Women's health

To the Editor: In Australia, gestational diabetes mellitus is diagnosed by 75 g oral glucose tolerance test (OGTT). The diagnostic criteria are fasting plasma glucose (FPG) ≥ 5.1 mmol/L, one‐hour glucose level ≥ 10.0 mmol/L, and/or 2‐hour glucose level ≥ 8.5 mmol/L.1,2 International consensus favours OGTT over single measures of glucose because, in the pivotal Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study, hyperglycaemia at each time point was independently associated with adverse outcomes, individual measures were not well correlated with one another, and no single measure was clearly superior in predicting adverse outcomes, such as birthweight above the 90th percentile, shoulder dystocia and pre‐eclampsia.2,3 To reduce contact time at pathology collection centres during the coronavirus disease 2019 (COVID‐19) pandemic, measurement of FPG alone has been advocated.4,5 One guideline advised that a result below 4.7 mmol/L may not merit a follow‐up OGTT.4 Another advised diagnosing gestational diabetes mellitus by stand‐alone FPG greater than 5.1 mmol/L.5 To determine the proportion and characteristics of gestational diabetes mellitus cases that would be missed by using alternative criteria, we extracted the results of all obstetrician‐referred OGTTs performed by our private community‐based laboratory between January 2017 and April 2020. The analysis, including determination of Wilson score confidence intervals (CIs), was performed with SAS 9.4 (SAS Institute). Of 16 169 patients, 1790 (11.1%) were diagnosed with gestational diabetes mellitus by OGTT. A rule‐out threshold of FPG below 5.1 mmol/L would have resulted in 1202 cases (67%; 95% CI, 65–69%) being missed, and a threshold below 4.7 mmol/L would have resulted in 831 cases (46%; 95% CI, 44–49%) being missed (Box). Women with gestational diabetes mellitus and normal fasting glucose did not have significantly lower one‐ or 2‐hour concentrations than those with increased fasting glucose (data not shown). Missing the diagnosis of gestational diabetes mellitus exposes women and their newborns to significant risks, including birth weight above the 90th percentile, primary caesarean delivery, neonatal hypoglycaemia, premature delivery, shoulder dystocia or birth injury, intensive neonatal care, hyperbilirubinaemia and pre‐eclampsia. Use of fasting glucose to screen for gestational diabetes mellitus would miss a large proportion of cases, with the potential for significant harm to mothers and their offspring. Clinicians must recognise the substantial limitations of stand‐alone FPG so that pregnant women can be adequately counselled and, if opting out of OGTT, considered for careful monitoring for consequences of undiagnosed gestational diabetes mellitus, such as accelerated growth or polyhydramnios. In regions without significant community spread of COVID‐19, modifying sample collection procedures to ensure strict physical distancing and having dedicated collection centres for vulnerable populations may be better than using deficient diagnostic criteria. Box – Distribution of fasting glucose results at 24–28 weeks’ gestation in patients with (n = 1790) and without (n = 14 379) gestational diabetes mellitus* (GDM) The vertical grey lines denote thresholds below which new guidelines propose that oral glucose tolerance testing is not required during the coronavirus disease 2019 (COVID‐19) pandemic. * Diagnosed using oral glucose tolerance test.

Ranita Siru · Johan H Conradie · Melissa J Gillett · Emily Gianatti · Michael M Page

Objective: To synthesise what is known about women combining motherhood and a career in medicine by examining the published research into their experiences and perspectives. Study design: We reviewed peer‐reviewed articles published or available in English reporting original research into motherhood and medicine and published during 2008–2019. Two researchers screened each abstract and independently reviewed full text articles. Study quality was assessed. Data sources: CINAHL, MEDLINE, PsycINFO, Web of Science, and Scopus abstract databases. Data synthesis: The database search identified 4200 articles; after screening and full text assessment, we undertook an integrative review synthesis of the 35 articles that met our inclusion criteria. Conclusions: Three core themes were identified: Motherhood: the impact of being a doctor on raising children; Medicine: the impact of being a mother on a medical career; and Combining motherhood and medicine: strategies and policies. Several structural and attitudinal barriers to women pursuing both medical careers and motherhood were identified. It was often reported that women prioritise career advancement by delaying starting a family, and that female doctors believed that career progression would be slowed by motherhood. Few evaluations of policies for supporting pregnant doctors, providing maternity leave, and assisting their return to work after giving birth have been published. We did not find any relevant studies undertaken in Australia or New Zealand, nor any studies with a focus on community‐based medicine or intervention studies. Prospective investigations and rigorous evaluations of policies and support mechanisms in different medical specialties would be appropriate. Protocol registration: PROSPERO CRD42019116228.

