Women's health

Clinical Record A 30-year-old woman in the 30th week of pregnancy was admitted with a two-day history of fever, malaise, dysuria, frequent micturition and mild lower abdominal pain. Slight lower abdominal tenderness was the only clinical abnormality. Results of urine microscopy were white blood cell (WBC) count, 33 × 106/L (normal range, 0–10); red blood cell count, 15 × 106/L (normal range, 0–12); epithelial cell count, 21 × 106/L (normal range, 0–5); and culture was sterile. Full blood count revealed haemoglobin, 113 g/L (normal range, 100–180); WBC count, 11.6 × 109/L (normal range, 5–18); platelet count, 215 × 109/L (normal range, 150–450); and lymphocyte count, 0.23 × 109/L (normal range, 2–8). Liver function tests were mildly abnormal at presentation (Table). The patient was treated with empirical ampicillin and gentamicin, with resolution of her symptoms. However, her liver function tests worsened. Leptospiral serology was negative and blood cultures were sterile. Hepatitis A, B and C, flavivirus, Ross River virus, cytomegalovirus, Epstein–Barr virus, HIV, parvovirus and toxoplasmosis were all excluded. Negative antinuclear, mitochondrial and smooth muscle antibodies and normal immunoglobulin levels indicated that autoimmune hepatitis was unlikely. From the fifth day after admission, her condition deteriorated, with marked upper abdominal pain and worsening liver function tests (Table). On admission to the intensive care unit she was confused, febrile (37.5°C) and tachycardic (112/min). Blood pressure was 105/70 mmHg and results of cardiorespiratory examination were normal. Right hypochondrial tenderness was present. There were no clinical stigmata of hepatic decompensation. Results of laboratory tests (Day 7) were international normalised ratio of prothrombin time, 1.7 (normal, < 1.2); lymphocyte count, 0.57 × 109/L; leukocyte count, 3.1 × 109/L; and liver function tests as shown in the Table. Renal function and platelet counts were normal. Delivery was deemed necessary to preserve the baby's life. A live baby was delivered by caesarean section (Day 10). There were no orogenital lesions on the mother. The baby was well, with no clinical abnormalities. After the caesarean section, the patient remained stable for 24 hours and then suffered progressive circulatory insufficiency. Despite escalating doses of vasopressors, she developed renal failure. Bilateral pneumonia and pleural effusions led to respiratory failure, and the patient was intubated for assisted mechanical ventilation. Results of liver function tests (Table) confirmed worsening of disordered hepatic synthesis, progressive hepatocellular injury and coagulopathy. An abdominal computed tomography scan revealed gross hepatomegaly, with diffuse low attenuation of the left lobe of the liver and mottling of the right lobe of the liver. Liver biopsy, precluded by coagulopathy during the caesarean section, was accomplished on Day 13. Histology revealed hepatic necrosis, with 40%–50% of the hepatic parenchyma showing haemorrhagic necrosis with a neutrophilic infiltrate (Box 1A). At the interface between necrotic areas and surviving parenchyma, many liver cells showed glazed amphophilic chromatin consistent with herpesvirus inclusions. Polyclonal herpes simplex virus immunoperoxidase stain showed strong nuclear staining in these cells (Box 1B). Polymerase chain reaction testing of her serum subsequently revealed herpes simplex virus (HSV) DNA and HSV 2 was cultured from a vaginal swab. The patient was treated with intravenous aciclovir (750 mg every 8 h), but remained critically ill, with persistent circulatory shock, anuric renal failure and fulminant hepatic failure. Enterococcus faecalis bacteraemia compounded her shock. On Day 25, she died of fulminant hepatitis and multiorgan failure. Autopsy revealed severe hepatic architectural distortion, with almost complete absence of portal tracts and central veins. The necrotic foci were more extensive than those seen at biopsy. HSV immunohistochemical stain showed cytoplasmic staining. Interstitial pneumonitis and autolysis of the kidneys were seen, with no evidence of glomerulonephritis. Viral inclusions were seen only in the liver. Her infant was treated empirically with aciclovir and is growing and developing normally. Days after admission Normal range 1 4 7 10 13 16 19 25 Serum aspartate transaminase (U/L) 7–56 66 919 1738 3814 2499 1592 144 103 Serum alanine transaminase (U/L) 7–56 62 558 522 700 443 335 77 25 Bilirubin (µmol/L) < 17 8 10 11 24 47 68 400 600 Albumin (g/L) 35–45 20 15 12 17 14 15 18 16 Serum alkaline phosphatase (U/L) 30–120 123 333 378 471 345 294 155 125 Serum γ-glutamyltransferase (U/L) 10–75 16 76 105 126 100 71 28 25 Many pregnancy-specific liver disorders occur in the third trimester; thus, an aetiological diagnosis of liver diseases can be difficult. Common liver disorders in pregnancy are intrahepatic cholestasis of pregnancy, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), and acute fatty liver of pregnancy. The commonest cause of jaundice in pregnancy is acute viral hepatitis, which can result from primary infections with hepatitis viruses A to E or as part of a systemic infection with viruses such as cytomegalovirus, Epstein–Barr virus, varicella zoster virus and herpes simplex virus (HSV).1 Except when caused by hepatitis E virus or HSV, viral hepatitis does not usually increase maternal or fetal mortality.2 Hepatitis due to HSV infection is a rare but frequently fulminant disease. Most reports have been in immunocompromised patients3 or newborns.4 Fulminant HSV hepatitis has been reported in immunocompetent adults,5-7 mostly pregnant women.8-10 Two per cent of susceptible women acquire HSV infection during pregnancy, and seroconversion can be asymptomatic.6 Most reported cases of HSV hepatitis followed a primary orogenital infection with HSV type 1 or 2.5,8-10 As in our patient, the reported cases included initially normal serum bilirubin levels, markedly elevated serum transaminase levels, and very high AST/ALT ratios. In our patient, liver histology and immunohistochemistry established the diagnosis. Serology, PCR and vaginal swab cultures were complementary. Early administration of aciclovir has been successful in treating HSV hepatitis.5,7 Liver transplantation is another treatment option,11 but the risk of recurrent HSV hepatitis with overwhelming viral dissemination and concurrent enterococcal sepsis were contraindications in our patient. A high index of suspicion for HSV infection is warranted, as hepatitis can occur without orogenital herpetic lesions. HSV serology, PCR testing for HSV DNA, and vaginal swab cultures are recommended in undifferentiated liver disorders. Liver biopsy should be considered in patients with hepatitis when a definitive aetiology is elusive. Empirical treatment with aciclovir should be considered. 1: Photomicrographs of liver biopsy A: H&E stain, showing significant necrosis of liver parenchyma (lower and lateral edges of micrograph); typical intranuclear herpesvirus inclusions are visible (arrow). Nuclear chromatin is completely effaced and is darkly amphophilic and glazed. Viable hepatocytes are seen uppermost in the photomicrograph. Magnification × 400. B: Immunohistochemical stain for herpes simplex virus, showing strong positive intranuclear staining. Magnification × 400. 2: Lessons from practice Herpes hepatitis can occur without preceding orogenital lesions. Diagnostic tests for herpes simplex infection should be performed in patients with fulminant hepatic failure. Detection of HSV DNA by the polymerase chain reaction, and histological examination of liver tissue, are diagnostic. Empirical treatment with aciclovir may be indicated in patients with liver failure where the aetiology is unclear.

Ramesh Nagappan MD, FRACP · Geoffrey Parkin MB BS, FFICANZCA · Ian Simpson MB BS, FRCPA · William Sievert MD, FRACP

To the Editor: The recent article by the Obstetric Medicine Group of Australasia alluded to the increasing relevance and importance of thrombophilia screening following adverse pregnancy outcomes, namely recurrent miscarriage, stillbirth, retarded intrauterine growth and pre-eclampsia.1 Formerly, these outcomes were generally attributed to "placental insufficiency", where a cause was not readily identified. Screening for disorders in the uteroplacental circulation after such adverse pregnancy outcomes was formerly confined to investigations for an autoimmune basis, such as antinuclear antibodies, anticentromere antibodies, anti-DNA antibodies and the lupus inhibitor. However, in recent years, it has become more apparent that inherited or acquired thrombophilias may play a significant role in certain adverse pregnancy outcomes.2-5 Reports from Israel2,3 and elsewhere have suggested that thrombophilias can be found in up to 65% of women with recurrent pregnancy loss of unknown cause, as well as in cases of intrauterine growth retardation, stillbirth, placental abruption and pre-eclampsia. It is also known that certain thrombophilic factors are more likely to produce thrombogenic changes and hence are possible deficiencies in the uteroplacental circulation. Preliminary work has shown that treating women who have had recurrent pregnancy loss complicated by thrombophilia with antithrombotic agents (low molecular weight heparins) is beneficial, with improved pregnancy outcomes in a significant number of these cases.3 With the growing understanding of the role of thrombophilias in pregnancy, it seems that thrombophilia screening will assume a more prominent role in investigating patients after recurrent miscarriage, stillbirth, intrauterine growth retardation and pre-eclampsia.

David Morgans

In 1991, the "organised approach to preventing cancer of the cervix" recommended Pap smears every two years for women aged 18–70 years who have ever been sexually active. The two-year interval was a compromise step towards the scientifically supported three-year interval, as many influential groups were strongly attached to annual screening. When other components of the organised approach were in place, the policy was to be reviewed. Since the safeguards in the "organised approach" have been proven effective, it is appropriate to change the policy to recommend a three-year interval. Increasing the interval would allow more resources to be allocated to enrolling women currently underscreened and to evaluating and improving the program. The age of commencing smears could also be reconsidered to reflect the balance of potential benefits and harm in young women, for whom cancer is very rare but follow-up investigation common. If consensus is not reached within the profession, an evidence-based decision may need to be made at the political level.

James A Dickinson FRACGP, PhD

John St George was born in Malaya on 2 December 1924. His family returned to Ceylon in 1925, where he studied at St Patrick's College in Jaffna. In 1950, he graduated with Honours in medicine from the University of Ceylon in Colombo. Between 1957 and 1959, John worked with Professor T Jeffcoate at the University of Liverpool, UK, then with Dr P Myerscough at the Eastern General Hospital, Edinburgh. He was accepted as a Member of the Royal College of Obstetricians and Gynaecologists (1958) and a Fellow of the Royal College of Surgeons (1959), the International College of Surgeons (1968), and the Royal College of Obstetricians and Gynaecologists (1970). After working as a Consultant in Obstetrics and Gynaecology for the Government of Ceylon from 1959 to 1964, John spent a number of years (1964–1967 and 1972–1975) as Chief Consultant in Obstetrics and Gynaecology for the government of northern Nigeria. It was there that he perfected his technique of vesicovaginal fistula repair. These fistulae, which are relatively common among rural women, arise from obstructed labour or from application of potassium permanganate by "bush doctors" (local herbalists). While in Nigeria, John initiated the obstetric "flying squad" to enable women in remote areas to receive emergency medical treatment, and helped to invent a two-wheel collapsible trolley for bush track roads to help reduce maternal mortality. In 1974, the London School of Hygiene and Tropical Medicine awarded him the Langley Memorial Prize for this work. In 1975, John migrated to Australia and set up practice at Burwood and Lakemba, in Sydney, working as a gynaecologist at the Western Suburbs Hospital until 1993. He retired in 1998. John was passionately interested in sports and the Church. From his early years at St Patrick's College, where he was the captain of both the athletics and soccer teams, he took to heart the College's motto "fide et labore" (faith and work). He based his entire life on this simple yet profound philosophy, which saw him succeed in his career and adapt to many different cultures and countries with ease. John died peacefully (of hypostatic pneumonia) at Concord Hospital on 9 December 2001, at the age of 77.

Lourdes I St George LRCPS FRCOG FRACOG

A 34-year-old woman (gravida 5, para 2) presented to the Government Hospital in Katsina, northern Nigeria, in 1973. She was in labour and had had no antenatal care. She successfully delivered a live 3.2 kg infant. A 14 cm right adnexal pelvic mass was noted postnatally. An x-ray and hysterosalpingogram (see picture) performed four months after the birth showed the calcified remains of an extrauterine pregnancy. The woman stated that four years earlier she had missed her periods and had consulted a "bush doctor" (local herbalist) about abdominal swelling and pain. The herbs he prescribed to rub on her abdomen had eased the pain, and her periods had returned after seven months. The mass was easily removed from the omentum at subsequent laparotomy. Histology confirmed an advanced lithokelyphopaedion (ie, calcified fetus, membranes and placenta).

Lourdes I St George LRCPS, FRCOG, FRACOG · John St George FRCS, FRCOG, FRACOG

The latest triennial review of maternal deaths showed a rise in the maternal death ratio. Whether this represents a new trend or just a statistical fluctuation remains to be seen. The Report on maternal deaths in Australia, 1994–961 was released in September 2001. It is the eleventh in a series of triennial reports that detail maternal deaths in a case summary format. The principal aim of the Report is to improve the quality and safety of healthcare during pregnancy and the puerperium through the education of obstetric practitioners. The Report defines a "maternal death" as the death of a woman while pregnant or within 42 days of the pregnancy being delivered or terminated, and classifies maternal deaths occurring in Australia into three categories: Direct deaths, resulting from obstetric complications of the pregnant state; Indirect deaths, resulting from pre-existing disease or disease that developed during pregnancy and was not due to obstetric causes, but which may have been aggravated by the physiological effects of pregnancy; and Incidental deaths, due to condition(s) occurring in pregnancy, in cases where the pregnancy is unlikely to have contributed significantly to the death. The current Report documents the first rise in the maternal death ratio in Australia since the 1988–1990 triennium — a rise from 10.9 deaths per 100 000 confinements in 1991–1993 (total number of deaths, 84) to 13.0 deaths per 100 000 confinements in 1994–1996 (total number of deaths, 100). Of particular concern is the finding that the rise in the number of deaths was almost exclusively in the "direct deaths" category (see Box). However, as the rise was non-significant in a statistical sense, we will not know, until the next two triennial maternal death reviews are completed, whether this represents the beginning of a new trend or just a statistical fluctuation in very rare events. Although a high proportion of the direct deaths (22/46 [48%]) involved the presence of avoidable or preventable factors, the lack of uniform assessment of avoidable factors across all States and Territories, and the absence of any single factor that could account for the rise in deaths, suggests the apparent increase in avoidable factors should be interpreted with caution. The disparity between Indigenous and non-Indigenous maternal mortality rates has previously been observed2 and remains an issue of concern. The Indigenous maternal mortality rate did decline, from 41.4 to 34.8 deaths per 100 000 confinements, between the 1991–1993 and 1994–1996 reviews. However, changes in ascertainment of Indigenous status over the past nine triennia make it difficult to determine whether there has been a consistent decline, particularly among direct Indigenous maternal deaths. A number of factors may have contributed to the increase in deaths in the most recent triennium. In other countries,3 improved ascertainment of maternal deaths through the use of multiple data sources, including vital statistics and hospital morbidity collections, has resulted in the identification of more deaths. However, in the latest Australian Report, only three of the 12 deaths identified using additional data sources were direct deaths. The changing risk profile of women becoming pregnant may account for some of the increase in deaths. Many women are delaying child-bearing,4 leading to an older cohort of women being pregnant and at increased risk of maternal death.5 Furthermore, with advances in technology an increasing number of women who previously were unable to have children because of infertility or complex medical problems are now having children. Also to be considered is the largely unevaluated impact on maternal death rates of the implementation of multiple models of delivery of obstetric care as well as the larger structural changes in healthcare delivery. Both require further investigation. Despite recent publicity to the contrary, the rise in maternal deaths does not appear to be attributable to the increasing caesarean section rate. The proportion of maternal deaths associated with caesarean section has remained higher than the proportion of all caesarean births over the past four triennia. However, despite rising caesarean section rates (18.4% of all births in 1991–1993 and 19.4% in 1994–1996), maternal deaths associated with caesarean section, excluding those on recently dead or moribund women, fell from 29.8% of deaths in 1991–1993 to 24.0% in 1994–1996. There are no data causally relating the rising caesearan section rate with the increase in the number of maternal deaths. With a small number of deaths from a range of very different causes, it is difficult to draw meaningful conclusions about the impact of the many factors purported to relate to maternal death in Australia. Furthermore, without the availability of the 1997–1999 and probably the 2000–2002 results, it cannot be determined whether the increase in deaths represents a new trend or merely an aberration. Overall, the risk of maternal death during pregnancy and the puerperium remains small. Although differences in definition and collection procedures make international comparisons difficult, Australia appears to compare well with other developed countries, having a similar adjusted maternal mortality ratio to Canada, and a lower ratio than New Zealand, the United States and the United Kingdom.6 With improved general health status and family planning and increased access to general and specialised healthcare, maternal mortality declined considerably in the 20th century. Nevertheless, life-threatening complications still occur, often unpredictably and relatively more often among Indigenous women. It is therefore important that we closely monitor and review all maternal deaths and develop a surveillance system for severe maternal morbidity to ensure the health and safety of all women during pregnancy and the puerperium. The inclusion of pregnancy tick-boxes on Australian death certificates and the use of a standardised national maternal death reporting form should facilitate more accurate reporting of maternal deaths in the future. Summary of key findings from the Report on maternal deaths in Australia, 1994–961 The 1994–1996 Australian maternal mortality ratio was 13.0 per 100 000 confinements, compared with the 1991–1993 ratio of 10.9 per 100 000 confinements. In the 1994–1996 triennium, there were 100 maternal deaths, of which 46 (46%) were direct deaths, 20 (20%) were indirect deaths and 34 (34%) were incidental in nature. This represented an increase of 19% in the number of deaths compared with the 1991–1993 triennium. The increase in deaths occurred almost exclusively in the direct deaths category: 27 (32%) direct deaths were reported in the 1991–1993 triennium, compared with 46 (46%) direct deaths in 1994–1996. There was an increase in the proportion of direct maternal deaths in which avoidable factors were considered to be possibly or certainly present from 7 (26%) of 27 deaths in 1991–1993 to 22 (48%) of 46 deaths in 1994–1996. The principal causes of direct maternal deaths remained pulmonary embolism (8 deaths [17%]), amniotic fluid embolism (8 deaths [17%]) and pre-eclampsia (6 deaths [13%]). Cardiorespiratory disease was the most common cause of indirect maternal death, with 10 (50%) indirect deaths falling into this category, while the leading causes of incidental death were injuries (16 deaths [47%]), neoplasms (5 deaths [15%]) and cerebrovascular disease (4 deaths [12%]). The Indigenous maternal mortality ratio (34.8 deaths per 100 000 confinements) remains about three times that of the non-Indigenous maternal mortality ratio (10.1 deaths per 100 000 confinements).

William AW Walters FRCOG FRANZCOG PhD · Jane B Ford BA (Hons) PhD · Elizabeth A Sullivan MPH FAFPHM · James F King

Objectives: To assess the intentions of Australia's specialist obstetricians to cease practice and their reasons for abandoning this specialty.Design: A structured questionnaire posted to Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), issued 11 July 2001 with a return date of 31 July 2001 (in practice, responses were accepted up to 31 August 2001).Participants: Australian specialists holding a Fellowship of the RANZCOG.Main outcome measures: Demographic data (eg, age, sex); type and location of practice; past, current and intended future obstetric practice; reasons for stopping practice; cost of indemnity premiums; experience of litigation and its influence on practice; and experience in giving medicolegal opinion.Results: The response rate was 74% (829/1116), with 826 responses fulfilling our selection criteria. The median number of years since admission as a Fellow was 17 (range, 1–47 years), and 19% (158/817) of respondents were women (9 people did not specify their sex). Of the 826 respondents, 596 (72%) were currently practising obstetrics, 548 (66%) intended to still be practising after one year, 365 (44%) intended to be practising after five years, and 196 (24%) intended to be practising after 10 years. The median indemnity premium in 2001–02 was $35 515 (range, nil to $156 000) for practising obstetricians. The main reasons given for ceasing obstetrics were intention to specialise in gynaecology, fear of litigation, high indemnity costs, family disruption, and long working hours. About two-thirds of respondents (557/818) had experienced the threat of litigation, and almost all (768/803) desired some type of "no-fault" indemnity scheme. Thirty-three of the 314 respondents who had given medicolegal opinions accounted for 71% of the total number of opinions. Many of these were non-practising obstetricians who were not accredited RANZCOG expert witnesses.Conclusion: There will soon be a shortage of experienced practising obstetricians in Australia.

