Women's health

In reply: As a practising physician, Morton clearly understands the issues faced by prescribers and consumers regarding drug categorisation in pregnancy.1 Currently, the Therapeutic Goods Administration provides no references for the data on which it bases its drug categorisations for pregnancy. It is therefore left to the conscientious prescriber to try to find the data (not always easy or obvious) and then attempt to interpret it in a clinically relevant way. The more narrative approach suggested by Morton is an improvement but would still need clinical context and interpretation for optimal use. The system proposed by the United States Food and Drug Administration (FDA) would provide appropriate referenced data so that clinicians and consumers could see the latest available evidence (and not, as Morton points out, just the limited studies performed up to 30 years ago) about the safety (or otherwise) of medication to enable rational decision making regarding medication use during pregnancy and breastfeeding. The FDA’s proposed new labelling would include contact details of any pregnancy registries, if applicable, for the agent in question.2 At present, there are over 20 pregnancy registries collecting prospective data on the effects of exposures, including antiepileptic drugs and vaccines, as well as registries for pregnant women being treated for chronic medical conditions such as rheumatoid arthritis and HIV/AIDS.3 It is unfortunate that Australian regulators have not properly discussed these issues with interested professionals in the past few years. Even if we cannot remain world leaders in this field, it behoves us to at least embrace innovation occurring in other parts of the world.

Debra S Kennedy

Objectives: To document temporal trends in maternal overweight and obesity in Australian women and to examine associations with pregnancy outcomes....

H David McIntyre MB BS, FRACP, MD · Kristen S Gibbons BMaths(Hons), BInfoTech · Vicki J Flenady MMedSc(ClinEpid) · Leonie K Callaway MB BS, PhD, FRACP

When “should not” becomes “must not” — how mandatory compliance with guidelines can threaten professional independence There is a proliferation of rules and red tape at all levels of society. In New South Wales, for example, the Department of Health has been generating around 70–100 policy directives a year. Among other things, such directives tell obstetricians when and how to deliver babies — compliance is mandatory, under threat of disciplinary action and loss of indemnity cover. One of the most prominent recent directives, PD2010_045 (Maternity — towards normal birth in NSW), requires a reduction in caesarean section rates to 20% by 2015,1 a target that is illusory and possibly dangerous. Others are worse. Policy directive PD2007_024 (Maternity — timing of elective or pre-labour caesarean section) states: The risk of respiratory morbidity is increased in babies born by caesarean section before labour, but this risk decreases after 39 completed weeks. Therefore elective or pre-labour caesarean section must not routinely be carried out before 39 completed weeks. These findings are supported by recent studies.2 This text is taken almost verbatim from a guideline of the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom3 and, at the time, accorded with the relevant Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) guideline on the timing of elective caesarean section, the wording of which has since been softened slightly.4 However, there is one very substantial difference: the “should not” of NICE and RANZCOG became a “must not”. The NICE guideline was produced by a committee of 16 members, two of whom were obstetricians. Nicholas Fisk, then chairman of the Royal College of Obstetricians and Gynaecologists (RCOG) Scientific Advisory Committee, strongly criticised the outcome and stated that the committee “selectively interpreted” the facts to suit its case.5 Timing of elective caesarean delivery is a complex issue. There are factors (mainly related to pulmonary maturity) suggesting delay until 39 weeks’ gestation, and others (mainly related to unexplained stillbirth6,7) supporting the traditional timing between 38 weeks and 38 weeks and 6 days. A large randomised controlled trial (RCT) or a carefully conducted observational study employing propensity scoring would be required to provide a solid evidence base. For the moment it remains a matter of opinion, and RCOG, NICE and RANZCOG can, and should, express expert opinion and review the available evidence. Guideline committees and their products make an important contribution to improving clinical practice, and the voluntary work of countless individuals in this regard should not be denigrated. However, the situation may be altered completely once bureaucrats become involved. Changing the “should” of a College guideline to a “must” in a NSW Health policy directive has major implications. PD2007_024 effectively forbids doctors in NSW public hospitals to schedule routine elective caesarean section before 39 weeks. Anyone doing so risks disciplinary action and may forfeit their indemnity cover. PD2007_024 is not currently supported by high-level evidence, and even if there were solid data from a large RCT or a meta-analysis, it would be inappropriate to stipulate “mandatory compliance”. Evidence-based medicine has great potential to improve patient care, but it is a tool to inform clinicians, not an excuse to switch off one’s brain. As recently argued in the case of mesh use in pelvic reconstructive surgery,8 guidelines derived from a large RCT (or a valid meta-analysis of appropriate trials) are of limited use as a guide to the care of an individual patient if that patient is far off the trial sample mean in predictors of outcome. The Term Breech Trial9 is an excellent example. If there is a very high likelihood of an uncomplicated birth for an individual woman (eg, fast progress, small baby, previous normal births), a clinician may want to ignore the findings of the Term Breech Trial when deciding how to advise her. The process of starting with some initial information (probabilities of events of interest) and combining it with data related to an individual case or circumstance has been mathematically formalised by statisticians as “Bayesian updating”.10-13 Information from a clinical guideline, prevalence study or meta-analysis provides the “prior probability”, the data related to the individual case at hand are embodied in the “likelihood”, and the application of Bayes’ theorem13,14 gives the updated “posterior probability” on which a decisionmaker can act. This implies that even the best evidence in literature and guidelines can provide only prior probabilities. It is our job to adapt these to the clinical management of the individual patient, generating posterior probabilities that have been updated by the relevant particulars of the patient and processed by clinical intuition and common sense. However, in a trend that is encouraged by guidelines and policy directives, clinicians increasingly omit this updating process. Once a document — a seminal paper, a guideline, a policy directive — is published, it is likely to be interpreted cautiously (ie, as widely as possible) because of the litigious, risk-averse nature of our society. We do not particularise to the individual patient because our work environment strongly discourages doing so. Finally, even if a guideline is produced after an optimally diligent process and published so rapidly that it is up to date at its launch, it still freezes current best practice. Inevitably, today’s best practice will be obsolete tomorrow. Practice guidelines therefore have the potential to slow down progress, and unthinking adherence to such documents is unlikely to deliver the best outcomes to the greatest number of individuals. The expert system of our brains, employed in the assessment and treatment of the individual patient — and using relevant prior information from evidence-based sources — is a potentially superior tool when compared with the replication of a course of action outlined in a document issued by a government agency or professional body. It is time to reassert our professional independence.

Hans Peter Dietz MD, PhD, FRANZCOG · Barrie J Stokes BSc, MMath

Objective: To document the prevalence of polycystic ovary syndrome (PCOS) and its associated characteristics in a sample of urban Indigenous women.Design: A cross-sectional survey of Indigenous women, including biochemical and anthropometric assessments. PCOS was assessed using the National Institutes of Health 1990 criteria.Setting and participants: Indigenous women, aged 15–44 years, living in a defined area in and around Darwin, Northern Territory, Australia, September 2003 – March 2005.Main outcome measures: Proportion of participants with PCOS overall and measures of obesity.Results: Among 248 women eligible for assessment, the proportion who had PCOS was 15.3% (95% CI, 10.8%–19.8%). The proportion with PCOS was similar across age groups, but was significantly higher (P = 0.001) in women with a body mass index (BMI) of ≥ 30.0 kg/m2 (30.5%) compared with women with a BMI of 25.0–29.9 kg/m2 (8.2%) or a BMI of < 25.0 kg/m2 (7.0%).Conclusions: A high proportion of these Indigenous women had PCOS. The significant relationship with obesity gives a strong rationale for screening for PCOS during routine care of Indigenous women who are obese and of reproductive age.

Jacqueline A Boyle FRANZCOG, MPH · Joan Cunningham ScD · Kerin O'Dea PhD · Terry Dunbar BBus, MProfEdTraining, PhD Candidate · Robert J Norman MD, FRANZCOG, FRCPA

To calculate cost savings to the Australian federal and state governments from the reduction in twin and triplet birth rates for infants conceived by assisted reproductive technology (ART) since 2002, and to determine the number of ART treatment programs theoretically funded by means of these savings.

Georgina M Chambers BAppSci(MLS), MBA, PhD · Peter J Illingworth MD(Hons), FRANZCOG, CREI · Elizabeth A Sullivan MD, MPH, FAFPHM

To describe the clinical outcomes for all HIV-serodiscordant couples attending an assisted reproduction program.

on behalf of the CVI Study Group

Objective: To describe why, when and to whom general practitioners refer women with symptoms possibly attributable to cervical, endometrial or ovarian cancers, and to identify patient and GP factors that predict referral to either a gynaecologist or a gynaecological oncologist.Design and setting: A national survey of GPs between 1 April and 31 August 2009 using a randomised incomplete block design based on case vignettes, and using a self-completed postal or online questionnaire.Participants: A sample of GPs, stratified by location and randomly selected from a database of GPs maintained by the Australasian Medical Publishing Company.Main outcome measures: Proportion of vignettes that were deemed to reflect a high probability of cancer being referred; and the patient and clinician factors that were the strongest predictors of referral.Results: Of the 3082 GPs who were selected for participation, 1402 responded, giving a response rate of 45.5%. Overall, for vignettes identified as describing women with a high probability of cancer, 75% were referred by metropolitan GPs and 73% by rural practitioners. Metropolitan GPs were significantly more likely to refer women in scenarios indicative of endometrial cancer than rural GPs. For all three cancers, GPs were significantly more likely to refer a patient to a gynaecologist (between 70.8% and 95.4%) than a gynaecological oncologist. Metropolitan GPs had significantly greater access to both private and public gynaecological oncologists than their rural counterparts. Referral rates were higher for ovarian and cervical cancer (83% and 80%, respectively) and lower for endometrial cancer (68%). For all three cancers, patient factors were stronger predictors of referral than the demographic factors of participating GPs.Conclusion: There appears to be significant variation in referral practices among GPs and this variation is greater for endometrial cancer, for which there are currently no evidence-based clinical practice guidelines in Australia. There is a need for further research into understanding the basis of these differences, including a review of the existing guidelines for ovarian and cervical cancer and the development of guidelines for endometrial cancer.