Rebekah Hoffman · Judy Mullan · Marisa Nguyen · Andrew D Bonney

To the Editor: A recent article highlighted a case where self‐collection enabled detection of an early cervical adenocarcinoma and curative treatment in a previously underscreened woman.1 This case underlines the important benefits from self‐collection making cervical screening more accessible and acceptable to women who have previously declined or delayed screening. Unfortunately, self‐collection is currently very underutilised in Australia. Although it is currently restricted to women aged 30 years and over who are 2 or more years overdue for cervical screening, potentially around a million women are eligible.2 In contrast, data from Medicare, VCS Pathology, and the National Cancer Screening Register suggest that fewer than 6000 self‐collected tests were processed over 2018 and 2019, indicating that less than 1% of eligible women have had a self‐collected test. What drives this discrepancy? Self‐collection is highly acceptable to underscreened Australian women, and very high uptake can be achieved with appropriate clinical support.3 A recent survey reported that many practitioners, especially outside Victoria, do not yet feel comfortable discussing or recommending self‐collection, and lack confidence that self‐collection is a reliable test.4 Potentially, this is due to an initial delay in self‐collection being available, confusion about eligibility, and current restrictions giving the false impression that self‐collection is less sensitive. Self‐collection is now available to eligible women nationally (provided samples are sent to one of two accredited laboratories, which accept samples from anywhere in Australia), and updated evidence demonstrates that polymerase chain reaction‐based human papillomavirus (HPV) testing is equally sensitive for detecting pre‐cancer in self‐collected and clinician‐collected samples.5 Another barrier may be difficulties for providers in checking whether women are eligible. The rollout of the provider portal into the National Cancer Screening Register, allowing providers to view a woman's screening history at the point of care, will be important in addressing this issue. Many screening‐eligible women who have not had their first HPV test are now overdue and could be eligible for self‐collection. Self‐collection is a reliable test now available nationally to eligible women, which can have a transformative effect in the lives of underscreened women, as shown in the recent case study.

Megan Smith · Marion Saville · Karen Canfell

Our new birthweight charts may facilitate more accurate diagnosis and improve care for small-for-gestational age babies

Farmey A Joseph · Jonathan A Hyett · Philip J Schluter · Andrew McLennan · Adrienne Gordon · Georgina M Chambers · Lisa Hilder · Stephanie KY Choi · Bradley Vries

To the Editor: Gestational diabetes mellitus (GDM) is being diagnosed with increasing frequency in Australia, with the greatest prevalence reported in South Asian women.1,2 South Asian women, comprising Indians, Sri Lankans, Bangladeshis, Afghanis and Pakistanis, are more likely to have GDM and develop type 2 diabetes than Caucasian women.1,2 Data from the landmark Mothers after Gestational Diabetes in Australia trial show that about 40% of the 573 women recruited into the trial were from an Asian background.2 Retention rates for the intervention and usual care groups were 73% and 79%, respectively.2 The Royal Australian College of General Practitioners3 and the Australasian Diabetes in Pregnancy Society4 recommend oral glucose tolerance testing 6–12 weeks post partum for women who experienced a GDM‐complicated pregnancy. Repeat testing should be performed every 1–2 years among women with normal glucose tolerance and the potential for further pregnancies. If further pregnancy is not possible, follow‐up testing should be performed every 3 years, with more frequent retesting depending on clinical circumstances.5 Although studies have been conducted to evaluate the implementation of post partum guidelines generally in women with a history of GDM,6 there is no information about the implementation and uptake of guidelines in high risk ethnic populations. Additionally, there is evidence to suggest that culturally specific GDM follow‐up care would increase adherence to diet and lifestyle modifications during the interconception period in high risk ethnic women.7 Therefore, as a high risk group for progression to type 2 diabetes following GDM, South Asian women in Australia should be targeted for testing, and culturally appropriate lifestyle interventions, before conception. General practitioners have a critical role in the post partum, interconception and pre‐pregnancy care of women with previous GDM. This is even more pronounced in high risk populations such as South Asians. More culturally appropriate resources are therefore required to assist with recommended lifestyle modifications to reduce risks for future development of GDM or type 2 diabetes. There is an urgent need for qualitative research to focus on identifying the barriers and enablers to the implementation of the Royal Australian College of General Practitioners guidelines for the management of GDM, with a particular focus on GDM interconception care for South Asian women. Findings may be used to inform the development phase of an intervention aimed at improving the implementation and uptake of GDM guidelines among high risk populations in Australian general practice.

