, as it is in North America. This is in spite of the fact that helmet use is compulsory in Australia for school skiing and snowboarding competition events. Some skiers and snowboarders are gradually getting the message about helmets, and a recent informal survey at Mt Buller (Buller Ski Lifts personnel, personal communication) estimated the rate of helmet use to be 20% among adults and 68% among children — but this still leaves over 30% of children vulnerable. Snow-sports helmets now come in many colours, shapes and sizes, and are increasingly acceptable to young people. A helmet is probably the cheapest individual item of clothing for a ski holiday. And it may save your life.

Graham M Slaney · Judith Finn · Angus Cook · Philip Weinstein

Objectives: To determine (i) the relationship between asthma management and socioeconomic status; (ii) whether recent estimates from the International Study of Asthma and Allergies in Childhood (ISAAC) conducted in Melbourne apply to a broader cross-section of Victorian children; and (iii) age-related trends in asthma prevalence.Design: A questionnaire survey, based on the ISAAC protocol.Participants and setting: Subjects were children aged 4–13 years from a random sample of primary schools in the Barwon region of Victoria. The survey was conducted between March and September 2005.Main outcome measures: Parent-reported wheeze and wheeze-related use of health resources during the preceding 12 months.Results: Questionnaires were returned by 7813/9258 students (84%). Lower socioeconomic status was associated with increased frequency of regular asthma reviews (P < 0.01 for trend), but not of emergency department visits (P = 0.19). The prevalence of wheeze among 6- and 7-year-old children in the Barwon region was similar to that in Melbourne children (20.2% v 20.0%, respectively).There was an age-related increase in the proportion of children with ≥ 12 episodes of wheeze (P = 0.01); but an age-related decrease in emergency department visits (P = 0.02).Conclusions: Disadvantaged children have good access to regular asthma reviews and are no more likely to attend an emergency department with an episode of acute wheeze. Asthma prevalence in 6- and 7-year-old children in the Barwon region is similar to that in Melbourne. The prevalence of children with very frequent wheeze increases with age, but their use of health resources decreases.

Peter J Vuillermin FRACP · Mike South MD · John B Carlin PhD · Maree I Biscan Mstrs · Sharon L Brennan Mstrs · Colin F Robertson MD

To the Editor: Childhood overweight and obesity have become a major public health concern in Australia. Between July 2003 and December 2004, we conducted the Australian National Iodine Nutrition Study (NINS) among schoolchildren.1 While visiting primary schools across Australia, we observed that many children were overweight or obese. The NINS data allowed us to estimate the prevalence of overweight and obesity among 8–10-year-old Australian schoolchildren, and to determine whether the prevalence was associated with socioeconomic background. The study population comprised a one-stage random-cluster sample from all Year 4 school classes in 92 government and non-government schools.1 Children were aged 8–10 years (mean, 9.3 years). Height and weight were measured by standard techniques and were used to calculate body mass index. Overweight and obesity were identified using international standard definitions.2 Socioeconomic status was defined by the Index of Relative Socio-Economic Advantage/Disadvantage of the Census of Population and Housing’s Socio-Economic Indexes for Areas (postal areas).3 This index is a continuum of advantage to disadvantage. A higher score indicates that an area has a relatively higher proportion of people with higher incomes or a skilled workforce. The prevalence of overweight and obesity in 8–10-year-old schoolchildren was 18.5% and 6.5%, respectively. There was no significant sex difference in prevalence and no significant evidence of an association between socioeconomic status and overweight or obesity (Box). The prevalence of overweight and obesity combined and of obesity alone was similar to previously reported prevalence,4,5 although the age range of the participants was more limited than in other studies. We minimised measurement error bias by using the same equipment throughout, in the same setting. Furthermore, most measurements were taken by the same person. We could not demonstrate an association between socioeconomic status and the prevalence of overweight and obesity combined, or of obesity alone. This suggests that childhood overweight and obesity is common to all Australian communities, irrespective of socioeconomic background. Preventing overweight and obesity in children may reduce the risk of adult overweight and obesity and related diseases. Regular monitoring and surveillance of the situation is needed. Australia is one of the first countries in the world to develop a national strategy for overweight and obesity.6 However, the strategy needs to be communicated to the wider community and turned into action to combat this public health problem. Proportion (number) of boys and girls categorised as overweight or obese by index of advantage/disadvantage* SEIFA percentile Not overweight or obese Overweight Obese n Overall Boys Girls Overall Boys Girls Overall Boys Girls Lowest 10 130 79% (102) 77% (56) 82% (46) 12% (16) 12% (9) 13% (7) 9% (11) 11% (8) 5% (3) 10–25 286 72% (207) 72% (103) 73% (103) 22% (64) 22% (31) 23% (33) 5% (15) 6% (9) 4% (6) 25–50 210 74% (156) 72% (72) 76% (84) 17% (35) 18% (18) 16% (17) 9% (19) 10% (10) 8% (9) 50–75 505 75% (379) 72% (183) 79% (195) 19% (98) 21% (53) 18% (45) 6% (28) 8% (20) 3% (8) 75–90 427 75% (319) 78% (179) 71% (140) 18% (78) 17% (39) 20% (39) 7% (30) 6% (13) 9% (17) Highest 10 225 77% (174) 79% (84) 76% (89) 17% (39) 16% (17) 19% (22) 5% (12) 6% (6) 5% (6) Total 1782 75.0% (1337) 74.4% (677) 75.6% (657) 18.5% (330) 18.4% (167) 18.8% (163) 6.5% (115) 7.3% (66) 5.6% (49) * Overall χ2 = 11.42, P = 0.33; Boys χ2 = 8.73, P = 0.56; Girls χ2 = 12.36, P = 0.26. SEIFA = Socio-Economic Indexes for Areas (a higher score corresponds to higher socioeconomic status).