Shanthi A Ramanathan BA, MHlthSci(Hons) · Genevieve Baratiny BSc(Hons), PhD · Nigel P Stocks MD, FRACGP, FAFPHM · Andrew M Searles BEc, MMedStats, PhD · Russell J Redford BSc, DipCompSc

Safe, legal abortions and comprehensive reproductive health care are crucial for women, but there is still a long way to go It was the first autopsy I attended and it left a lifelong impression. The year was 1970, and I was a medical student in Dublin. A young woman had come from the country to work in a bank. She became unwell and was cared for by her landlady, who diagnosed the flu. When her condition worsened, she refused a doctor until she was moribund. By the time an ambulance was called, she had developed septicaemia, and she died soon after reaching hospital. The autopsy revealed extensive peritonitis and infected placental tissue in the uterus, which showed signs of interference, although by whom, or where, or when was never established, as was often the case. As a junior doctor in Papua New Guinea in the 1970s I was to see more such deaths among women who had wanted to conceal their pregnancies, consuming toxic herbs or using sticks to try to induce an abortion. In particular, I remember a nursing student from a distant province. Top of her class in her home village, she had come to Port Moresby to train. Like the Irish bank-teller, she was too terrified to seek help until it was too late. Those experiences provided much of my motivation for advocating — with many others — reforms in women’s reproductive health care in Australia, in particular the introduction of mifepristone (RU486) for medical abortion and the decriminalisation of abortion in state legislation. Over 40 years, I have seen many advances in my chosen specialty of obstetrics and gynaecology. When I began training, the only use of ultrasound was to locate the placental site after antepartum haemorrhage. Now, sophisticated ultrasound techniques are used on a daily basis to assess both normal and abnormal pregnancies. Perinatal mortality rates have dropped to a fraction of what they were due to closer fetal surveillance, and we have better management of diabetes and pre-eclampsia, and better facilities for care of pre-term babies. In-vitro fertilisation now enables many women, who would have previously remained childless, to give birth. There has been great progress in hormonal contraception, and the progestogen intrauterine device has made a huge difference to management of menstrual disorders, so that hysterectomy, common 20 years ago, is much less needed. However, I believe that among all these advances, the most dramatic and beneficial development in the provision of women’s health care in this time has been the change from unsafe, clandestine abortion to safe, open practice. In Australia, as in most other developed countries, there has been abortion law reform. Of course, there is still a long way to go. Only some states and territories have reformed or decriminalised their quaintly worded 19th-century legislation. But even without reform, case law has made the provision of abortion less uncertain for doctors, and more accessible for women. Medical abortion using mifepristone remains available only in restricted circumstances in Australia, and generally only to urban women; hopefully, in the near future, the drug will be accessible to all Australian women. Abortion is now much more widely discussed in society generally, as well as in the medical literature. There is increasing recognition that abortion is an important health issue for Australian women. However, there are still many countries in the developing world, including Papua New Guinea, where women die or suffer chronic ill health from complications of unsafe abortion. Making abortion, in particular medical abortion, widely and safely available has the potential to prevent many maternal deaths. Like everybody else interested in improving women’s health, I would like to see abortion rates reduced in Australia and elsewhere. However, this needs to be achieved by reducing the rates of unplanned and unwanted pregnancies, rather than by forcing reluctant women to continue their pregnancies. In Australia, certainly, effective contraception is available, including a variety of hormonal preparations. There are intrauterine devices with minimal side effects and long life spans, and the morning-after pill can be bought over the counter in Australian pharmacies. Yet our abortion rates are still more than three times higher than those of Belgium, the Netherlands and Scandinavia, where there are very liberal abortion laws and accessible abortion services. Clearly, we are not providing effective sex education at a standard equal to these countries. Little attention is given to contraceptive information and services in the course of antenatal and postnatal care, especially in the public sector. A more integrated system of women’s reproductive health care is needed, in which sexual health care, contraceptive advice and provision, prepregnancy and pregnancy advice, and care during and after pregnancy and birth would complement one another. Such a system would also incorporate abortion provision into mainstream health care. All women should have access to appropriate information and care in pregnancy, regardless of whether or not they intend to continue that pregnancy. I look forward to working towards improvements in abortion provision, and in other aspects of women’s reproductive health care, for the rest of my professional life.

Caroline M de Costa PhD, FRANZCOG, FRCOG

Professor Sir Graham Collingwood Liggins (24 June 1926 – 24 August 2010)Sir Graham Liggins, who died last year aged 84, made arguably the greatest contribution of any Australian or New Zealand practitioner to modern obstetric practice. Educated at the University of Otago, his work in the 1960s on causes of prematurity led to the publication of a landmark randomised controlled trial. This 1972 report demonstrated a two-thirds reduction in the incidence of respiratory distress syndrome in preterm neonates who had received antenatal corticosteroids. Although not immediately universally accepted, subsequent work substantiated the benefit of this simple, ground-breaking treatment. The administration of antenatal glucocorticoids, now standard obstetric practice, is widely acknowledged as the single most effective therapy in minimising mortality from prematurity. Image courtesy: Bruce Jarvis, Auckland, New Zealand. Professor Ian Frazer (6 January 1953 –)Named Australian of the Year in 2006, Professor Ian Frazer’s development of a vaccine against the human papillomavirus (HPV) is arguably the most significant advancement in the prevention of gynaecological cancer in modern times. After completing medical studies in his native Scotland, he emigrated to Melbourne. Initial research into HIV-related immunodeficiency led to work on HPV and subsequently the creation of virus-like particles, from which the HPV vaccine would eventually develop. The recipient of numerous scientific and medical accolades, including the 2009 Australian Medical Association Gold Medal, he is currently Director of the Diamantina Institute at the University of Queensland. Sir Albert William Liley (12 March 1929 – 15 June 1983) Born and educated in Auckland, the “Father of Fetology” was a pioneer in maternal and fetal physiology. Practising at a time when Rhesus isoimmunisation was a major disease, he developed a graph that enabled interpretation of amniotic bilirubin levels into prognostic “Liley’s zones”, allowing more accurate prediction of stillbirth risk. Over 4 years, Rhesus-associated perinatal mortality in Auckland fell from 22% to less than 9%. Liley is also credited with the first successful intrauterine fetal transfusion, in 1963. This case laid the foundation for the evolution of fetal therapy and the acceptance of the fetus as a person in his or her own right in the decades that followed. Ian Alexander McDonald (1 April 1922 – 4 September 1990)Ian McDonald was born in Perth, Western Australia, but throughout his career practised mostly at the Royal Melbourne Hospital. His most significant contribution to modern obstetric care is the cervical cerclage (suture) that bears his name. The concept of inserting a stitch to close an incompetent cervix was first introduced by Vithal Shirodkar in 1955. In 1957, McDonald published a technically easier approach: a simple purse-string suture involving circumferential bites around the cervix at the level of the internal os, without the need for bladder dissection. The McDonald cerclage now forms part of the standard surgical armamentarium of the contemporary obstetrician. Image courtesy: Archives of the Royal Melbourne Hospital. George Simpson (14 May 1899 – 24 November 1960)Born in Clifton, Victoria, the young George Simpson was introduced to a number of ministers from the Presbyterian Church, including Reverend John Flynn. This was the beginning of a collaboration from which the Aerial Medical Service (later known as the Royal Flying Doctor Service of Australia) would eventually emerge. Simpson graduated from the University of Melbourne and, in 1927, undertook a 3-month survey to assess the medical needs of the Australian outback. In that year, he undertook the first unofficial flight of the Service, evacuating a miner with a spinal fracture from Mount Isa. Later, he established Melbourne’s first family planning clinic. Appointed an Officer of the Order of the British Empire in 1957, he died 3 years later aged 61. Image courtesy: National Archives of Australia

Jennifer N Lees MB BS · Colin A Walsh MB BCh, BAO, MRCOG

Incorrect symbol: In the supplement to the 19 September 2011 issue of the Journal, “Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline” (Med J Aust 2011; 195: S65-S112), there was an error in Algorithm 5. Under Pharmacological management, the third evidence-based recommendation contained a ≥ symbol instead of a ≤ symbol. The recommendation should read: Metformin could be used alone to improve ovulation rate and pregnancy rate in women with PCOS who are anovulatory, have a BMI ≤ 30 kg/m2 and are infertile with no other infertility factors. The html and pdf versions of this article have been corrected.

Helena J Teede · Marie L Misso · Amanda A Deeks · Lisa J Moran · Bronwyn G A Stuckey · Jennifer L A Wong · Robert J Norman · Michael F Costello

To the Editor: We wish to report Queensland data regarding vitamin D levels during pregnancy, to contribute to the debate on screening during pregnancy raised in Lau and colleagues’ article1 and Ebeling’s accompanying editorial.2 In 2009, we measured serum 25-hydroxyvitamin D (25[OH]D) levels, using a DiaSorin radioimmunoassay (DiaSorin, Stillwater, Minn, USA), in 75 women who attended general antenatal clinics at the Royal Brisbane and Women’s Hospital (RBWH) and Mater Mothers’ Hospital. Both institutions’ Human Research Ethics Committees approved the study. Participants gave written consent. The RBWH Private Practice Fund covered pathology expenses. Fifty-seven of the 75 women were white; the remainder were Asian (five), Indian Subcontinental (seven), Polynesian (four), Middle Eastern (one) and black African (one). Mean age was 28.6 years (SD, 5.4 years), mean gestational age was 28.7 weeks (SD, 2.7 weeks) and mean body mass index was 26.4 kg/m2 (SD, 5.5 kg/m2). Median serum 25(OH)D level was 92 nmol/L (interquartile range, 74–118 nmol/L). Using cut-offs of < 25 nmol/L for deficiency and < 50 nmol/L for insufficiency, two women were vitamin D deficient (one was Middle Eastern and one was South-East Asian) and five women were vitamin D insufficient (three were white, with lowest serum 25[OH]D level of 40 nmol/L, and two were Indian Subcontinental). The result of a Fisher exact test suggested an association with ethnicity (P = 0.01). A χ2 value of 21.36 (P < 0.001) confirmed that the proportions of deficiency and insufficiency in our study population were significantly different to those of Lau et al’s study population. The majority of serum samples (40) were obtained in winter, followed by spring (21), summer (10) and autumn (three). Six of the seven results of deficiency and insufficiency were from samples obtained in winter; the other was from a sample obtained in September. Excluding autumn, categorical and continuous analyses showed borderline significant variation of 25(OH)D level by season (Mann–Whitney U test [P = 0.08] and Kruskal–Wallis test [P = 0.08], respectively). Several factors may account for the difference in vitamin D deficiency and insufficiency prevalence between our study and that of Lau et al. The most obvious is the “Sunshine State” factor, because several studies in southern states have reported higher prevalence of vitamin D insufficiency than in our study.3-5 In Lau et al’s study, a large proportion of women were at high risk of vitamin D deficiency (only 19% were white) and the women were recruited from a gestational diabetes mellitus clinic. Care should be taken in extrapolating such findings to the wider population. Although our study was not population based, it included a majority white and healthy general obstetric population, rather than sampling at a clinic where women are at high risk of vitamin D insufficiency. We are not asserting that gestational vitamin D levels are unimportant. The increasing incidence of rickets in Australia,2 along with other potential hazards, dictate that increased awareness is mandatory. However, as opposed to routine screening in all pregnancies, our data suggest that local assessment of vitamin D status and demographic risk factors (in gestational diabetes mellitus and general obstetric populations) should be the priority.