Asvini K Subasinghe · Alison J Nankervis · Jacqueline A Boyle · Danielle Mazza

Caution is needed so that population‐level reductions in the stillbirth rate are not offset by iatrogenic harm to healthy babies The federal Minister for Health the Honourable Greg Hunt MP recently launched the Safer Baby Bundle — a national stillbirth program that aims to reduce stillbirth in Australia by 20% by 2023.1 The program is one of the responses to recommendations arising from the federal Senate's Select Committee on Stillbirth Research and Education.2 It draws from similar bundles of care in the United Kingdom that have been associated with successful reductions in stillbirth.3,4 Undoubtedly, these whole‐of‐population level programs are important and effective. However, because late pregnancy stillbirth can be prevented simply by delivering all babies early, they have the potential for harm. There are five components of the Safer Baby Bundle: supporting women to stop smoking in pregnancy; improving awareness of a safe maternal sleeping position; improving decision making about timing of birth; improving the detection and management of fetal growth restriction (FGR); and raising awareness and improving care for women with decreased fetal movements (DFM). Of these five components, the latter two have the potential to increase early delivery. FGR is the strongest contributor to the burden of stillbirth. If detected and managed, the risk of stillbirth is 20‐fold lower than if FGR remains undetected.5 Improving the detection of FGR is central to any program aiming to reduce stillbirth. But increasing FGR detection may also cause harm. In a French population, half of the babies suspected of FGR antenatally had normal growth.6 In Victoria, a greater focus on improving the detection of FGR quadrupled the number of babies delivered early for suspected FGR, from 741 in 2000 to 2996 in 2017.5 The number and proportion of these babies with a birthweight in the 10th centile or greater increased from 307 (41%) to 1597 (53%).5 Striving to increase the sensitivity of FGR detection decreased specificity. This is a problem because unwarranted early delivery is harmful to both immediate perinatal5,6 and longer term developmental outcomes.7 Similar risks exist for increasing awareness of DFM. It has long been recognised that there is a relationship between DFM and stillbirth. Women who report DFM have a 2.4‐fold increased risk of stillbirth.8 However, translating this into an effective intervention has been challenging. Thirty years ago, it was shown that the use of formal fetal movement counting charts failed to reduce stillbirth.9 More recently, a large randomised controlled trial — the AFFIRM trial — assessed a care package for women presenting with DFM. In over 400 000 women attending 33 health services in the UK, increasing the awareness of DFM and standardising the care of those women presenting with DFM did not significantly reduce stillbirth.10 Moreover, there was evidence of harm to both mother and baby. Despite clear guidance for clinicians about what investigations to offer women with DFM and under what circumstances delivery was merited,11 there was an increase in the rates of induction of labour and caesarean delivery,10 with an additional 500 babies born between 32 and 34 weeks’ gestation and 5000 more born between 34 and 37 weeks’ gestation. The number of babies requiring admission to a neonatal unit also increased.10 The fact that most women with DFM will go on to give birth to a healthy baby suggests that the care package assessed by AFFIRM needs to be better targeted to women at risk. So what lessons can be drawn from these experiences for the Australian Safer Baby Bundle? Foremost, it is to be aware of the potential harm of any intervention and to look for this harm. This is possible with the use of balance performance measures12 —essentially, measures of unnecessary early delivery such as the proportion of babies delivered for suspected FGR but who were normally grown, or the number of neonatal unit admissions of term babies. Stillbirth programs elsewhere did not embed balance measures as part of their planned evaluation. Benefiting from the lessons learned by others, the Australian Safer Baby Bundle will include these measures to ensure that strategies designed to reduce stillbirth are targeted towards babies who are at most risk.1 The ultimate goal of balance measures is to reduce the unintended harm of our interventions. At present, no strategy has been shown to increase the sensitivity of FGR detection without causing harm. Neither is there a reliable tool to differentiate patterns of fetal movement that correspond to adverse outcome from those that are just a normal event. It is likely that more discriminatory screening tools reside in improved use of ultrasonography and biomarkers that assess fetoplacental function13 or in a better understanding of circadian patterns of fetal movements.14 Until then, caution is needed so that population‐level reductions in the stillbirth rate are not offset by iatrogenic harm to healthy babies. It is crucial that the potential for unintended harm is made explicit and that measures of unnecessary early delivery are used to monitor progress of the Safer Baby Bundle implementation in Australia.