Mu Li · Karen Byth · Creswell J Eastman

To the Editor: Recent studies provide evidence that having a low serum vitamin D level is a risk factor for autoimmune disease, including type 1 diabetes mellitus (T1DM).1,2 Available data come from northern hemisphere countries where sunlight exposure levels and the genetic background of the population are different from those in Australia. We compared vitamin D levels in stored serum from Brisbane children and adolescents with T1DM who attended the Mater Children’s Hospital clinic with local historical control data from a previous study.3 Levels of 25-hydroxyvitamin D (25-OHD; the major circulating form of vitamin D) were lower in those with T1DM than in the control group, with no difference in levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D; the biologically active form). Children and adolescents with T1DM were more than three times as likely to have vitamin D deficiency4 as those in the control group. There was a trend towards seasonal variation in 25-OHD levels, with mean levels (95% CI) being 53.8 nmol/L (47.0–60.6 nmol/L) in summer, 61.4 nmol/L (54.9–67.9 nmol/L) in autumn, 56.4 nmol/L (51.7–61.0 nmol/L) in winter and 64.7 nmol/L (58.8–70.6 nmol/L) in spring (P = 0.06), but no difference in seasonal variation between T1DM and control groups (P = 0.73). There was no difference in the ages or proportions of males and females in the two groups (Box). There were no differences in vitamin D levels between the sexes in either T1DM or control groups, nor any correlation with duration of diabetes. These observations support previous reports. One found low 25-OHD levels in 459 Swedish patients aged between 15 and 34 years who were newly diagnosed with T1DM compared with age-matched and place-matched controls.1 Another found low 25-OHD levels in 88 newly diagnosed children and adolescents.2 Understanding the nature of low vitamin D levels in people with diabetes is important because it potentially clarifies the mechanisms of autoimmune β-cell destruction, and may lead to interventions for preventing or delaying insulin dependence by using vitamin D or its analogues. Vitamin D probably acts by modifying the autoimmune response, as 1,25-(OH)2D modulates dendritic cell function to promote tolerogenic T cells. It may be relevant that we have recently found low blood dendritic cell counts in children and adolescents with T1DM.5 Vitamin D levels in our Queensland sample of children and adolescents were lower overall than those found in the subjects of the Swedish study, (mean 25-OHD levels [± SEM] were 96.7 ± 2.7 nmol/L for the control group and 82.5 ± 1.3 nmol/L for those with T1DM); this is unexpected given Brisbane’s latitude (29°S) compared with that of Sweden (about 55–65°N). These differences might be explained by differences in dietary intake, sun avoidance behaviours promoted in Queensland, or differences in the assays used, as the Swedish group used the Nichols chemiluminescence assay (Nichols Institute, San Juan Capistrano, Calif, USA) and we used the DiaSorin radioimmunoassay (DiaSorin Inc, Stillwater, Minn, USA). The observation in the Swedish study that the deficit in 25-OHD level did not resolve over time after diagnosis concurs with our finding of low levels in children and adolescents several years after diagnosis. While our pilot data cannot support causal inference, and is limited by being retrospective and our lack of information about history of sunlight exposure, dietary vitamin D intake, cultural factors such as sun avoidance or veiling, skin tone, and not having contemporaneous controls, it strongly supports the case for prospective clinical studies of vitamin D in T1DM. Comparison of clinical characteristics and vitamin D levels in healthy children and adolescents and those with type 1 diabetes mellitus Variable Control group Type 1 diabetes mellitus group P No. of children and adolescents 94 47 Age (range) 13.2 years (12.5–13.8 years) 13.6 years (12.6–14.6 years) 0.47* No. of males/females 44/50 21/26 0.81† Mean duration of diabetes (95% CI) — 4.7 years (3.9–5.5 years) Sample collection period July 2000 – December 2001 June 2001 – July 2006 Mean 25-OHD level (95%CI)‡ 64.6 nmol/L (61.3–67.9 nmol/L) 54.7 nmol/L (50.3–58.9 nmol/L) 0.0005* Mean 1,25-(OH)2D level (95% CI)‡ 126.7 pmol/L (115.8–137.6 pmol/L)§ 127.6 pmol/L (114.8–140.4 pmol/L) 0.92* Proportion 25-OHD-deficient (≤ 50 nmol/L) 18% (17/94) 43% (20/47) 0.002† (OR,¶ 3.4; 95% CI, 1.5–7.3) Proportion with 1,25-(OH)2D level below reference range (40–150 pmol/L) 0 (0/84) 4% (2/47) 0.13** (OR,¶ 9.3; 95% CI, 0.4–197.6) * t test. † χ2 test. ‡ DiaSorin radioimmunoassay double antibody assay (DiaSorin Inc, Stillwater, Minn, USA), performed by Queensland Health Pathology Services. § 84 controls; insufficient serum for analysis in 10. ¶ Odds ratio for deficiency in type 1 diabetes mellitus. ** Fisher’s exact test. 25-OHD = 25-hydroxyvitamin D. 1,25-(OH)2D = 1,25-dihydroxyvitamin D.

Ristan M Greer · Meredith A Rogers · Francis G Bowling · Helen M Buntain · Mark Harris · Gary M Leong · Andrew M Cotterill

To the Editor: V-shaped pillows (“tri-pillows”) may cause suffocation of an infant left to sleep between the two arms of the pillow when he or she slips into the crevice between the arms, or beneath the pillow. The deaths of two infants who died in this manner were reported in South Australia in 1997, and a third death was the subject of a coronial inquiry.1,2 In 1998, the SA State Coroner recommended that “a public warning be issued against the use of tri- or U-shaped pillows by infants under two years of age for sleeping”.2 This message has also been issued in subsequent safe-sleeping campaigns, with a statement in the SIDS and Kids national “Safe sleeping” brochure that “tri-pillows are too soft and can cover baby’s face”, and a statement on the SA Child and Youth Health website that “. . . babies should not be left in these pillows while they are sleeping”.4 Despite these clear messages, deaths continue to occur in SA,5 and V-shaped pillows are still being sold in the foyer of a local obstetric hospital. Although the pillows are being promoted to assist breastfeeding, infants who have been left to sleep on them will be exposed to the risk of suffocation. Deaths of infants in shared sleeping situations may also occur due to suffocation from “overlaying”. However, parents are still being advised by health advice telephone enquiry services to sleep in the same bed with their children. This was the unequivocal message given to one of the authors (G C) when she recently telephoned for advice following the birth of her first child. No mention was made of the potential danger of suffocation if parents are physically large, intoxicated, sedated, or simply exhausted, or if the infant is placed between the parents under bedcovers. It appears, despite clear evidence that certain sleeping situations are potentially dangerous for infants, as well as the widespread dissemination of this information in safe-sleeping literature, that certain organisations or individuals continue to give a contrary message. What hope do parents have of understanding these issues and making informed decisions to optimise the safety of their infant’s sleeping environment if they are exposed to such conflicting messages and advice? Perhaps another question to ask is, “What responsibility do organisations and employees bear if an infant dies as a result of parents following such advice or purchasing equipment such as a V-shaped pillow?”

Roger W Byard · Glenda Cains · Helen Noblet · Maxine Weber

Objective: To examine changing demand for specialist food allergy services for children aged 0–5 years over the 12 years from 1995 to 2006 as an index of changing prevalence.Design, setting and participants: Retrospective analysis of the records of 1489 children aged 0–5 years referred to a community-based specialist allergy practice in the Australian Capital Territory (population, about 0.33 million).Main outcome measures: Trends in demand for assessment for food allergy, dietary triggers and severity over 12 years, compared with Australian hospital morbidity data.Results: 47% (697/1489) of 0–5 year-old children seen in private practice had food allergy (175 with food-associated anaphylaxis), most commonly to peanut, egg, cows milk and cashew. Over 12 years, the number of children in this age group evaluated each year increased more than fourfold, from 55 cases in 1995 to 240 in 2006. There was no change in the proportion diagnosed with allergic rhinitis in 1995 and 2006 (14.5% and 13.3%, respectively), urticaria (14.5% and 12.9%) or atopic eczema (54.5% and 57.0%). By contrast, the proportion with asthma dropped from 33.7% in 1995 to 12.5% in 2006 and the number with food allergy increased 12-fold, from 11 to 138 patients (and from 20.0% to 57.5% of children seen) The number with food anaphylaxis increased from five to 37 children (9.0% to 15.4%) over the same period. There were similar trends in age-adjusted Australian hospital admission rates for anaphylaxis in children aged 0–4 years, which increased from 39.3 to 193.8 per million population between the financial years 1993–94 and 2004–05, a substantially greater increase than for older age groups, or for the population as a whole (36.2 to 80.3 per million population).Conclusions: There is an urgent need for coordinated systematic studies of the epidemiology of food allergy in Australia, to ascertain risk factors and guide public health policy. An increased prevalence of food allergy has implications for public health and medical workforce planning and availability of allergy services in Australia.

Raymond J Mullins PhD, FRACP, FRCPA

About a thousand Australian children are seriously injured in motor vehicle accidents each year, despite 92% using seatbelts or child restraints. Premature graduation of children to adult seatbelts, misuse of seatbelts and use of lap-only belts increase the risk of injury or death. In Australia, use of a child restraint or booster seat is not mandatory for children aged > 1 year, while other countries mandate their use for children up to 5–12 years old. Australian parents are confused about the safest restraint and seating position, particularly for children aged > 2 years. Australian child restraint legislation needs to be reviewed to increase the rate of optimal restraint use.