Alastair H MacLennan MD, FRANZCOG · Michael K Spencer BSc(Hons), LLB(Hons)

Preamble: the burden of osteoporosis in Australia The clinical manifestations of osteoporosis affect nearly two million Australians.1 In the absence of interventions, the prevalence of osteoporosis-related conditions is predicted to increase over the next two decades from 10% of the population currently to 13.2% by 2021.1 The incidence of osteoporotic fractures is also predicted to increase, from one every 8.1 minutes in 2001 to one every 3.7 minutes in 2021. Total costs relating to osteoporosis are currently estimated at $7.4 billion per annum, of which $1.9 billion are direct costs. Its disease burden can be expressed in terms of premature mortality and disability, which together represented over 25 000 healthy years of life lost to Australians in the financial year 2000–01.1 In Australia there are three ongoing prospective cohort studies of fracture epidemiology: The Dubbo Osteoporosis Epidemiology Study (DOES) of a cohort of about 1600 men and 2100 women aged over 60 years with pre-fracture assessments;2 The Geelong Osteoporosis Study (GOS) of about 109 900 men and women aged over 35 years;3 and The Tasmanian Older Adult Cohort (TASOAC) study of about 229 600 men and women of all ages.4 The participants in these studies were selected because their age and sex distribution were considered to reflect the Australian population. Importantly, each study used substantially the same method for capturing "events", namely x-ray reports containing the word "fracture" in radiology service records in each region. These studies provide different estimates of the number of fractures occurring in Australia. DOES reported 306 fractures in 3.25 years (1989–1992), giving an estimated residual lifetime fracture risk of 29% for men and 56% for women aged over 60.5 TASOAC reported 2140 fractures over two years (1997–1999), with an estimated residual lifetime fracture risk of 27% for men and 44% for women aged over 50.4 GOS reported 2184 fractures over two years (1994–1996), with an estimated lifetime risk of fracture of 42% in women aged over 503 (the estimate for men is not yet available). From these studies, the total number of fractures each year among Australians aged over 60 has been estimated at 73 000 (DOES), 57 000 (TASOAC) and 51 000 (GOS). Using a different methodology, Access Economics has estimated there were 65 000 osteoporotic fractures in Australia in 2001.1 Using the GOS estimates, it is calculated that the total number of hip fractures in Australia will increase from 15 000 in 1996 to 21 000 by 2006.6 In 1996, the Pharmaceutical Benefits Advisory Committee of the Commonwealth Department of Health and Family Services sponsored a Consensus Conference on Osteoporosis. Since then there have been advances in our understanding of the epidemiology, pathogenesis, diagnosis and treatment of osteoporosis. Accordingly, Osteoporosis Australia and the National Prescribing Service convened a Fracture Prevention Summit in September 2001. The aims were to estimate the size of the problem of osteoporosis and to formulate appropriate practice in primary care, with special emphasis, where possible, on evidence-based guidelines for the treatment of osteoporosis. The National Health and Medical Research Council (NHMRC) levels of evidence (see Box, this page) are a useful guide for defining the quality of available data on the treatment of osteoporosis. The most important criteria for a high-quality trial include randomisation, placebo controls, double-blinding, large sample sizes, prolonged observation, low dropout rates, preplanned intention-to-treat analyses, and replication. Replication and internal consistency are particularly important, as low event rates will often result in wide confidence intervals and type 2 errors (ie, failing to detect a difference when it is really present). Meta-analyses should be done to adequately define the point estimate of outcomes such as fracture risk reduction. Uncritical acceptance of reported "significant" results when a study is poorly designed and executed creates uncertainty and is not useful in decision-making in clinical practice. Lack of rigorous design in a drug trial does not mean a drug is necessarily ineffective, only that there is not good evidence to support the hypothesis that it is effective. Whether one drug has better antifracture efficacy than another can not currently be determined, as there have been no comparator trials using antifracture efficacy as an endpoint. Most trials compare a group treated with a single drug with a control group receiving a placebo (calcium). Rating of the evidence for recommendations Evidence is graded according to the level-of-evidence classifications endorsed by the National Health and Medical Research Council (NHMRC) in 1995.* E1 Level I: Evidence obtained from a systematic review of all relevant randomised controlled trials. E2 Level II: Evidence obtained from at least one properly designed randomised controlled trial. E3 Level III: Evidence obtained from all well designed controlled trials without randomisation; well designed cohort or case–control analytic studies, preferably from more than one centre or research group; or from multiple time series with or without intervention. E4 Level IV: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees. * A guide to the development, implementation and evaluation of clinical practice guidelines. Canberra: National Health and Medical Research Council, 1995. Summary of key recommendations Diagnosis Measurement of bone mineral density (BMD) of the hip and spine should be used to diagnose osteoporosis and for monitoring response to interventions. Wider availability of Medicare Benefits Schedule (MBS) rebates for bone densitometry items, particularly for older people and those with a family history of osteoporosis, is recommended. Biochemical markers of bone turnover provide additional information to assess fracture risk. The finding of an elevated bone resorption marker in addition to low BMD strengthens the case for treatment in an individual. In selected patients, biochemical markers may have a role in assessing therapeutic response and enhancing compliance. Initiation of treatment The presence of a spinal fracture is an indication that treatment should be given, provided that BMD is in the range for "osteoporosis" (T-score < –2.5) or "osteopenia" (T-score between –1 and –2.5) (see Box 1). If a non-spinal fracture is present, treatment should be considered if BMD is in the osteoporosis range (T-score < –2.5). However, prospective studies evaluating the antifracture efficacy of drugs in patients with osteoporosis and non-spinal fractures at baseline are not available. Women with osteoporosis (T-score < –2.5), with or without fractures, should be investigated and considered for treatment. Evidence in men is limited, and recommendations must await further research. First-line drug therapies for postmenopausal women with osteoporosis The potent bisphosphonates alendronate and risedronate are the first-line agents for treating postmenopausal osteoporosis. For women with osteoporosis and one or more baseline spinal fractures, treatment with these bisphosphonates reduces the relative risk of subsequent spinal fractures by approximately 50% (E1). It also reduces the risk of non-spinal fractures, including hip fractures. These potent bisphosphonates can reduce bed-day use and healthcare costs (E2). Treatment with raloxifene is an alternative first-line approach to prevent spinal fractures, but not non-spinal fractures. A dose of 60 mg daily is associated with a 36% reduction in the relative risk of spinal fractures (but not non-spinal fractures) over four years (E1). The anabolic agent parathyroid hormone (PTH) is associated with a 65% reduction in the relative risk of spinal fractures in women who have osteoporosis and one or more baseline spinal fractures (E2). It also reduces the relative risk of non-spinal fractures. Although not yet available in Australia or elsewhere, it is likely to become first-line therapy in patients with severe osteoporosis given its marked effect on bone structure. Other drug therapies for postmenopausal women with osteoporosis Other, less rigorously evaluated agents include etidronate, a less potent bisphosphonate, and hormone replacement therapy (HRT). Both agents are likely to reduce the risk of spinal fractures (E3). A reduction in non-spinal fractures is not well established. There is weak evidence for the efficacy of calcitriol in reducing fracture risk in women with postmenopausal osteoporosis (E3). There are no randomised controlled trial (RCT) data to support a role for anabolic steroids such as nandrolone in reducing the risk of fractures. 1: Explanation of T- and Z-scores, with World Health Organization thresholds Relationship between hip bone mineral density (BMD) and age in women, showing the difference between: (i) Z-score (number of SDs from population mean for age). Z = –2.0 to +2.0 is the reference range; and (ii) T-score (number of SDs from mean for a young, healthy population). A T-score of –2.5 is defined as the threshold for osteoporosis. • Indicates a woman aged 70 years with a BMD Z-score of –1, which is within the reference range for age. However, this Z-score means the woman has double the risk of fracture compared with a 70-year-old woman with mean BMD for age. Further, her T-score is –2.5, indicating her BMD is at the threshold for osteoporosis (adapted from Prince7). Calcium and vitamin D Dairy products are the largest source of calcium in the diet. Increased calcium intake, from dietary sources or supplementation, should always be adjunctive therapy in the treatment of postmenopausal osteoporosis (E4). Studies suggest that calcium monotherapy has a modest effect in reducing fracture incidence. Vitamin D, alone or in combination with calcium, reduces the risk of non-spinal fractures in institutionalised elderly people (E2), among whom there is generally a high prevalence of vitamin D deficiency. A calcium–vitamin D combination is recommended for such people. Exercise Engaging in regular exercise, to maximise peak bone mass and prevent age-related and menopause-related bone loss, is a potentially important approach to reducing fracture risk (E4). However, there is currently no RCT evidence supporting the efficacy of exercise in preventing fractures at any specific site. Exercise increases muscle strength and may improve coordination and balance and reduce the risk of falls. Evidence that the reduction in falls leads to fewer fractures is not currently available. Fall-prevention strategies and hip protectors Fall-prevention programs that involve balance training and environmental modifications reduce the risk of falls (E2). Hip protectors prevent hip fractures in people at high risk of falls, but compliance remains an issue (E1). Therapies for osteoporosis in men Alendronate or etidronate are the drugs of choice for men with primary osteoporosis (E2). Testosterone replacement therapy is indicated in men with hypogonadism (E3). There is no evidence to support the use of calcitriol for osteoporosis in men. Men with osteoporosis should be considered for investigation and treatment. Therapies for glucocorticoid-induced osteoporosis Postmenopausal women and older men receiving glucocorticoids are at the greatest risk of spinal fracture and should be considered for prophylaxis, usually with a bisphosphonate plus calcium as the first choice (E1). Adjunctive therapy with some form of vitamin D should also be considered. Other strategies to reduce the fracture burden As the risk of fracture increases after the first fracture and the initial osteoporotic fracture often goes undiagnosed and untreated, education and awareness programs are one key strategy to increase rates of treatment in people who have already sustained an osteoporotic fracture. Liaison with orthopaedic units to ensure patients with fractures are adequately investigated and treated is recommended. Secondary prevention by special clinics in teaching hospitals or initiatives in primary care are another strategy that may increase treatment rates in people who have sustained their first osteoporotic fracture. Specific programs are needed to address the high prevalence of vitamin D deficiency in elderly people in both residential care and the general community. Public health prevention strategies, including increasing dietary calcium intake from dairy sources and promoting exercise for people of all ages, are recommended. Wider availability of drugs under the Pharmaceutical Benefits Scheme (PBS) for subgroups at high risk of fracture, such as people with very low BMD or those using glucocorticoids, is recommended. Diagnosis Use of densitometry Dual-energy x-ray absorptiometry (DEXA) is the current "gold standard" for the diagnosis of osteoporosis. BMD predicts fracture risk. Each standard deviation reduction in femoral-neck BMD increases the age-adjusted risk of hip fracture by a factor of about two (range, 2.0–3.5) and the risk of any atraumatic fracture by almost the same amount (range, 1.7–2.4).8 Similarly, each SD reduction in lumbar spine BMD increases the risk of spinal fracture by a factor of about 2.3 (range, 1.9–2.8). Proximal femur BMD appears to be the best overall predictor of fracture risk, particularly as it is unaffected by osteoarthritis, which can spuriously elevate spine BMD values. DEXA is reliable, with a reported precision of about 1%. However, these precision data are obtained under idealised conditions — in clinical practice such values are rarely achieved. At a realistic clinical precision of 2%, a change of at least 5.6% between measurements is necessary to be 90% confident the change is real. In postmenopausal women, the rate of bone loss is generally 1%–2% per annum, and hence, in most patients, an interval of two years between scans is satisfactory, unless there is an accelerated rate of bone loss (eg, as a result of glucocorticoid medication), in which case yearly measurements may be warranted. BMD is expressed in terms of a "T-score", representing the number of SDs from the young normal mean BMD. Diagnosis based on bone densitometry, measured by DEXA and the T-score, provides a normal distribution of values as defined by a working group for the World Health Organization (see Box 1): 9 Normal bone density: T-score greater than –1; Osteopenia (low bone mass): T-score between –1 and –2.5; Osteoporosis: T-score less than –2.5. Population screening is inappropriatePopulation screening is a seemingly simple solution to the problem of fractures. Screening may appear to be justifiable: fractures are a public health problem, densitometry is a safe screening tool, BMD measurements identify high-risk individuals, and drugs are available that reduce fracture rates. So why not screen, and treat those at high risk? A BMD measurement should only be done if the decision to treat (or not to treat) is influenced by the result of the test. Thus, it is a valid and essential investigation in patients at high risk of osteoporotic fracture who seek medical advice, but not justified for screening a population of healthy people. At present, the decision to measure BMD in patients is supported by a Medicare rebate for certain high-risk categories only.10 The usefulness of population screening also depends on the prevalence of the disease and cost of the screening test. Screening of unselected populations (eg, using ultrasound in pharmacies) is not recommended by any authoritative group in the field of bone biology. Moreover, the definition of osteoporosis is not without problems. The BMD cut-off of –2.5 SD below the young normal mean used to define osteoporosis was developed to apply to DEXA measurements of BMD at the spine or hip. This cut-off value, when applied to other techniques such as ultrasound, quantitative computed tomography or forearm measurements, does not identify the same number or the same proportion of individuals.11,12 Moreover, reference ranges may differ between people of different ethnic origin. In summary, measurement of BMD by DEXA of hip and spine is the current gold standard for diagnosing osteoporosis and monitoring response to lifestyle interventions or pharmacological treatments. It should be used as part of patient care rather than screening. Biochemical markers of bone remodelling Several biochemical markers of bone turnover can be measured in serum and urine. Although measuring the levels of biochemical bone markers can not quantify total skeletal bone mass, it can provide additional information to assess fracture risk and may have a clinical role in measuring a patient's compliance and response to therapy. Serum and urine levels of several biochemical markers of bone resorption and formation have been used as surrogate endpoints for gauging drug efficacy. In women aged 75 years or older, urine C-telopeptide and free deoxypyridinoline crosslinks of type I collagen have been shown to be independent predictors of an increased risk of hip fracture, and their combination with low BMD is an even stronger predictor.13 Two other prospective studies, one of hip fractures in elderly women and the other of spinal and peripheral fractures in women closer to the menopause, have confirmed these observations.14,15 An elevated bone resorption marker in addition to low BMD strengthens the case for treatment in an individual. In clinical trials of HRT or bisphosphonates, the percentage decrease in bone turnover markers correlates with the change in BMD at two years.16,17 There is no good evidence that reduced levels of bone-turnover markers in response to therapy predict fracture-risk reduction. Treatment of osteoporosis in postmenopausal women The purpose of treatment is to reduce morbidity and mortality associated with the first fracture and all subsequent fractures. Treatment of osteoporosis is needed because (i) fractures are associated with significant morbidity and mortality; (ii) bone loss and fracture risk accelerate with advancing age; and (iii) treatments are available to prevent accelerated bone loss, slow the deterioration of microarchitecture and reduce the risk of fractures. Who to treat and when 1. Women with osteoporosis or osteopenia and fractures — treat Perhaps the single most easily recognised risk factor for osteoporotic fracture is the presence of any spinal18 or non-spinal fragility fracture. The risk for further spinal fractures increases 3–5-fold as the number or severity of prevalent deformities increases, rising to an 11-fold increase if three or more fractures are present. The risk of hip fracture increases after one or more spinal fractures. The risk of forearm fracture is higher if there has been a previous forearm fracture: of patients who had had a distal forearm fracture, 46% of women and 30% of men suffered further fractures over the following seven years.19 Moreover, in people having an incident fracture (with or without a prevalent [pre-existing] fracture at baseline), the risk of a further fracture is increased by 30%–40% within three years. Thus, if a spinal fracture is present, treatment should be given, provided that BMD is in the "osteoporosis" range (T-score < –2.5) or should be strongly considered if BMD is in the "osteopenia" range (T-score between –1 and –2.5). Values in the osteopenia range should not deter the clinician from proceeding with assessment and treatment — the lower the BMD, the greater the imperative to treat. If the T-score is above –1, assessment and investigation should proceed with a high index of suspicion that the fracture may be due to trauma or local pathology rather than bone fragility. Although there have been no RCTs of prevention of fracture in patients with non-spinal fractures and osteoporosis, it is likely that treatment would reduce future fracture rates. This is an area in need of further research, and studies designed to examine this are under way. 2. Women with osteoporosis without fractures — treat The aim of treatment is to prevent the first and all subsequent fractures safely and cost-effectively, reducing total morbidity and mortality. Women aged over 50 years with a T-score below –2.5 are already at increased risk for fracture. Even though the absolute risk of fracture in the ensuing five years may be low, menopause-related oestrogen deficiency will increase bone remodelling, prolong osteoclast life span, reduce osteoblast life span and increase the negative bone balance, thus accelerating bone loss and further increasing the risk. There is evidence that existing treatments can reduce the risk of fracture in these women. Trials of alendronate and raloxifene have been carried out in women who have osteoporosis but no prevalent fracture. Treatment reduces spinal fracture rates and, at least with bisphosphonates, the reduction in fracture rate is seen within 12–18 months.20,21 Data from alendronate studies indicate that a BMD T-score below –2.5 indicates a level of fracture risk comparable to that associated with a pre-existing low-trauma fracture. 21,22 The number needed to treat (NNT) to prevent a spinal fracture was 15 in women with a prior spinal fracture and 35 in women with low BMD without a prior fracture; for hip fracture, the NNTs were 81 and 90, respectively. Women with osteoporosis, even if they have no fractures, should be treated. 3. Women with osteopenia or normal BMD — defer treatment Should women with BMD T-scores between –1 and –2.5 but no prevalent fracture be treated? The issue in this group is that it comprises such a large proportion of women in the general population (estimated to be about 50% of all women over 50 years). In the Geelong Osteoporosis Study, 80% of the fractures occurred in women over 60 years; of the women under 60 years who had fractures, about 40% had osteoporosis and about 60% had normal BMD or BMD in the osteopenic range.3 As the majority of fractures occur after 60 years of age, it is difficult to justify treating large numbers of 50–60-year-old women with osteopenia, as the modest deficit in BMD and younger age confer only a low absolute risk of fracture over the following five years. When absolute risk is low, the NNT to prevent one fracture is large. Thus, large numbers of people would be exposed to the inconvenience of treatment, side effects and costs without likelihood of benefit. Early treatment may maintain or increase BMD, but most 50–60-year-old women are at low risk of an event, even if they have not received therapy. Few data are available on the antifracture efficacy of drugs in women with osteopenia, as most trials have been carried out in women with osteoporosis. For this reason alone, making recommendations for treatment of women with osteopenia is difficult and not evidence-based, and making recommendations about universal treatment of large sectors of the population at modest risk for fracture is inappropriate. In RCTs, bisphosphonates have been shown to reduce by about 50% the risk of spinal fractures in women with BMD T-scores between –1 and –2.5, but this was not statistically significant, as event rates were low.20 Although antiresorptive drugs (oestrogen, bisphosphonates, raloxifene) prevent bone loss, lifelong treatment of women from the age of 50 onwards can not be recommended except for those with osteoporosis. Drugs have not been shown to reduce fracture rates in women with normal BMD or in women with osteopenia but no fracture. 4. Women with other clinical risk factors for bone loss and falls — more data needed Risk factors are used in the clinical decision-making process, but there is limited evidence that women selected solely on the basis of risk factors for osteoporotic fractures or falls benefit from drug treatment. Risk factors that are common and have a large effect may be important for both the individual and the population. For example, suboptimal dietary calcium intake and vitamin D deficiency are important public health problems in Australia. Surveys of dietary calcium intake in Sydney, Dubbo and Geelong suggest that 75%–87% of premenopausal and postmenopausal women receive less than the recommended daily calcium intake of 800 mg/day (premenopausally) and 1000 mg/day (postmenopausally).23-25 Among older people and those with low exposure to sunlight, there is a high prevalence of vitamin D deficiency. For example, vitamin D deficiency has been found to be remarkably high among residents of hostels and nursing homes in Sydney and Melbourne. Whether calcium intake or vitamin D status can be altered in the whole population, and whether this would reduce the population burden of fractures, is unknown. However, on the basis of current evidence,26 calcium and vitamin D supplementation is recommended for nursing-home residents in Australia. How long should treatment continue? In principle, drug therapy should be continued indefinitely, because stopping treatment results in increased remodelling, bone loss, progression of structural damage and increased fracture risk. Most of the increase in BMD that is observed occurs within the first two years of treatment, although continued increases have been reported with alendronate beyond that time. The longest study of bisphosphonates has been for seven years.27 If BMD increases into the normal range, it may be reasonable to consider stopping treatment and monitoring bone turnover markers and rates of bone loss. However, further research is needed to address the optimal duration of therapy. Barriers to identification and treatment and case-finding strategies Although there are deficiencies in our knowledge of the barriers to identification and treatment of osteoporosis in primary care, some areas that have been identified include a doctor's knowledge, perception and interpretation of diagnostic methods. In a study on diagnosis and treatment of osteoporosis by primary care physicians compared with specialists, the records of 1743 patients who had undergone bone densitometry scans were reviewed. The study revealed that primary care physicians were less likely to recognise and treat osteoporosis than specialist endocrinologists or rheumatologists, as they had had less exposure to specific education about osteoporosis.28 Despite evidence that the incidence of further fracture increases markedly after the first fracture, most people (over 80% in Australia) who present with their first osteoporotic fracture fail to be investigated or treated.29 Initiatives to increase rates of treatment, such as specialised multidisciplinary hospital-based first-fracture clinics, in cooperation with Divisions of General Practice, are one approach to this problem. Orthopaedic surgeons should heighten their awareness of the need for secondary prevention after a fracture in people aged over 50 years. Barriers to identification, treatment and prevention of osteoporosis include inaccessibility of bone densitometry testing facilities and limited availability of subsidised medication. Patients and their treating practitioners require physical and financial access to bone densitometry testing facilities for effective clinical management. Current indications for bone densitometry under Medicare restrict access to densitometry,10 and PBS guidelines restrict the use of some agents to patients who have already had an osteoporotic fracture. Densitometry testing has been subsidised by the MBS for selected indications since 1994. This followed a comprehensive evaluation by the National Health Technology Advisory Panel, with input from the medical profession, mainly the Australian and New Zealand Bone and Mineral Society and the Australian Medical Association. In the year 2000, Medicare funded 110 737 densitometry services in Australia at a cost of $7.6 million. There is a case for expanded indications for densitometry that might include patients at high risk of fracture, such as older patients, or people with a family history of spinal or hip fracture in a first-degree relative.30 For over 50 years, Australia has had in operation a subsidised scheme for pharmaceuticals as part of a comprehensive national health cover for all residents. Of all pharmaceutical expenditure in Australia (including prescription and over-the-counter products), the PBS system pays about 50%. The cost-effectiveness of medications is relevant to whether they are PBS-listed. The relative risk reduction in the incidence of new spinal fractures associated with most anti-osteoporotic medications is fairly consistent at around 50%, regardless of baseline risk or history of fracture. The NNT to prevent a fracture varies with the absolute difference in fracture rates between treatment and control groups and is higher in groups whose baseline fracture risk is lower. However, RCT data suggest that the cost-effectiveness is comparable between people with bone density T-scores less than –2.5 and those with a pre-existing osteoporotic fracture. As over 90% of hip fractures result from a fall, people found to be at high risk of falls are a group worthy of further investigation. Simple assessments for falls risk have been developed that discriminate (with sensitivities and specificities of 75%) between "faller" and "non-faller" groups living in the community and in institutions.31,32 Evidence for specific therapies in postmenopausal women with osteoporosis Bisphosphonates Three bisphosphonates are available in Australia for the treatment of osteoporosis: alendronate, risedronate and etidronate. Alendronate has been reported to reduce the risk of single and multiple spinal fractures, asymptomatic (morphometric) and symptomatic spinal fractures in women with osteoporosis and one or more baseline spinal fractures (E1).22,33 Risedronate has also been reported to reduce the risk of single and multiple spinal fractures and morphometric spinal fractures in women with osteoporosis and one or more baseline spinal fractures (E1) (see Box 2).34,35 Alendronate halves the risk of spinal fractures in women who have osteoporosis without a pre-existing spinal fracture.20 No studies with risedronate in this population are available. Although the BMD response and the suppression of bone remodelling with alendronate 70 mg once weekly is no different from alendronate 10 mg daily,38 there are no fracture studies with the latter formulation. Etidronate may also prevent spinal fractures (E2), but problems in design, execution, and analysis make the results of existing studies difficult to interpret.39,40 2: Major fracture-prevention randomised controlled trials with bisphosphonates in postmenopausal women with osteoporosis The risk reduction with potent bisphosphonates is seen early, usually within 12 months. There is evidence that the reduction in spinal fracture risk with alendronate reduces bed-days, days of sickness and pain and healthcare costs.36 Non-spinal fracture rates are also reduced with alendronate and risedronate in patients with a prevalent spinal fracture (E1).33-35 Data for anti-hip-fracture efficacy are also available. In the alendronate trials there was consistency in hip-fracture risk reduction, but event rates were low and hip fracture was not a primary endpoint.20,22 In one risedronate trial,37 in which hip fractures were the primary endpoint and there were many events (232 hip fractures), there was a 40% reduction in hip-fracture risk among women aged 70–79 with a baseline femoral-neck T-score below –4 (or below –3 together with one non-skeletal risk factor for hip fracture) (E2). In women aged over 80 years and selected primarily on the basis of non-skeletal risk factors (such as poor gait or propensity to fall) but not low BMD, there was no significant reduction in hip-fracture risk overall. However, a recent analysis suggests that there was a reduction in intertrochanteric fractures in this group.41 Selective oestrogen-receptor modulators Selective oestrogen-receptor modulators (eg, raloxifene) are compounds that have oestrogen agonist activity at some sites and antagonist activity at others. RCTs of the effects of raloxifene have shown increases in bone density,42 but less than those reported with bisphosphonates or oestrogen. Despite this, in postmenopausal women with osteoporosis, raloxifene treatment has been found to be associated with a 36% reduction in the risk of one or more spinal fractures using a 60 mg daily dose for four years.21 Non-spinal fractures were not reduced, for reasons that are unclear. Raloxifene treatment is also associated with a 60%–70% reduction