Donald S A McLeod · Katherine A Scott · Karin M C Lust · H David McIntyre

Polycystic ovary syndrome: an introductionFunding: The development of this guideline was funded by the Australian Government Department of Health and Ageing, through the Jean Hailes Foundation for Women’s Health on behalf of the PCOS Australian Alliance. Editorial independence: This guideline is editorially independent. The funders were not involved in the development of the guideline and have not influenced the scope or recommendations of this guideline. Polycystic ovary syndrome (PCOS) has recently been shown to affect a striking 12%–21% of Australian reproductive-age women, being more common among those who are overweight or of Indigenous background.1 PCOS can be a frustrating experience for women, a complex syndrome for clinicians and a scientific challenge for researchers, and is a major public health concern. Although reproductive features are prominent, PCOS has potential for major metabolic consequences, including obesity and related type 2 diabetes mellitus (DM2) as well as cardiovascular disease (CVD), all of which are currently national health priority areas.2,3 It also has significant mental health and psychological impact, impairing quality of life (QoL).4,5 Because increased obesity exacerbates incidence, prevalence and severity of PCOS, and weight loss improves reproductive, metabolic and psychological features, lifestyle change should be first-line therapy for PCOS.6 It is estimated that 70% of Australian women with PCOS remain undiagnosed;1 clinical practice is inconsistent;7 psychological issues are under-recognised;5 and there is little focus on lifestyle and prevention, with most services targeting infertility and costly assisted reproductive technology. Given the prevalence, disease burden, health costs and clear gaps in care, PCOS is highlighted in national policy and has been prioritised by government, with funding for development of a national PCOS evidence-based guideline and translation of evidence into practice. Here, we present a brief general clinical introduction to PCOS, concise guideline algorithms and clinical pathways and a comprehensive summary of the Evidence based guideline for assessment and management of PCOS (available at http://www.managingpcos.org.au/pcos-evidence-based-guidelines).8 PresentationPCOS has significant and diverse implications, including reproductive (hyperandrogenism, hirsutism, anovulation, infertility), metabolic (insulin resistance [IR], impaired glucose tolerance, DM2, adverse cardiovascular risk profiles) and psychological features (increased anxiety and depression and worsened QoL).9 Presentation varies across the life span. Hyperandrogenic features are often most prominent among adolescents,10 fertility issues most prominent among women in their 20s and 30s, and metabolic challenges most notable after this.11 The propensity to weight gain and psychological challenges affect all ages, and metabolic features can occur early, especially among those who are overweight. Variations across ethnic groups should also be noted, such as fewer hyperandrogenic dermatological features and more severe metabolic features in Asian women, even without weight gain. Indigenous women appear to have a higher prevalence and severity of PCOS.1,12 The clinical presentation of PCOS is outlined in Figure 1. Figure 1. The aetiological, hormonal and clinical features of polycystic ovary syndrome Adapted and reproduced from Teede at al with permission from the Royal Australian College of General Practitioners.13 Diagnosis and investigationsDiagnosis of PCOS is now largely based on the Rotterdam criteria,14 which are inclusive of the original National Institutes of Health (NIH) criteria15 and require two of three key features: oligo- or anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries on ultrasound (Figure 2). However, as noted, PCOS phenotypes vary widely depending on life stage, genotype, ethnicity and environmental factors, including lifestyle and body weight. Diagnostic investigations must exclude other causes and include thyroid function tests and prolactin and follicle-stimulating hormone (FSH) levels.9 For diagnosis, androgen levels should be measured; however, optimal methodology remains very controversial and is addressed in Section 1. Vaginal ultrasound is often needed for diagnosis where hyperandrogenism and anovulation are not both clearly present. Ultrasound can check for polycystic ovaries and endometrial thickness. However, vaginal ultrasound should be reserved for sexually active women. The role of ultrasound remains controversial for adolescents, among whom a polycystic appearance of the ovaries is very common, potentially leading to overdiagnosis;16 hence, this area is also covered in the guideline. Other diagnostic investigations are based on clinical discretion. Screening is also vital to detect PCOS complications and guide prevention and treatment. Comprehensive cardiovascular risk-factor screening, including family history, ethnic group, body mass index (BMI), waist circumference, smoking status, blood pressure, glycaemic status (oral glucose tolerance test [OGTT]) and lipid profile, is important at diagnosis and should be repeated with a frequency informed by metabolic risk (eg, body weight, age, family history, ethnicity) as outlined in Section 3. Optimal methodology for the routine screening for prediabetes and DM2 has been controversial in PCOS, but because lifestyle change and metformin improve IR in PCOS, and among other at-risk groups these measures have been shown to dramatically reduce progression to diabetes, early detection, including detection of prediabetes, is vital and is addressed in the guideline. Figure 2. The Rotterdam criteria for diagnosis of polycystic ovary syndrome (PCOS)14 The Rotterdam criteria are inclusive of National Institutes of Health (NIH) criteria in that a woman diagnosed with PCOS using the NIH criteria will also meet Rotterdam criteria; however, a woman diagnosed with PCOS using Rotterdam criteria may not meet NIH criteria. AetiologyPCOS is an endocrine disorder, the pathophysiology of which remains unclear. Genetic and environmental contributors combine with obesity, ovarian dysfunction and hormonal drivers to contribute to the aetiology of PCOS.17,18 The underlying hormonal imbalance may include a combination of increased androgens and/or hyperinsulinaemia secondary to IR (Figure 1). Greater understanding of cause has been hampered by a lack of ideal methods to assess either hyperandrogenism or IR. Hyperandrogenism is detected in around 60%–80% of women with PCOS, and IR is a pathophysiological contributor in around 50%–80%.19 Obesity increases reproductive features — hyperandrogenism, hirsutism, infertility and pregnancy complications — both independently and by exacerbating PCOS.20,21 Furthermore, obesity exacerbates the PCOS-related increased risk factors for impaired glucose tolerance, DM2 and CVD,22 while obesity also affects psychological features of PCOS. Clinical featuresPCOS is a chronic condition that manifests across the life course. Women with PCOS present with psychological,5,23 reproductive24 and metabolic implications. In terms of psychosocial implications, challenges to feminine identity and body image due to obesity, acne, excess hair, infertility and long-term health-related concerns compromise QoL and adversely affect mood and psychological wellbeing. With a higher prevalence and greater severity of depression and anxiety, low self-esteem, negative body image, and psychosexual dysfunction,5,25 assessment of psychological functioning in women with PCOS is vital. This is relevant to clinical care as mood disturbance, in turn, impairs QoL and adversely affects ability to self-manage and optimise lifestyle. Optimal approaches to screening and assessment of psychological functioning in PCOS are unknown and recognition is generally poor; hence, this area was prioritised in the guideline (Section 4). If mood disturbance is detected during screening, further assessment and management is required. Reproductive and reproductive hormonal features are often the best-recognised features in PCOS as they form the basis of the diagnostic criteria.14 These include clinical and biochemical hyperandrogenism, anovulation, subfertility and polycystic ovaries on ultrasound. A key point is that fertility is not necessarily impaired in all PCOS cases — some women conceive without medical intervention, depending on the severity of the condition. Age and BMI have a critical role in infertility risk in PCOS; therefore, early family initiation (before the age of 30–35 years) combined with maintaining a BMI < 31 kg/m2 is ideal for increasing the chance of conceiving. Metabolic features of PCOS include an apparent propensity for excess weight gain, an increased prevalence of prediabetes and DM2, a 5–10-fold risk of progression from prediabetes to DM2 and a 4–7-fold risk of DM2.11 Cardiovascular risk factors are increased and CVD appears more prevalent among women with PCOS despite inadequate long-term studies to appropriately address this question.22 In the general population, IR is a predictor of CVD.26,27 Women with PCOS also have an increased prevalence of metabolic syndrome (associated with an increased risk for DM2 and CVD),28 individual risk factors for CVD and clinical signs of atherosclerosis,29,30 which are all exacerbated by obesity. Women with PCOS are therefore a population at high risk of developing DM2 and CVD. As DM2 and subsequent CVD are the primary cause of death in Australian women, any increase in prevalence will have significant public health implications. It is also important to note that relatives of women with PCOS may have increased risk of diabetes and increased CVD risk factors. Metabolic features are often poorly appreciated in PCOS; hence, recommendations on screening and assessment of DM2 and CVD risk factors are covered in the guideline. Obesity or excess weight is a major cause of chronic disease in Western countries. In Australia, 56% of the adult population is overweight (BMI ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2). In 2007, 31% of women were overweight and 24% of women were obese. Recent data from the Australian Longitudinal Study on Women’s Health showed that among 26–31-year-old women, 20.4% were overweight and a further 13.9% were obese.31 Overall, the proportion of adults who are obese has doubled in the past 20 years.32 Obesity is now the primary cause of chronic disease among Australian women, with adverse outcomes including DM2 and CVD.31 Obesity has a specific impact on women’s reproductive health, increasing the prevalence and severity of PCOS, infertility, pregnancy complications, gestational diabetes and fetal pregnancy complications, with substantial and escalating economic costs.33,34 Indeed, the adverse impact of obesity on fertility, exacerbated by delay in childbearing, is resulting in a significant social, health and economic burden in Australia.35 Given the dramatic increase in obesity, the guideline addresses weight loss and prevention of weight gain through lifestyle intervention (Section 5). ManagementTherapy should focus on both the short- and long-term reproductive, metabolic and psychological features. It is important to address psychological factors initially to optimise self-efficacy, readiness to change and sustainability of lifestyle interventions as well as to improve QoL. Screening, assessment and treatment of depression and anxiety are vital, and recognition of other aspects of emotional wellbeing, including poor body image, sexual dysfunction, disordered eating and eating disorders — all more common among women with PCOS — is important for improving QoL. Optimal approaches to screening and assessment of emotional wellbeing among women with PCOS remain unclear and are also addressed in this guideline (Section 4). Once recognised, poor emotional wellbeing and mood disorders should be addressed to improve QoL among women with PCOS. PCOS management should focus on support and education, and needs to strongly emphasise healthy lifestyle, with targeted medical therapy as required. Given the putative aetiological role of IR and obesity in PCOS, prevention of weight gain is important across the life span. Furthermore, among those who are already overweight, multidisciplinary lifestyle intervention aimed at improving IR and aiding weight management is recognised as first-line therapy for most women who are overweight.6 Modest weight loss of 5%–10% of initial body weight significantly reduces IR and has been demonstrated to ameliorate many of the features of PCOS.6 Optimal methods for achieving weight loss and prevention of weight gain remain unclear and are a focus of this guideline (Section 5). Short-term diets rarely lead to permanent weight loss, and lifestyle change requires behavioural change. Health-coaching principles can be incorporated to optimise readiness to change, and include education and accurate risk perception, which can assist with motivation through education and tailoring the knowledge relevant to the individual. Once ready to change, support is needed to convert this to action with effective strategies including patient-driven goal setting (eg, 5% of body weight loss, small improvements in exercise), so that these incremental changes are seen as achievements. Multidisciplinary involvement in care is often useful in the early stages to support education and behaviour change and is explored further in this guideline (Section 2). In addition to lifestyle measures, therapy in PCOS can be targeted to specific clinical presentations. Although there is a plethora of options for therapy in PCOS, in this guideline we have focused on the most controversial interventions, where little guidance is currently available. Assessment of mood disorders and emotional wellbeing is prioritised in the guideline, yet treatment is well guided by a range of existing clinical guidance tools.36-43 Hirsutism treatment is also guided by a recent and comprehensive international statement,44 so these areas are not covered in the guideline. Infertility remains a highly controversial area and is covered in detail in the guideline (Sections 6, 7 and 8). DM2 and CVD risk assessment is included (Section 3); yet treatments for these established complications are covered in other specific national evidenced-based guidelines,45,46 and have not been reproduced here. Optimal therapy for infertility is one of the most controversial areas of PCOS management and includes lifestyle interventions, medical and surgical ovulation induction, consideration of bariatric surgery for preconception weight loss, and in-vitro fertilisation (IVF). All these areas are covered in the guideline except for IVF therapy, as this was deemed to be of a lower priority than the first-line lifestyle measures and ovulation induction therapies. Potential targeted treatment options for PCOS are summarised in Box 1. Box 1. Summary of potential targeted treatment options for polycystic ovary syndrome (PCOS) Oligomenorrhoea/amenorrhoea Lifestyle change (5%–10% weight loss + structured exercise) Oral contraceptive pill (OCP) (low oestrogen doses [eg, 20 μg] may have less impact on insulin resistance)47 Cyclic progestins (eg, 10 mg medroxyprogesterone acetate 10–14 days every 2–3 months) Metformin (improves ovulation and menstral cyclicity) Hirsutism Choice of options depends on patient preferences; impact on wellbeing; and access and affordability:44 Self-administered and professional cosmetic therapy are first line (laser recommended) Eflornithine cream can be added and may induce a more rapid response If cosmetic therapy is not adequate, pharmacological therapy can be considered Pharmacological therapy Medical therapy if patient is concerned and cosmetic therapy is ineffective/inaccessible/unaffordable Primary therapy is the OCP (monitor glucose tolerance in those at risk of diabetes) Anti-androgen monotherapy (eg, spironolactone or cyproterone acetate) should not be used without adequate contraception Trial therapies for ≥ 6 months before changing dose or medication Combination therapy — if ≥ 6 months of OCP is ineffective, add anti-androgen to OCP (twice daily spironolactone > 50 mg or cyproterone acetate 25 mg/day, days 1–10 of OCP) Infertility Lifestyle intervention (to optimise preconception health and fertility and reduce pregnancy and long-term complications) Advise on folate, smoking cessation and optimal weight and exercise before conception Given age-related infertility, advise women to optimise family initiation Infertility therapies may include clomiphene citrate, metformin, gonadotrophins, surgery and in-vitro fertilisation. Cardiometabolic risk Lifestyle change: > 5% weight loss in those who are overweight reduces diabetes risk by approximately 50%–60% in high-risk groups48 Optimise cardiovascular risk factors Consider metformin* (reduces the risk of diabetes by ~ 50% in adherent high-risk groups)48 Adapted and reproduced with permission from Teede et al,9 not generated directly from the evidence-based guidelines. Hirsutism therapy is summarised from existing hirsutism clinical practice guidelines.44 * Metformin and the OCP are not currently approved for use to manage PCOS by many regulatory bodies. The OCP is indicated for contraception and metformin for diabetes. However, their use is supported by evidence and is recommended by international and national specialist societies.49 Considerations for Indigenous women with PCOSThe prevalence of PCOS among Indigenous Australian women appears to be as high as 21% by the Rotterdam criteria12 and the NIH criteria,50 and increases with rising BMI.12 In a group of Indigenous women with PCOS, 30.3% were obese and 7.0% had a normal BMI.12 DM2 and obesity are associated with major morbidity among Indigenous women. The National Aboriginal and Torres Strait Islander Health Survey (NATSIHS) found that Indigenous Australians are 1.2 times more likely to be overweight or obese