Roshan Selvaratnam · Mary‐Ann Davey · Euan M Wallace

The negative impact of cannabis use by pregnant women is independent of tobacco use

Luke E Grzeskowiak · Jessica A Grieger · Prabha Andraweera · Emma J Knight · Shalem Leemaqz · Lucilla Poston · Lesley McCowan · Louise Kenny · Jenny Myers · James J Walker · Gustaaf A Dekker · Claire T Roberts

Iron deficiency anaemia, which affects 14–22% of women of reproductive age,1 has adverse effects on pregnant women and their infants. Oral iron supplementation is the first‐line treatment, but intravenous iron therapy is sometimes preferred because of gastrointestinal effects, low patient adherence, and the delayed effect of oral iron therapy. Further, guidelines now recommend intravenous iron therapy in certain situations,2 and more rapidly infusible intravenous iron preparations have recently become available in Australia. We investigated the use of intravenous iron by women of reproductive age, analysing dispensing data for a 10% random sample of Australians eligible to receive subsidised medicines under the Pharmaceutical Benefits Scheme (PBS).3 We included data for all women aged 18–44 years with a dispensing claim for intravenous iron during January 2013 to December 2017. Three preparations were available: iron polymaltose and iron sucrose during 2013–2017, and ferric carboxymaltose from June 2014. We calculated the annual number and rate of intravenous iron dispensing claims and iron preparation types by age group, using Australian Bureau of Statistics 2017 population data,4 and estimated overall dispensing rates by extrapolating these numbers to the national level (Supporting Information). The study was approved by the New South Wales Population and Health Services Research Ethics Committee (reference, 2013/11/494) and the federal Department of Human Services External Request Evaluation Committee. An estimated 259 700 intravenous iron dispensing claims were made for 190 490 women of reproductive age during 2013–2017; the annual number of dispensing claims increased from 17 920 in 2013 to 97 040 in 2017, and the annual rate of intravenous iron dispensing rose from 0.4 per 100 women in 2013 to 2.1 claims per 100 women in 2017 (Box). By iron type, 187 800 dispensing claims were for ferric carboxymaltose (72.3%), 71 110 for iron polymaltose (27.4%), and 790 for iron sucrose (0.3%). Most preparations were prescribed by general practitioners (111 870 claims, 43%), specialists (54 640 claims, 21%), and other medical practitioners (50 868 claims, 20%). The number of dispensing claims increased with age (18–24 years, 1.6 per 100 women; 35–44 years, 2.5 per 100 women). In 2017, intravenous iron was dispensed to one in fifty Australian women of reproductive age, five times the proportion in 2013; in 2017, 90% of these women received ferric carboxymaltose. The optimal rate of intravenous iron treatment is unknown, and there are no comparable overseas data. As possible adverse outcomes include permanent skin staining and the risk (albeit rare) of potentially fatal anaphylaxis,5 intravenous iron should be administered in settings where allergic reactions can be treated promptly, but whether this is generally the case is not known. Intravenous iron therapy for women of reproductive age also has considerable financial implications: based on average PBS prices,6 its total annual cost increased 35‐fold, from $0.75 million in 2013 to $26.9 million in 2017. However, we have probably underestimated the use of intravenous iron therapy, as we included only PBS‐subsidised dispensing, which may not include preparations administered to public hospital inpatients. The reasons for the rise in the use of intravenous iron are unclear, but may include increased awareness of patient blood management guidelines, the ease of treatment, and the perception that its side effect profile is more favourable than for oral iron therapy. The rapid growth raises concerns about whether it is being employed appropriately and cost‐effectively, given the potential harms and the lack of strong evidence for its value for improving quality of life and reproductive health outcomes. Box – Pharmaceutical Benefits Scheme dispensing claims for intravenous iron preparations for women aged 18–44 years, Australia, 2013–2017 *The small numbers of dispensing claims for iron sucrose are not separately depicted, but were included when calculating the rates of dispensing.

Antonia W Shand · Jane Bell · Amanda Henry · Luke E Grzeskowiak · Giselle Kidson‐Gerber · Sallie Pearson · Natasha Nassar