Katie N Reeve MB BS(Hons), MRCPCH, MRCP · Yvonne A Zurynski BAppSc, MAppSc, PhD · Elizabeth J Elliott MD, FRACP, FRCPCH · Lynne Bilston BE(Mech)(Hons), MSE, PhD

Clinical records Patient 1 A 6-month-old infant presented with eczema in January 2006 and was initially treated with antiseptic bath oil, emollients and topical corticosteroid ointments. The infant presented again 3 weeks later with a 7–10-day history of groin and axillary desquamation. Brown hyperpigmentation and superficial brown desquamation were notable around the nappy area. Erythematous areas were noted in the skin folds (Figure A). The infant’s mother reported using an antiseptic bath oil (containing 6% benzalkonium chloride, 2% triclosan, and 55.8% light liquid paraffin) up to three times a day in his bath. Emollient cream and low potency topical corticosteroid ointment had been applied to the nappy and axillary areas. The emollient cream and a high potency topical corticosteroid ointment had been applied to other unaffected areas. Cessation of the antiseptic bath oil was recommended. The patient continued to use corticosteroid ointments, plain emollient bath oil, and 50% white soft paraffin with 50% liquid paraffin. Use of the emollient cream was later recommenced without problems. Patient 2 A 7-year-old girl with moderate eczema developed a flare around her neck in February 2006. She had previously been educated on the use of bath oil in wet wraps and cool compresses for treating flares, and had started using the same antiseptic bath oil as Patient 1 (at the concentration recommended by the manufacturer for use as a rinse) in cool compresses. Eleven days after starting use of the cool compresses, she presented with a painful, weeping raw neck, upper chest (Figure B), back, and cubital fossae, requiring opioid analgesia and admission to hospital. Her reddened weepy areas settled with cessation of the antiseptic bath oil, and use of plain bath oil, topical corticosteroid ointment, oral corticosteroid, and regular moisturising with 50% liquid paraffin and 50% white soft paraffin. Patient 3 A 14-year-old girl with previously mild eczema presented in November 2006 with a flare affecting her cubital fossae. She was advised to use an antiseptic bath oil (containing 6% benzalkonium chloride, 2% triclosan, and 52.5% light liquid paraffin), emollients and potent topical corticosteroid ointment, and was given advice on using wet wraps to settle the affected areas. Over a 10-day period, the patient’s eczema settled. She then acutely developed large bullae bilaterally in the cubital fossae, in a sharp “cut-off” distribution (Figure C). She could not fully extend her elbows due to the pain, and was admitted to hospital. Acute contact dermatitis was diagnosed, and use of the antiseptic bath oil was ceased. Her symptoms settled with the use of oral corticosteroid, frequent moisturising with 50% liquid paraffin and 50% white soft paraffin, and potent topical corticosteroid ointment. Photographs of each patient at time of discharge, clockwise from below left: A: Patient 1 — a 6-month-old infant with contact dermatitis from frequent bathing with antiseptic bath oil. B: Patient 2 — a 7-year-old girl with contact dermatitis on her neck from using antiseptic bath oil in cool compresses. C: Patient 3 — a 14-year-old girl with contact dermatitis on the cubital fossa from using antiseptic bath oil in wet wraps. These three children all presented with acute contact dermatitis from use of antiseptic bath oil. The distribution of the reaction in each case suggested that cumulative irritant contact dermatitis was the likely cause. However, in all of these cases the reaction did not develop immediately, so allergic contact dermatitis was also a possible cause. Patch testing for an allergic cause was not undertaken in these children, as it was felt that this would not alter management in their acute care. Ingredients in the two antiseptic bath oils used by these patients include benzalkonium chloride (6%), triclosan (2%), and paraffin. Direct contact with triclosan in formulated products has only rarely been associated with skin irritation or sensitisation in humans.1 Allergic contact dermatitis to benzalkonium chloride is also rare.2 Benzalkonium is a known strong cutaneous irritant and is reported to be corrosive to mucous membrane at a concentration of 10%.3 For Patient 1, the antiseptic bath oil was frequently being applied to his skin in the bathwater and not rinsed off. We believe that secondary occlusion to the groin (and axilla) by skin folds and the close fit of his nappy contributed to ongoing irritation. Prolonged contact with another bath oil with the same active ingredients in the same concentration has previously been reported to cause irritant dermatitis.3 Lessons from practice Consider a diagnosis of acute contact dermatitis if brown hyperpigmentation and superficial desquamation complicate eczema, particularly if the patient is using an antiseptic bath oil. Use antiseptic bath oils in a diluted concentration, not exceeding the manufacturer’s instructions. If antiseptic bath oil is used, rinse off after use. Use only plain bath oils for cool compresses and wet wraps. It remains unclear whether the frequent application of cool compresses to the softer skin of the neck of Patient 2 resulted in irritant contact dermatitis, or whether true allergy developed. Similar eruptions have been described in reaction to standard concentrations of bath oil, as well as to concentrations greater than the manufacturer’s recommendations.3-6 However, the distribution in this case suggested irritant contact dermatitis. The older child, Patient 3, stated that she had had marked initial improvement after starting use of the bath oil. Her mother thought that after this improvement there may have been a decrease in vigilance in measuring the concentration of the oil, as well as possible prolonged exposure time, which probably resulted in the subsequent acute burn seen in Figure C. A case has been previously described where an increased concentration of the same antiseptic bath oil caused subcorneal pustular dermatitis, with some features resembling a chemical burn, and restriction of movement.6 It is notable that, in all three cases, the thinner skin folds were preferentially affected. This has been previously described, when total body application of antiseptic bath oil to a 27-year-old man resulted in diffuse swelling of his penis and scrotum only.5 In view of the increasing frequency of use of these products, and the subsequent increase in incidence of contact dermatitis as a result (personal observation), we suggest that clinicians, nurses and pharmacists should be aware of the potential for this complication to occur. Using the appropriate concentration of antiseptic bath oils should be emphasised. We recommend that antiseptic bath oils be used only for rinse-off type applications, and, if used in the bath, we suggest rinsing after bathing. Furthermore, we strongly suggest that only plain bath oils should be used as part of a cool compress or wet wrap regimen.

Mignon Moyle MB BS, BAppSci(AdvClinNsg) · Elizabeth J Moore RN, PgDipACN(Paed), MN · George A Varigos MB BS, PhD, FACD

To the Editor: Growth charts are important tools in assessing the physical development of infants and children. Understanding and comparing the derivation and applicability of the new World Health Organization Child Growth Standards1 and the Centers for Disease Control and Prevention (CDC) growth charts2 is essential. Arguments for and against the standard use of the new WHO growth charts are being discussed on the basis of differences in study designs used and growth patterns found.3,4 The WHO charts show the growth of breastfed infants on the basis of data from about 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the United States); these children were from selected populations in which no health, environmental or economic constraints on growth existed.1 In contrast, the CDC charts represent the combined growth pattern of artificial-formula-fed and breastfed infants in the United States, where about 50% of infants are never breastfed and only around 33% are breastfed for 3 months or longer.2 Is it possible to misdiagnose breastfed infants who are growing normally as failing to thrive if the CDC growth charts are used? The simplest common definitions used for failure to thrive are a drop below the 3rd or 5th percentile for weight, or when growth deviates from an established growth curve for 3 consecutive months.5 By the CDC growth charts, the normal growth pattern described by the WHO Child Growth Standards for a 15th percentile, breastfed, female infant at 18 months would meet all three definitions of failure to thrive. The clinical response to this perceived failure to thrive may be to provide additional energy in the form of energy-dense foods or supplements (eg, artificial formula). This would at best be unnecessary, and at worst might contribute to the development of overweight and obesity. So, where to from here? We recommend that all health professionals who use growth charts be cognisant of which chart they are using and its application, especially for breastfed infants. There is also a need for Australian national and state governments to debate which growth charts should be used and in what contexts. Finally, irrespective of the choice of growth charts, it must be recognised by practitioners and the general public that these charts are guides only, and should be used as part of a holistic approach to infant growth assessment and management.

Barbara Radcliffe · Jan E Payne · Helen Porteous · Simone G Johnston

Objective: To investigate the relationship between a child’s weight and a broad range of family and maternal factors.Design, setting and participants: Cross-sectional data from a population-based prospective study, collected between January 2004 and December 2005, for 329 children aged 6–13 years (192 healthy weight, 97 overweight and 40 obese) and their mothers (n = 265) recruited from a paediatric hospital endocrinology department and eight randomly selected primary schools in Perth, Western Australia.Main outcome measures: Height, weight and body mass index (BMI) of children and mothers; demographic information; maternal depression, anxiety, stress and self-esteem; general family functioning; parenting style; and negative life events.Results: In a multilevel model, maternal BMI and family structure (single-parent v two-parent families) were the only significant predictors of child BMI z scores.Conclusion: Childhood obesity is not associated with adverse maternal or family characteristics such as maternal depression, negative life events, poor general family functioning or ineffective parenting style. However, having an overweight mother and a single-parent (single-mother) family increases the likelihood of a child being overweight or obese.