than non-Indigenous Australians, and this disparity is greatest for women.51 DM2 is the second-commonest cause of mortality and disability-adjusted life-years (DALY) among Indigenous women.52 The DALY rate ratios (age-standardised to total Indigenous population) for ischaemic heart disease and DM2 among Indigenous women, compared with all Australian women, are 6.6 and 6.3, respectively; and the mortality rate ratio is 5.0 for ischaemic heart disease and 18.9 for DM2.52 The risk of metabolic complications is already high among Indigenous women, independent of PCOS; therefore, PCOS can amplify metabolic risk in these women. Given that these metabolic complications are largely preventable, it is important to provide early access to care. The leading cause of burden of disease among Indigenous women in the NATSIHS was anxiety and depression, accounting for 10% of the burden.51 Little is known about the prevalence of eating disorders and disordered eating among Indigenous women. Social and cultural factors influence emotional wellbeing, and the challenges facing many Indigenous women are likely to amplify the impact of PCOS on emotional wellbeing. Further research in this area is needed. Access to culturally appropriate care, services and programs is currently not optimal. Access issues are a key barrier for many Indigenous women, as health services generally, and women’s health services in particular, are limited in rural and remote locations. There are many barriers to healthy lifestyles, including the high cost of maintaining a healthy diet in rural and remote locations. Socioeconomic factors, such as poverty and overcrowding, make the use of refrigerators and kitchen equipment to cook healthy food difficult. Lifestyle programs may need to be applied in different ways to engage Indigenous women and incorporate exercise into daily activities, especially in rural and remote locations, due to a lack of service provision and facilities. Other issues for Indigenous women include that the role of ultrasound in the Indigenous setting is questionable due to limitations in care and access to ultrasound facilities and service provision in rural and remote locations; and there may be cultural factors and potential issues around acceptability of bariatric surgery. It is important to encourage and enable Indigenous women with PCOS to access services that are available and address potential barriers presented by cultural and traditional health practices. Work is currently underway to adapt, translate and implement the recommendations outlined here to Indigenous settings. Development of an evidence-based guidelineRationale and methodsGiven its heterogeneous clinical features across the life span, PCOS is a condition that engages many health disciplines. The associated complications are serious yet are often largely preventable; however, there is a lack of awareness of PCOS among consumers and health professionals. It is essential that consumers and health professionals recognise the life-course implications of PCOS, identify the early signs and symptoms and work together to manage PCOS and prevent its complications — especially as the burden and cost of PCOS complications, including infertility, DM2, CVD and emotional wellbeing issues are significant. Currently, there is limited consensus among different medical specialties as to the optimal management of PCOS in Australia.7,53 Diagnosis and treatment of PCOS can therefore differ depending on the health professional consulted (eg, general practitioner, endocrinologist or gynaecologist).7 There are limited clinical guidelines and no evidence-based guidelines, either in Australia or internationally, for assessment or management of women with PCOS; rather, PCOS is briefly mentioned within guidelines for the management of obesity and DM2.45,54 Where international clinical guidelines for the assessment and management of women with PCOS exist, they are informed by expertise and, in some cases, evidence, but are not rigorously developed evidenced-based guidelines; they do not consider psychological issues; and they offer simplistic advice on lifestyle management of PCOS. There is no guidance on the assessment and management of PCOS among Indigenous women, nor any adaptation for the Australian context. Overall, many areas of controversy remain in PCOS. Comprehensive evidence-based guidelines are warranted to optimise diagnosis, assessment and management. Accordingly, the Jean Hailes Foundation for Women’s Health has facilitated the formation of an independent PCOS Australian Alliance, bringing together health professionals, researchers, consumers and policymakers to advance knowledge and quality of care in PCOS. The federal government has funded the PCOS Australian Alliance, under the auspices of the Jean Hailes Foundation, to produce national evidence-based guidelines. The full version of the guideline has been approved by the National Health and Medical Research Council (NHMRC) (for detail about obtaining NHMRC approval, please see the full guideline), is endorsed by the Royal Australian College of General Practitioners and is freely available at http://www.managingpcos.org.au/pcos-evidence-based-guidelines.8 This is a summary version of the full guideline. The Jean Hailes Foundation was funded to translate the guideline into practice, including freely available independent evidence-based information on PCOS for health professionals and women at http://www.managingpcos.org.au. ScopeThe purpose of the guideline is to integrate the best available evidence with clinical expertise and consumer preferences; to provide health professionals, consumers and policymakers with guidance on timely diagnosis, accurate assessment and optimal management of PCOS; and to promote consistency of care and prevention of complications in primary care and specialist settings. The guideline is relevant to the assessment and management of reproductive-age adolescents and women with PCOS, including women with PCOS who are experiencing infertility. The guideline will apply in all health care settings and to a broad audience, including: community care practitioners; Indigenous health care workers; GPs; nurses; endocrinologists; obstetricians and gynaecologists; allied health professionals — psychologists, dietitians, exercise physiologists and physiotherapists; patients; community support groups (eg, the Polycystic Ovary Syndrome Association of Australia [POSAA]); the general public; students; and policymakers. PCOS is a syndrome, and as such, no single diagnostic criterion is sufficient for diagnosis. The 2003 Rotterdam consensus workshop concluded that PCOS diagnosis requires at least two of: oligo- or anovulation, hyperandrogenism (clinical and/or biochemical) and polycystic ovaries on ultrasound (Figure 2).14 The evidence-based guideline development groups and the Alliance agreed to endorse the Rotterdam diagnostic criteria for the guideline, while recognising there are current limitations of all definitions. MethodologyGuidelines are intended to improve patient outcomes, promote standardised care, develop standards to assess the clinical practice of health care professionals, and promote research and translation into practice. Guidelines are developed by drawing from clinician judgement, patient preference and research evidence, and are intended to aid clinical judgement and patient preference, not to replace it (Figure 3). The ultimate decision about clinical management of an individual patient will always depend on the clinical circumstances, patient preferences, and the clinical judgement of the health care team. Although there are many types of guidelines, this NHMRC-approved evidence-based guideline followed a rigorous, systematic process of development, which is briefly outlined below and in detail in the full guideline.8 Figure 3. Evidence-based guidelines are intended as an aid to clinical judgement and patient preference, not to replace it An independent PCOS Australian Alliance was formed in 2008 after a national workshop facilitated by the Jean Hailes Foundation for Women’s Health, which brought together key leaders from the research and multidisciplinary clinical sectors, with consumers providing a driving force through the peak national support group, POSAA. The vision of the Alliance is to improve the lives of Australian women with PCOS through education, research and evidence-based health care. One of the priorities of the Alliance was to develop an evidence-based guideline for PCOS. This guideline was developed as outlined in the NHMRC standards and procedures for externally developed guidelines.55 The Alliance identified key clinical objectives for the guideline based on highest clinical priority, greatest knowledge gaps, factors identified by the Australian government (which funded the guideline), and the expertise of Alliance members. The identified key clinical priorities focused on care of women with PCOS to facilitate early diagnosis of PCOS; early detection and treatment of depression, anxiety and mood disorders; early detection and diagnosis of risk factors for prediabetes, DM2 and CVD; and early detection and treatment of fertility problems and prevention of pregnancy complications. Multidisciplinary guideline development committees included a Project Board, PCOS Australia Alliance Strategic Advisory Group and four guideline development groups. Each guideline development group comprised a chair, professional group members with specific expertise in PCOS and the clinical area of interest (eg, psychologist in the emotional wellbeing guideline development group), a consumer representative from POSAA, evidence officers and, where possible, a representative to provide context for the Indigenous setting. Indigenous representation was present on the PCOS Australian Alliance Strategic Advisory Group, and the guideline development groups comprised clinicians with experience working with Indigenous communities. These multidisciplinary groups determined and prioritised the clinical questions addressed in this guideline and developed the clinical practice and research recommendations from the evidence reviews. For more detail about the development and prioritisation of clinical questions, please see the full guideline.8 To facilitate this process using an evidence-based approach, the chairs of each guideline development group attended a 1-day workshop, facilitated by the Southern Health Centre for Clinical Effectiveness, where the methods of identifying, appraising and synthesising evidence; grading the strength of evidence and its suitability to support evidence-based recommendations; and the process of guideline development overall were described in detail. Evidence reviews were conducted for each of the 22 identified clinical questions. Search strategies were developed according to a-priori selection criteria for each clinical question. Searches were limited to English language articles and there were no limits on year of publication. The literature was searched until November 2010. The following electronic databases were employed to identify relevant evidence: Australasian Medical Index, CINAHL, the Cochrane Library, the Cochrane Database of Systematic Reviews, DARE (Database of Abstracts of Reviews of Effects), the Cochrane Central Register of Controlled Trials, the Cochrane Database of Methodology Reviews, the Cochrane Methodology Register, Health Technology Assessment Database, the United Kingdom National Health Service Economic Evaluation Database, EMBASE, EBMR, MEDLINE and PsycINFO. Bibliographies of relevant studies identified by the search strategy and relevant reviews/meta-analyses were also searched. Included studies were classified according to the NHMRC levels of evidence56 and appraised using a-priori criteria according to study design, using a descriptive component approach to assign a risk of bias rating.57 In accordance with the selection criteria, data were extracted from included studies using a specially developed data extraction form,57 and meta-analyses were performed where appropriate. The guideline development groups were able to develop guideline recommendations from these evidence reviews. The evidence reviews for each question can be found in the supporting document to the full guideline: Evidence report: evidence based guidelines for assessment and management of PCOS, available at http://www.managingpcos.org.au/pcos-evidence-based-guidelines. The guideline contains 38 recommendations, each of which is assigned a grade. In developing the guideline recommendations, the guideline development groups placed emphasis on accurate assessment and management of PCOS. The recommendations in this guideline are strengthened by the use of rigorous methodology for evidence review and guideline development, including use of: study designs least susceptible to bias; a-priori criteria for inclusion and appraisal of studies; extraction of study data; and meta-analysis where appropriate. The recommendations were formulated using a considered judgement process that took into account the amount and quality of available evidence as well as its generalisability and applicability to current practice in Australia. Each evidence-based recommendation was given an overall grading from A to D, according to the NHMRC grades of recommendations for guideline developers (Table 1).56 Evidence grading is provided primarily to inform users about the strength of the evidence underpinning each recommendation. Where there was insufficient high-quality evidence in specific patient groups, lower-quality evidence or data from other patient groups, and where there was consensus among the guideline development group, combined with clinician and patient preferences, clinical consensus recommendations were developed. Clinical practice points have also been included, where important issues (such as safety, side effects or risks) arose from discussion of evidence-based or clinical consensus recommendations. Further points of relevance to the clinical implementation of recommendations were made in “implications of the recommendations” sections, including consideration of resource implications. Table 1. National Health and Medical Research Council grades for recommendations56 A Body of evidence can be trusted to guide practice. B Body of evidence can be trusted to guide practice in most situations. C Body of evidence provides some support for recommendation but care should be taken in its application. D Body of evidence is weak and recommendation must be applied with caution. The words “should”, “could” and “should not” do not directly reflect the grade or classification allocated to a recommendation, and are independent descriptors intended to reflect the judgement of the multidisciplinary guideline development group about the practical application of the recommendation, balancing benefits and harms. Where the word “should” is used in the recommendations, the guideline development group judged that the benefits of the recommendation (whether evidence-based or clinical consensus) clearly exceed the harms, and that the recommendation can be trusted to guide practice. Where the word “could” is used, either the quality of evidence was underpowered, or the available studies demonstrated little clear advantage of one approach over another, or the balance of benefits to harm was unclear. Where the words “should not” are used, there is either a lack of appropriate evidence, or the harms outweigh the benefits. In formulating the recommendations for this guideline, the guideline development groups recognised and took into account several factors and limitations pertaining to the available evidence. For many aspects of PCOS, there is little or no evidence or the evidence is of poor quality, with other potential biases resulting from different methods for diagnosis of PCOS and differing end points. Public and targeted consultation on the draft guideline was conducted for 30 days commencing 5 March 2011, in accordance with the legislative requirements for approval of externally developed guidelines under Section 14A of the National Health and Medical Research Council Act 1992 (Cwlth). All aspects of the guideline were developed as outlined in the NHMRC standards and procedures for externally developed guidelines,55 and accordingly, the guideline was approved by the NHMRC in July 2011. In approving the full version of the guideline, the NHMRC is satisfied that it is based on the systematic identification and synthesis of the best available scientific evidence and makes clear recommendations for health professionals practising in an Australian health care setting. This guideline does not seek to provide full safety and usage information on pharmacological and surgical interventions. The pharmacological and surgical interventions recommended in the guideline should not be applied without consideration of the patient’s clinical profile and personal preferences. It is recommended that the reader consults the Therapeutic Guidelines (http://www.tg.com.au) and the National Prescribing Service (http://www.nps.org.au) for detailed prescribing information, including indications, drug dosages, methods and routes of administration, contraindications, supervision and monitoring, product characteristics, and adverse effects. It is intended that this evidence-based guideline summary be used alongside the full guideline.8 The guideline should be considered according to the limitations outlined within, and used in conjunction with clinical judgement and patient preference. For a detailed description of the methodology used to develop the guideline, please see the full guideline.8 Translation of the guideline, including the production and dissemination of guideline-associated tools and resources, is the responsibility of the Jean Hailes Foundation for Women’s Health as a national not-for-profit women’s health organisation funded by the federal government. The PCOS Alliance and POSAA provided significant contribution to these resource developments.