in risk of breast cancer43 and with reduced low-density- lipoprotein cholesterol and total cholesterol (the latter being surrogate endpoints for cardioprotection).42 An increased risk of venous thrombosis has been reported with raloxifene, similar to that seen with oestrogen. Raloxifene should be stopped if patients are immobilised for any prolonged period. Unlike oestrogen, raloxifene is not useful for control of menopausal symptoms, and indeed may worsen them. Raloxifene has also been shown to be effective in preventing postmenopausal bone loss,44 and can be considered as an alternative in women unable to take oestrogen for this indication. Currently, there are no RCTs with preplanned endpoints supporting the use of selective oestrogen-receptor modulators for the prevention of non-spinal fractures. Hormone replacement therapy Numerous RCTs have shown that oestrogen therapy can prevent bone loss in postmenopausal women (E1). Oestrogen is not only effective in preventing bone loss when given at or near menopause, but also continues to reduce bone loss for 10–15 years after menopause, with increases in bone density averaging 5% over three years.45,46 However, the paucity of trials demonstrating antifracture efficacy of HRT has led to questions about its value in the treatment of osteoporosis. Two recent meta-analyses of the effects of HRT on spinal and non-spinal fractures have reviewed 22 controlled trials of at least one year's duration in which HRT was compared with either placebo, no treatment, calcium, or vitamin D.47,48 In the pooled analysis, the relative risk of non-spinal fracture in women randomly assigned to receive HRT was 0.73 (95% CI, 0.56–0.94; P = 0.02). For hip and wrist fractures alone, the relative risk was 0.60 (95% CI, 0.40–0.91; P = 0.02). Significant effects were seen only in women under the age of 60.47 The finding that risk reduction was not significant in women over 60 was dependent on the inclusion of the HERS study,49 which involved relatively obese older women with cardiovascular disease who may not have had osteoporosis. For spinal fractures, the relative risk in women randomised to receive HRT was 0.67 (95% CI, 0.45–0.98; P = 0.04) and the effect was not confined to women under 60 years.48 Thus, although some positive data exist, there is a need for RCTs of the effect of HRT on spinal and non-spinal fractures. Ideally, oestrogen therapy should be continuous, not cyclical, and long-term. Women with a uterus should take oestrogen in combination with progestogens to protect against endometrial cancer. Progestogens may be given cyclically for 10–14 days each month in perimenopausal women or as continuous therapy combined with oestrogen in postmenopausal women. The latter treatment is more suitable for women who are more than two years postmenopausal, to prevent the initial irregular bleeding (normally seen with this regimen) being unduly prolonged. Tibolone, a synthetic steroid reported to have activity through oestrogenic, progestogenic and androgenic receptors, can also improve bone density.50 Moreover, it can be taken without unwanted progestogen-induced withdrawal bleeding. However, there are no data evaluating its antifracture efficacy. CalciumIt is important to realise that most RCTs discussed so far have used calcium as adjunctive therapy and compared a single treatment (plus calcium) with a calcium control group. Dairy products or calcium-enriched soy drinks represent the best source of calcium in the diet. Although there are other dietary sources, dairy products are the primary dietary source for most people. Three or more servings of dairy products per day, combined with a normal diet, should allow most individuals to achieve their recommended daily intake. Controlled trials of calcium as a monotherapy have found small but consistent effects of calcium on BMD (E1), averaging 1%–2% over two to three years and showing accumulation over time.51,52 Several studies have reported a significant beneficial effect of calcium monotherapy on fracture incidence.51,53-55 However, these findings should be interpreted with caution, as the studies were small and not powered to assess the effects of calcium supplementation on fractures. They may represent selective reporting of fracture results in that fracture data were probably recorded in other RCTs but not reported because no significant effect was found. The effect of this bias towards the reporting of positive results will only be addressed when adequately powered studies with fracture rate as the primary endpoint are undertaken. Vitamin D Vitamin D is better regarded as an endogenously produced pro-hormone than as an essential dietary constituent. It is produced in the skin as a result of sunlight exposure. With increasing age and frailty, vitamin D levels tend to decline, resulting in malabsorption of calcium and increased secretion of PTH, which in turn leads to accelerated bone loss. Physiological supplements of calciferol (eg, 400 IU/day) reduce PTH concentrations and lead to increases in BMD. Similar changes in biochemical endpoints can be achieved with regular sunlight exposure for 15–30 minutes daily. Two large studies have assessed the effect on fracture rates of calciferol supplementation alone. Lips et al56 reported no change in fracture incidence among 2578 community-dwelling men and women aged over 70 years who were randomised to receive calciferol 400 IU/day or placebo, whereas Heikinheimo et al57 reported that 150 000 IU/year of vitamin D reduced symptomatic fracture rates by 25% in a cohort of 800 elderly subjects in Finland. Two other studies have reported the effects of calcium plus calciferol given to elderly people. Chapuy et al26 reported a reduction of more than 25% in non-spinal and hip fracture rates in a cohort of 3000 elderly institutionalised women studied over three years. Dawson-Hughes et al58 reported a reduction of more than 50% in non-spinal fracture rates among 400 older men and women randomised to receive calcium 500 mg/day plus 700 IU vitamin D per day, or placebo. It is not possible to determine whether the calcium, the vitamin D or the combination were the essential components in the success of these two studies. However, the studies point to the possibility that a safe and inexpensive intervention with calcium and vitamin D may reduce morbidity among institutionalised elderly patients. Calcitriol Evidence is less straightforward for the vitamin D metabolite calcitriol. There are a number of studies demonstrating both small beneficial and small detrimental effects on BMD and reports of both increased and decreased numbers of fractures. A recent study of 489 postmenopausal women compared the effects of HRT and calcitriol over three years.59 HRT increased BMD by 3% at the femoral neck (P < 0.0001) and by 4.4% at the spine compared with placebo (P < 0.0001). By comparison, calcitriol had no significant effect on BMD at the femoral neck (0.1% increase; P = 0.57), but significantly increased BMD at the spine (1.7% increase; P = 0.01). An open-label trial of 622 women found a threefold reduction in new spinal fractures among women with postmenopausal osteoporosis treated with calcitriol compared with women receiving supplemental calcium60 — fracture rates remained stable in calcitriol-treated patients but increased in the calcium-treated patients. This study suffered from several design flaws, making the results difficult to interpret (E3). In summary, the paucity of available data from well-designed, large-scale RCTs provides only weak evidence for the efficacy of calcitriol as a treatment for postmenopausal osteoporosis. Parathyroid hormone The possibility that PTH might have an anabolic effect on bone has been explored over many decades. Recently, RCTs have confirmed that PTH substantially increases bone density and reduces the incidence of spinal and non-spinal fractures (E2). It is well tolerated in human studies, but there remains some concern based on long-term animal toxicology results. The largest study, involving 1637 postmenopausal women with prior spinal fractures, assigned participants randomly to receive placebo or one or two doses of subcutaneous recombinant human PTH over a median period of 19 months.61 New spinal fractures occurred in 14% of placebo-treated women versus 5% of women treated with 20 µg PTH. A 20 µg dose of PTH increased BMD by 9% (spine) and 3% (femoral neck) over and above the control group. Fracture-risk reduction with 20 µg PTH was 65% for spinal fractures and 55% for non-spinal fractures. Other drugs Androgenic steroids such as nandrolone have been widely used in Australia for management of osteoporosis. While there is some evidence of beneficial effects on bone density (E3),62 their antifracture efficacy is untested and there are no adequate safety data. Recently, anabolic effects of statins on bone have been reported in vitro and in animal experiments. However, observational epidemiological studies of bone density and fracture rates among statin users are conflicting and may be confounded by the metabolic abnormalities that led to statin use in the first place. Two RCTs of statin use in non-osteoporotic populations have failed to demonstrate an effect of statins on fracture risk.63,64 Plant constituents with a phenol structure similar to oestrogen are known as phyto-oestrogens. Epidemiological studies, primarily comparing Asian and Western populations, have been interpreted to indicate that a phyto-oestrogen-rich diet ameliorates oestrogen-deficiency symptoms in postmenopausal women and may protect against breast cancer, bone loss and cardiovascular disease. However, the interindividual diversity and complexity of dietary phyto-oestrogen absorption and metabolism make the bioactivity of these compounds unpredictable, and results of in vitro and in vivo studies are inconsistent. There is a paucity of data on the effects of phytooestrogens on bone65,66 and no evidence that phyto-oestrogen supplements prevent bone loss. In one prospective, randomised, placebo-controlled study of 474 women treated with ipriflavone, no significant differences in BMD, biochemical bone markers or spinal fracture rates were observed after 36 months.67 Fall-prevention strategies and hip protectors Risk factors for falls include impairments of vision, sensation, strength and balance, and patient thinness and frailty. In the Dubbo Osteoporosis Epidemiology Study, quadriceps strength and postural sway were of similar importance to BMD in predicting fractures in both men and women.2 Most fractures occur after falls, but not all falls result in fractures. Nevertheless, interventions that reduce falls risk may prevent fractures. Several studies have examined single and multiple risk factors and the use of hip protectors. Of the single risk factor interventions, programs that involve balance training, such as home-based physiotherapy and tai chi, reduce the risk of falls (pooled relative risk [RR], 0.80; 95% CI, 0.66–0.98; and RR, 0.51; 95% CI, 0.36–0.75, respectively).68,69 Environmental modifications by occupational therapists (eg, removing mats, improving lighting) may reduce falls.70 One study has reported that a reduction in psychoactive medications reduces the risk of falls (RR, 0.34; 95% CI, 0.16– 0.74), but adoption and compliance rates in the study were low.71 Studies in nursing homes in Denmark and Sweden of the effect of hip protectors have reported reductions in hip fracture rates of 56% and 67%, respectively (E2).72,73 However, hip fractures did occur in the intervention subjects when not wearing their hip protectors, so that compliance remains an issue (one reason for non-compliance is that women believe it makes them look "fat" around the hips). Systematic reviews74 suggest that hip protectors reduce the risk of hip fracture in high-risk populations (E1). Exercise Evidence that exercise reduces fractures is derived from retrospective and prospective observational cohort studies and case–control studies (E3). Maximising the attainment of peak bone mass and preventing age- and menopause-related bone loss by exercise, as well as attending to related risk factors (such as loss of muscle mass, poor gait and balance and depression), are potentially important approaches to reducing fracture risk in older people. However, no RCTs have examined the efficacy of exercise in preventing fractures at specific sites and this remains a gap in our knowledge. Vigorous exercise undertaken by athletes during growth is well documented as increasing peak bone mass by biologically worthwhile amounts.75-77 The difference in bone density between athletes and sedentary controls ranges from 5% to 25%, depending on the sport and duration of participation. After retirement from intensive training, the effects appear to persist for many years, but whether the benefits are maintained into old age, when fractures and falls become common, is uncertain. The sparse data on 70–80- year-old retired athletes suggest that the effects may be eroded in people who have substantially reduced training volumes. The same pattern is seen for other physiological adaptations to exercise, such as muscle hypertrophy, increased aerobic capacity, and increased insulin sensitivity. Whether moderate exercise during growth produces benefits in terms of BMD and bone structure is less well established. There have been several exercise studies in school children in which loading (such as jumping and other sporting activity) is incorporated into the physical education program for 20–30 minutes three times weekly. The results are generally positive, with variable evidence of increased bone size, increased BMD and thickening of cortices.78-80 However, there are few data on whether the modest improvements in bone mass and structure are maintained after these exercise programs are stopped. There have been no long-term (> two years) exercise intervention studies using moderate exercise programs in normally active children. Moderate- to high-intensity weight-bearing aerobic exercise, high-intensity progressive resistance training and high-impact loading (such as jumping) increase BMD by 1%–4% in pre- and postmenopausal women (E1).81-85 Excessive exercise carries some risk, especially in premenopausal women, in whom it may induce amenorrhoea. In studies of generally one year's duration, with sample sizes ranging from 30 to 150, exercise has been found to slow the rate of bone loss in older women by about 1.5% per year compared with sedentary controls (E1).86 More robust exercise interventions appear to produce greater effects, but optimal prescriptive elements await further RCTs. Inclusion of weight-lifting and balance-training exercises should provide the widest range of benefits relevant to fracture protection, as well as reducing muscle weakness, falls risk and depression, and increasing muscle mass and mobility. Whether these benefits translate into fracture-risk reduction is currently unknown. Pain management and rehabilitation after osteoporotic fracture There is little evidence available regarding pain management after osteoporotic spinal fracture. The general principles of management of acute, subacute and chronic pain include use of non-pharmacological modalities and recognition of the potential for comorbid mood disorders, particularly in elderly people. Non-pharmacological, non-evidence-based modalities include physiotherapy and other physical modalities, transcutaneous electrical nerve stimulation, cognitive behaviour therapy, and procedures such as vertebroplasty, kyphoplasty and nerve blockade. Pharmacotherapy should employ a stepwise approach in the use of analgesics and other pain-modifying agents. Subcutaneous calcitonin has been reported to reduce the pain of acute spinal fractures in two small placebo-controlled trials (E2).87,88 Rehabilitation to independent living is the primary goal after any fracture. Rehabilitation after hip fracture has been the most investigated. Systematic reviews of randomised and non-randomised trials89,90 have concluded that coordinated geriatric hip-fracture programs and early discharge (with support) for selected patients can significantly increase rates of returning home and reduce length of hospital stay and costs (E1). No controlled trials are available to guide recommendations specifically for spinal fractures. Given the absence of evidence for this condition, strategies that encourage independence and limitation of disability, together with interventions directed at secondary prevention of fractures, should be applied in clinical practice. Evidence for treatment of other populations While there are multiple published RCTs assessing the benefits of different therapies for osteoporosis in postmenopausal women, studies of osteoporosis in other populations (such as men, glucocorticoid-treated patients, and frail older people) are relatively few. Here we attempt to summarise the evidence for treatments in these "neglected" populations, using the same NHMRC levels of evidence. Evidence and recommendations regarding children with osteoporosis and athletes with stress fractures can be found at the Osteoporosis Australia website (<http://www.osteoporosis.org.au>). Treatment of osteoporosis in men Osteoporotic fractures occur in about 28% of men aged over 60 years.5 While fractures tend to occur in elderly men with multiple comorbid disorders, secondary underlying causes of osteoporosis are common and need to be rigorously excluded. Up to 16% of men with spinal fractures have evidence of hypogonadism. Chronic smoking, excessive alcohol use, glucocorticoid therapy, malabsorption and underlying bone-marrow malignancies are some of the important risk factors for osteoporosis that need to be identified. Osteoporosis remains a neglected area in men's health, with less than 10% of men with osteoporotic fractures currently receiving antifracture therapy. RCTs of men with osteoporosis are generally of smaller sample size and lesser quality than in those involving postmenopausal women (see Box 3). The limited RCTs that have been conducted suggest that alendronate, followed by cyclical etidronate, are the drugs of choice for men with primary osteoporosis. 91,92,94 The effects of risedronate have not yet been reported, except in men receiving corticosteroids, but its efficacy should be similar to that of alendronate and etidronate. Preliminary studies also suggest that subcutaneous PTH may be as effective in reducing fracture rates in men as it is in postmenopausal women. Adequate supplementation with calcium and vitamin D (if required) is recommended for all men with osteoporosis. There are no RCTs assessing the role of calcium or vitamin D3 alone in men. In a single small RCT (20 treated subjects and 19 controls) in osteoporotic men with pre-existing fractures conducted over two years,95 calcitriol was no better than calcium in reducing spinal fracture (E3). Testosterone replacement therapy is indicated for men with hypogonadism (serum total testosterone concentration < 8 nmol/L), but there are no data to assess the antifracture efficacy of testosterone in men with osteoporosis. Testosterone therapy and its effect on BMD are largely dependent on the gonadal and growth status of the individual, the duration of pre-existing hypogonadism, the degree of osteopenia and the duration of testosterone therapy. Two RCTs (E2) have demonstrated the positive effects of testosterone therapy on both cortical and trabecular bone, with maximal responses occurring in men before epiphyseal closure.96,97 The results of studies of testosterone therapy in hypogonadal, osteoporotic eugonadal and normal elderly men are summarised in Box 3.96-100 Large, well designed RCTs with adequate power to demonstrate spinal and hip fracture prevention in men with osteoporosis are needed. 3: Summary of randomised trials in male osteoporosis Glucocorticoid-induced osteoporosis A number of RCTs of bisphosphonates, in which the primary efficacy endpoint was BMD, have shown a consistent reduction in spinal fracture risk in postmenopausal women taking glucocorticoids (E1).101-105 In these studies, the risk of spinal fracture in control-group women taking glucocorticoids ranged from 13% to 22% over 12 months. For etidronate, alendronate and residronate, the number of postmenopausal women taking glucocorticoids who would need to be treated to prevent one fracture over 12 months was low. Treating these women would be more cost-effective than treating postmenopausal women with osteoporosis unrelated to glucocorticoid use. A number of RCTs of active vitamin-D metabolites, such as calcitriol and alfacalcidol, have reported prevention of spinal bone loss in patients starting glucocorticoids.106,107 None of these studies were powered for fracture as an endpoint, and mild hypercalcaemia occurred in about 10%–20% of patients. In trials in which calcium alone was used as the control therapy for patients starting glucocorticoids, calcium did not prevent rapid spinal bone loss.106,108 However, in patients receiving chronic low-dose glucocorticoids, treatment with calcium and simple vitamin D resulted in small increases in spine BMD.109 Although none of these studies were powered for fracture as an endpoint, meta-analyses have concluded that adjunctive therapy with some form of vitamin D should be considered.110 There is limited evidence for the effects of HRT (either oestrogen or testosterone) on bone density (E2), and there are no data on the effectiveness of HRT in reducing fractures among people with glucocorticoid-induced osteoporosis. Nevertheless, HRT should probably be considered if hypogonadism is present.111,112 Fracture risk with glucocorticoids is a function of multiple factors, including the severity of reduction in bone density and the duration of exposure to glucocorticoids. The available evidence suggests that postmenopausal women and older men receiving glucocorticoids are at the greatest risk of spinal fracture and should be considered for prophylaxis, usually with a bisphosphonate as the first choice. Adjunctive therapy with some form of vitamin D should be considered. If an active vitamin D metabolite is used, calcium supplementation should be avoided, unless dietary calcium intake is low. In premenopausal women and young men who are taking glucocorticoids, the risk of spinal fracture is less clear but appears to be lower, so the decision to use antiosteoporosis prophylaxis is less straightforward. Osteoporosis in frail older people About a third of older Australians with profound and severe disability are resident in nursing homes and hostels (which provide a total of around 150 000 beds), and there is evidence of undertreatment for osteoporosis in this group. In one study, 26% of hostel residents and 36% of nursing home residents were known to have previous osteoporotic fractures, but anti-osteoporosis therapy was prescribed for only 17% and 11% of residents, respectively (Leon Flicker, Professor of Geriatric Medicine, Royal Perth Hospital, personal communication). Older people are more likely to have several risk factors for fracture, including previous fractures. NNT analyses suggest that older people are more likely to derive greater benefit per year of anti-osteoporotic treatment than younger people.113 However, in frail older subjects, osteoporosis treatments must take account of the likelihood of comorbidity and the use of multiple other therapies. Calcium and vitamin D supplementation may have a special role in treating older frail people, particularly those in residential care. In Australia, 22% of women in low-level care and 45% of women in high-level care have frank vitamin D deficiency, and virtually all the remainder have a 25-hydroxy-vitamin-D level in the lower half of the reference range.114 Other factors that need special consideration in frail older people are the use of hip protectors and interventions to prevent falls. Summary and recommendations Osteoporosis represents a substantial health burden on the Australian community. In the financial year 2000–01, it led to an estimated 65 000 fractures. Total financial costs in 2001 were estimated at $7.4 billion per annum, of which $1.9 billion were direct healthcare system costs. If nothing is done, it is estimated that the number of Australians sustaining a fracture will increase from one every 8.1 minutes in 2001 to one every 3.7 minutes in 2021. Relative to other diseases, management of osteoporosis is expensive — more costly in absolute terms than either diabetes or asthma, both of which are National Health Priority Areas. In terms of disease burden, more years of healthy life are lost in Australia due to osteoporosis than to Parkinson's disease, HIV/AIDs, rheumatoid arthritis or cervical cancer. New strategies to reduce the fracture burden Increased education and awareness programs Education and awareness programs are a key strategy for reducing the fracture epidemic. Because the risk of fracture increases after the first fracture and the initial osteoporotic fracture often goes undiagnosed and untreated, increasing the rate of treatment in people who have already sustained an osteoporotic fracture is important. Despite the evidence, most people do not realise they are at risk of osteoporosis. The role of lifestyle changes (including specific exercise regimens, changes in diet and quitting smoking) has not been evaluated adequately. Regardless of whether or not such strategies can reduce fracture risk, they are likely to have other major public health benefits. Wider use of effective treatments The most rigorously investigated drugs in the field of osteoporosis are the potent bisphosphonates alendronate and risedronate, and the selective oestrogen-receptor modulator raloxifene (see Box 4). Calcium, in combination with vitamin D, has been reported to reduce fracture risk in nursing-home residents and ambulant individuals. Lower levels of evidence exist for the effectiveness of HRT and etidronate. Still weaker and contradictory evidence for anabolic steroids and calcitriol makes these drugs difficult to recommend. Introduction of fall-prevention programs Fall-prevention strategies and hip protectors are potentially effective in preventing fractures, particularly in elderly people, for whom treatment of vitamin D insufficiency is also vital. 4: Algorithm for treatment of osteoporosis in postmenopausal women A national strategy The international Bone and Joint Decade (2001–2010), endorsed by the World Health Organization, provides an opportunity to launch a strategic plan against osteoporosis. In light of the enormous and growing prevalence, costs and disease burden of osteoporotic fractures in Australia, we make two recommendations: Osteoporosis should be adopted by the Federal Government as a National Health Priority Area, with commensurate funding; and The Federal Government should support a National Strategic Plan for urgent implementation during the international Bone and Joint Decade (see Box 5). 5: Components of a National Strategic Plan (a) Awareness programs implemented through State-based osteoporosis organisations with national coordination, including programs targeted at general practitioners. (b) Public health prevention strategies such as school-based programs to increase dietary calcium intake and exercise in young people. (c) Specific programs to address the high prevalence of vitamin D deficiency in elderly people, as well as fall-prevention programs and provision of hip protectors for older people in residential care and in the general community. (d) Secondary prevention strategies, such as special clinics in teaching hospitals or initiatives in general practice, to increase treatment rates in people who have sustained their first osteoporotic fracture. (e) Wider availability of Medicare Benefits Schedule rebates on bone densitometry items for elderly people and those with a family history of osteoporosis. (f) Wider availability of drugs under the Pharmaceutical Benefits Scheme to treat subgroups of people at high risk of suffering fractures (eg, people with very low bone mineral density [BMD] and glucocorticoid users). There is a need to identify a BMD level at which the cost-effectiveness of treatment is similar to that for a pre-existing fragility fracture. (g) Research initiatives in cooperation with the National Health and Medical Research Council and other funding agencies. (h) Monitoring and evaluation of fracture rates, the cost-effectiveness of treatments and the prevalence and burden of osteoporosis in Australia at specific time points over the next decade (eg, 2005 and 2010). (i) Liaison with orthopaedic units to ensure that patients with fractures are adequately investigated and treated. Abbreviations BMD bone mineral density DEXA dual energy x-ray absorptiometry DOES Dubbo Osteoporosis Epidemiology Study GOS Geelong Osteoporosis Study HRT hormone replacement therapy MBS Medicare Benefits Schedule NHMRC National Health and Medical Research Council NNT number needed to treat PBS Pharmaceutical Benefits Scheme PTH parathyroid hormone RCT randomised controlled trial RR relative risk TASOAC Tasmanian Older Adult Cohort Writing Group Philip N Sambrook, MD, LLB, FRACP Professor of Rheumatology, Institute of Bone and Joint Research, University of Sydney Ego Seeman, MD, FRACP Associate Professor of Medicine, Department of Endocrinology, Austin and Repatriation Medical Centre, Melbourne Stephen R Phillips, MB BS, FAMA Chairman, National Prescribing Service, Surry Hills, Sydney Peter R Ebeling, MD, FRACP Associate Professor of Medicine, Departments of Diabetes and Endocrinology, Royal Melbourne Hospital, and Department of Medicine, University of Melbourne Working Group Shona L Bass, PhD, MSc Senior Lecturer, School of Health Sciences, Deakin University, Victoria Kim L Bennell, BAppSc, PhD Associate Professor, and Director, Centre for Sports Medicine Research and Education, School of Physiotherapy, University of Melbourne Ian D Cameron, MB BS, PhD Associate Professor of Rehabilitation Medicine, Motor Accidents Authority of NSW, and Department of Medicine, University of Sydney Chris T Cowell, MB BS, FRACP Clinical Associate Professor, Institute of Endocrinology, The Children's Hospital at Westmead Susan R Davis, MB BS, FRACP, PhD Associate Professor, Department of Epidemiology and Preventive Medicine, Monash University, and Director of Research, Jean Hailes Research Unit, Clayton, Victoria Terry Diamond, MB BCh, FRACP Associate Professor of Medicine, Department of Endocrinology, St George Hospital, and University of NSW, Sydney John A Eisman, AO, PhD, FRACP Professor of Medicine, and Head, Bone and Mineral Research Division, Garvan Institute of Medical Research, Sydney Leon Flicker, MB BS, PhD Professor of Geriatric Medicine, Royal Perth Hospital, University of Western Australia Linda R Ferris, MB BS, BSc(Med), FRACS(Orth) Head, Orthopaedic Unit, Modbury Hospital, Adelaide Maria A Fiatarone Singh, MD, FRACP Professor of Medicine, John Sutton Chair of Exercise and Sport Science, University of Sydney Paul P Glasziou, MB BS, PhD Professor of Evidence-Based Practice, School of Population Health, University of Queensland, Herston, Queensland Michael J Hooper, MB BS, FRACP Clinical Associate Professor, Department of Medicine, Concord Hospital, Sydney Graeme Jones, MD, FRACP Associate Professor, and Head, Musculoskeletal Unit, Menzies Research Institute, Hobart Stephen R Lord, PhD Associate Professor, and Principal Research Fellow, Prince of Wales Medical Research Institute, Sydney Lyn M March, PhD, FRACP Associate Professor, Departments of Rheumatology and Public Health, Royal North Shore Hospital, Sydney Sheila M O'Neill, MB BCh, BAO, MICGP Clinical Director of Research, Betty Byrne Henderson Centre, Royal Women's Hospital, Brisbane Nick A Pocock, MD, FRACP Associate Professor of Medicine, and Senior Staff Specialist in Nuclear Medicine, Department of Nuclear Medicine, St Vincent's Hospital, Sydney Richard L Prince, MD, FRACP Associate Professor of Medicine, Department of Medicine, University of Western Australia, and Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth Ian R Reid, MD, FRACP Professor of Medicine and Endocrinology, Department of Medicine, University of Auckland, New Zealand Kerrie M Sanders, MHN, PhD Research Fellow, Department of Clinical and Biomedical Sciences, University of Melbourne, Barwon Health, Geelong John D Wark, PhD, FRACP Professor of Medicine, Department of Medicine, University of Melbourne, and Royal Melbourne Hospital