Lisa Y Gibson MPsych, PhD · Susan M Byrne MPsych, PhD, DPhil(Oxon) · Elizabeth A Davis MB BS, FRACP · Eve Blair BSc, PhD · Peter Jacoby BA(Hons), MSc · Stephen R Zubrick MSc, MA, PhD

Aim: To describe the pattern of disease and other health problems in children living in remote Far North Queensland (FNQ).Design, setting and participants: Retrospective review of the FNQ Paediatric Outreach Service’s Medical Director database for the period June 2001 to February 2006. Three subpopulations were compared: children from predominantly Aboriginal communities, predominantly Torres Strait Islander communities, and other communities. All children referred to the service during the study period were reviewed.Main outcome measures: Number of children seen and common diagnoses.Results: 3562 children were referred during the study period, and a total of 3932 diagnoses were made; 56% of the paediatric population of the Aboriginal communities and 23% of the paediatric population of Torres Strait Islander communities were seen. Of 40 separate diseases/health problems reviewed, the three most common reasons for presentation were chronic suppurative otitis media, suspected child abuse and neglect, and failure to thrive. In the paediatric population of Aboriginal communities, the prevalence of fetal alcohol spectrum disorder was at least 15/1000 (1.5%), and in Torres Strait Islander children, rheumatic heart disease prevalence was at least 6/1000 (0.6%). Rheumatic fever rates were among the highest in Australia.Conclusion: Rates of preventable complex and chronic health problems in Aboriginal and Torres Strait Islander children in remote FNQ are alarmingly high. Areas requiring urgent public health intervention include alcohol-related conditions and rheumatic fever.

Jonty Rothstein MB BS, FRACGP, DCH · Richard Heazlewood MB BS, FRACGP, FACRRM · Marnie Fraser MB BS, MPHTM

Australian youth engage in behaviour that threatens their health and wellbeing. National surveys report that about a third of young Australians have tried an illicit drug. High rates of substance use and risky sexual behaviour among young Australians suggest that effective prevention efforts based on empirical evidence need to be expanded. Church-associated organisations are an untapped resource that could be used to improve the health and welfare of young people. We describe eight evidence-based elements to consider in designing strategies to prevent high-risk behaviour in young people.

Gary L Hopkins MD, DrPH · Duane McBride PhD · Helen H Marshak PhD · Kiti Freier PhD · John V Stevens Jr JD · Wendi Kannenberg MPH · James B Weaver III PhD · Stephanie L Sargent Weaver PhD · Peter N Landless MMed, FCP(SA), FACC · Jonathan Duffy BEd, MPH

Molecular genetics can facilitate a successful switch to oral diabetes therapy The increase in type 1 and type 2 diabetes in childhood has been well documented worldwide and in Australia.1,2 In addition, the separate entity of monogenic diabetes is increasingly recognised in paediatric diabetes, and now encompasses neonatal diabetes mellitus and maturity onset diabetes of the young (MODY)3 (Box 1). Monogenic diabetes is defined as diabetes caused by a single gene defect. A diagnosis of monogenic diabetes should be considered in a child who is diabetes-associated-autoantibody negative, is diagnosed with diabetes in the first 6 months of life, has a parent with diabetes, and/or is not markedly obese. Although uncommon — its frequency is estimated to be 1%–3% of all childhood diabetes3 — the clinical relevance of this condition is that at least some of those affected (in particular, those with MODY1 and MODY3) can achieve very good diabetes control with sulfonylurea rather than insulin therapy. Neonatal diabetes mellitus presents in the first 6 months of life with signs of hyperglycaemia — polyuria, dehydration, failure to thrive and, in many, frank diabetic ketoacidosis. Diabetic ketoacidosis is an important diagnosis to consider in an infant who presents critically unwell because the clinical picture may mimic sepsis. While the reported incidence of neonatal diabetes mellitus is one in 500 000 newborns,4 the estimated incidence is thought to be a lot higher, and it may be the cause of some unexplained infant deaths. About half of affected patients will have transient neonatal diabetes mellitus, where insulin treatment can be discontinued within a median of 3 months (although diabetes mellitus may recur in the second or third decade of life). In contrast, patients with permanent neonatal diabetes mellitus have, until recently, required insulin therapy for life. The revolution in patient management we describe here is due to molecular genetic analysis of the ATP-sensitive potassium (KATP) channel of the pancreatic beta cell (Box 2). Sulfonylureas have traditionally been used to treat type 2 diabetes mellitus. They act by binding the sulfonylurea receptor (SUR1), which closes KATP channels, thereby stimulating endogenous insulin production from the pancreatic beta cell. Gloyn et al demonstrated that some patients with Kir6.2 potassium channel activating mutations secreted insulin in response to the intravenous sulfonylurea tolbutamide.5 Subsequently, the Neonatal Diabetes International Collaborative Group conducted a trial of glibenclamide, an oral sulfonylurea, in 49 patients with Kir6.2 mutations. This trial included two Australian centres, with three children — one white and two of Middle Eastern ethnicity. An impressive 90% of the trial patients were successfully switched from insulin to glibenclamide.8 Importantly, the responsiveness in vitro of mutant ATP channels to tolbutamide was proportionate to the patient’s response to glibenclamide. This enables a degree of predictability of whether a patient is likely to successfully switch from insulin to oral therapy. Not only was oral therapy welcomed by families of patients, but the switch from insulin resulted in significant improvement of metabolic control, with glycated haemoglobin levels dropping from 8.1% to 6.4% after 12 weeks of treatment.8 Insulin response to oral glucose load was increased in those tested. Continuous glucose monitoring has also shown fewer fluctuations in postprandial glucose,9 which families report improves the child’s general wellbeing. However, the story is not all rosy — some patients with Kir6.2 activating mutations known to have poor in-vitro response to tolbutamide may not be able to switch to oral therapy. It is therefore important to determine the exact genetic mutation involved, so that families can be counselled about the chances of a successful switch. In our experience, such counselling was helpful in lessening the disappointment when a 7-year-old girl with a Kir6.2 mutation, who had presented with ketoacidosis at 7 months of age, remained insulin-dependent despite maximal glibenclamide dose. The diagnosis of neonatal diabetes mellitus should be considered in any critically ill infant, and the International Society for Pediatric and Adolescent Diabetes recommends that all infants who develop diabetes mellitus in the first 6 months of life be tested for a genetic mutation in the KATP channel.10 DNA from peripheral blood can be sent to a diabetes research laboratory in Exeter in the United Kingdom for testing (see http://www.diabetesgenes.org). To date, 20 Australian children, who had been insulin-dependent from less than 6 months of age, have been genotyped. Seven tested positive for mutations in Kir6.2 and three for mutations in SUR1 (Professor Andrew Hattersley, Peninsula Medical School, Exeter, UK, personal communication), and some have gained insulin independence. While molecular genetics can now help classify and facilitate management of childhood diabetes, regardless of the type of diabetes (type 1, type 2, or monogenic), all children who present with severe fasting hyperglycaemia and ketoacidosis will initially require insulin therapy to reverse the metabolic abnormalities. 1 Classification of primary diabetes mellitus in children Type 1 diabetes is characterised by the presence of diabetes-associated autoantibodies (islet cell, insulin, glutamic acid decarboxylase, and tyrosine phosphatase). A number of children with type 1 diabetes may be obese at diagnosis. Type 2 diabetes is characterised by obesity, negative antibodies and raised C-peptide levels. It is more common in non-white people than type 1 diabetes. Comorbid obesity can make the distinction between these two types of diabetes difficult. Monogenic diabetes is caused by a single gene abnormality. Maturity onset diabetes of the young (MODY) 1 and MODY3 are due to transcription factor mutations. Children with monogenic diabetes are not generally obese. Some children with monogenic diabetes present in the neonatal period with ketoacidosis. 2 Subunit structure of the ATP-sensitive potassium (KATP) channel of the pancreatic beta cell* The KATP channel consists of four sulfonylurea receptor (SUR1) subunits and four potassium channel (Kir6.2) subunits. Closure of the KATP channel is required for glucose-stimulated insulin secretion from the pancreatic beta cell. Conversely, opening of the KATP channel inhibits insulin secretion. Inactivating mutations of genes encoding both SUR1 (ABCC8) and Kir6.2 (KCNJ11) subunits keep the channel closed and are known to cause uncontrolled insulin secretion, resulting in congenital hyperinsulinism. It was hypothesised that activating mutations of these genes would keep the KATP channel open and cause permanent neonatal diabetes mellitus (PNDM). In 2004, Gloyn et al reported six novel heterozygous mutations in 10 of 29 patients with PNDM, including a 5-year-old Sydney girl who had been treated with insulin from 6 weeks of age.5 Subsequently, Proks et al reported a patient with activating mutations of ABCC8,6 and Babenko et al reported ABCC8 mutations in two of 29 patients with PNDM and seven of 44 patients with transient neonatal diabetes mellitus.7 KATP channels are also found in skeletal muscle and neurones throughout the brain, and some patients with Kir6.2 activating mutations have extrapancreatic features — motor skill and language delay, muscle contractures, epilepsy, and dysmorphic features — leading to the description of a new syndrome, known as DEND (Developmental delay, Epilepsy, Neonatal Diabetes) syndrome. In-vitro studies of mutant KATP channels have shown a correlation between the degree of KATP channel insensitivity and severity of the clinical phenotype.5 * Adapted from: Sperling MA. ATP-sensitive potassium channels — neonatal diabetes mellitus and beyond [editorial]. N Engl J Med 2006; 355: 507-510. PIP2 = phosphatidyl-inositol-4,5-bisphosphate.