Helena J Teede MB BS, FRACP, PhD · Marie L Misso PhD, BSc(Hons) · Amanda A Deeks BMed, GradDipPsych, PhD · Lisa J Moran BSc(Hons), BND, PhD · Bronwyn G A Stuckey FRACP · Jennifer L A Wong MB BS(Hons), FRACP, MIH · Robert J Norman MB ChB(Hons), MD, FRANZCOG · Michael F Costello MB BS, FRANZCOG, CREI · on behalf of the Guideline Development Groups

To the Editor: The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, a large, blinded, multinational study, showed an increased risk of adverse maternal and neonatal outcomes in relation to maternal glycaemia, at glucose levels below the current Australian criteria for diagnosing gestational diabetes mellitus (GDM).1 The International Association of Diabetes and Pregnancy Study Groups (IADPSG), an international consensus group, has proposed new criteria for the diagnosis of GDM.2 As a result, these new criteria have been adopted by the American Diabetes Association, which predicts a significant increase in the prevalence of GDM.3 The new criteria were discussed at the Australasian Diabetes in Pregnancy Society annual scientific meeting in 2010. Moses and colleagues accurately outline the increased prevalence of GDM if IADPSG criteria are adopted in Australia.4 An increased prevalence has implications for resource allocation, and the anticipated increase in workload can be managed by appropriate planning and exploration of alternative models of care. We surveyed attitudes to the management of GDM among general practitioners already involved in antenatal shared care programs in the Liverpool and Fairfield areas of Sydney (GDM is not currently part of the shared care program in this urban area, which has a high prevalence of diabetes). Around 120 GPs are enrolled in the antenatal shared care program in the Liverpool and Fairfield areas. Forty-six of these GPs attended an educational meeting at which the survey was distributed, and of the 46 (who all completed the survey), only seven believed that GDM can always be managed in the antenatal shared care program. Seventeen felt that, due to lack of time or lack of access to appropriate resources, GDM cannot be managed at all by GPs as part of shared antenatal care; eight of these 17 indicated that they never initiated insulin for patients with type 2 diabetes. Only two indicated that no up-skilling was required for them to manage GDM. These attitudes may be limited to GPs in urban practices. Whether the involvement of GPs in the management of GDM is appropriate is unclear, and the provision of supporting resources requires further review. Additionally, as determined by Moses and colleagues,4 the predicted increase would come from older women who are possibly more likely to have other comorbidities that make them less suitable for shared care.