Philip N Sambrook MD, LLB, FRACP · Ego Seeman MD, FRACP · Stephen R Phillips MB BS, FAMA · Peter R Ebeling MD, FRACP

The widespread application of public iodine supplementation programs, which cover about 3–4 billion people worldwide,1,2 is a response to the paucity of iodine in the natural diet in many regions of the world and the severe public health consequences of iodine deficiency.3 However, in some countries, the tendency to low iodine intake has mostly been corrected by haphazard increases in the iodine content of certain parts of the diet.4 In the United Kingdom, dairy products may contain extra iodine as a result of adding iodine to cow feed to increase the animals' reproductive performance or of using iodine-containing cleansing agents in the dairy industry. As reviewed by Phillips,5 this unplanned increase in iodine intake has eliminated endemic goitre in Britain during the last 30–40 years. In the United States, London and colleagues encountered cases of unexplained very high iodine intakes (1100–1300 µg per day) in 1964. Subsequently, they discovered that bakers used iodine-containing conditioners in bread and that this caused high levels of iodine intake.6 Obviously, such unplanned variation in dietary iodine is a hazardous way of providing a population with an adequate intake of iodine, as mechanisms unrelated to disease prevention can profoundly alter iodine intake. To some extent, Australia may be a country where factors other than disease prevention have modulated the intake of iodine, and iodine intake may now be in an unplanned phase of decrease.7 A report by McElduff et al8 (page 317) in this issue of the Journal seems to support this proposition. McElduff and colleagues looked at the frequency distribution of whole-blood thyroid-stimulating hormone (TSH) concentrations in newborns in the northern Sydney area. TSH is measured as part of screening for congenital hypothyroidism. In 5%–10% of infants around 72 hours after birth, TSH values were above 5 mIU/L. The World Health Organization (WHO) recommends assessment of TSH concentrations in newborns to detect population iodine deficiency, and specifies that less than 3% of newborns should have a whole-blood TSH concentration over 5 mIU/L. In a subsample of neonates, McElduff et al found that, during pregnancy, their mothers had a median urinary iodine concentration of 109 µg/L, indicating borderline mild iodine deficiency. WHO specifies that the median urinary iodine concentration in adults should be over 100 µg/L, and an extra iodine intake of 50 µg/day in pregnant and lactating women.1 Thus, the corresponding median urinary iodine concentration of pregnant women would be around 130 µg/L. McElduff et al warn that Sydney may be an area of iodine deficiency, and suggest that iodine intake and risk of disease should be investigated in more detail. Their concern is well founded. Even if there is no documentation that these borderline iodine values are harmful to a mother and child, the margin of safety is small. Furthermore, in Australia, there is apparently no regular surveillance of population iodine status, or of the variable iodine content of dairy products and other foods. The iodine intake may well be even lower in other sections of the Australian population. Severe iodine deficiency may cause brain damage and other developmental disorders,3 and goitre and its complications may affect a significant proportion of the population at all levels of iodine deficiency.9 Any public healthcare system should evaluate iodine intake and prevent disorders caused by iodine deficiency. Several factors need to be taken into account in such an evaluation and prevention program: The relationship between iodine intake and the risk of thyroid disease is not a simple one. Even if iodine supplementation may decrease the risk of some thyroid disorders, the risk of other disturbances at a younger age, such as hypothyroidism and Graves' disease, may increase.4 Severe iodine deficiency, with a median urinary iodine excretion of less than 25 µg/24 h, is an instance where giving any type of iodine supplementation is better than doing nothing. However, at higher levels of intake, careful planning and surveillance are needed. The methods often used for evaluating iodine intake and the risk of disease are not perfect. Neonatal screening showing more than 3% of TSH values over 5 mIU/L is not, by itself, enough to indicate insufficient maternal iodine intake. Detection of neonatal hypothyroidism requires identification of relatively high TSH levels (20–25 mIU/L), and many TSH assays and screening programs are not designed to identify TSH values around 5 mIU/L with reasonable confidence. Technical aberrations can easily give an increased frequency of elevated blood TSH concentrations. One such aberration occurs with sampling of blood before TSH has fully returned to baseline levels after the early postnatal surge. As discussed by McElduff et al,8 early sampling may have contributed to their findings. Iodine deficiency is not the only pathogenetic mechanism leading to an increase in blood TSH levels in neonates. Iodine has an autoregulatory inhibitory effect on the thyroid gland, with a fall in both thyroid hormone synthesis and secretion. Possibly, this mechanism has been developed to protect against hyperthyroidism induced by a sudden iodine load. In a variety of abnormal states the thyroid gland overreacts, producing hypothyroidism. The thyroid of the fetus and infant is considerably more sensitive to iodine inhibition than the maternal thyroid. Excess iodine intake, rather than iodine deficiency, in mother or infant has been a more common cause of transient neonatal hypothyroidism in countries with a relatively low iodine intake, such as Germany, Italy and Belgium.4 In severe iodine deficiency, iodine supplementation to the mother decreases the abnormally high serum TSH in both the mother and the newborn.10 On the other hand, in pregnant women with urinary iodine concentrations around 50 µg/L, iodine supplementation decreases TSH levels in mothers, but not in cord blood. TSH levels in the newborn may even be higher after iodine supplementation.11 The finding of McElduff et al of a positive correlation between maternal urinary iodine concentrations during pregnancy and whole-blood TSH levels in neonates needs further elaboration,8 but it may be an example of iodine autoregulation of the fetal thyroid. Should pregnant women living in mild and moderately iodine-deficient areas receive iodine supplements, and does supplementation involve any risk? An increase in iodine intake will improve thyroid function in pregnant women, which is important for early brain development in their infants.12 There are still things to be learned about the influence of small amounts of iodine on neonatal thyroid function in mild iodine deficiency, and about pituitary/thyroid feedback regulation in the fetus and small infant. A tendency to a slight increase in neonatal TSH level after iodine supplementation may be of little importance, as, in these infants, the serum concentration of T4 (which may be the major thyroid hormone influencing brain development12) does not show a concomitant reduction.11 Finally, iodine supplementation imposes no risk of worsening of postpartum thyroid dysfunction in the mother.13 In conclusion, pregnant women should not be iodine deficient. To strictly follow WHO guidelines on iodine intake, pregnant women with similar urinary iodine levels to those found by McElduff et al could alter their diet towards more iodine-rich foods, or they could take a small iodine supplement as part of the vitamin and mineral supplements recommended for pregnant women in most countries. However, there is at present no evidence that a supplement will have beneficial effects. Ideally, iodine intake should be evaluated and kept optimal in the entire population, taking into account that unnecessary high iodine intakes may be associated with more hypothyroidism.4 The studies by McElduff et al8 and other researchers7 demonstrate the need for national monitoring and adjustment of iodine intake as part of a program of prevention of thyroid disorders and their complications. Such initiatives normally involve government nutrition or public health agencies in collaboration with experts in thyroid diseases, nutrition and epidemiology and prevention.1,2 It would be an added bonus if the program elucidated some of the unresolved issues in the field of population iodine supplementation in developed countries. This would continue the considerable contribution of Australian scientists to the understanding and correction of iodine-deficiency disorders.3,14

Peter Laurberg MD, DMedSci · Susanne B Nøhr

Objective: To determine whether thyroid-stimulating hormone (TSH) concentrations in a large sample of neonates meet World Health Organization criteria for an iodine-replete population (< 3% of neonates with whole-blood TSH concentrations > 5 mIU/L), and, in a small subset of neonates, to examine the correlation between maternal urinary iodine and neonatal TSH concentrations.Design: Cross-sectional study of neonatal whole-blood TSH values obtained as part of a routine newborn screening program.Setting: Royal North Shore Hospital (RNSH) in northern Sydney.Participants: Two anonymous samples of neonates born at RNSH (1316 infants born between August 1998 and April 1999 and 1457 infants born between 1 March and 31 December 2000); and 84 infants whose mothers had attended RNSH between September 1998 and August 1999 and supplied a urine sample for iodine measurement.Main outcome measures: Iodine status of neonates (proportion with whole-blood TSH values > 5 mIU/L), and urine iodine concentrations of pregnant women.Results: In the two large population samples of neonates, 8.1% (95% CI, 6.6%–9.5%) and 5.4% (95% CI, 4.3%–6.6%), respectively, had whole-blood TSH values > 5 mIU/L (prevalence range for mild thyroid deficiency, 3%–19%). Comparing the TSH values of the 1316 anonymous infants and the 84 identified infants showed no difference between the proportions with TSH values > 5 mIU/L (8.1% v 10.7%, respectively; P = 0.39). Urine iodine concentrations in the 84 pregnant women indicated borderline mild iodine deficiency. TSH values in their 84 infants were positively correlated with maternal urine iodine concentrations.Conclusions: Our results suggest that the population of northern Sydney may have mild iodine deficiency. However, the expected relationship between maternal urine iodine levels and neonatal TSH concentrations was not found.

Aidan McElduff PhD, FRACP · Patrick McElduff BMath, PhD · Jenny E Gunton MB BS, FRACP · Graham Hams MAppSc · Veronica Wiley PhD · Bridget M Wilcken MB ChB, FRACP

Screening by high-quality programs successfully detects cancers at an earlier stage In 2002, the 10th anniversary of Australia's national program of mammographic screening for breast cancer, it is perhaps timely to reflect and review. The need for reassessment is highlighted by the recent furore in the breast-screening world1-4 precipitated by a Cochrane review by Olsen and Gøtzsche.1 In this issue of the Journal, the article by Barratt et al5 (page 266) also encourages us to review breast-screening policies — in this case for women 70 years and over who are no longer in the target group for free mammographic screening (50–69 years). Barratt et al5 estimated the benefit of screening women 70–79 years to be about one-third to three-quarters that achieved in women aged 50–69 years. As women age, the benefit of screening — reduced risk of death from breast cancer — is increasingly offset by the other causes of death. Furthermore, while the benefit is delayed, the hazards of screening — tests for false-positive films, discomfort and anxiety — are immediate. Thus, with increasing age, the data show a further decline in benefit, which is exaggerated when adjustment is made for qualit-of-life factors.5 Barrett et al also provide a rough estimate of the cost-effectiveness of screening older women. The wide range of cost estimates (per quality-adjusted life-year saved) underlines their imprecise nature, but suggests that mammographic screening of women aged 70–79 years is as cost-effective as screening the other outlier group — women 40–49 years. However, Barratt et al remind us that the estimation of benefits, harms and costs would be improved with data from randomised trials in the appropriate age group — which unfortunately are still lacking. In 1999, 63.7% of women in the target age group for mammographic screening in Victoria (50–69 years) were screened.6 In view of Barratt and colleagues' estimates of benefits and costs per quality-adjusted life-year saved, it could be argued that money for screening older — or younger — women could be better spent on recruiting more women in the target group to achieve the desired 70% participation. Trials of mammographic screening commenced in the 1960s and seven have been completed and reported. On the basis of these trials, which showed a reduction in mortality from breast cancer in screened women, mammographic screening recommendations have been drawn up (eg, in the United States), and in several countries political decisions were made to institute national programs (eg, in the United Kingdom, Australia and New Zealand). In 2000, Gøtzsche and Olsen, publishing a "Cochrane review" of the seven trials in the Lancet,7 reported that they found no reliable evidence that screening for breast cancer reduced mortality. However, this report did not fulfil the Cochrane Group protocol for such a review. Since then Gøtzsche and Olsen have worked with the Cochrane Breast Cancer Editorial Group, and in October 2001 part of their review was accepted and included in the Cochrane Library.1 Almost simultaneously, the Lancet published Gøtzsche and Olsen's review in full on its website, and a research letter in its printed journal2 with an editorial commentary3 criticising the Cochrane Breast Cancer Editorial Group for interference. The whole episode has drawn a flurry of criticism and countercriticism.4. After all this, what should women believe, especially as the systematic review of Barratt et al5 suggests that screening for women over 70 years may be of some benefit (and as cost-effective as it is for those under 50 years), on the basis that screening is beneficial in women aged 50–69 years? Although clinical-trial methodology has improved in four decades, population-health intervention studies remain notoriously difficult to perform because of problems associated with large cohort numbers, the randomisation process and guaranteeing reliable stratification. It is not surprising that the seven, now old, trials can be criticised. However, not all would suggest ditching them and their conclusions on these grounds. The Cochrane Breast Cancer Editorial Group has not accepted the other conclusion of Olsen and Gøtzsche — that screening leads to more aggressive treatments8 — and has not included that section of their review in the Cochrane Library. Others4 reject Olsen and Gøtzsche's conclusions because they are based on all-cause mortality, which may be inappropriate in population studies. Do we have other surrogate measures to guide us? Cancer registry data from Victoria9 suggest a "slight downward trend since 1994" in breast cancer mortality, but it cannot be assumed that any of this trend is due to screening. However, from 1982 to 1996, there was no change in breast cancer mortality in Australia.10 The impact of breast screening may be seen more readily in the stages at which breast cancer is detected. In 1997, when the national program was six years old and well established, 30% of new breast cancers were detected through screening. Data suggest that screen-detected invasive cancers were smaller, less likely to involve nodes, and, if node positive, more likely to involve fewer nodes (Box).11 Tumour size, nodal involvement and number of nodes involved — the basis of the tumour–node–metastases (TNM) staging system — are all known to be of prognostic significance. Hence, it is likely that the cohort of women with screen-detected invasive cancer will have a better prognosis and live longer, provided lead-time bias does not negate the prognostic effect of lower staging by detecting cancer earlier while not influencing the natural history of the disease. The prognostic significance of non-invasive cancer (ductal carcinoma in situ), its treatment and the appropriateness of various local and systemic treatments for any breast cancer can be debated and argued. However, the histopathological prognostic (TNM) data would suggest that mammographic screening by high-quality programs successfully detects cancers at an earlier stage, giving a better prognosis and probably improved survival. Women should be made aware of these facts, along with any doubts raised by reviewers of somewhat out-of-date trials. Impact of breast screening on stage at which cancer is detected11 Tumour size/node involvement Screen detected All cancers < 15 mm 60.3% 42.7% Node positive 22.5% 30.0% 1–3 nodes positive 18.7% 23.4% > 3 nodes positive 8.4% 14.2%