Shubha Srinivasan MB BS, MRCP, FRACP · Kim C Donaghue MB BS, PhD, FRACP

Objective: To establish the nature and efficacy of Australian school-based prevention and early intervention programs for anxiety and depression.Data sources: Cochrane, PsychInfo and PubMed databases, and the Primary Mental Health Care Australian Resource Centre database, were searched in June 2006. Additional materials were obtained from program websites, reference lists and authors.Study selection: Programs that were developed in Australia or trialled in Australia and addressed anxiety, depression, or resilience were included.Data synthesis: 24 efficacy or effectiveness trials of 9 intervention programs were identified. Most were based on cognitive behaviour therapy, interpersonal therapy or psychoeducation. Six were universal interventions, two were indicated programs and one was a treatment program. Most were associated with short-term improvements or symptom reduction at follow-up.Conclusions: A number of schools programs produce positive outcomes. However, even well established programs require further evaluation to establish readiness for broad dissemination as outlined in the standards of the Society for Prevention Research.

Alison L Neil BAppPsych(Hons) · Helen Christensen PhD

To the Editor: The adverse health effects of environmental tobacco smoke (ETS) are well documented. Workplaces are increasingly smoke-free, and restrictions on smoking in restaurants, pubs and clubs are increasing. Paediatricians counsel parents to make their children’s home smoke-free and to smoke outside if they can not quit. In Australia, attention is turning to ETS exposure in cars, in the belief that the confined space may result in increased exposure, even if the windows are wound down. However, few, if any, objective data on the health effects of ETS exposure in cars have been published. We report here the risks of current wheeze at the age of 14 years in children exposed to ETS in their parents’ car. Questionnaire data were available from parents of 1427 children taking part in the 14-year assessment of a longitudinal birth cohort in Perth. Characteristics of the cohort have been described elsewhere.1 Information about current wheeze (defined as the occurrence of wheeze in the previous 12 months) and asthma risk factors, including ETS exposure in the house and car, was obtained. Standard spirometry, methacholine challenge and skin prick tests to local aeroallergens were performed in 1400, 1334 and 1308 children, respectively. Current wheeze was reported in 191 children (14.0%) at the age of 14 years, compared with 537 (38.2%) when they were seen at 6 years of age. Persistent wheeze, at both 6 and 14 years of age, was reported in 145 children (10.2%). ETS exposure in the parents’ car was common. The 14.6% of children who were exposed at 14 years had increased risk of both current wheeze (odds ratio [OR], 1.55; 95% CI, 1.02–2.35; P = 0.038) and persistent wheeze (OR, 2.14; 95% CI, 1.34–3.42; P = 0.001). These risks were higher than those for ETS in the home: for the 8.9% of children exposed in the home, the OR for current wheeze was 1.33 (95% CI, 0.80–2.22; P = 0.27) and the OR for persistent wheeze was 1.98 (95% CI, 1.12–3.50; P = 0.016). Those with current wheeze and ETS exposure in the car had increased methacholine responsiveness: PC20 (provocative concentration required to produce a 20% fall in forced expiratory volume in 1 second) was 5.9 mg/mL in children with ETS exposure compared with 15.2 mg/mL in those not exposed (P = 0.004). These effects were independent of sex and atopic status. These data provide evidence that the community needs to be educated about the adverse health consequences of ETS exposure in cars and suggest that health care professionals should include such education in counselling sessions for families of children with asthma. Teenagers can escape ETS exposure in the home, either by removing themselves or by their parents smoking outside. However, children of this age and younger have no choice but to travel with their parents in the car, especially given the phenomenon of “mum’s taxi” transporting children to school and extracurricular activities. Smoke-free cars are important for all children.

Peter D Sly · Marie Deverell · Merci M Kusel · Patrick G Holt

Re: “Shrinking bottle syndrome”, by Sarah Newton, Hemant Agarwal, Joane Coleman and Srinivas Bolisetty, in the 20 February issue of the Journal (Med J Aust 2006; 184: 187). The second author’s name was incorrectly given as “Hemant Agarwal”. The correct name is “Hemant Jain”. The html and pdf versions of this article were corrected on 9 Nov 2006.