Barbara Depczynski · Vincent W Wong · Hamish D Russell · Nicole Opie

Emergency contraception and medical abortion are options, but education about them is vital Prevention is better than cure — especially in the field of sexual and reproductive health. Australia’s teenage pregnancy rates (17.3 per 1000 women in 2003)1 and abortion rates (19.7 per 1000 women in 2008)2 are high compared with other Western countries. Such rates are not inevitable, and recent contraceptive strategies were developed to help in reducing them. One such strategy was the rescheduling in Australia of the emergency contraceptive pill (ECP) containing levonorgestrel to Schedule 3 (over-the-counter) status, making it available from pharmacists without a prescription. Improved access to the ECP is a crucial issue, given that the sooner it is taken after unprotected intercourse, the more effective it is. By rescheduling the ECP, it was hoped that women would be able to obtain it more easily within the narrow time frame recommended, especially after hours and on weekends, when it is more difficult to access a general practitioner. A second-generation antiprogestin ECP, ulipristal acetate (30 mg), has now been released and is thought to be a more effective option up to 120 hours after unprotected intercourse.3 Our recently published Australian population study of over 600 women aged 16 to 35 years found that although 95% had heard of the ECP and 26% had used it, just under half (48%) were aware that the ECP was available over the counter.4 In addition, under half (45%) thought it was safe for the health of women, most (61%) erroneously believed that it would damage a pre-existing pregnancy, and 32% that it was an abortifacient, similar to mifepristone — all findings consistent with overseas studies.5,6 Women’s attitudes towards the ECP revealed various views and beliefs influencing their use, including moral and religious reasons, fear of side effects, and unrealistically low perceptions of pregnancy risk.4 Unsurprisingly, women with good knowledge of the ECP were more likely to report having used it. Some women (12%) thought they were unlikely to become pregnant, even when having unprotected intercourse at the most fertile time of the menstrual cycle.4 Although our linked study found that pharmacists believe further information provision following ECP dispensing is their responsibility,7 most women (84%) prefer to receive information from a doctor rather than a pharmacist.4 This offers an important opportunity for GPs to help patients prevent unintended pregnancy and abortion. GPs could include discussion of the ECP in all general consultations with women of reproductive age regarding contraception or reproductive issues, such as cervical cancer screening. Ideally, GPs should seek opportunities to discuss the ECP within an overall contraceptive strategy and with all female adolescents during routine health care visits. GPs can play a critical role in informing and educating women about their risks of becoming pregnant, the use of contraceptives generally and how to use them correctly and consistently. They can also counsel about risky sexual behaviour and the higher risk of an unplanned pregnancy resulting from such behaviour. They could encourage women to keep an advance supply of the ECP at home, if appropriate. Access to such ECP options would be more widely available if it were to be subsidised or free for women who are socioeconomically disadvantaged (eg, health care card holders). As well as the prevention of unplanned pregnancy, assistance with pregnancy termination may be necessary and should always be available if women are unable to continue with a pregnancy. There are parts of Australia where sex education is inadequate, access to contraceptive advice or support is lacking, and hospitals do not provide pregnancy termination services. This can lead to problematically late presentations for abortion.8 In Australia, the removal of the requirement for ministerial approval for the importation and supply of mifepristone means that doctors can now apply to the Therapeutic Goods Administration for approval to provide this drug to their patients for medical termination of pregnancy. Mifepristone is widely used in many countries, including the United Kingdom, the United States, France, New Zealand, Sweden and China and has been shown to be a safe, effective and highly successful treatment for the termination of early pregnancy.9,10 Already, women are being offered greater options when making the decision about an unintended pregnancy — they can choose to continue with the pregnancy, to place the baby for adoption, or if they opt for termination, a limited number of clinics, such as Marie Stopes International Australia,11 are now able to provide medical termination with mifepristone as an alternative to referral for surgical abortion. This option could, and probably should, be more widely available, but a greater emphasis on prevention is clearly needed. At the very least, a sustained public information campaign should address the misconceptions we have uncovered, and publicise the availability of effective contraceptive options. At most, a more comprehensive national sexual and reproductive health strategy should be implemented.

Angela J Taft MPH, PhD · Melissa K Hobbs MPH, PhD · Safeera Y Hussainy BPharmSci, PhD · Lisa H Amir MB BS, PhD · Kay Stewart BPharmSci, PhD · Anthony M A Smith BA(Hons), PhD · Julia M Shelley MPH, PhD · Colin B Chapman BPharmSci, BVSci, PhD

Improving health outcomes for mothers, children and families Mental health morbidity associated with the perinatal period — from conception to the end of the first postnatal year — is now recognised as a major public health issue, with depression affecting up to 15% of women during this period.1 It has been reported that 45% of postnatal depression begins in pregnancy,2 and about 38% of women with postnatal depression have a comorbid anxiety disorder.3 About 3% of women experience moderate to severe depression during the perinatal period and 0.2% experience a puerperal psychosis,4 and maternal suicide continues to be identified as one of the leading causes of indirect maternal mortality.5 There is growing evidence of the negative impact of poor mental health outcomes not only for the mother, but also for her child and family.6 The existence of well established maternal and infant health care systems across Australia has provided a unique opportunity for integrating mental health care into mainstream services. Increasingly, the maternal and infant health care sectors are introducing routine, universal psychosocial assessment aimed at detecting women who are at risk of, or suffering from, mental health morbidity. This approach, underpinned by a philosophy of prevention and early intervention, has been developed in the Australian perinatal setting over the past decade through the work and advocacy of leading clinicians and researchers, policymakers and beyondblue: the national depression initiative.7-9 Feasibility of widespread screening for depression in the perinatal period was evaluated in the National Postnatal Depression Research Program (2001–2005).7 It was concluded that screening for depression was feasible in routine clinical settings and acceptable to women and their health care providers (including general practitioners). In addition, maternal mental health morbidity often went undetected and untreated if routine screening was not used. The National Action Plan for Perinatal Mental Health (2008) went on to recommend implementing universal psychosocial assessment, training primary health care staff who administer the assessments, and establishing structures that optimise coordination of, and access to, appropriate services.8 This was followed by the establishment, by the Department of Health and Ageing, of the National Perinatal Depression Initiative (2008–2013), which enabled the introduction of a specific perinatal mental health Medicare stream (under the Access to Allied Psychological Services initiative) and the development of national clinical practice guidelines for depression and related disorders in the perinatal period.9 The clinical practice guidelines are aimed at all clinicians who have a “primary health care” role in detecting possible mental health morbidity in the perinatal period — including midwives, GPs, child and family health nurses, obstetricians and paediatricians. They are underpinned by a systematic literature review that points to a paucity of quality evidence, especially on routine psychosocial assessment and the safety of psychotropic medication in pregnancy. The guidelines recommend routine, universal screening for depression (antenatal and postnatal) using the Edinburgh Postnatal Depression Scale (EPDS)10 and treatment of mild to moderate postnatal depression with evidence-based psychological interventions (eg, cognitive behaviour therapy). Where there is insufficient evidence for recommendations, good practice points (based on lower-quality evidence and/or expert consensus) have been formulated. These include using comprehensive, universal psychosocial assessment (eg, the Antenatal Risk Questionnaire11) in addition to the EPDS, considering mother–infant interaction and risk to infant as integral parts of the assessment, monitoring women with an existing mood disorder closely to reduce risk of relapse, and providing specific advice about the safety of psychotropic medication during pregnancy and breastfeeding.9 While the guidelines recommend routine use of the EPDS in the perinatal period, they emphasise that it should only be used as an adjunct to clinical assessment in the primary care setting. They also highlight that universal psychosocial assessment is an area of debate, has significant resource implications (including training, service organisation and workload requirements), and needs to be closely integrated with access to mental health services. The clinical effectiveness of routine psychosocial assessment remains to be evaluated. A recent randomised controlled trial of early postnatal screening using the EPDS (including supportive counselling where indicated) demonstrated improved maternal mental health outcomes at 6 months postpartum for women receiving the intervention compared with those receiving usual care.12 In a meta-analysis of screening interventions for general depression, screening was found to be beneficial as long as it was integrated with clear pathways to care.13 This is in line with the National Action Plan for Perinatal Mental Health and the clinical practice guidelines — the first steps in translating evidence into practice and developing a broader evidence base. There is now a need to evaluate the effectiveness of combining psychosocial assessment with integrated pathways to care. In addition, an evaluation of the impact of the National Perinatal Depression Initiative on mental health outcomes for mothers is critical if we are to optimise the quality and uptake of services for this vulnerable, yet highly accessible, population.

Marie-Paule V Austin MB BS, FRANZCP, MD · Philippa F Middleton BSc(Hons), GradDipLibSt, MPH · Nicole J Highet DPsych

To the Editor: The number of vulvoplasty or labioplasty procedures rebated by Medicare Australia has more than doubled over the past 10 years;1 in the United Kingdom, a similar trend was observed in the National Health Service (NHS) (Box).2 Recent media debate in Australia highlights this as a concerning problem.3 The community assumes that surgical operations are clinically effective treatments performed for identifiable pathological features. In the context of female genital cosmetic surgery (FGCS), there is a blurring between disease and dissatisfaction, the latter being at least partly informed by cultural pressure about physical appearances. In addition, there is an absence of evidence on clinical effectiveness,4 and an apparent lack of commitment to monitor adverse events. This raises the question of how clinicians justify referring women for FGCS. A recent audit of referral letters for labioplasty in an NHS gynaecology clinic in the UK (University College London Hospitals project no. 03/0173) offers interesting insights. Of the 48 letters reviewed, the mean age of the women referred was 25 years (range, 9–50 years). Complaints about genital appearance were identified in 34/48 (71%) of letters (eg, embarrassment about undressing in public changing rooms). Physical discomfort was mentioned in 23/48 (48%) letters (eg, difficulty with activities such as cycling). Sexual problems were mentioned in 21/48 (44%) letters (eg, a reluctance to engage in sexual relationships). In two of the letters, the referrers mentioned disparaging comments by previous sexual partners, and one mentioned harassment by other girls at school. Alarmingly, a further seven letters (15%) alluded to concerns being flagged by the girls’ mothers. Only 77% of referrers reported examining the patient. A third of referrers judged the labia to be “normal”, yet nevertheless requested surgery for their patients. Pejorative language such as “leathery in appearance” or “pendulous and elongated” was used in 12 (25%) of the letters. Medical training may cover basic vulval anatomy, but detailed study of morphology is not included. This knowledge gap would have been less problematic in the past. However, in recent years, where intense marketing of FGCS5 is contributing to soaring demand, medical practitioners may not be sufficiently informed about female genital anatomy to assess and advise women about their concerns. Reasons for the increasing prevalence of female distress about genital appearance are likely to be complex and rooted in social and cultural changes. In the absence of identifiable diseases, referral for operations may not be the most appropriate way of managing women’s body insecurities. Labioplasty and vulvoplasty operations rebated by Medicare Australia1 and covered by the United Kingdom National Health Service2 over the past 10 years* INR = international normalised ratio. * Graph shows abbreviated, not daily, data. Intervals are weekly up to Week 9, then vary according to when INR was measured.