Alan Rodger

Comprehensive management of pregnancy loss is enhanced by psychological support and follow-up counselling It is generally accepted that 12%–15% of confirmed pregnancies do not progress to term, with the risk of pregnancy loss increasing with maternal age. In particular, early pregnancy loss (< 20 weeks' gestation) is experienced by one in four women. In about half these women, a medical explanation can be found,1 although, in clinical practice, investigations to identify the cause are rarely pursued. Most women go on to have successful subsequent pregnancies, although there is a slightly increased risk of a second miscarriage that increases incrementally with each subsequent loss.1 Although early-pregnancy loss is relatively straightforward medically, the psychological outcome is more problematic and the grieving process is complicated.2 First, there is no tangible life or memory to grieve. Instead, the woman has to come to terms with grieving for a potential life with all its hopes and aspirations. Second, the grieving is often complicated by feelings of self-blame, particularly when there is no medical explanation for the loss or the woman has engaged in potentially hazardous behaviour (eg, alcohol consumption or smoking). Her partner may also harbour feelings of responsibility for the loss. Other factors which may influence the grieving process and the emotional outcome include miscarrying later in gestation (especially if the woman has felt the fetus move and formed an emotional attachment to it);2,3 the importance and meaning of the pregnancy (eg, a first, wanted pregnancy lost near the end of the reproductive lifespan); and the difficulty experienced in conceiving the pregnancy (eg, an assisted conception). Finally, psychosocial factors, such as a woman's support network (especially her intimate relationship) and her personality style and culture, will affect how she appraises her loss and her level of distress. The psychological sequelae after a late pregnancy loss and stillbirth are well described;3 those after an early pregnancy loss are similar but may not be as severe. There can be high levels of psychological distress characterised by anxiety, depression and somatisation, which can persist for at least six months4 and are only partly accounted for by grieving for the loss of a potential child. There is an increased risk of developing a depressive or anxiety disorder in the six months after a pregnancy loss, and any pre-existing psychotic disorders can be precipitated. The risk of developing depression is high, with studies reporting rates between 10%5 and 48%,6 depending on the study methods.7 One of the more rigorous controlled studies5 reported that 10.9% of women developed major depression after a miscarriage, compared with 4.3% of women (controls) from the same community who had not been pregnant in the previous year. Depression is more likely in women with a history of depression or past psychopathology, and in women who have had a previous pregnancy loss or have no other children. Other factors precipitating depression, such as poor social support or having a vulnerable personality style, are well recognised. The rates of anxiety disorder are lower than those for depression. Recently, exacerbation of obsessive–compulsive disorder after miscarriage has been reported.8 Finally, if the pregnancy loss has been traumatic (eg, an ectopic pregnancy or the woman's life was at risk), post-traumatic stress disorder can arise.9 The comprehensive management of pregnancy loss will be enhanced by psychological support and follow-up counselling.7,10 This can be provided by the woman's obstetrician, general practitioner or another health professional involved in her care, who can address medical as well as psychological issues.11 The purpose is to allow open discussion about the loss, monitor progress and counsel the woman about future pregnancies. In the initial stages, she will benefit from the opportunity to talk about her loss and have her grieving acknowledged. Providing information about the normal grief process may help a woman who is masking her grief or does not believe it is legitimate. The grief process will be facilitated by the opportunity to talk about feelings of guilt and self-blame, particularly when there is no medical explanation.12,13 In our opinion, there should also be an opportunity to discuss dissatisfaction with medical care, as the woman may feel angry and blame her medical practitioner for the loss. An open discussion about this will help her, and may reduce the possibility of litigation. Medical practitioners, particularly when the issue is pregnancy loss or stillbirth, are often reluctant to use the phrase "I'm sorry" because of fears that this equates with an acknowledgement of guilt and may have legal implications. Bereaved parents are often highly aware of this omission, angered by it, and may actually retaliate through litigation. Both obstetricians and insurance companies need to seriously look at the distinction between empathic expression of "sorrow" for the distress experienced as opposed to an apology for negligent action. Regular follow-up is recommended for the first six months. Distinguishing between feelings of grief (which may require grief counselling) and the onset of a depressive illness (which may require specific treatment) can be difficult. Depression is suggested by persistence of depressed mood, lack of enjoyment in pleasurable activities, low self-esteem or excessive guilt, and sleep or appetite disturbance or fatigue.14,15 A pathological grief reaction, characterised by excessive distress, guilt feelings or a preoccupation with the loss, may require more specific counselling. Sometimes a woman may have her depressed feelings dismissed as "grieving" and miss out on appropriate and effective treatment for a depressive disorder. Other family members may also need psychological support. The woman's partner may experience similar feelings of loss.16 In such situations, the father is often neglected ("men aren't expected to talk about their feelings"). He will also benefit from an opportunity to talk about his feelings of loss, as will other children in the family, especially as they may feel responsible if they had feelings of jealousy about the new sibling. The sense of loss may dissipate when the woman becomes pregnant again, and some studies suggest that the shorter the time between a pregnancy loss and a subsequent pregnancy the better the outcome for the woman.13 Such women usually feel anxious during the stage of pregnancy at which the previous loss occurred. Finally, women may benefit from the opportunity to talk to other women who have experienced a pregnancy loss through support groups such as SANDS <http://www.sands.org.au/>.

Philip M Boyce MD, FRANZCP · John T Condon MD, FRANZCP · David A Ellwood DPhil(Oxon), FRANZCOG

Current practices should be re-examined in light of current evidence Antenatal care includes screening asymptomatic pregnant women, with the aim of detecting, and thereby preventing, both maternal and neonatal adverse events. The introduction of antenatal care in 1913 has been widely attributed to the efforts of Ballantyne at the University of Edinburgh. He suggested that the high maternal and perinatal mortality rates observed at the beginning of the 20th century reflected inadequate maternity care during pregnancy and lack of supervision of the progress of labour. Ballantyne's flow diagram, an antecedent of guidelines, defined interactions of many disciplines in antenatal care. During the 1930s, there was increased emphasis on educating healthcare professionals who provided maternity care. Women were encouraged to present during pregnancy, and were advised to give birth in hospital. The subsequent fall in perinatal mortality rates was attributed to antenatal care, without consideration of the contribution from social and other medical improvements.1 The falling mortality rates corresponded with a gradual increase in the number of antenatal visits recommended. By the 1950s, a schedule of monthly visits to 28 weeks, fortnightly visits to 36 weeks, and then weekly visits until birth had become standard.1 Although programs with fewer visits have been proposed, this schedule is widely accepted in clinical practice. This has remained largely unchallenged, as noted by Archie Cochrane, who stated "by some curious chance, antenatal care has escaped the critical assessment to which most screening procedures have been subjected".2 Traditional antenatal care was critically appraised in a retrospective review of 1907 pregnant women who gave birth at the Aberdeen Maternity Hospital in 1975.1 Antenatal and birth records were reviewed to determine the rates at which complications were diagnosed, misdiagnosed and overdiagnosed, in addition to the rate at which complications occurred despite routine antenatal care. Breech presentation and pre-eclampsia were the only complications reliably detected in the antenatal period, and the benefit in the detection of pre-eclampsia was confined to primigravid women beyond 34 weeks' gestation. Most antenatal admissions, apart from admissions for labour and birth, were for conditions that had arisen despite routine antenatal care — conditions that had not been prevented or detected by it. More recently, randomised controlled trials have assessed the optimal frequency of antenatal visits in preventing maternal and fetal complications. The main hypothesis tested in these trials is that models of care with fewer antenatal visits are as effective as the traditional model in terms of clinical outcomes and maternal satisfaction.3 A systematic review of seven randomised controlled trials involving 57 418 women found no differences in the detection of pre-eclampsia (odds ratio [OR], 0.91; 95% CI, 0.66–1.26), urinary tract infection (OR, 0.93; 95% CI, 0.79–1.10), low birthweight (OR, 1.04; 95% CI, 0.93–1.17) or maternal mortality (OR, 0.91; 95% CI, 0.55–1.51) when a schedule of reduced antenatal visits was compared with more traditional regimens of antenatal visits.4 However, women were more dissatisfied with fewer visits. Whether increased maternal satisfaction is of measurable benefit in terms of pregnancy and birth outcomes remains less certain. Clinical practice guidelines should define best practice, limit variations in the provision of care, recommend care that is cost-effective, and provide care in a way that meets the needs of all patients. In this issue of the Journal (page 255), Hunt and Lumley have reviewed guidelines used in Australian maternity units.5 They found that recommendations for the content of antenatal visits and screening procedures vary considerably across Australia. The value of certain tests or interventions can be readily appreciated in terms of a low cost treatment capable of disease modification (eg, provision of anti-D to rhesus-negative women); however, evidence of benefit is lacking in other circumstances (eg, routine screening for carbohydrate intolerance), although current clinical trials will address some of these issues. Routine antenatal screening for syphilis, although low cost and with effective therapy available for patients testing positive, could be questioned given the low prevalence of the disease among pregnant white Australians. However, selective testing and treatment has not been supported.6 Hunt and Lumley also demonstrate the other end of the clinical spectrum, where good-quality evidence exists to support a treatment or policy but institutions have no relevant guidelines. Good-quality evidence exists to support the cessation of smoking during pregnancy,7 and yet remarkably few institutions had a guideline providing practical information for caregivers to support women in smoking cessation. This also highlights the difficulty of implementing changes in policy, despite evidence of an important clinical effect, and reflects the wider challenges of translating research findings into clinical practice. The article by Hunt and Lumley describes the broad range of accepted antenatal care in Australia. Where to from here? The purpose of antenatal care needs to be redefined. The aims may differ for consumers and caregivers, and both should be incorporated into the "ideal" model of care. In addition, current practices (including timing and frequency of visits, and "routine" screening investigations) should be questioned in light of predetermined outcome measures and best available evidence. The principles of antenatal care were adopted over half a century ago; their maintenance can only be supported when rigorously tested against the best currently available evidence, which can then be incorporated into national guidelines for best practice.

Jodie M Dodd · Caroline A Crowther · Jeffrey S Robinson

Objective: To describe the variability and evidence base of recommendations in Australian protocols and national policies about six aspects of routine antenatal care.Design: Comparison of recommendations from local protocols, national guidelines and research about number of visits, screening for gestational diabetes (GDM), syphilis, hepatitis C (HCV), and HIV, and advice on smoking cessation.Setting: Australian public hospitals with more than 200 births/year, some smaller hospitals in each State and Territory, and all Divisions of General Practice were contacted in 1999 and 2000. We reviewed 107 protocols, which included 80% of those requested from hospitals and 92% of those requested from Divisions.Main outcome measures: Frequency and consistency of recommendations.Results: Recommendations about syphilis testing were notable in demonstrating consistency between local protocols, national policies and research evidence. Most protocols recommended screening for GDM, despite lack of good evidence of its effectiveness in improving outcomes. Specific approaches to screening for GDM varied widely. Coverage and specific recommendations about testing for HIV and HCV were also highly variable. Smoking-cessation information and advice was rarely included, despite good evidence of the effectiveness of interventions in improving outcomes. No national policies about the number of routine visits and smoking cessation could be identified. There were inconsistent national policies for both HIV and GDM screening.Conclusions: Antenatal care recommended in protocols used in Australia varies, and is not always consistent with national policies or research evidence. Producing and disseminating systematic reviews of research evidence and national guidelines might reduce this variability and improve the quality of Australian antenatal care.

Jennifer M Hunt MPH, FAFPHM · Judith Lumley PhD, FFPHM(UK)

Some infections are more serious in pregnant than non-pregnant women because of the potential for vertical transmission to the fetus or infant (eg, varicella, rubella, cytomegalovirus infection, toxoplasmosis and listeriosis). Pre-pregnancy or routine antenatal screening for presence of, or susceptibility to, some of these infections and appropriate management can prevent adverse fetal or perinatal outcomes; screening should include rubella IgG, hepatitis B surface antigen, serological tests for syphilis and HIV antibody. If certain other vertically transmissible infections are suspected because of a positive antenatal test result, confirmatory tests for maternal and, if indicated, fetal infection are essential before intervention is considered (eg, cytomegalovirus infection). For some vertically transmissible infections that are not readily preventable, appropriate management of maternal infection can reduce fetal damage (eg, toxoplasmosis).

Series Editors:

Should Australia follow the US decision to base prophylaxis on results of maternal screening? Ever since group B streptococcus (GBS) emerged as the commonest cause of perinatal sepsis in the late 1970s, there has been controversy about prevention strategies. A few hospitals in Australia were among the first in the world to introduce routine antenatal screening for GBS carriage and intrapartum antibiotic prophylaxis for carriers.1 This approach was later vindicated by randomised controlled trials in selected carriers2 and the demonstration of lower rates of sepsis after intrapartum prophylaxis compared with historical rates.3 However, problems remain. Group B streptococcus is a normal vaginal commensal in healthy women, but colonisation is often intermittent, and rates of colonisation can vary from 18% to 27%, depending on the detection method.4 Moreover, vaginal carriage is a very crude predictor of perinatal sepsis, with fewer than 1% of the infants of carriers affected (1–2/1000 overall) without intervention.1,5 In 1996, the Centers for Disease Control and Prevention (CDC) in the United States published consensus guidelines for selecting women for intrapartum antibiotic prophylaxis using either of two alternative strategies. One strategy was based on maternal GBS carriage, and the other on clinical risk factors — preterm labour (< 37 weeks' gestation), prolonged rupture of membranes (> 18 hours) or intrapartum fever (> 38oC).6 The rationale for the latter strategy was that, before widespread use of intrapartum antibiotics, one or more of these risk factors was found in up to 80% of mothers of infants with GBS sepsis.1,7 Gradual implementation of these consensus guidelines in the US was associated with a fall in the incidence of perinatal GBS sepsis from 1.7/1000 in 1992 to 0.5/1000 in 1999.8 In Australia, there was also a decrease in the incidence of perinatal GBS sepsis, from 1.2/1000 in 1991–1993, when three of nine neonatal units surveyed had prevention strategies in place, to 0.5/1000 in 1995–1997, when all 11 units surveyed had prevention strategies.5 A recent review concluded that there is evidence, albeit from relatively poor-quality trials, that intrapartum prophylaxis reduces the incidence of neonatal sepsis, but not deaths.9 Despite this evidence, concern continues about excessive use of intrapartum antibiotics. There have been several reports that their increasing use is associated with an increased proportion of cases of neonatal sepsis caused by penicillin-resistant bacteria.10,11 Although it is sometimes difficult to prove, there is considerable empirical evidence that increased antibiotic use generally leads to increasing bacterial resistance. It is plausible that exposure to antibiotics in utero might delay colonisation of the infant gut with penicillin-sensitive anaerobes and allow penicillin-resistant facultative bacteria — many of which are potential pathogens — to become established. Recently, the CDC published revised guidelines, recommending a single strategy for prevention based on universal prenatal screening for vaginal or rectal GBS colonisation.12 The recommendation was based on a retrospective cohort study, which showed that perinatal GBS sepsis was significantly less frequent in infants of women given intrapartum antibiotics on the basis of documented GBS screening results (0.33/1000 births) than in infants of women managed on the basis of risk factors (0.59/1000 births; relative risk, 0.48; 95% CI, 0.37–0.63).13 This result is not surprising. A risk factor-based protocol cannot, by definition, prevent sepsis in infants whose mothers have no risk factors. On the other hand, the proportion of cases prevented by a protocol based on GBS colonisation depends on the sensitivity of the screening method, effectiveness of prophylaxis and compliance with the protocol.4,14 What was surprising in the CDC study was that the anticipated overall rate of intrapartum antibiotic use was similar for both prevention strategies (31% and 29%).13 In contrast, we showed that in Australia a strategy based on risk factors would lead to significantly less use of intrapartum antibiotics (18%–20% of women) than a strategy based on antenatal screening at 35–37 weeks' gestation (35%).4 This difference is apparently due to a higher incidence of risk factors in the US compared with Australia, and failure to account for women given intrapartum antibiotics during preterm labour before results of screening are available. They suggest that obstetricians in Australia should not immediately discard the option of a risk-based strategy. Neither strategy is ideal, but either, if properly implemented, can reduce the incidence of perinatal GBS sepsis. The GBS screening strategy results in at least a third of healthy young women (and their infants) being given intravenous antibiotics during labour, at significant cost and with some risks, but can achieve a lower rate of perinatal GBS sepsis.13 In Australia, with a risk-based strategy, significantly fewer women and infants would receive intravenous antibiotics. Whichever strategy is chosen, the most important determinant of its effectiveness will be compliance.

Gwendolyn L Gilbert MD, FRACP, FRCPA

Objective: To review the clinical management of young women with intellectual disabilities with menstrual and contraceptive concerns.Design: Prospective cohort study of all girls and young women with a significant intellectual disability and moderate to high support needs who presented at my gynaecology clinic for management of menstrual and contraception-related issues in the period 1990–1999.Setting: Gynaecology clinic at the Centre for Adolescent Health, Royal Children's Hospital, Melbourne, and my private consulting rooms.Outcome measures: The clinical management options considered most appropriate for these women, including advice, reassurance, medication (oral contraceptive pill, non-steroidal anti-inflammatory drugs, depo-medroxyprogesterone acetate, hormone replacement therapy) and surgical options.Results: For 2 of 107 young women, surgical approaches were required to manage their menstrual problems or contraception-related issues. For the remainder of the women, information, advice or medical management were sufficient.Conclusions: Management of the menstrual and contraceptive needs of young women with an intellectual disability is similar in most cases to the management of non-disabled women. Surgical management is required infrequently.

Sonia R Grover MD BS, FRANZCOG

To the Editor: The 50 g glucose challenge test (GCT) is widely recommended as a screening test for gestational diabetes (GD).1 The test consists of a 50 g oral glucose load given at any time of the day, followed one hour later by the measurement of the plasma glucose concentration.2 This test is recognised as imperfect for screening, as sensitivity and specificity are not 100%.2,3 It is known that glucose tolerance deteriorates in the afternoon,4 which raises the question of whether time of day influences the response to the 50 g GCT. At Royal North Shore Hospital, screening for GD is performed at the 26–28-week visit by means of the 50 g GCT. In 2000, screening for GD was introduced into a morning midwives antenatal clinic, whereas previously it had only been performed in the afternoon. The population attending the clinic at the 26–28-week visit includes many women receiving shared care, and is regarded as being at low obstetric risk. The Table shows the results of screening at the morning clinic compared with screening in the afternoon over the same time period. The two groups were identical in terms of age, weight, ethnicity, and family history of diabetes or past history of GD. The percentage of women with a positive screening test result during the morning clinic (17.0%) was significantly lower than that during the afternoon clinic (31.1%). Positive screening results were followed up with a diagnostic 75 g glucose tolerance test, and GD was diagnosed according to the Australian Diabetes in Pregnancy Society criteria.5 Women with a positive screening test result confirmed with a 75 g glucose tolerance test in the afternoon were less likely to have GD than those with a positive test in the morning (31.5% v 40.0%). Despite the fact that a smaller percentage of women who screened positive in the afternoon had GD, a greater percentage of the total number screened in the afternoon had GD than in the morning group. In this cohort, the difference (9.8% v 6.8%) was not significant (Table; P = 0.15). These results are consistent with the hypothesis that a 50 g GCT test performed in the afternoon results in a greater number of positive results, a greater number of women undergoing diagnostic testing and a greater number of women identified with GD. The morning GCT appears to increase specificity, with an associated decrease in sensitivity. These results need to be taken into consideration when designing or implementing a screening program. Screening for gestational diabetes (GD): the effect of screening time Time Morning (0930–1200) Afternoon (1205–1710) Number screened 176 470 Age in years (mean ± SD) 31.2 ± 4.7 31.7 ± 5.0 Weight (mean ± SD) 59.4 kg ± 10.5 kg 60.8 kg ± 12.9 kg Family history of diabetes 27 24 Past history of gestational diabetes 1 3 % White/Asian/Middle Eastern 62.6/28.0/9.0 67.5/25.9/5.8 Positive result, 50 g glucose challenge test 30 (17.0%) 146* (31.1%) Abnormal result, 75 g glucose tolerance test 12 (6.8%)† 46‡ (9.8%)† *P < 0.001, χ2. † % Of number screened. ‡ P = 0.15, χ2.