Sarah Newton · Hemant Jain · Joane Coleman · Srinivas Bolisetty

Moving beyond the uncertainties of risk, and limited, often difficult, preservation options, will require consensus and collaborative research The remarkable cure rates achieved in childhood cancer mean that large numbers of survivors are currently among the young adult population. However, the treatment that has achieved this success may have adverse effects in many organ systems, including the reproductive organs. These adverse effects may result from the impact of cytotoxic chemotherapy (alkylating drugs such as cyclophosphamide, iphosphamide, procarbazine and busulfan, in particular) on gametogenesis, from radiation damage to the gonads, or from radiation delivered to the hypothalamic–pituitary axis. To preserve fertility, it is necessary to determine the risk of fertility impairment before instituting cancer therapy. Predicting the impact of treatment on reproductive function in individual children based on expected exposures is notoriously unreliable. Current tools, both biochemical and biophysical, are unsuitable for assessing actual reproductive impacts in prepubertal and peripubertal children. Even when pubertal onset and progression is apparently normal, the integrity of gametes may have been compromised. A case–control study of 33 male survivors of childhood cancer showed that only a third had normal semen quality, and even in those who were not azoospermic, there were significant differences from normal controls. Seven of 11 azoospermic young adults were prepubertal at treatment, implying that the prepubertal state does not afford protection.1 Similarly, a study of young adult female survivors treated in childhood, all of whom had regular menses or had a history of normal menses if they were using combined oral contraception, revealed partial reduction in ovarian reserve as shown by elevated follicle-stimulating hormone (FSH) levels, lower anti-Mullerian hormone levels and smaller ovary size on ultrasound in those with spontaneous menstruation, and failure to elevate inhibin B levels in response to FSH stimulation in those using combined oral contraception.2 On the other hand, pregnancies have been noted in individuals predicted to be sterilised by their exposures to cancer therapies. The treatment protocols applicable to a child’s particular diagnosis may suggest higher risk. Those exposed to dose-intensive regimes of cyclophosphamide3 and other alkylators, particularly those with Hodgkin’s lymphoma treated with MOPP (mustine hydrochloride [nitrogen mustard], Oncovin [vincristine], procarbazine and prednisone) and other alkylator-intense regimens, including those with metastatic sarcomas, or bone marrow transplantation, are at increased risk. Others at higher risk are those who need pelvic or testicular irradiation, or total body irradiation before marrow transplantation. At the other end of the spectrum, children about to commence therapy on low-intensity protocols, such as those used for low-stage Wilms’ tumour or acute lymphoblastic leukaemia, are at minimal risk of infertility. However, a substantial proportion of children beginning treatment fall into an intermediate risk category for which prediction is fraught with inaccuracy. The cut-off of 7.5 g/m2 of cyclophosphamide recommended by the Children’s Oncology Group as the exposure level to trigger screening for fertility is a reasonable approximation of elevated risk, but not a reliable predictor of outcome at the beginning of therapy. Given the uncertainty of predicting fertility outcomes, what options exist for preserving fertility in children facing cancer therapy, and how should parents and patients be counselled? Cryopreservation of semen and subsequent in-vitro fertilisation is the only standard option for postpubertal males, and spermarche is the watershed around which options for boys are defined. Spermarche typically is an early to mid-pubertal event and occurs before the ability to achieve ejaculation.4 In the mature adolescent, semen is usually obtained by masturbation, with electrostimulation or vibratory stimulation as alternatives (the latter two may be applicable in peripubertal boys). However, the rate at which viable samples are obtained is highly variable. These adolescents are often sick as well as embarrassed and uncomfortable. One study of 62 attempts by adolescents to bank sperm before therapy resulted in totally normal semen in only four.5 Adolescents may be more successful if unaccompanied by parents.6 The advent of intracytoplasmic sperm injection (ICSI) enables in-vitro fertilisation of ova with even single sperm and so, despite the low yield rate, semen cryopreservation should be encouraged — as appears to be the case in the survey of practice in Australia and New Zealand by Heath and Stern in this issue of the Journal.7 Whether ICSI will increase the incidence of abnormalities in the offspring of cancer survivors remains to be seen — the incidence of abnormalities in offspring of cancer survivors conceived by natural means is not elevated.8,9 However, ICSI may bypass the normal protective mechanisms which terminate abnormal embryos. In adult men unable to produce semen for cryopreservation, harvesting of testicular sperm has been undertaken, either from testicular biopsy or percutaneous aspiration. However, in the presence of circulating cancer cells, breaching the blood–testicular barrier may pose the risk of testicular cancer recurrence analogous to the increased rate of central nervous system leukaemia after traumatic lumbar puncture. Of interest, even when sperm is banked, studies in adults suggest that a small proportion of men (10%–30%) retrieve and use the banked specimen.10 For prepubertal males, no current routine option exists. Approaches that may develop include testicular tissue cryo-preservation, and germ cell cryopreservation and autografting. Both are entirely experimental at this time.11 For female patients, the options are more limited. For mature women, oocytes can be harvested and fertilised, and resulting embryos preserved. However, this requires at least 2 weeks of hormonal preparation (daily injections of FSH), and an existing sperm source. Similarly, oocytes can be preserved and subsequently fertilised when a sperm donor is available, although success rates are lower.12 Neither technique is applicable to children or adolescents. As ovarian tissue contains significant numbers of primordial follicles in younger females, the harvesting and storage of ovarian tissue (preferably removed as ovarian cortical strips by laparoscopic techniques) before starting cancer therapy, with subsequent autotransplantation, is an experimental option. There is some evidence of successful restoration of hormone production and two reports of successful pregnancy.13,14 Which patients should be subjected to such invasive techniques needs clarification and consensus, and this procedure should only be undertaken under strict clinical trial conditions in centres with the necessary expertise. The risk of reintroducing cancer cells has not been accurately assessed, but is a real possibility.11 In the face of uncertainty and limited options, many of which are invasive, the paediatric oncology community has been slow to embrace routine and consistent counselling of families about fertility preservation options. Heath and Stern have demonstrated this hesitation among Australian and New Zealand oncologists,7 and similar results have been obtained in North America.15 To be able to provide effective counselling and improve pre-emptive interventions to preserve fertility, paediatric oncologists must inform themselves of the options for their patients, forge links with paediatric endocrinologists and reproductive medicine specialists, define at-risk patients by consensus, and commit to participating in research in this area — as they have already done so well in the context of defining best cancer treatments.

Mark L Greenberg MB ChB, FRCPC · Stacey L Urbach MD, MPH, FRCPC

Objective: To establish the extent to which sperm, oocyte and gonadal tissue collection and storage is offered to children newly diagnosed with cancer.Design, participants and setting: A cross-sectional survey of all paediatric oncology services in Australia and New Zealand (ANZ) in December 2005.Main outcome measures: Sperm, oocyte and gonadal tissue collection and storage practices at paediatric oncology services; comparisons with recently published North American practices and with current recommendations for best practice.Results: 12 of the 13 centres (92%) completed the survey. All centres offered sperm preservation, but only 10 (83%) offered oocyte/ovarian tissue preservation. Two centres were using gonadotrophin-releasing hormone analogues for fertility protection in postpubertal females. Five (42%) had offered fertility preservation to patients before the completion of their sexual development. All centres were more likely to offer sperm preservation than oocyte preservation for any given disease. The most common diseases for which conservation was offered were lymphomas and sarcomas. The anticipated cumulative dose at which centres elected to offer fertility preservation varied widely, both for the alkylator cyclophosphamide (any to 10 g/m2) and for abdominal/pelvic irradiation (any to 12 Gy) and spinal irradiation (any to 18 Gy). Fertility counselling was offered in a variety of settings by nine (75%) of the centres. Despite 11 centres (92%) agreeing that fertility preservation guidelines would be helpful, only two (17%) had guidelines in place.Conclusions: There are inconsistencies in the indications for and methods of gamete conservation in paediatric oncology centres throughout ANZ. Variations in practice on a background of unresolved medical, legal and ethical issues suggest the development of guidelines would be helpful.