Rebecca Deans · Lih-Mei Liao · Naomi S Crouch · Sarah M Creighton

Promising outcomes from the Australian register include a fall in fetal malformation rates associated with changes in antiepileptic drug prescribing The burden of epilepsy for those with the disorder is significant. For women of childbearing age, the uncertainty surrounding their ability to bear children who are free of the disorder, without birth defects, and cognitively and psychologically normal adds to this burden. Although factors other than medication exposure influence these questions, there is no doubt that antiepileptic drugs (AEDs) used to prevent seizures, such as valproate, have a significant, and possibly preventable, role in teratogenicity.1 Pregnancy registers are now showing promising results in elucidating this role and influencing changes in practice for the benefit of women with epilepsy and their children. Some detailed information on the relative risks associated with AEDs has emerged over the past three decades,2 but it has largely been based on small-scale retrospective studies, with various and incomplete methods of recording data, no set protocols, and other shortcomings. It was clear that better information regarding teratogenicity, preferably from prospective studies, was needed. It was also clear that the expectant mother, as well as the infant, should be a primary consideration. The process of studying pregnancies in women with epilepsy should start well before conception and requires extensive consultation with the expectant mother about the planned management of her pregnancy and medication administration.3 In the late 1990s, these issues provided the rationale for setting up registers of pregnant women with epilepsy who were taking AEDs. There are now several international collaborative, independent and pharmaceutical company-initiated registers. The latter are concerned with single drugs and are not prospective. The collaborative and independent registers generally aim to collect prospective observational data from participating women according to an extensive protocol, with the data computerised for subsequent analysis. None of the registers dictate treatment and all have ethics approval, as well as informed consent from the participating women.4 The major registers are the International Registry of Antiepileptic Drugs and Pregnancy (EURAP),4 which includes data from 46 countries in Europe and elsewhere, and registers in North America, Denmark and the United Kingdom that publish reports independently. The Australian Pregnancy Register of Antiepileptic Drugs for Women in Pregnancy with Epilepsy and Allied Conditions (the Australian Pregnancy Register), established in 1999, is affiliated with EURAP, but also publishes its findings independently. It collects data from women who have volunteered to participate through a series of five interviews held at various times during pregnancy and after the infant’s birth.5 Over the past decade, all these registers have contributed considerable knowledge, improved prescribing practices and, although they were initially intended to focus on teratogenicity, have been extended to examine maternal wellbeing and seizure control, and cognition of the offspring. In terms of teratogenicity, the data collected in the registers can be used to assess the contributing roles of heredity, social factors, substance misuse, alcohol consumption, social status, intake of other medications, and accurately defined type and activity of epilepsy. The registers represent prospective studies on treatment efficacy and compliance, seizure freedom before pregnancy, interactions between AEDs and hormones, the role of folate supplementation, and many other factors involved in producing normal pregnancies and outcomes. The international registers have not used untreated control groups until recently — the North American register has used historical controls but is now enrolling a control group of pregnant untreated women, while EURAP compares the effects of different drugs. The Australian Pregnancy Register has from the outset collected data from a control group of untreated women with epilepsy, comprising about 10 per cent of the total, as well as (less successfully) women receiving AEDs for non-epileptic indications such as pain or bipolar disorder. Although there is no ideal control group, collecting data from untreated women with epilepsy provides an important comparison baseline.6 Recent analyses of data from the Australian Pregnancy Register have examined the role of AEDs in teratogenicity. For several decades, the use of AED polytherapy has been enshrined in the international literature as being harmful to the fetus, but our recent analysis of register data casts doubt on this, suggesting that it is the specific composition of polytherapy that is critical, not intake of multiple drugs per se.7 Most recently, analysis of register data has focused on dose issues that are associated with most of the AEDs, and examined the question of whether lower doses of drugs such as valproate may be effective in achieving seizure control without posing a higher risk of teratogenicity than other, less effective drugs.8 The role of AEDs in teratogenicity has become even more complicated as a series of new second-generation drugs have become available, because it takes a long time with many participants to define their role compared with the traditional drugs.9 Findings from the Australian Pregnancy Register have shown that seizure freedom before conception is demonstrably important in predicting the course of future pregnancies; the longer a woman is seizure-free, the better the outlook. The question of repeated pregnancies in women who have had a malformed baby while taking an AED, and advice to women contemplating extending their family, has also been studied. Findings such as these are of immediate importance to women and their babies, contribute to medical knowledge and have demonstrably altered prescribing practices in Australia and internationally. Recent data indicate that, while prescribing of valproate has risen in the general Australian population, possibly as a result of increasing use for patients with psychiatric illness, especially bipolar disorder, there has been a fall in the number of prescriptions and doses of valproate for women of childbearing age.10 This change in prescribing, which was influenced by register data, has been associated with a fall in fetal malformation rates.11 Increasing the number of women enrolled in the Australian Pregnancy Register is highly desirable to continue study of these important and complex topics. Pregnancy is an important health issue, and we must all collaborate to make it safer for women and their children.

Frank J E Vajda MD, FRCP, FRACP · Terence J O’Brien MB BS, MD, FRACP · Cecilie M Lander MB BS, FRCP, FRACP · Mervyn J Eadie MD, PhD, FRACP

Objective: To describe the trends in maternal smoking and smoking in the household for a cohort of Indigenous women followed from late pregnancy to 7 months postpartum.Design and setting: Prospective cohort study embedded within a randomised controlled trial (RCT) performed in the Northern Territory involving participants recruited between 30 June 2006 and 4 May 2010.Participants: 215 Indigenous women aged 17–39 years who had been recruited into the RCT, 162 of whom had completed their last study visit at 7 months postpartum by 1 June 2010.Main outcome measures: Smoking status of women, and smoking within their households, in their third trimester, and at 1 month, 2 months and 7 months postpartum.Results: There were complete data on women’s smoking status for 121 participants. Among these, the self-reported smoking rate was 45% (95% CI, 36%–55%) during pregnancy, increasing to 63% (95% CI, 54%–71%) at 7 months postpartum. Of the 66 women who were non-smokers at the antenatal visit, 23 (35%; 95% CI, 23%–47%) were smoking by the time their baby reached 7 months of age. Thirty-one per cent (95% CI, 23%–39%) of households included people who smoked inside during the antepartum period, whereas 16% (95% CI, 10%–23%) included people who smoked inside at 7 months postpartum.Conclusions: While an apparent reduction in indoor exposure to tobacco smoke during the postpartum period is encouraging, this is offset by an increase in the proportion of antenatal non-smokers who subsequently reported smoking after the birth of their child. More health care service delivery and research attention needs to be directed to smoking during pregnancy and to postpartum relapse in this population.

Vanessa Johnston MB BS, MPH, PhD · David P Thomas MMedSc, FAFPHM, PhD · Joseph McDonnell MSc, GradDipCompSci · Ross M Andrews MAppEpid, MPH, PhD

Women’s health in general practice. 2nd edition. Danielle Mazza. Sydney: Elsevier, 2011 (ix+346 pp, $94.95). ISBN 9780729538718. DANIELLE MAZZA, an associate professor at the School of Primary Health Care, Monash University, is a general practitioner with broad experience in women’s health and evidence-based research. She was previously medical director of Family Planning Victoria and is currently a member of the Royal Australian College of General Practitioners National Standing Committee on Quality Care. Her credibility is reflected in this comprehensive text on women’s sexual and reproductive health issues, with particular relevance to Australian general practice. This second edition has been fully revised to include developments in the field, such as the latest guides to taking “the pill”, the contraceptive vaginal ring, human papillomavirus epidemiology and polycystic ovary syndrome. The chapter on contraception provides practical and definitive information on all methods in current use — a mandatory knowledge base for all GPs providing such advice. The inclusion of chapters on violence against women, unplanned pregnancy and sexual problems is to be commended. Mazza’s style of frank discussion of the issues, legalities and practicalities presents these difficult subjects in an informative, non-judgemental manner. Registrars starting in practice and studying for their exams ignore this text at their peril! The layout is educationally sound, with learning objectives, case studies and key points. The chapters are extensively referenced. Mazza also uses many tables, photographs and helpful diagrams (although some of these could be larger). Mazza is to be commended for strongly presenting the evidence, or lack thereof, for treatments. Mostly, the evidence is cleverly mixed with practical approaches for the clinician. At times, however, evidence overwhelms practicality, discouraging some harmless treatments (eg, for mastalgia and premenstrual syndrome) and leaving options of reassurance only, or active drugs. Purchase of the softcover book includes online access to the complete book. In summary, this is an authoritative and comprehensive reference for new GPs as well as experienced practitioners wanting to update or check the latest evidence.