Aidan McElduff · Rosemary Hitchman

To the Editor: We have recently noticed changes in the incidence of invasive cervical carcinoma in the Gippsland Health Region and would like to know whether other regions have noticed similar demographic changes. During 24 months in 1999–2000, 19 women (median age, 59 years; range, 33–88 years) with squamous carcinoma were registered in our pathology practice. Based on information from the Victorian Cervical Cytology Register, almost half (10 women) had no previous cervical smear history whatsoever, while three had had smears, but at irregular intervals up to 14 years apart. The remaining six women had had regular Pap smears, with 1–3 negative smears preceding the diagnosis of cancer. Sixteen of the women had consulted their general practitioner for some other ailment before the cervical cancer was discovered (median interval, 14 months), but no cervical smear had been obtained. Of particular interest is the fact that six of the 19 patients are in their seventh decade or older, with a median age of 80 years (range, 79–88 years). The Victorian Department of Human Services reports that the cervical-smear participation rate for eligible women in the Gippsland region is 68%, a rate not much different from the other regions.1 The two-yearly participation rate for the 60–69-years age group is 56%, and, although no official figure is available for women in their seventh or eighth decades, it is likely to be considerably lower. The Cancer Epidemiology Centre has recorded that, over a 16-year period, the incidence of cervical carcinoma in Victorian women aged over 70 years fell by 50%, and simultaneously there has been a shift in the peak incidence from the 70–74-years age group to one a decade older (Vicky Thursfield, Information Manager, personal communication). Accordingly, we suspect that women over 70 years of age still have a significant incidence of invasive cervical carcinoma, but are not being offered cervical smears, even when the National Health and Medical Research Council guidelines indicate the necessity.

Nicholas J Mulvany · Norman R Sonenberg

Objectives: To describe the management of early-pregnancy bleeding and miscarriage reported by general practitioners in Victoria.Design, setting, and participants: Self-administered, mailed survey of a stratified random sample of GPs in Victoria. Responses weighted by strata to reflect GP population.Main outcome measures: Reported management in referral; investigation (especially ultrasound); expectant versus interventional management; and prevention of rhesus iso-immunisationResults: 382 of 621 eligible GPs responded (response rate, 62%). GPs' reported referral was more likely if the patient had painful bleeding (55%) or if the pregnancy was not viable (77%). Ultrasound strongly influenced the assessment of bleeding. Two-thirds of doctors (262/369; 66%) would routinely order ultrasound for painless bleeding, and 328/369 (84%) for painful bleeding. Expectant management was recommended by 15/353 (4%) for incomplete miscarriage with light bleeding and by 6/351 (2%) when bleeding was heavy. Some GPs are uncertain of the indications for anti-D prophylaxis, including instrumentation of the uterus, for which 261/337 (77%) said they would routinely offer anti-D. There was less agreement about anti-D after threatened miscarriage, for which 213/353 (57%) said they offered the injection.Conclusions: GPs need a working knowledge of the management of early-pregnancy bleeding, and can probably encourage more rational management. There are significant areas where GPs are uncertain, often reflecting uncertainty elsewhere, and some areas where a minority of GPs are not aware of essential requirements.

Bruce McLaren DRANZCOG, FRACGP, MPH · Julia M Shelley MPH, PhD

Medicine and the Community For editoral comment, see Mason and Diamond; see also Nozza and Rodda Abstract - Methods - Subjects - Assay - Risk assessment - Results - Discussion - Acknowledgements - Reference - Authors' details - - - More articles on Obstetrics & gynaecology and women's health Abstract Objectives: To determine the vitamin D status of veiled or dark-skinned pregnant women, because of their known increased risk of vitamin D deficiency. Design: An audit of vitamin D status. Setting: An antenatal clinic in a major metropolitan teaching hospital, Melbourne, Victoria. Participants: Pregnant women attending the clinic who agreed to be screened. Main outcome measures: Serum 25-hydroxyvitamin D3 (25OHD3) level at first visit to the antenatal clinic. Results: Of 94 women, 82 were screened. Sixty-six women (80%) had 25OHD3 values below the test reference range (22.5-93.8 nmol/L). Conclusions: Our findings are a cause for concern, because vitamin D deficient women are at risk of bone disease and their children at risk of neonatal hypocalcaemia and rickets. Most of our vitamin D comes from the action of ultraviolet light on skin.1 People with a darker skin produce less vitamin D for a given sunlight exposure,1,2 and veiled women, regardless of the climate, are at a high risk of vitamin D deficiency because of their reduced skin exposure to sunlight.3-6 In pregnant women there is the added risk of vitamin D deficiency in the baby. We screened veiled or dark-skinned pregnant women attending an antenatal clinic at a major metropolitan teaching hospital in Melbourne, Victoria, to determine their vitamin D status. Methods Subjects Veiled and/or dark-skinned women attending the antenatal clinic at the Royal Women's Hospital, Melbourne, were advised that they were at increased risk of vitamin D deficiency, putting them at risk of osteomalacia and their children at risk of vitamin D deficiency related problems. Over a 10-month period (July 1999 - April 2000), all such women were asked to provide a blood sample so that their serum level of 25-hydroxyvitamin D3 (25OHD3) could be measured. Those who consented were given a pathology request form for a blood sample to be taken. Assay Serum samples were stored at - 20ºC, and the 25OHD3 assays were performed in batches in the complex chemistry laboratory at the Royal Children's Hospital, Melbourne, using the Incstar radioimmunoassay kit (Dade Behring, Melbourne). The reference range for this test was 22.5-93.8 nmol/L. The coefficient of variation between successive assays at a mean concentration of 43.9 nmol/L was 11.7%. The assay fulfilled the acceptability criteria of the Royal College of Pathologists of Australasia endocrinology quality assurance program. Risk assessment We recorded the date the blood sample was taken (summer was defined as November to April, and winter as May to October); the patient's facial skin colour (fair, intermediate or very dark skinned); and the degree and consistency of skin covering (women who covered their arms and wore a veil or scarf over their hair and neck at all times when outdoors were coded as "consistently covered"; those who uncovered in a private, outdoor environment as "inconsistently covered"; and those who did not generally cover their arms, hair and neck when outdoors as "uncovered"). Results Of 94 veiled or dark-skinned women attending the clinic during the study period, 82 had a blood sample taken. Two did not agree to be tested, and the remaining women did not go to have a blood sample taken. Serum levels of 25OHD3 are shown in Box 1. The median value was 14 nmol/L (range, 3-77 nmol/L). In 66 women (80%) the vitamin D level was below the reference level (< 22.5 nmol/L). Of the women with values below 22.5 nmol/L, 66% (21/32) had blood samples collected in summer and 90% (45/50) in winter (95% CI for difference, 6%-43%; P < 0.01 by χ2 test). Information on skin colour and covering was complete for 70 of the 82 women. The proportion of women with serum 25OHD3 values below 22.5 nmol/L, according to skin colour and covering, is shown in Box 2. Although numbers in some subgroups were extremely small, it did not appear that this additional information was helpful for clinical management. Among the 12 women with missing information, 11 (92%) had vitamin D levels under 22.5 nmol/L, and nine were tested in winter. Discussion Of the dark-skinned and/or veiled pregnant women we tested, 80% were at high risk of vitamin D deficiency, with serum 25OHD3 values below the reference range. The number of veiled and/or dark-skinned pregnant women attending the Royal Women's Hospital each year is not recorded, but, if they were evenly distributed among the five weekly clinics (as appears likely), we estimate that around 560 such women would attend each year. Inadequate sunlight exposure can occur even in Australia, especially among women with a modest dress code or those who limit sunlight exposure for other reasons (eg, valid concerns about the risk of skin cancer). However, vitamin D deficiency can be prevented or treated with dietary supplements. Dark-skinned or veiled women should be screened for vitamin D deficiency and those who are deficient should be given vitamin D supplements, whether or not they are pregnant, because of their high risk of bone disease. Their children are also at risk of vitamin D deficiency and their infants, if breast fed, should be given suitable infant vitamin D supplements (Penta-vite, Roche). We did not measure maternal parathyroid hormone (PTH) levels during the period of this audit, but now do so routinely. PTH is an important marker of bone health in the mother, and there is some evidence that fetal growth is inversely related to maternal PTH level and positively related to maternal calcium level at delivery.7 Research is needed to determine the optimal vitamin D level in pregnant women, in terms of outcome for themselves and their offspring, and to determine whether other groups of women are also vitamin D deficient. Data from Queensland (Associate Professor John McGrath, Director, Department of Psychiatry, University of Queensland, Brisbane, personal communication8) and from the Geelong Osteoporosis Study (Dr Julie Pasco, Study Coordinator, personal communication) suggest that vitamin D deficiency in women of reproductive age is not limited to specific ethnic or cultural groups. Acknowledgements We thank Peter Vervaart and Rhonda Greaves for undertaking the laboratory assays and staff in the Monday clinic at the Royal Women's Hospital for their help. Ruth Morley is supported by the Victorian Health Promotion Foundation (VicHealth). References Norman AW. Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutr 1998; 67: 1108-1110. Feleke Y, Abdulkadir J, Mshana R, et al. Low levels of serum calcidiol in an African population compared with a North European population. Eur J Endocrinol 1999; 141: 358-360. el-Sonbaty MR, Abdul-Ghaffar NU. Vitamin D deficiency in veiled Kuwaiti women. Eur J Clin Nutr 1996; 50: 315-318. Ghannam NN, Hammami MM, Bakheet SM, Khan BA. Bone mineral density of the spine and femur in healthy Saudi females: relation to vitamin D status, pregnancy, and lactation. Calcif Tissue Int 1999; 65: 23-28. Taha SA, Dost SM, Sedrani SH. 25-Hydroxyvitamin D and total calcium: extraordinarily low plasma concentrations in Saudi mothers and their neonates. Pediatr Res 1984; 18: 739-741. Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res 2000; 15: 1856-1862. Brunvand L, Quigstad E, Urdal P, Haug E. Vitamin D deficiency and fetal growth. Early Hum Dev 1996; 45: 27-33. McGrath JJ, Kimlin MG, Saha S, et al. Vitamin D insufficiency in south-east Queensland [letter]. Med J Aust. 2001; 174: 150-151. (Received 14 Aug 2000, accepted 2 May 2001) Authors' details Royal Women's Hospital, Melbourne, VIC. Sonia R Grover, MD, FRACOG, Obstetrician. Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Melbourne, VIC. Ruth Morley, MB BChir, FRCPCH, Senior Research Fellow. Reprints will not be available from the authors. Correspondence: Dr Ruth Morley, Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052. morleyrATcryptic.rch.unimelb.edu.au Make a comment 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/> Back to text 2: Proportion of women with serum vitamin D (25-hydroxyvitamin D3) levels under 22.5nmol/L, according to skin covering and skin colour Skin colour Skin covering* Very dark Intermediate Light Total Consistently covered 6/6 (100%) 1/2 (50%) 23/25 (92%) 30/33 (91%) Inconsistently covered 3/5 (60%) 1/3 (33%) 18/24 (75%) 22/32 (69%) Uncovered 2/2 (100%) 2/3 (67%) 0 (0) 4/5 (80%) Total 11/13 (85%) 4/8 (50%) 41/49 (84%) 56/70 (80%) *Consistently covered - women always covered up, including arms, hair and neck, when outdoors; inconsistently covered - women did not usually cover fully in their own garden; and uncovered - women did not generally cover their arms, hair and neck when outdoors. Back to text