John A Heath PhD, FRACP · Catherine J Stern MB BS, FRACOG

On balance, new guidelines for parents and practitioners are helpful and workable Which infants at the margins of viability should receive neonatal intensive care and how should such decisions be made? These challenging questions are posed in this issue of the Journal by Lui and colleagues.1 Their answers, arrived at by means of a multidisciplinary conference, are presented as a consensus statement that makes several recommendations for practice. Although similar multidisciplinary conferences have been held in Australia over the past 20 years, there are no contemporary publications on the subject and this statement is timely. As has been apparent from other commentaries both here and overseas,2 these guidelines for New South Wales and the Australian Capital Territory confirm that the area of most debate concerns infants of 23–25 weeks’ gestation. However, several important questions can be asked about the consensus statement itself, including: How appropriate was the process undertaken to arrive at the statement? Was consensus reached? And, are the recommendations helpful and “workable”? As to the appropriateness of the process, there are several options for dealing with these difficult ethical and management decisions. I recall that, at two earlier conferences held at Westmead, Sydney, in 1985–1986, four approaches were identified: a “look to the courts” approach (this approach is not readily available, is expensive and generally produces conservative rulings); a “right to life” approach or, “if it can be done, it should be done”, whatever the burden this imposes on the patient, their family and society; a “muddle through” approach or, “doing what seems best at the time”; and an “institutional” approach. The “muddle through” approach has been a pragmatic solution in the past, leading to a great deal of sensible practice, and it is increasingly subject to controls, including audits and peer review. However, the “institutional” approach — particularly in the guise of a multidisciplinary conference — was, at that time, put forward as the most logical and coherent way of informing community debate and public policy. This approach has worked well in other areas (eg, providing guidelines for human organ transplantation). It would also seem very appropriate for this current debate. A prerequisite for this process would be that good data are available on the consequences of choosing resuscitation over comfort care. In this instance, the process worked well, because the workshop was presented with comprehensive population-based data from NSW and ACT on survival after live birth and neurodevelopmental status at 2–3 years of age. Although the numbers of infants at each gestational age were relatively small, the data are similar to those obtained from other Australian population-based studies.3 A longer-term follow-up would have been preferable, but such data are subject to the problem that elements of neonatal intensive care change over time. On the question of whether consensus was reached, the statement revealed that not all recommendations were agreed to by all participants; not surprisingly, there was considerable divergence of views in some areas. Delegates were asked to vote anonymously (using a five-point scale) on a range of scenarios and related statements. “Consensus” was defined as more than 90% “agree” or “strongly agree” or, for some statements “of lesser gravity”, as 75% “agree” or “strongly agree”. The process was rigorous and likely to have honestly reflected the group’s views. However, only 72% of participants agreed with a statement about not initiating resuscitation at a gestational age of between 25 weeks and 25 weeks 6 days (250–6) if requested by parents in an otherwise uncomplicated pregnancy. Although this was clearly a majority view, it did not, strictly speaking, reach the stated definition of “consensus”, but was incorporated in the consensus statements. The composition of the multidisciplinary group would also seem crucial to the process. Here, perhaps, there were some shortcomings. The group of 112 delegates convened by Lui and colleagues were mainly health professionals, although eight were non-clinical health administrators and seven were parents or community advocates. Including others, such as educationalists, ethicists, lawyers and religious leaders, would have made the delegates more broadly representative of society, and possibly different views would have emerged. However, various professional and consumer groups as well as the NSW Health Clinical Ethics Advisory Panel have subsequently reviewed the agreed guidelines. Are the guidelines helpful and “workable”? Certainly, it is helpful to have widely agreed and ethically approved written guidelines in this area of neonatal practice. In a commentary published in 2004, Jerold Lucey, the long-serving Editor-in-Chief of the leading United States journal Pediatrics, made it clear that in his view any treatment of these infants is experimental.4 In some sense, all medical treatment is an experiment, although commonly the outcome is more predictable than in the case of extreme prematurity. At these gestational ages, there are too few data relating to treatments found to be effective in more mature infants (eg, exogenous surfactant) to pretend that their use is evidence- based. Thus, as a key consensus recommendation says, within this gestational age range (23 weeks to 25 weeks 6 days) when gestation is known with reasonable certainty, “parents’ involvement in the decision-making process during prebirth counselling or subsequent management is mandatory”. The issue of non-directive counselling was discussed at the workshop. Not all parents demand total autonomy in decision making;5 indeed, some may be impossibly overburdened by the prospect.6 The important issue, as emphasised in these and earlier guidelines on preterm care,7 is that good communication is at the very core of the partnership between the medical team (the current caregivers) and parents (the future caregivers) that unfolds as perinatal and neonatal intensive care progresses. Information provided to parents by different members of the team should be consistent. Having appropriate written material, which will be available as a result of this consensus workshop, will facilitate this process. Perhaps the most important consensus recommendation states that, at gestational ages between 23 weeks and 25 weeks 6 days, treatment is discretionary. Lui and colleagues use the term “grey zone” to emphasise that, at these gestations, there is a complexity of maternal, obstetric and clinical factors known to influence outcome that need to be considered in making individualised decisions. Sex of the infant was not included in the discussions because it was stated that it was not usually known before birth. However, there is now extensive evidence that, at these short gestations, female infants do have a better survival rate, to some extent a better long-term outcome, and essentially are the equivalent of a week more mature than their male counterparts.8 Increasingly, the sex of the neonate is known before birth, and otherwise is immediately apparent at birth. It could be argued that there should be different grey zones for female and male infants. Certainly, not to consider the infant’s sex may be to discriminate against female infants.9 Many factors, including the sex of the neonate, should influence decisions not only within the zone but at its margins. Data from the Australian and New Zealand Neonatal Network show that survival rate at these short gestations increases by about 3% with each day of increased maturity.10 This, added to the fact that gestational age is often an estimate, means that the margins of any grey zone are somewhat indistinct. The consensus statement’s abstract states that “poor condition at birth” has an important influence on the decision not to initiate intensive care in this zone. However, there are few data to support the predictive value of condition at birth for survival and certainly not for neurodevelopment.11 A prediction that an infant of a certain gestational age will do poorly, coupled with non-aggressive resuscitation, is likely to be a self-fulfilling prophecy. However, a poor response to adequate resuscitative measures must clearly be a factor in decisions about ongoing intensive care. In their statement, Lui and colleagues have provided valuable guidelines for parents and practitioners dealing with impending extremely preterm delivery; they should be congratulated on the rigour of their process. It is now up to others to use these guidelines wisely. In the abstract (which may be the only part some people will read), the description of the grey zone seems a little too black and white, with clear margins. The main text of the statement — which should be read in its entirety — makes it clear that this zone is not uniform grey and that its limits are indistinct.

Brian A Darlow MD, FRACP

Perinatal care at the borderlines of viability demands a delicate balance between parents’ wishes and autonomy, biological feasibility, clinicians’ responsibilities and expectations, and the prospects of an acceptable long-term outcome — coupled with a tolerable margin of uncertainty. A multi-professional workshop with consumer involvement was held in February 2005 to agree on management of this issue in New South Wales and the Australian Capital Territory. Participants discussed and formulated consensus statements after an extensive consultation process. Consensus was reached that the “grey zone” is between 23 weeks’ and 25 weeks and 6 days’ gestation. While there is an increasing obligation to treat with increasing length of gestation, it is acceptable medical practice not to initiate intensive care during this period if parents so wish, after appropriate counselling. Poor condition at birth and the presence of serious congenital anomalies have an important influence on any decision not to initiate intensive care within the grey zone. Women at high risk of imminent delivery within the grey zone should receive appropriate and skilled counselling with the most relevant up-to-date outcome information. Management plans can thus be made before birth. Information should be simple, factual and consistent. The consensus statements developed will provide a framework to assist parents and clinicians in communication, decision making and managing these challenging situations.

Kei Lui MB BS, MD, FRACP · Barbara Bajuk MPH · Kirsty Foster MB ChB, DRCOG, MEd · Arnolda Gaston MPH · Alison Kent BM BS, FRACP · John Sinn MB BS, FRACP, MMed(Epi) · Kaye Spence RN, BEd(N), MN, FCN · Wendy Fischer BA(Hons), RN, CM · David Henderson-Smart MB BS, PhD, FRACP