Karen M Flegg

Screening plus equitable provision of vitamin D supplements could mitigate many adverse outcomes For nothing worthy proving can be proven, Nor yet disproven: wherefore thou be wise, Cleave ever to the sunnier side of doubt. Alfred, Lord Tennyson, The ancient sage Tennyson may not have been alluding to the need for high-level evidence from randomised controlled trials (RCTs) to alter clinical practice, but he would have been aware of children with rickets. Evidence has accumulated linking vitamin D deficiency to adverse outcomes in pregnancy, such as pre-eclampsia, hypertension, higher rates of caesarean section and preterm delivery. Lau and colleagues (→ Serum 25-hydroxyvitamin D and glycated haemoglobin levels in women with gestational diabetes mellitus) contribute to this evidence by demonstrating that, in women with gestational diabetes mellitus (GDM), a lower serum 25-hydroxyvitamin D (25[OH]D) concentration was independently associated with poorer glycaemic control.1 Of 147 women who were studied late in pregnancy (at a mean of 35 weeks’ gestation), about 40% had vitamin D insufficiency or deficiency (serum 25[OH]D concentrations ≤ 50 nmol/L). Most of the women in this study were not white, and ethnicity, occupational status and season, not surprisingly, all influenced 25(OH)D concentrations, while body mass index did not. Perhaps more surprisingly, however, 25(OH)D concentrations were inversely associated with fasting and 2-hour glucose levels measured during an oral glucose tolerance test and with the marker of glycaemic control, glycated haemoglobin. Most importantly, serum 25(OH)D was an independent predictor of glycaemic control. In adults, a number of large cross-sectional studies have shown a consistent, independent and positive relationship between serum 25(OH)D and insulin sensitivity, and an inverse relationship with risk of diabetes.2-5 Serum 25(OH)D levels have been shown to account for 42% of the variation in insulin sensitivity assessed by hyperglycaemic clamp.3 Consistent with Lau et al’s findings, fasting and 2-hour levels of glucose and insulin have been shown to be independently and inversely associated with serum 25(OH)D levels.3-5 In a United States study, the odds ratio for diabetes was 0.25 (95% CI, 0.11–0.60) for non-Hispanic white participants in the highest versus the lowest serum 25(OH)D quartile.2 The highest-level evidence to date comes from a large prospective study with a 17-year follow-up that showed people in the highest quartile of serum 25(OH)D had a 40% decreased risk of type 2 diabetes compared with those in the lowest quartile.6 Based on these data, RCTs of vitamin D supplementation in adults to improve insulin sensitivity and reduce diabetes risk are underway. GDM is becoming increasingly more common, affecting up to 10% of pregnancies. The presence of GDM is not trivial and has long-term implications for the health of mothers and their children. The former have an increased risk of developing type 2 diabetes, while their offspring have an increased risk of obesity and diabetes later in life. Vitamin D deficiency is also very common in pregnancy. The prevalence of inadequate levels of vitamin D in Lau et al’s study is comparable with rates of vitamin D insufficiency of 47.1% and 83.5% in white and black pregnant women, respectively, in the northern US (defined as 25[OH]D < 80 nmol/L)7 and 65.3% in pregnant women in rural Victoria (defined as 25[OH]D < 75 nmol/L).8 RCTs of vitamin D supplementation, initiated early in pregnancy, are now required to demonstrate whether vitamin D supplementation might reduce the incidence or severity of GDM. International debate is currently focused on the optimal level of serum 25(OH)D. Based on meta-analyses using musculoskeletal end points in older individuals, cut points of 60 nmol/L and 75 nmol/L seem appropriate to prevent falls and fractures, respectively.9 However, a recent Institute of Medicine report recommended at least 50 nmol/L,10 which appears overly conservative and does not take season into account. The public health implications of vitamin D deficiency in pregnancy are far broader than glycaemic control. In Australia, there has been a resurgence of rickets — partly owing to an increased refugee population comprising dark-skinned and veiled women with vitamin D deficiency, and also because of decreased exposure of babies to sunlight, lack of supplementation of infant feeds with vitamin D and weaning of infants onto non-milk liquids. Milder forms of bone disease may also occur with vitamin D deficiency. Recently, a study that used three-dimensional ultrasonography in pregnant women showed that vitamin D deficiency was associated with increased femur metaphyseal cross-sectional area and increased femur splaying (the ratio of femoral metaphyseal cross-sectional area to femoral length) at as early as 19 weeks’ gestation.11 In addition, it was previously shown that children born to mothers with vitamin D deficiency (< 50 nmol/L) during pregnancy exhibit deficits in total body bone mineral content as great as 11% at 9 years of age.12 This could lead to an increased risk of osteoporotic fracture later in adult life, but this is unlikely to be evaluated in long-term studies. In addition, maternal or early life vitamin D deficiency has been linked to an increased risk of several other disorders, including neonatal craniotabes, prematurity, type 1 diabetes mellitus, schizophrenia, and childhood respiratory infections and wheeze.13,14 Current evidence strongly supports routine screening for vitamin D deficiency early in pregnancy. Furthermore, vitamin D supplementation to correct deficiency should be initiated early in pregnancy as it might reduce the incidence or severity of GDM and because changes in skeletal morphology of the fetus associated with deficiency are seen as early as 19 weeks’ gestation. The most common recommended daily doses of cholecalciferol are 1000 IU–2000 IU, however, daily doses of up to 4000 IU have recently been shown to be safe in pregnancy (Bruce W Hollis, Professor, Department of Paediatrics, Medical University of South Carolina, USA, personal communication). What is problematic is the equitable provision of vitamin D supplements to pregnant Australian women with deficiency. Pregnant and breastfeeding women who are most at risk of vitamin D deficiency are often the least likely to be able to afford supplements. In the United Kingdom, vitamin D supplements are provided free of charge to such women through the Healthy Start program.15 There is evidence to support more widespread use of vitamin D supplements during pregnancy in Australia, although more research is required. One way to increase access might be to alter the scheduling of higher-dose, lower-cost vitamin D supplements.

Peter R Ebeling MB BS, MD, FRACP

Objective: To test the hypothesis that lower 25-hydroxyvitamin D (25[OH]D) levels in late pregnancy are associated with poorer glucose control in gestational diabetes mellitus (GDM).Design and setting: Retrospective cross-sectional study, in a GDM clinic at a tertiary referral centre.Patients: Women attending the GDM clinic at Westmead Hospital from 1 February 2007 to 1 February 2008, excluding those with prepregnancy glucose intolerance.Main outcome measures: Levels of glycated haemoglobin (HbA1c) and 25(OH)D measured during the third trimester; maternal age, ethnicity, body mass index (BMI) and occupational status; and results of oral glucose tolerance testing (OGTT).Results: 147 women with a mean gestational age of 35 ± 2 weeks were included, of whom 41% had insufficient or deficient levels of 25(OH)D (≤ 50 nmol/L). Ethnicity, occupational status and season significantly influenced 25(OH)D levels (P < 0.01 for all) but BMI did not. 25(OH)D levels were inversely associated with fasting and 2-hour blood glucose levels during OGTT (Spearman r = − 0.16; P = 0.05 for both) and with log[HbA1c] (Spearman r = − 0.32; P < 0.001). BMI and insulin doses were also associated with HbA1c levels. Multivariable analysis identified 25(OH)D and blood glucose levels during the OGTT as independent predictors of HbA1c levels.Conclusions: Lower 25(OH)D levels are independently associated with poorer glycaemic control. Future randomised trials are needed to determine whether vitamin D plays a role in glycaemic control in GDM. Regardless, maternal vitamin D insufficiency has adverse effects including neonatal hypocalcaemia and rickets. The 41% prevalence of inadequate 25(OH)D levels in the women in our study is unacceptably high. We propose routine 25(OH)D testing of all pregnant women at screening for GDM or earlier, and treatment of women who are found to be deficient.

Sue Lynn Lau MB BS, FRACP · Jenny E Gunton MB BS, FRACP, PhD · Neil P Athayde MB BS(Hons), FRANZCOG, CMFM · Karen Byth PhD · N Wah Cheung MB BS, FRACP, PhD

Objective: The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has proposed new criteria for the diagnosis of gestational diabetes mellitus (GDM). The aim of this study was to compare the prevalence of GDM when IADPSG criteria were used with the prevalence when the current Australasian Diabetes in Pregnancy Society (ADIPS) criteria were used.Design, setting and participants: This was a prospective study over a 6-month period, examining the results of all glucose tolerance tests (GTTs) conducted for the diagnosis of GDM in Wollongong, a city using the public and private sectors.Main outcome measures: The prevalence of GDM using the existing (ADIPS) and the proposed (IADPSG) criteria.Results: There were 1275 evaluable GTTs (571 public and 704 private). Using the current ADIPS diagnostic criteria, the prevalence of GDM was 8.6% (public), 10.5% (private) and 9.6% (overall). Using the proposed IADPSG criteria, the prevalence of GDM was 9.1% (public), 16.2% (private) and 13.0% (overall).Conclusions: The proposed IADPSG criteria would increase the prevalence of GDM from 9.6% to 13.0% (P < 0.001). In our study in the Wollongong area, which has a population with a predominantly white background, this increase came mainly from older women attending a private pathology provider. Data from both the public and private sectors need to be included in any discussion on the change in prevalence of GDM.

Robert G Moses MD · Gary J Morris BAppSc · Peter Petocz PhD · Fernando San Gil PhD · Dinesh Garg MD

Kenneth Hugh Atkinson’s death late last year ended the career of one of Sydney’s most accomplished gynaecologists. Ken was born on 1 August 1939 in Moss Vale, New South Wales. He grew up in Armidale, where he attended The Armidale School and finished as dux of his year. He studied medicine at the University of Sydney, living at St Paul’s College and graduating with honours in 1963. He then worked at Royal Prince Alfred Hospital (RPAH) and, 2 years later, became a registrar at the associated King George V Memorial Hospital for Mothers and Babies (KGV). In his second year there, he sat the membership examination for the Royal College of Obstetricians and Gynaecologists (RCOG) and received the top mark in Australia. In 1968, he was appointed clinical superintendent at KGV. He single-handedly altered the whole ethos of the hospital — introducing formal resident training and running regular seminars incorporating interaction with other clinical specialities. In 1970, Ken was awarded a Joseph Foreman Fellowship. This took him to Massachusetts General Hospital in Boston, where he was surgical resident to Howard Ulfelder, one of the greatest gynaecological surgeons of the time. In 1971, he returned to Sydney and was appointed visiting medical officer in obstetrics and gynaecology at KGV and then, from 1974, at Ryde Hospital, Poplars Private Hospital and Sydney Adventist Hospital. After he gave up obstetrics in the mid 1990s, Ken concentrated on gynaecological cancer surgery. He handled most of the gynaecological cancer surgery on Sydney’s upper north shore, and was on call at RPAH for surgical emergencies. He never complained about being called in at any time of the day or night; he did it all with good humour and no one equalled him “when the chips were down”. In 1974, Ken became a member of the NSW state committee of the RCOG. In 1984, he served on the executive committee of the Australian Society for Colposcopy and Cervical Pathology and became chairman of the committee in 1994. In the same year, he was elected to the council of the NSW Medical Defence Union and, in 1995, he served on its executive committee. In 1996, he became a director of United Medical Protection and later deputy chairman. Ken’s interests included art, oriental snuff bottles and rugs, sport, good food and fine wine. He died on 25 November 2010 from complications after a myocardial infarction. He is survived by his wife Susan, and children Tracey, Josephine and Bill.

Andrew R Korda