Sonia R Grover · Ruth Morley

Position Statement Anticoagulation in pregnancy and the puerperium A Working Group on behalf of the Obstetric Medicine Group of Australasia MJA 2001; 175: 258-263 Abstract - Management and prophylaxis of venous thromboembolism in pregnancy and the puerperium - Acute venous thromboembolism - Prophylaxis of venous thromboembolism - General - Previous thromboembolism - Previous single VTE and no recognised thrombophilia - Previous recurrent VTE or idiopathic VTE - Familial thrombophilia - Hyperhomocysteinaemia - Antiphospholipid syndrome and VTE - Management and prophylaxis of obstetric problems associated with uteroplacental thrombosis - References - Authors' details - - More articles on Obstetrics & gynaecology and women's health Abstract For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain. Low molecular weight heparins (LMWH) are being used increasingly as standard treatment for venous thrombosis, replacing unfractionated heparin (UH) for both therapeutic and prophylactic anticoagulation. Compared with UH, LMWH have increased bioavailability and a longer half-life. They also have the benefits of ease of administration, often as a single daily dose, have reduced requirements for monitoring, and are associated with less heparin-induced thrombocytopenia, reduced bleeding complications and improved patient acceptability.1Heparins do not cross the placenta, whereas warfarin does.2,3 By contrast, warfarin is teratogenic between six and 12 weeks' gestation, and may cause fetal and neonatal bleeding if used during the second or third trimester. Except perhaps in women with mechanical heart valves, there is general agreement that UH or LMWH should be substituted for warfarin as soon as pregnancy is diagnosed. Long-term treatment with UH carries risks of maternal osteoporosis4-6 and heparin-induced thrombocytopenia. Consistent, long term therapeutic anticoagulation can be hard to achieve with subcutaneous UH, because of low bioavailability and the changing anticoagulant response to UH as pregnancy progresses, often requiring close laboratory monitoring. LMWH require much less monitoring and appear to carry a smaller risk of heparin-induced thrombocytopenia, bleeding, and probably osteoporosis.7-9 Data on the effectiveness and safety of LMWH in pregnancy are limited but systematic reviews are becoming available.10 Given the convenience of LMWH and doctors' increasing familiarity with their use, there is growing opinion that LMWH have a role in pregnancy in preference to UH. In this position paper we summarise current views and make consensus recommendations for anticoagulation in pregnancy and the puerperium. The consensus process followed for this article is summarised in Box 1. Management and prophylaxis of venous thromboembolism in pregnancy and the puerperium Acute venous thromboembolism Antenatal management: Clinical trials in non-pregnant patients show that LMWH are at least as effective and safe as UH in the initial management of acute proximal or calf deep venous thrombosis (DVT).1 Recurrence of thromboembolism is reduced by ongoing warfarin therapy and, in the case of proximal DVT, treatment should be continued for at least six months (C1). The standard initial treatment for pulmonary embolism, whether during pregnancy or not, remains intravenous UH (C2). For an antenatal DVT, treatment should start with a LMWH at the therapeutic dose recommended by the manufacturers9(Box 2) (C1). Intravenous UH may be preferred in situations where its short half-life and predictable reversibility by protamine sulfate are important (eg, when delivery or surgery may be imminent). Calf DVT should be treated in the same way as proximal DVT in pregnancy because of ongoing hypercoagulability during pregnancy (C2). If intravenous UH is used for the initial treatment of pulmonary embolism, therapeutic doses of LMWH may be commenced once the patient is haemodynamically stable (C1). Anticoagulation therapy should then be maintained until delivery (C1). It is generally recommended that therapeutic doses of UH or LMWH be continued throughout pregnancy.9,11,12 In practice, some clinicians change to a prophylactic dose of LMWH after 12 weeks of therapy if the woman is still pregnant, and continue with this dose until labour (Box 2) (C3). The rationale for this approach includes a declining risk of recurrence with time after acute venous thromboembolism (VTE),13 a desire to reduce osteoporosis associated with LMWH, and the suggestion from small trials in non-pregnant patients that lower prophylactic or intermediate doses of LMWH may be as effective as warfarin in preventing secondary recurrence of VTE.14-16 The safety of such a reduction of LMWH dose before 12 weeks after acute VTE in pregnancy needs to be established in clinical trials. Monitoring: There is no need to use an anti-factor Xa assay to monitor either therapeutic or prophylactic doses of LMWH (C2). Therapy with UH can be monitored and managed according to the activated partial thromboplastin time (APTT). Management of labour and delivery: Women requiring therapeutic anticoagulation should be counselled before delivery, which should be planned under the care of a specialist team (C1). Elective delivery allows for dose adjustment to minimise the opposing risks of bleeding at delivery and of further thrombosis.13 Vaginal delivery is preferable, as there is less risk of haemorrhage than with caesarean section. Delivery by caesarean section should be determined on the basis of obstetric indications (C1). The use of regional anaesthesia requires special consideration, and is outlined in Box 3. The intensity of anticoagulation therapy required during delivery depends on how recently the VTE occurred. If within the last month, each day without anticoagulation therapy is associated with a 1% absolute increase in the risk of recurrence.13 It is therefore important to minimise the time off anticoagulation. Intravenous UH should be substituted for LMWH 24-36 hours before obstetric intervention, aiming to maintain the APTT at 1.5-2 times baseline. After induction, UH therapy is ceased once labour is established, allowing the APTT to return to normal, usually within 4-6 hours. Women requiring elective caesarean section should cease UH therapy six hours before surgery to allow for the full range of obstetric and anaesthetic options (C1). If the VTE occurred between one and three months previously, therapeutic LMWH can be reduced to a prophylactic dose for 24-48 hours and labour can then be induced. The last dose of LMWH is given the night before induction. In women whose cervical assessment suggests that labour is likely to be established within a few hours of induction, the last dose of LMWH before induction may be withheld (C2). Women who have had a VTE more than three months previously and who are still receiving a therapeutic dose of LMWH can be switched to a prophylactic dose at 38 weeks' gestation, allowing spontaneous labour to occur. Again, LMWH are withheld at the onset of labour (C2). Alternatively, if a woman wishes to be assured of access to epidural anaesthesia, induction of labour can be offered, with the last dose of LMWH on the day before the day of induction (C2). Anti-embolism stockings, compression devices and electrical calf stimulators may be used and continued postpartum, especially if caesarean delivery is undertaken (C1). In all women in whom anticoagulants have been used, the third stage of labour should be managed actively with oxytocic therapy and controlled cord traction to minimise the risk of postpartum haemorrhage (C1). Postpartum management: Postpartum, anticoagulation therapy is usually recommenced at the same intensity as that used antenatally. Prophylactic doses can be recommenced within 2-6 hours of both vaginal and caesarean deliveries (C1). This may be prophylactic doses of LMWH or low-dose (12 000 U/24 h) UH infusion, if rapid reversal of anticoagulation may be required. Therapeutic doses of UH or LMWH may be reintroduced 24 hours after vaginal delivery (C2). Caution should be exercised in recommencing therapeutic doses of LMWH earlier than 24 hours after operative delivery because of the risk of surgical bleeding, but most women can be receiving therapeutic doses by 36-48 hours after caesarean section (C1). Warfarin therapy can then be initiated and, once therapeutic levels have been achieved, continued in place of LMWH to complete the six months of therapy and for at least six weeks postpartum. Neither medication contraindicates breastfeeding (C1). Prophylaxis of venous thromboembolism General VTE remains a major cause of maternal mortality in Australia, the United Kingdom and in the United States, occurring at a rate of approximately one death per 100 000 maternities.11,12,18 The rate is much higher in older women; in the UK, women aged over 39 years had a mortality rate of 1 per 3300 pregnancies.19 VTE can occur at any time during pregnancy; its prevalence is approximately equally distributed between the three trimesters.20 Although two-thirds of events occur antenatally, the day-by-day risk is greatest in the first weeks after delivery.20Major known risk factors for VTE in pregnancy and postpartum include caesarean section (particularly in labour), obesity, prolonged bed rest and immobility, pre-eclampsia, nephrotic syndrome, current infection and other recent surgery, in addition to previous VTE and thrombophilia. These risk factors often coexist and reinforce each other. A risk-assessment profile may be constructed, as suggested in the consensus report from the Royal College of Obstetricians and Gynaecologists,21 which recommends that: all "at risk" women should be monitored for symptoms and signs of VTE during the first week postpartum; hydration should be maintained and early mobilisation encouraged; graduated compression stockings with or without calf stimulation should be used during and after caesarean section in women at moderate risk (one or two risk factors); in women at high risk (three or more risk factors), LMWH or UH prophylaxis should be used and continued for at least five days. The efficacy or benefit of these interventions is unknown, as no high grade evidence is available. Previous thromboembolism In women who have had previous VTE, the risk of recurrence will be influenced by a number of factors, including whether the index event was spontaneous or provoked, the presence or absence of a family history of VTE, the presence of a known thrombophilia, or whether there has been more than one episode of VTE. The decision as to whether VTE prophylaxis is required throughout pregnancy or only postpartum may be based on this information (Box 4).22Women requiring prophylaxis during pregnancy can be managed with low-dose LMWH (Box 2). They can then be allowed to come into spontaneous labour (C2). LMWH are withheld at the onset of labour (C2). Alternatively, if such a woman wishes to be assured of access to regional anaesthesia, induction of labour can be offered, with the last dose of LMWH on the day before the day of induction (Box 3) (C2). Previous single VTE and no recognised thrombophilia Both earlier and more recent cohort data suggest that most pregnant women with a past history of a single precipitated thrombotic event in or out of pregnancy, or associated with the combined oral contraceptive pill, and who have no underlying thrombophilia, can be safely managed by careful observation before delivery and postpartum thromboprophylaxis for six weeks23 (C2). Previous recurrent VTE or idiopathic VTE Women who have either recurrent VTE, previous idiopathic VTE, or a previous VTE and a strong family history of VTE but with no demonstrated cause for thrombophilia, may be given thromboprophylaxis throughout pregnancy and for six weeks postpartum23,24 (C1). Familial thrombophilia Thromboembolism is a multifactorial disease, in many cases developing as a result of a thrombotic tendency (a thrombophilia) interacting with other factors, such as pregnancy.25,26 Situations in which such a thrombophilia may require consideration during pregnancy are: previous personal thromboembolic disease and known thrombophilia; no previous VTE, but a strong family history (ie, one or more first-degree relatives affected) and known thrombophilia; no previous VTE, strong family history, no previous investigations; no previous VTE, weak family history (ie, incidental finding of thrombophilia in a family member); and no personal or family history of VTE, but known thrombophilia detected after screening (eg, after obstetric complications or before starting to take the combined oral contraceptive pill). The known causes of familial thromboembolism differ in their risk of associated thrombosis.27 The prevalence of such thrombophilic disorders varies between populations.28 A combination of any two or more inherited factors substantially increases the risk of thromboembolism. Box 4 summarises the risk profiles of the various genetic thrombophilias and offers guidelines for therapy. Box 5 describes management during pregnancy of medical problems requiring anticoagulation outside pregnancy. Hyperhomocysteinaemia In women with a previous history of VTE and hyperhomocysteinaemia, it may be prudent to reduce plasma homocysteine concentrations by folate supplementation throughout pregnancy, in addition to other thromboprophylaxis (C2). Antiphospholipid syndrome and VTE The presence of a lupus anticoagulant or of moderately to strongly positive titres of anticardiolipin antibody (ACA) is a strong risk factor for recurrent VTE, especially in pregnancy. Suggestions for treatment are shown in Box 4. Unless there is an associated history of poor obstetric outcome (see below), low-dose aspirin therapy need not be added (C2). On the other hand, it is contentious whether women with a positive lupus anticoagulant with or without ACA with no previous history of VTE (eg, women with systemic lupus erythematosus) require any prophylactic treatment at all during pregnancy. Low-dose aspirin may be a reasonable option for such women (C1). Management and prophylaxis of obstetric problems associated with uteroplacental thrombosis A common pathophysiological link between various poor pregnancy outcomes, including recurrent miscarriage, stillbirth, placental abruption, fetal growth restriction and pre-eclampsia, is thrombosis in the uteroplacental circulation. Antiplatelet agents (especially low-dose aspirin) have been trialled, particularly for preventing pre-eclampsia. A recent systematic review has shown a 15% reduction in the incidence of recurrent pre-eclampsia when low-dose aspirin is used, less benefit for the prevention of preterm birth and no benefit for the prevention of fetal growth restriction.35 Whether LMWH or UH can be used safely and more effectively than just aspirin in placental vasculopathy, with or without thrombophilia, is currently under investigation. Only in the case of recurrent miscarriage associated with the antiphospholipid syndrome has the addition of UH to aspirin been shown to be beneficial.36 A number of small cohort studies in women with previous obstetric complications who were treated with LMWH showed a good outcome, but whether the outcome was related to the use of LMWH is uncertain.37,38While awaiting the results of further studies, and given the small numbers of affected women, no specific treatment recommendations can be made. We encourage clinicians to refer such patients to centres where randomised controlled trials are being carried out or where cohort studies are under way. Competing interests: The authors are grateful to Pharmacia Upjohn for an unrestricted financial grant towards the costs involved in the preparation of this article, although the company did not contribute in any way either to the analysis or to the recommendations. There are no other known conflicts of interest. Future research questions The working party identified further areas for research. These include: Comparison of LMWH versus intravenous UH in acute DVT and pulmonary embolism in pregnancy. High-dose versus low-dose LMWH therapy for secondary prophylaxis after acute DVT in pregnancy. The value of prospective blinded anti-Xa levels in the use of therapeutic LMWH in pregnancy. The timing, benefits and risks of any dose adjustment of LMWH/UH, particularly peripartum. Controlled longitudinal studies of bone density and fracture rates in women using long-term LMWH. Prevention of pregnancy-associated VTE: the risks and benefits of LMWH thromboprophylaxis during pregnancy and postpartum for specific groups. Prevention of adverse pregnancy complications related to placental insufficiency. Randomised studies to determine the efficacy of LMWH in improving subsequent pregnancy outcome in women with specific pregnancy complications and an underlying thrombophilia. A register of women being treated with anticoagulants during pregnancy. A register to determine the clinical significance of thrombophilias in particular patient groups. References Weitz J. Drug therapy: low molecular weight heparins. N Engl J Med 1997; 337: 688-698. Flessa H, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. Am J Obstet Gynecol 1965; 934: 570-573. Forestier F, Sole Y, Aiach M, et al. Absence of transplacental passage of fragmin (Kabi) during the second and the third trimesters of pregnancy. Thromb Haemostas 1992; 67: 180-181. Dahlman TC, Sjoberg HE, Ringertz H. Bone mineral density during long-term prophylaxis with heparin in pregnancy. Am J Obstet Gynecol 1994; 170: 1315-1320. Douketis JD, Ginsberg JS, Burrows RF, et al. The effects of long-term heparin therapy during pregnancy on bone density — a prospective matched cohort study. Thromb Haemost 1996; 75: 254-257. Barbour LA, Kick SD, Steiner JF, et al. A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 1994; 170: 862-869. Nelson-Piercy C. Heparin-induced osteoporosis in pregnancy. Lupus 1997; 6: 500-504. Farquharson RG. Heparin, osteoporosis and pregnancy. Br J Hosp Med 1997; 58: 205-207. Ginsberg J, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001; 199: 122S-131S. Sanson BJ, Lensing AW, Prins MH, et al. Safety of low molecular weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668-672. Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999; 353: 1258-1265. Toglia M, Weg J. Current concepts: venous thromboembolism during pregnancy. N Engl J Med 1996; 335: 108-114. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336: 1506-1511. Pini M, Aiello S, Manotti C, et al. Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemost 1994; 72: 191-197. Gonzalez-Fajardo J, Arreba E, Castrodeza J, Perez J, et al. Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis. J Vasc Surg 1999; 30: 283-292. Das S, Cohen A, Edmonson R, et al. Low molecular weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial. World J Surg 1996; 20: 521-527. Tryba M. European practice guidelines: thromboembolism prophylaxis and regional anesthesia. Regional Anesthes Pain Med 1998; 23 (6 Suppl 2): 178-182. Maternal mortality committee. Maternal deaths in Australia 1991-1993. Canberra: NHMRC, 1998. Department of Health. Why mothers die. Report on confidential enquiries into maternal deaths in the United Kingdom 1994-1996. London: The Stationery Office; 1998. Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999; 54: 265-271. Royal College of Obstetricians and Gynaecologists. Report of the RCOG Working Party on prophylaxis against thromboembolism in gynaecology and obstetrics. London: RCOG, 1995. McColl MD, Walker ID, Greer IA. The role of inherited thrombophilia in venous thromboembolism associated with pregnancy. Br J Obstet Gynaecol 1999; 106: 756-766. Brill-Edwards P, Ginsberg J, Gent M, et al. Safety of withholding antepartum heparin in women with a previous episode of venous thromboembolism. N Engl J Med 2000; 343: 1439-1444. Letsky EA. Peripartum prophylaxis of thrombo-embolism. Baillieres Clin Obstet Gynaecol 1997; 11: 523-543. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-1173. Preston FE, Rosendaal FR, Walker ID, et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348: 913-916. Gerhardt A, Scharf RE, Beckmann MW, et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000; 342: 374-380. Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001; 344: 1222-1231. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves — a systematic review of the literature. Arch Intern Med 2000; 160: 191-196. Arnaout M, Kazma H, Khalil A, et al. Is there a safe anticoagulation protocol for pregnant women with prosthetic valves? Clin Exp Obstet Gynecol 1998; 25: 101-104. Elkayam U. Pregnancy through a prosthetic heart valve. J Am Coll Cardiol 1999; 33: 1642-1645. Lee LH, Liauw PCY, Ng ASH. Low molecular weight heparin for thromboprophylaxis during pregnancy in 2 patients with mechanical mitral valve replacement. Thromb Haemost 1996; 76: 628-630. Sadler L, McCowan L, White H, et al. Pregnancy outcomes and cardiac complications in women with mechanical, bioprosthetic and homograft valves. Br J Obstet Gynaecol 2000; 107: 245-253. Rowan J, McCowan L, Raudkivi P, North R. Enoxaparin treatment in women with mechanical heart valves during pregnancy. Am J Obstet Gynecol. In press. Knight M, Duley L, Henderson Smart DJ, King JF. Antiplatelet agents for preventing and treating pre-eclampsia. Cochrane Database Syst Rev 2000; 2. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253-257. Brenner B, Hoffman R, Blumenfeld Z, et al. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 2000; 83: 693-697. Riyazi N, Leeda M, de Vries J, et al . Low-molecular-weight heparin combined with aspirin in pregnant women with thrombophilia and a history of preeclampsia or fetal growth restriction: a preliminary study. Eur J Obstet Gynecol Reprod Biol 1998; 80: 49-54. The authors of the Position Statement are listed below Authors' details Department of Obstetrics, University of Adelaide, Women's and Children's Hospital, North Adelaide, SA. William M Hague, FRCP, FRCOG, Senior Physician in Obstetric Medicine and Clinical Senior Lecturer. National Women's Hospital, Auckland, New Zealand Robyn A North, PhD, FRACP, Associate Professor in Obstetric Medicine. Flinders Medical Centre, Bedford Park, SA. Alexander S Gallus, FRCPA, FRACP, Haematologist and Professor. King Edward Memorial Hospital, Subiaco, WA. Barry N J Walters, MB BS, FRACP, Physician in Obstetric Medicine and Clinical Associate Professor, Department of Obstetrics and Gynaecology, University of Western Australia. Christopher Orlikowski, MB BS, FANZCA, Anaesthetist. Monash University, Monash Medical Centre, Melbourne, VIC. Robert F Burrows, FACOG, FRANZCOG, Professor of Maternal-Fetal Medicine. Mater Mothers' Hospital, South Brisbane, QLD Robert B Cincotta, FRANZCOG, CMFM, Specialist in Maternal-Fetal Medicine. North Western Adelaide Health Service, Adelaide, SA. Gustaaf A Dekker, PhD, FRANZCOG, Professor of Obstetrics and Gynaecology. Mercy Hospital for Women, East Melbourne, VIC. John R Higgins, MD, FRANZCOG, Senior Lecturer in Obstetrics and Gynaecology (currently, Professor of Obstetrics and Gynaecology, University College, Cork, Ireland). Royal Hospital for Women, Sydney, NSW. Sandra A Lowe, MD, FRACP, Physician in Obstetric Medicine. Royal North Shore Hospital, Sydney, NSW. Jonathan M Morris, MD, FRANZCOG, Senior Lecturer in Obstetrics and Gynaecology. Nepean Hospital, Sydney, NSW. Michael J Peek, PhD, FRANZCOG, Professor of Obstetrics and Gynaecology. Reprints will not be available from the authors. Correspondence: Dr W M Hague, Department of Obstetrics, Women's and Children's Hospital, North Adelaide, SA 5006. bill.hagueATadelaide.edu.au Make a comment 1: Consensus process The authors of this position statement are members of the Obstetric Medicine Group of Australasia (OMGA), with a particular clinical and research interest in managing pregnant women with thromboembolic problems. The authors were all members of the working party, and include six obstetricians, four obstetric physicians, an obstetric anaesthetist and a clinical haematologist. We met collectively in October 1999 to discuss the broad issues of the use of low molecular weight heparins in pregnancy before producing a draft document; this was subsequently modified by written comments and refined at teleconferences in May, June and September 2000. The position statement is a consensus statement inasmuch as there is little high-grade evidence from either randomised trials or other cohort studies on which to make recommendations, especially for management. Our recommendations have been annotated to reflect the degree of agreement among us as follows: C1 Complete consensus; C2 Near-complete consensus (nine or more of the 12 authors); and C3 No consensus. Back to text 2: Doses of low molecular weight heparins Low molecular weight heparin Therapeutic dose Prophylactic dose Dalteparin (Fragmin) 100U/kg twice daily 5000U daily Enoxaparin (Clexane) 1 mg/kg twice daily 40mg daily or 1.5mg/kg daily Back to text 3: Suggested guidelines for regional anaesthesia and levels of consensus (Box 1) Regional anaesthesia (epidural or spinal block) is contraindicated during anticoagulation therapy because of the increased (although unquantified) risks of spinal haematoma17 (C1). If a regional anaesthetic is desired in women who require anticoagulation therapy, an elective delivery will allow for a planned reduction in dose or a change to intravenous unfractionated heparin (UH) (C1). Therapeutic subcutaneous injections of low molecular weight heparins (LMWH) or UH should be ceased at least 24 hours, and preferably 36 hours, before regional anaesthesia (epidural or spinal block) (C1). Intravenous UH (used to permit a rapid return of the APTT to normal after cessation of the infusion) should be discontinued at least six hours, and preferably 12 hours, before regional anaesthesia (C1). In women receiving prophylactic LMWH, an interval of more than 20 hours from the last dose should allow the placement of a regional block with minimal risk of complications (C2). A normal activated partial thromboplastin time (APTT) does not ensure minimal anticoagulant effect of LMWH, and the platelet count should be determined to exclude heparin-induced thrombocytopenia (C2). If caesarean section is being undertaken, further doses of LMWH should be delayed for at least four hours after placement of an uncomplicated regional block, and longer if the regional block has been complicated (C1). Low-dose LMWH therapy can be continued after delivery if there have been no complications in the siting of the regional block.17 An epidural catheter can be removed 12-20 hours after a prophylactic dose of LMWH, and the next injection should be delayed by at least four hours after removal (C1). Women should be closely monitored postpartum for any symptoms or signs of spinal haematoma, in particular for numbness and weakness in the lower limbs, severe back pain, and bladder or bowel incontinence (C1). Back to text Box 4 consists of 4a, 4b, 4c, 4d. 4a: Suggested management guidelines and levels of consensus (see Box 1) Thromboprophylaxis against recurrent venous thromboembolism (VTE) in pregnant women with previous VTE and no identified thrombophilia, according to estimated pregnancy-related risk of thrombosis Single episode of VTE Thrombosis history Recurrent VTE Spontaneous Probable cause* Family history of VTE in one or more 1st degree relatives PrA (option ThA) (C2) PrA (C2) Negot (C2) No family history of VTE PrA (C1) Negot (C2) Nil (C2) *Risk factors present such as surgery, combined oral contraceptive pill. Back to text 4b: Anticoagulation to prevent venous thromboembolism (VTE) in pregnant women testing positive for lupus anticoagulant or anticardiolipin antibodies (ACA), according to estimated pregnancy-related risk of thrombosis Lupus anticoagulant and/or ACA IgG ACA IgG weak moderate-strong positive,* ACA Thrombosis history positive* IgM positive Recurrent VTE in pregnancy despite prophylaxis ThA (C1) ThA (C1) Recurrent VTE outside pregnancy ThA (C2) ThA (C2) Previous VTE PrA (C1) Negot (C1) No previous VTE Nil (C1) Nil (C1) *Based on the highest-ever titre measured in the individual patient. Back to text 4c: Preventing venous thromboembolism (VTE) in pregnant women with established thrombophilias, according to estimated pregnancy-related risk of thrombosis Thrombosis history Antithrombin deficiency (Very rare) Protein C deficiency (Rare) Protein S deficiency (Rare) FVL* or PGM† homozygous (Uncommon) FVL* or PGM† heterozygous (Common) Personal history of VTE independent of family history ThA (C2) PrA (C1) PrA (C1) PrA (C1) Negot (C1) Family history of VTE in one or more 1st degree relatives ThA/PrA (C3) PrA (C1) PrA (C1) PrA (C1) Negot (C1) Family history of VTE in a distant relative ThA/PrA (C3) PrA (C1) Negot (C1) Negot (C1) Nil (C1) No personal or family history of VTE ThA/PrA (C3) PrA (C1) Nil (C1) Nil (C1) Nil (C1) *G1691A mutation in the factor V gene [Factor V Leiden] causing activated protein C resistance; †G20210A mutation in the prothrombin (factor II) gene. Back to text 4d: Key to management recommendations ThA Therapeutic anticoagulation necessary throughout pregnancy and postpartum - very high risk (>20%). PrA Prophylaxis necessary throughout pregnancy and puerperium - high risk (10%-20%). Negot Need for prophylaxis negotiable on a case-by-case basis until further data become available - moderate risk (3%-10%). Nil Postpartum prophylaxis or no prophylaxis - low risk (3%). Back to text 5: Management during pregnancy of medical problems requiring anticoagulation therapy outside pregnancy (consensus levels are described in Box 1) Women with mechanical heart valves require therapeutic doses of anticoagulant medication throughout pregnancy to prevent valve thrombosis or maternal thromboembolic events9 (C1). Women with mechanical heart valves should be managed under joint subspecialty care (C1). The maternal benefits of warfarin (prevention of valve occlusion and systemic embolism) must be balanced against hazards to the fetus (congenital anomalies, intracranial haemorrhage and fetal loss).29 Unfractionated heparin (UH) and low molecular weight heparins (LMWH) are safe for the fetus, but there is still debate as to their therapeutic efficacy in the mother compared with that of warfarin.29-33 UH is associated with higher rates of maternal thromboembolic complications, including fatal events.29,33 There are limited data on the efficacy of LMWH in mechanical valves during pregnancy, but valve thrombosis may occur.34 High rates of maternal valve thrombosis occur if subtherapeutic doses of UH or LMWH are used.9,30 Women should participate in the choice of anticoagulation therapy (C2). In women with other diseases (eg, dilated cardiomyopathy) who require anticoagulation therapy to prevent thromboembolic complications, the use of therapeutic or prophylactic doses of LMWH will depend on the perceived risk of thromboembolism (C1). Back to text