Rotavirus vaccines are finally available, and introducing them into the routine vaccination schedule will have a significant impact on the health of children After a dramatic false start, oral rotavirus vaccines are now available to prevent severe, dehydrating diarrhoea in small children. Rotavirus infection in children can be as severe as cholera in adults, but affects a group who cannot complain. Since its discovery in Australia in 1973, rotavirus has become accepted as the single most common cause of severe diarrhoea in children worldwide. It still kills over 500 000 young children each year. In Australia, it is estimated that 10 000 children require hospitalisation annually1,2 (more than 4000 actually coded for proven rotavirus3), and as Schultz reports in this issue of the Journal, the impact on Indigenous children is especially severe.4 Oral rehydration has greatly reduced mortality, but the World Health Organization recognises the potential of rotavirus vaccines to further reduce under-5-year mortality rates, Goal 4 of the Millenium Development Goals.5 It is exciting to have two efficacious oral rotavirus vaccines, RotaRix (GlaxoSmithKline [GSK], Boronia, VIC) and RotaTeq (Merck/CSL, Parkville, VIC) licensed this year in Australia. Each has been extensively tested in placebo-controlled trials of more than 60 000 participants. Both vaccines prevented severe disease, and reduced the need for hospitalisation by 85%–94%. There was a reassuring lack of intussusception, a rare (one in 10 000–32 000) event associated with RotaShield, the first licensed rotavirus vaccine, which led to its withdrawal from the United States market in 1999, just 12 months after its introduction.6 Re-analysis of the data suggested that the intussusception risk emerged in infants receiving the first vaccine dose after 3 months of age.7 Thus both GSK and Merck/CSL state that the first dose should be administered before that time. Several issues remain to be resolved with these two new vaccines. Efficacy has not been established in developing countries. Availability will depend on distribution (including the need for a cold chain), the ability to piggyback rotavirus vaccines with other routine vaccinations, and manufacturing capacity. The greatest uncertainty is the cost of the vaccine. Current prices exceed $200 per course in the private market. While tier pricing and subsidisation by international agencies for poorer countries is being considered, it is not clear whether these mechanisms will sustain programs in most parts of the world. Hence, other candidate vaccines linked to developing country manufacture are under early development in China, India, Indonesia and elsewhere. Who should get rotavirus vaccine in Australia? Ideally all children under 3 months of age, as all will eventually be exposed to rotavirus, and one in 25 will be admitted to hospital for rotavirus gastroenteritis during the first 5 years of life. Morbidity across our country is high. Apart from the 10 000 annual hospital admissions, there are 22 000 visits to emergency departments and 115 000 visits to general practitioners.2 Nosocomial infection rates are as high as 14% in children’s hospital wards and may be higher in childcare centres.8,9 Schultz’s report indicates that Indigenous children have 2–4 times the disease burden of non-Indigenous children.4 Gastroenteritis in Indigenous children comes with comorbidities and a significantly increased average length of hospital stay. Add to that the large costs of air transport of patients for hospital admission in northern and western Australia and the disruption to remote families, and the case for rotavirus vaccination of Indigenous infants becomes compelling. The Northern Territory Health Department recognised the importance of rotavirus infection by making it a notifiable disease, and Queensland recently followed suit. Breaking news is that from October 2006, the NT Government will include rotavirus vaccine in the routine vaccination schedule for NT children.10 The only real issue is cost. A 1999 cost–benefit analysis suggested that break-even vaccine cost was $78 per course,11 somewhat less than current prices. However, the community should be prepared to pay something to prevent this wretched disease. For maximum benefit, the first dose should be given before 3 months of age. Infants under 6 months of age accounted for 24% and 9% of rotavirus gastroenteritis cases in studies in the NT and Melbourne, respectively.4,12 In Africa, many infants are infected in the first 2 weeks of life.13 There is enthusiasm for giving the first dose of vaccine within the first month of life, but neither licensed vaccine has been tested at this age. Roll-out of a universal program in Australia has a few caveats. The inevitable concern about intussusception, in spite of the reassuring clinical trial results, probably means that catch-up campaigns, where the first dose is given after 3 months of age, will not happen. Evidence of the spectrum of protection afforded by both vaccines against the full range of human rotavirus serotypes is still lacking. There is a need to continue national strain surveillance to ensure that the current vaccines are appropriately protective against the range of serotypes in Australia, and to monitor the effect of vaccine pressure on the evolution of strains. After three decades, there is real excitement at suddenly having such an effective tool to prevent a common, miserable disease affecting infants and children. Rotavirus vaccination is not only justified on the basis of disease burden, but will be welcomed by all who care for sick children. It will not be hard to measure real improvement for Indigenous children in the NT, given the baseline data presented elsewhere in this issue of the Journal.4 While other candidate vaccines are in development, there is no excuse for waiting any longer for a national program. The improvement in child health will be obvious.

Graeme L Barnes MD, FRACP · Ruth F Bishop AO, DSc, PhD

Objective: To present data on rotavirus notifications in the Northern Territory to provide knowledge about the local epidemiology of rotavirus gastroenteritis that can be used to inform the use and funding of rotavirus vaccines.Design: Retrospective analysis of data from the Northern Territory Notifiable Diseases Database.Participants and setting: Patients with cases of rotavirus infection notified to the NT Centre for Disease Control from 1 January 1995 to 31 December 2004.Main outcome measures: Patterns of rotavirus notifications over time; infection rates in Indigenous versus non-Indigenous children aged 0–5 years; age groups infected with rotavirus.Results: Numbers of rotavirus notifications over the period 1995–2004 show annual, monthly and regional variability. The rotavirus notification rate for Indigenous children aged 0–5 years was 2.75 per 100 per year, compared with 0.98 for non-Indigenous children, with a relative risk for Indigenous children of 2.17 (95% CI, 1.97–2.39) over the 10 years. Indigenous children infected with rotavirus were younger than non-Indigenous children, with median ages of 11 months and 16 months, respectively. Rotavirus gastroenteritis occurred in outbreaks, transmitted over months throughout the NT.Conclusion: Large numbers of cases of rotavirus gastroenteritis affecting Indigenous and non-Indigenous children in the NT are notified every year. The rate in Indigenous children may be decreasing relative to non-Indigenous children. An effective rotavirus vaccine could prevent significant morbidity.

Rosalie Schultz MB BS, MPH

To the Editor: Meningitis is one of the most serious infections in young children. The annual incidence of Haemophilus influenzae type b (Hib) meningitis between 1984 and 1988 was 150 per 100 000 population in Aboriginal children and 27 per 100 000 in non-Aboriginal children younger than 5 years.1 A conjugate Hib vaccination program was introduced in Western Australia in January 1993, before a nationwide program commenced in July 1993. Subsequent marked declines in incidence of Hib meningitis have been reported.2-4 However, there are no recent reports on trends in overall admissions for meningitis. The WA Data Linkage System (WADLS) encompasses statewide population-based record linkage of the statutory birth and death registers, midwives’ notification system, and hospital morbidity database,5 and is one of few such resources worldwide. As part of a larger study to determine the burden of infection in a cohort of births between 1990 and 2000 using the WADLS, we investigated hospitalisation for all-cause meningitis (International classification of diseases, 9th revision, diagnosis codes 003.21, 036.0, 047, 049.0, 054.72, 320-322) in 17 296 Aboriginal and 252 775 non-Aboriginal children younger than 2 years between 1992 and 2000. In Aboriginal infants (< 12 months), the meningitis rate fell by 41% between 1992 and 1993–1994 and by a further 54% in 1995–1996, and has remained stable since (Box). In Aboriginal children aged 12–23 months, rates declined by 44% between 1993–1994 and 1995–1996 and again by 50% in 1997–1998, and no meningitis admissions were reported in 1999–2000. In non-Aboriginal infants, meningitis rates declined by 36%, from 1.8 per 1000 child-years in 1992 to 1.2 per 1000 child-years in 1993–1994, with a further 50% decline in 1997–1998, since when rates have remained stable. Rates declined by 57% between 1992 and 1993–1994 in non-Aboriginal children aged 12–23 months, declined a further 47% in 1995–1996, and have since remained stable at about 0.2 per 1000 child-years. With the decline in meningitis admissions, the disparity between Aboriginal and non-Aboriginal children has narrowed: the relative rate (RR) of Aboriginal to non-Aboriginal meningitis admissions fell from 7.3 in 1992 to 5.0 in 1999–2000 in infants, while in children aged 12–23 months, the RR was > 7.0 in 1993–1996, fell to 3.0 in 1997–1998, and was indefinable in 1999–2000 (Box). In the absence of other relevant interventions, we attribute declines in meningitis admissions to the introduction of Hib vaccine. This is supported by other studies showing a reduction in Hib meningitis following vaccination.2-4 Retrospective data provide an opportunity to assess overall trends in admissions. Future linkages with immunisation and laboratory data will allow us to investigate pathogen-specific admissions and evaluate vaccination programs. Our findings show that substantial improvements can be achieved given government commitment to implement appropriate preventive measures. Adequate funding and continued commitment is needed to ensure these measures are accessible to all WA children. Hospital admission rate for meningitis in Aboriginal and non-Aboriginal children aged (a) < 12 months and (b) 12–23 months in Western Australia, 1992–2000 Relative rate of Aboriginal to non-Aboriginal admissions is shown at the top of each graph.

Hannah C Moore · Deborah Lehmann

Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150 000 IU may be considered. Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/day if 1–12 months of age; 5000 IU/day if > 12 months of age). High-dose bolus therapy (300 000–500 000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Craig Munns MB BS, PhD, FRACP · Margaret R Zacharin MB BS, FRACP · Christine P Rodda MB BS, PhD, FRACP · Jennifer A Batch MB BS, MD, FRACP · Ruth Morley BA, MB BChir, FRCPCH · Noel E Cranswick MB BS, BMedSc, FRACP · Maria E Craig PhD, FRACP, MMed · Wayne S Cutfield BHB, MB ChB, MD · Paul L Hofman MB ChB, FRACP · Barry J Taylor MB ChB, FRACP · Sonia R Grover MB BS, FRACOG · Julie A Pasco BSc(Hons), PhD · David Burgner MB ChB, PhD, FRACP · Christopher T Cowell MB BS, FRACP