Medicine and the Community The physical, sexual and emotional violence history of middle-aged women: a community-based prevalence study Danielle Mazza, Lorraine Dennerstein, Corrine V Garamszegi and Emma C Dudley MJA 2001; 175: 199-201 Abstract - Methods - Questionnaire - Study participants - Statistical analysis - Results - Domestic violence - Unwanted sexual experiences with someone other than a husband or partner - Childhood abuse - Discussion - Acknowledgement - Reference - Authors' details - - More articles on Obstetrics & gynaecology and women's health - More articles on Social issues Abstract Objectives: To determine current and lifetime rates of the experience of partner abuse and sexual violence in a community-based sample of middle-aged women and compare these to figures obtained in a general practice setting. Design and methods: This research was part of the Melbourne Women's Midlife Health Project (MWMHP), an observational, longitudinal, population-based study of 438 Australian-born women conducted over nine years. In 1996, during the sixth year of the study, we asked the MWMHP participants to complete a self-administered "violence questionnaire", incorporating a modified Conflict Tactics Scale and questions on sexual abuse experienced during childhood and adult life. Results: Of the 395 women remaining in the sixth year of follow-up of the MWMHP, 362 (92%) completed the questionnaire. Overall, 28.5% (n = 101) of the women had experienced some form of domestic violence (physical, sexual or emotional) during their lifetime; 5.5% (n = 15) of women had experienced severe physical abuse in the past year at the hands of a partner; and 11.8% (n = 42) of the women had experienced rape or attempted rape between the age of 16 and the time of our survey. Regarding abuse in childhood, 8.9% (n = 32) of women had experienced physical abuse, 42.3% (n = 152) had experienced non-contact sexual abuse, and 35.7% (n = 128) contact sexual abuse. Compared with the general-practice-based study, rates of childhood physical abuse and penetrative sexual abuse were similar, but rates of less intrusive child sexual abuse were significantly higher in our study. Conclusions: Doctors in all areas of medicine who are dealing with middle-aged women need to be aware of the levels of violence sustained by women throughout their lives. Such experiences may have a substantial impact on women's physical and mental wellbeing. Over the past 20 years, the high prevalence of violence against women has been exposed by rigorous research. Women's Safety Australia,1 a large community-based survey of 6300 women undertaken by the Australian Bureau of Statistics, found that 2.6% of women who currently had partners had experienced an incident of physical violence in the previous 12-month period; 8.0% reported an incident of physical violence at some time during their current relationship; and 1.9% of women had experienced an incident of sexual violence during the 12 months prior to the survey. Mazza and colleagues2 examined the prevalence of physical, sexual and emotional violence experienced by women attending general practitioners in metropolitan Melbourne. Their study found that, of women aged 18 years and over who were in relationships, more than a quarter had been victims of physical or emotional abuse by a partner in the previous year, with one in 10 experiencing severe physical violence. In two Australian studies undertaken in hospital emergency departments,3,4 about 19% of female attendees disclosed histories of domestic violence. It is now recognised that domestic violence has an important influence on the morbidity and mortality of women. Increased utilisation of healthcare facilities,5 chronic pain (particularly pelvic pain),6,7 functional gastrointestinal disorders,8 drug and alcohol dependence or misuse,9-11 attempted suicide11 and psychopathology12-14 are all strongly associated with the experience of violence. The aims of our study were to determine current and lifetime rates of the experience of partner abuse and sexual violence in a community-based sample of middle-aged women and to compare these to figures obtained in a general practice setting in a previous study.2 Methods Questionnaire The "violence questionnaire" that was handed to participants for self-completion was the same as that used in a prevalence study of domestic violence experienced by women attending general practices in Melbourne,2 with which we wanted to compare our study data. The questionnaire incorporated the Conflict Tactics Scale,15 with the modification that respondents were asked whether the tactic had occurred never, once or more than once in the past year, and with the addition of questions on emotional abuse. Physical violence was classified as minor or severe.2 Questions about sexual abuse were derived from the studies of Wyatt16 and Russell,17 both of which used multiple screening questions to allow time for the respondent to become accustomed to the nature of the questions. Childhood sexual abuse was classified as "contact" abuse (involving physical contact) or "non-contact" abuse. (For the purposes of our study, a "child" was defined as a person under 16 years of age.) Study participants The subjects of our study were participants in the sixth year of the Melbourne Women's Midlife Health Project (MWMHP),18 a longitudinal study of a community-based cohort of Australian-born women aged 45-55 years at the beginning of the study. An initial cross-sectional study undertaken in 1991 of a randomly selected community-based sample of 2001 women gathered baseline information regarding women's health experiences and variables related to these experiences.19 The MWMHP study was approved by the Human Research Ethics Committee of the University of Melbourne. Eligibility for the longitudinal phase of the study included women who at baseline were premenopausal, were not taking the oral contraceptive pill or hormone therapy, and had an intact uterus. Of the 779 women eligible to enter the longitudinal study, 56% (n=438) chose to do so. Volunteers for the longitudinal study were more likely than non-participants to report better self-rated health, paid employment, more than 12 years of education, having ever had a Pap smear, exercising at least once a week, and having undergone dilatation and curettage.19 In the MWMHP study, women were interviewed annually face-to-face in their own homes by trained interviewers. Information was collected on a range of variables, including sociodemographic factors, health status, lifestyle behaviours, menopausal status and hormone therapy use. By 1996, when our study was conducted, the retention rate of MWMHP participants was 90% (n = 395). Of these women, 23 who had experienced surgical menopause were not given the violence questionnaire, and a further 10 women refused to complete the questionnaire, leaving 362 women who took part in our study. Statistical analysis The Statistical Package for the Social Sciences (SPSS)20 was used to analyse the sample and determine the prevalence of different forms of violence reported by the women. A statistical comparison was made between the results of our study and the data (previously unpublished) for the subset of women aged 50-69 years (n = 411) from an earlier, general-practice-based study of violence2(Box 1). Ninety-five per cent approximate confidence intervals were used. Results Of the 362 questionnaires available, there were missing data for eight women who did not answer questions on adult violence, four who did not complete the adult sexual abuse questions, and four who did not answer either one or more questions on childhood violence. At the time of completing the violence questionnaire the women were between 51 and 62 years of age (mean, 54.6; SD, 2.42). Sixty-six per cent (238/362) were in paid employment and 77% (277/362) were married or living with a partner. The median parity was 3 (range, 0-9), and 35% of the women had had more than 12 years' education. Domestic violence Overall, 28.5% (101/354) of the women in our study had experienced some form of physical or emotional violence over their lifetime (Box 2). A comparison between our sample and the general-practice-based sample with regard to prevalence of violence experienced in the past year is shown in Box 1. Unwanted sexual experiences with someone other than a husband or partner Overall, 40.8% (146/358) of respondents had, between the age of 16 years and the present, experienced either unwanted sexual advances or been in a situation in which the threat of sexual assault was associated with violence or threat of violence. This included one or more of the following: experiencing rape or attempted rape; encountering sexual advances from someone in authority; or narrowly missing being sexually assaulted. A comparison between the responses in our study and the general practice study is shown in Box 1. Childhood abuse Childhood physical abuse had been experienced by 8.9% (32/358) of the women in our study, and more than one in three women had experienced some form of childhood sexual abuse. Our study showed similar levels of physical abuse and penetrative sexual abuse in childhood, but significantly higher levels of less intrusive child sexual abuse, compared with the general practice sample (Box 1). Discussion Using a longitudinal cohort study such as the MWMHP provides many benefits in a prevalence study. Principal among these is that the women surveyed have been interacting with the research staff for over six years and have therefore built up a degree of trust and comfort with these people. This may facilitate disclosure of sensitive issues such as domestic violence and sexual abuse. A limitation of the study is that in order to obtain some comparative value with other work the questions were delivered by self-administered questionnaire, allowing no opportunity for clarification or exploration of the issues being recorded. Also, the additional questions about emotional abuse had not previously been validated. Of interest is the fact that, despite the participants being a self-selected group of relatively well-educated and health-conscious women, there is a considerable lifetime prevalence of domestic violence among them. The fact that our community-based survey results were similar to those of the general-practice-based survey2 confirms that violence affects the lives of all kinds of women and that it may be a very important contributor to concurrent morbidity occurring at the menopause. In the area of child abuse, our data show similar levels of physical abuse and penetrative abuse but significantly greater levels of less intrusive sexual abuse than those found in the general practice sample. This is surprising given that prevalence rates of most forms of abuse are usually lower in community-based settings than in general practice.2 The greater levels in our sample may reflect a cohort effect or may be owing to the long-term relationship developed over six years of follow-up that may have led to more disclosures. Many studies have demonstrated a relationship between experience of violence and long-term morbidity. Our findings of a high prevalence of violence experienced by women over their lifetime suggest that doctors practising in all areas of medicine need to recognise and explore violence issues when considering middle-aged women's reasons for presenting with ill health. Acknowledgement This study was funded by the National Health and Medical Research Council, the Victorian Health Promotion Foundation, and the Australasian Menopause Society. References Australian Bureau of Statistics. Women's Safety Australia 1996, Canberra: ABS, 1996. (Catalogue No. 4128.0.) Mazza D, Dennerstein L, Ryan V. Physical, sexual and emotional violence against women: a general practice-based prevalence study. Med J Aust 1996; 164: 14-17. de Vries Robbe M, March L, Vinen J, et al. Prevalence of domestic violence among patients attending a hospital emergency department. Aust N Z J Public Health 1996; 20(4): 364-368. Roberts GL, O'Toole BI, Lawrence JM, Raphael B. Domestic violence victims in a hospital emergency department. Med J Aust 1993; 159: 307-310. Stark E, Flitcraft A, Zuckerman D, et al. Wife abuse in the medical setting: an introduction for health personnel. Monograph No. 7. Rockville, Maryland: National Clearinghouse on Domestic Violence, 1981. Schei B. Psycho-social factors in pelvic pain. A controlled study of women living in physically abusive relationships. Acta Obstet Gynecol Scand 1990; 69(1): 67-71. Walling MK, Recter RC, O'Hara MW, et al. Abuse history and chronic pain in women: I. Prevalences of sexual abuse and physical abuse. Obstet Gynecol 1994; 84(2): 193-199. Drossman DA, Leserman J, Nachman G, et al. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med 1990; 113(11): 828-833. Burnam MA, Stein JA, Golding JM, et al. Sexual assault and mental disorders in a community population. J Consult Clin Psychol 1988; 56: 843-850. Winfield I, George LK, Swartz M, Blazer DG. Sexual assault and psychiatric disorders among a community sample of women. Am J Psychol 1990; 147: 335-341. McCauley J, Kern DE, Kolodner K, et al. The "battering syndrome": prevalence and clinical characteristics of domestic violence in primary care internal medicine practices. Ann Intern Med 1995; 123(10): 737-746. Gleason WJ. Mental disorders in battered women: an empirical study. Violence Vict 1993; 8(1): 53-68. Mullen PE, Romans-Clarkson SE, Walton VA, Herbison GP. Impact of sexual and physical abuse on women's mental health. Lancet 1988; 1: 841-845. Beitchman JH, Zucker KJ, Hood JE, et al. A review of the long-term effects of child sexual abuse. Child Abuse Negl 1992; 16: 101-118. Straus MA. Measuring intrafamily conflict and violence: the conflict tactics (CT) scales. J Marriage Fam 1979; 41(1): 75-88. Wyatt GE. The sexual abuse of Afro-American and white-American women in childhood. Child Abuse Negl 1985; 9: 507-519. Russell DEH. The incidence and prevalence of intrafamilial and extrafamilial sexual abuse of female children. Child Abuse Negl 1983; 7: 133-146. Dennerstein L, Smith A, Morse C, et al. Menopausal symptoms in Australian women. Med J Aust 1993; 159: 232-236. Burger HG, Dudley EC, Hopper JL, et al. The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample. J Clin Endocrinol Metab 1995; 80(12): 3537-3545. SPSS for Windows. Statistical package for social sciences. Version 9.0. Chicago, Ill: SPSS Inc, 1999. (Received 2 Mar 2000, accepted 29 Mar 2001) Authors' details Office for Gender and Health, Department of Psychiatry, University of Melbourne, VIC. Danielle Mazza, MD, FRACGP, Research Fellow; Lorraine Dennerstein, AO, PhD, FRANZCP, Director; Corrine V Garamszegi, MWH, SRN, Research Assistant; Emma C Dudley, BSc(Hons), GradDip Epidemiol, Research Fellow. Reprints will not be available from the authors. Correspondence: Professor L Dennerstein, Office for Gender and Health, Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Charles Connibere Building, Parkville, VIC 3050. ldennATunimelb.edu.au Make a comment 1: Number of women experiencing various types of violence among MWMHP* participants compared with the number of women aged 50-69 years reporting these experiences in a general practice setting† Type of abuse MWMHP study (%) General practice study (%) Difference in prevalence between the 2 studies (95% CI) P Adult experience of violence Overall physical and/or emotional abuse by partner in the past year 57 (20.9%) 80 (29.6%) -8.7% (-16.0%, -1.4%) Minor physical abuse by partner in the past year 46 (16.9%) 61 (22.8%) -5.9% (-12.6%, +0.8%) 0.088 Severe physical abuse by partner in the past year 15 (5.5%) 18 (6.7%) -1.2% (-5.2%, +2.8%) 0.550 Emotional abuse by partner in the past year 31 (11.3%) 54 (20.0%) -8.7% (-14.8%, -2.6%) All forms of sexual assault between 16 years of age and the present 146 (40.8%) 135 (33.3%) +7.5% (+0.6%, +14.4%) Unwanted sexual experience between 16 years of age and the present 85 (23.7%) 79 (19.8%) +3.9% (-2.0%, +9.8%) 0.189 Rape or attempted rape between 16 years of age and the present 42 (11.8%) 43 (10.7%) +1.1% (-3.4%, +5.6%) 0.640 Childhood experience of violence Physical abuse 32 (8.9%) 34 (8.6%) +0.3% (-3.7%, +4.3%) 0.856 Non-contact sexual abuse 152 (42.3%) 103 (25.5%) +16.8% (+10.2%, +23.4%) Contact sexual abuse 128 (35.7%) 110 (27.2%) +8.5% (+1.9%, +15.1%) Penetrative sexual abuse 24 (6.7%) 17 (4.2%) +2.5% (-0.8%, +5.8%) 0.129 * MWMHP = Melbourne Women's Midlife Health Project (our study was based on the cohort of women participating in the MWMHP study18 in its sixth year). † The group of women aged 50-69 years was a subset (previously unpublished data, n=411) of the 2181 women aged over 18 years who took part in a general-practice-based study of violence against women.2 ‡ Missing data from incomplete questionnaires were excluded when calculating prevalences. Back to text 2: Lifetime prevalence of domestic violence among middle-aged women (MWMHP* participants) Type of abuse Number of women Prevalence† (95% CI) Overall physical 101 28.5% and/or emotional (23.8%-33.2%) abuse Minor physical 79 22.4% abuse (18.4%-26.2%) Severe physical 31 8.8% abuse (5.9%-11.8%) Emotional abuse 60 17.0% (13.1%-20.9%) * MWMHP = Melbourne Women's Midlife Health Project (our study was based on the cohort of women participating in the MWMHP study18 in its sixth year). † Missing data from incomplete questionnaires were excluded when calculating prevalences. Back to text

Danielle Mazza · Lorraine Dennerstein

The continuing rise in the mean age for childbearing has a widespread impact on the practice of obstetrics. It has been accompanied by an escalation in the rate of caesarean section to around 25% in many tertiary centres and into the 35%–45% range in private practice. The reasons are complex, but advancing maternal age, patient request and obstetric litigation are all factors. Increasing maternal age has brought with it increased exposure to and awareness of the risks of fetal abnormalities. As a "screening test", maternal age alone performs poorly. At best, its sensitivity for detection of Down syndrome is only 30%, with a false positive rate of 5%–14%. Invasive procedures (chorionic villus sampling and amniocentesis) carry a risk to the pregnancy that is often unacceptable, especially for women who have used assisted reproductive techniques. There has been a rapid evolution of non-invasive screening methods. Biochemical screening of maternal serum in the second trimester (involving alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotropin [hCG]; the triple test), coupled with maternal age, has been shown to increase the sensitivity to 60% while maintaining the false positive rate at 5%. Technical advances have increased the application of ultrasonography. It can be used to examine the nuchal fold, which has been found to increase the risk of Down syndrome 10-fold when thickened to more than 6 mm in the second trimester. Large studies at 11–14 weeks' gestation have shown that "nuchal translucency" measurements, in combination with maternal age, increase sensitivity to 75%–80%.1 Combining this with first-trimester biochemical markers (free b subunit of hCG in serum, and pregnancy-associated plasma protein, PAPP-A) may increase the sensitivity to 90%. The latest report of the absence of nasal bone in the first trimester in fetuses with Down syndrome indicates that combination screening could improve the sensitivity to beyond 95% while maintaining a false positive rate of 5%.2 If these projections are substantiated in larger studies, Down syndrome screening will shift to the first trimester, with obvious benefit for the mother. The past decade has seen a veritable explosion in our understanding of fetal physiology and pathology. The concomitant development of ultrasound technology has enabled identification of a higher proportion of fetuses with structural abnormalities. Such diagnoses have made possible early correction of the developmental abnormalities. The most successful fetal therapy is the treatment of severe anaemia from Rhesus isoimmunisation by intrauterine fetal transfusions. Survival rates of over 90% have been achieved. With routine administration of anti-D immunoglobulin, and the consequent fall in the incidence of alloimmunisation, training and maintenance of skill and expertise will be a major challenge. Maternal drug therapies are widely used. They include folate for preventing neural tube defects; digoxin, with or without flecainide, for fetal tachyarrhythmias; corticosteroids for both fetal lung maturation and congenital adrenal hyperplasia; and immunoglobulin for fetal alloimmune thrombocytopenia. Direct invasive fetal procedures have also been tried over the last decade. Shunts have been inserted in fetuses with bladder-outlet obstruction, idiopathic pleural effusion, and congenital cystic adenomatous malformation of the lung. Open fetal surgery, such as for congenital fetal diaphragmatic hernia and fetal sacrococcygeal teratoma, is rapidly giving way to less invasive endoscopic approaches. With increasing maternal age and the widespread use of assisted reproductive technology comes a rise in multiple pregnancies, with the associated impact of prematurity and the specific complication of twin-to-twin transfusion syndrome, which affects 10%–15% of monochorionic twins. In severe cases, mortality is over 90%. Aggressive amnioreduction can result in survivals of about 60%, but up to 20% of the survivors have long term handicaps. Fetoscopic laser coagulation of the communicating vessels has improved the survival rate to 75%–80%, and reduced the long-term handicap rate to 5%.3,4 The principal changes in gynaecological therapy have come from the introduction of effective alternatives to major invasive surgery. The place of endoscopic surgery for treating ectopic pregnancy, investigation of pelvic disorders and removal of benign adnexal masses is established, but the true costs versus benefits of advanced laparascopic procedures, such as for hysterectomy, require further evaluation. The development of improved medical alternatives for treating menstrual disorders, including both oral and direct intrauterine delivery systems, have markedly reduced the number of major operations. Similarly, non-surgical therapies in other spheres of gynaecology, such as urogynaecology, are being developed and evaluated.5 Complementing these changes has been the active participation in the Cochrane Collaboration by women's health professionals, so that the specialty is no longer the holder of Archie Cochrane's "wooden spoon".

Fung Yee Chan · Jeremy J N Oats DM, FRANZCOG

Editorial The health of Australia's mothers and babies Improvements in the collection of perinatal statistics are needed to fill the gaps MJA 1996; 164: 198-199 Childbirth in Australia is relatively safe, as measured by the traditional outcomes of maternal and perinatal mortality. About 1 in 8000 mothers die from all direct, indirect and incidental causes associated with pregnancy and childbirth.1 The perinatal death rate, which includes fetal deaths and neonatal deaths up to 28 days of infants weighing at least 500 g, declined to 8.2 per 1000 births in 1993,2 the lowest level yet achieved. During the last two decades, all States and Territories have developed perinatal data systems that provide valuable information on maternal risk factors and complications and the outcomes of mothers and infants. This information, collected by midwives and medical practitioners, is increasingly being used for research and policy development and discussion about issues relating to pregnancy and childbirth. The 1992 report on Australian mothers and babies drew attention to births to teenage mothers, mothers born overseas and Australian Aboriginals and Torres Strait Islanders, and to factors associated with caesarean births.3 Teenage births. Births to teenage mothers in Australia, of just over 20 per 1000 in the early 1990s, were well below the peak of 55.5 per 1000 in 1971.4 However, these figures give an incomplete picture of teenage pregnancy because only South Australia and the Northern Territory have population-based data about induced abortions. Analysing trends in birthrates fails to indicate the total extent of teenage pregnancy. In 1992, 14 396 teenage mothers gave birth in Australia: 4115 were aged under 18 years (2503 were aged 17; 1133 were aged 16; 357 were aged 15; and 122 were under 15 years). The South Australian data showed that for every 100 births to teenage mothers, there were 82 induced abortions.5 Extrapolating from these data, the estimate of teenage pregnancies nationally in 1992 was in excess of 26 000. Based on these annual figures, about one in five teenagers will become pregnant at some stage between the ages of 15 and 19 years, and one in 10 will give birth. Women born overseas. Of all the women who gave birth in Australia in 1992, more than one in five (22.7%) were born overseas, and 6.3% of all mothers were born in Asia. Of those born in Asia, 3605 women (1.4% of all births) were from Vietnam, 2660 (1%) from the Philippines, 1881 (0.7%) from China, 1365 (0.5%) from Malaysia, 1164 (0.5%) from India and 1046 (0.4%) from Hong Kong. Perinatal outcome did not seem to differ greatly from that of infants of Australian-born mothers,6 but further research is needed to determine the effects of maternal risk factors on outcomes such as birthweight and perinatal mortality. The recent substantial increase in births to Asian-born mothers, notably Vietnamese and Chinese women, places extra demands on health services to ensure that their special needs are met, particularly in Sydney and Melbourne, where disproportionate numbers of people from non-English-speaking backgrounds live. These women often have vastly different cultural beliefs and practices associated with pregnancy and childbirth. Bicultural health workers are increasingly being recognised as having an important role in establishing support networks for these women, familiarising them with the Australian health system, and assisting them in overcoming language and attitudinal barriers. Australian Aboriginals and Torres Strait Islanders. Many aspects of caring for overseas-born women are also pertinent to health services for Australian Aboriginals and Torres Strait Islanders. In 1991, 7027 Aboriginal and Torres Strait Islander women gave birth, and 7257 did so in 1992, accounting for 2.9% of all mothers in both years. Many of these women travel long distances from remote communities to hospitals in larger centres, and thus frequently give birth in an unfamiliar environment. In 1992, one in four births in this group were to teenage mothers and almost one in three of these teenagers had had at least one other child. The average birthweight (3150 g) of babies born to Aboriginal Australians and Torres Strait Islanders was 206 g less than that of all Australian babies, and the proportion of babies that were of low birthweight (< 2500 g) was 12.9%, more than double the rate of 6.3% for all births. Caesarean births. The seemingly inexorable rise in deliveries by caesarean section in Australia continues unabated, with a peak at 18.3% of total deliveries in 1992. South Australia (22.1%) and Queensland (20.9%) consistently have the highest caesarean rates and Tasmania (16.1%) usually the lowest. The caesarean rate of 22.4% for women with private health insurance was more than 40% higher than the rate of 15.8% for women without insurance (partly attributable to more older women in the insured group). Caesarean rates for women with insurance having their first baby increased with maternal age, from 21.9% at 25-29 years to 28.1% at 30-34 years, 37.4% at 35-39 years, and 47.4% at 40-44 years. High caesarean rates were also associated with multiple births (39.2% for twins and 85.3% for triplets, compared with 18% for singleton births), with breech presentation in singleton births (73.8%), and with very low birthweight babies (53.8% for singleton babies weighing 1000-1499 g). Relatively simple measures, such as more detailed recording of the indications for caesarean section and obtaining an opinion from another obstetrician about whether operative intervention is indicated, have proved effective in reducing caesarean rates.7The Royal Australian College of Obstetricians and Gynaecologists should address the issue of high caesarean rates in Australia by requiring regular audits of hospitals and medical practitioners. The quality and usefulness of information about perinatal health can be enhanced in several ways. Firstly, it should be recognised that analysis of trends in teenage pregnancy and the formulation of preventive strategies require data about induced abortions as well as data about births. Secondly, by linking registrations of perinatal and infant deaths to information for all births from the perinatal data systems in every State and Territory, the association between maternal risk factors and outcomes can be better evaluated.8,9 Thirdly, while the patterns of risk factors, type of care and outcomes are remarkably consistent from year to year, shortening the interval between the year of birth and the publication of State and national reports is an important goal. Paul A L Lancaster Director, Australian Institute of Health and Welfare National Perinatal Statistics Unit, University of Sydney, NSW National Health and Medical Research Council. Report on maternal deaths in Australia 1988-90. Canberra: AGPS, 1993. Australian Bureau of Statistics. Perinatal deaths, Australia 1993. Canberra: ABS, 1994. (Catalogue No. 3304.0.) Lancaster P, Huang J, Pedisich E. Australia's mothers and babies 1992. Sydney: AIHW National Perinatal Statistics Unit, 1995. Australian Bureau of Statistics. Births, Australia 1993. Canberra: ABS, 1994. (Catalogue No. 3301.0.) Chan A, Scott J, McCaul K, Keane R. Pregnancy outcome in South Australia 1992. Adelaide: South Australian Health Commission, 1993. Guevara V, Taylor L. The health of mothers born in non-English-speaking countries and their babies, NSW 1990-1993. New South Wales Public Health Bull 1995; 6 Suppl S2: 1-52. Myers SA, Gleicher N. A successful program to lower cesarean section rates. N Engl J Med 1988; 319: 1511-1516. Perinatal Data Collection Unit. The Consultative Council on Obstetric and Paediatric Mortality and Morbidity. Births in Victoria 1983-1992. Melbourne: Department of Health and Community Services, 1994. Gee V. Perinatal statistics in Western Australia. Tenth annual report of the Western Australian Midwives Notification System, 1992. Perth: Health Department of Western Australia, 1993.