In 2014, we reported in the MJA our findings, based on linked data for cervical screening and human papillomavirus (HPV) vaccination of women in Victoria, that participation of young women in cervical screening during 2010 and 2011 was significantly lower among HPV‐vaccinated than among unvaccinated women.1 In 2018, we had the opportunity to repeat the study at the national level as part of a broader data linkage study of cancer outcomes and screening behaviour across the three national cancer screening programs in Australia.2 In the original study (2014), the Australian Institute of Health and Welfare (AIHW) data linkage unit applied probabilistic name‐based linkage to HPV vaccination and cervical screening data. We acknowledged it was likely that some screened women who were vaccinated would be incorrectly identified as unvaccinated because many young women would have changed their names and addresses between vaccination and cervical screening. In the more recent study (2018), the AIHW again used probabilistic name‐based linkage, but first updated HPV vaccination and cervical screening data by obtaining histories of name and address changes from the Medicare Enrolment File. Medicare registrants’ details are updated when new data are provided to Medicare, the national health care scheme, and are recorded in new records with dates of change. The Australian Department of Human Services agreed to provide these data to the AIHW for data linkage purposes for our 2018 study. Our investigation was approved by the AIHW Ethics Committee (reference, EO 2014‐4‐130) and by state and territory human research ethics committees. After incorporating Medicare data, annual cervical screening rates for Victorian women aged 20–24 years or 25–29 years were higher during 2010 and 2011 for vaccinated than unvaccinated women,2 contrary to our 2014 findings.1 For 20–24‐year‐old Victorian women, the difference in rate changed from 10.1% lower to 14.7% higher for vaccinated women, and for 25–29‐year‐old women from 13.5% lower to 10.0% higher (Box). Our updated findings are consistent with findings from other countries of higher cervical screening participation among women who have been vaccinated against HPV.3,4,5 Incorporating the Medicare Enrolment File into the 2018 linkage was a test of proof of concept. Its successful use in this and similar studies has led to the AIHW data linkage unit granting ethics approval and relevant authorisations for employing the Medicare Enrolment File as a tool for improving the quality of other data linkage studies. The key message of our original study, however, remains unchanged. All women, whether vaccinated against HPV or not, should be encouraged to participate in cervical screening: the HPV vaccine does not protect against all HPV types, and many women in Australia were sexually active before they were vaccinated. While it is as yet unclear whether the association between vaccination and screening will persist for women who were routinely vaccinated at school, it is crucial that we focus on strategies that effectively engage women who do not currently participate in screening. Box – Estimated participation of Victorian women in cervical screening during 2010 and 2011, by HPV vaccination status and age group: 2014 and 2018 data linkage studies HPV = human papillomavirus.

Alison C Budd · Andrew Powierski · Theresa Chau · Marion Saville · Julia ML Brotherton

A 39-year-old woman was referred for colposcopy with a positive human papillomavirus (HPV) type 16 infection result on a self-collected HPV vaginal swab

Monica FG McGauran · Adam Pendlebury

M ost cervical cancers can be prevented with HPV vaccination and screening

Julia ML Brotherton · Alison C Budd · Marion Saville

The change from vaginal births to operative births may entail unforeseen longer term consequences

David A Ellwood

To the Editor: As reported by Rowe and colleagues1 in their retrospective analysis of maternal immunisation, uptake of influenza and acellular pertussis vaccines among pregnant women remains unacceptably low. One contributing factor may be inconsistent messaging. Historically, vaccine manufacturers have included precautions about the lack of data on use in pregnancy in their product information sheets. Such precautions have been shown to lead to vaccination hesitancy and refusal among pregnant women.2,3 In contrast, the current edition of the Australian Immunisation Handbook states: “Pregnant women are routinely recommended to receive influenza vaccine … and pertussis‐containing vaccine”.4 In 2018, the Therapeutic Goods Administration asked its Advisory Committee on Vaccines to provide independent expert advice on the available safety data on influenza vaccination in pregnancy with regards to the pregnancy category of influenza vaccines. The Advisory Committee on Vaccines advised that “adoption of Australian Pregnancy Category A should be considered by sponsors for certain inactivated influenza vaccines”.5 Pregnancy Category A signals to doctors and the public that the vaccine has been used by large numbers of expectant mothers with no evidence of harm to their babies. This is in line with the Australian Immunisation Handbook: “Clinical trial data and observational studies show no increased risk of congenital defects or adverse effects in the fetuses of women who received influenza vaccine during pregnancy”.4 Following the publication of the Advisory Committee on Vaccines statement, two of the four adult influenza vaccines and one of the two acellular pertussis vaccines used to vaccinate pregnant women in Australia have changed their pregnancy category to Category A. These changes show that the Australian regulator is receptive to feedback from the medical community on how to improve immunisation rates. Hopefully, the reclassification of the pregnancy category of these vaccines will translate into increased maternal uptake and better outcomes for Australian mothers and babies.

Heidi Shukralla · Michael Coory

Changes in the modes of twin birth in Victoria, 1983–2015

Yizhen (Amy) Liu · Mary‐Ann Davey · Rilka Lee · Kirsten R Palmer · Euan M Wallace

Australia needs to develop and implement policies to ensure that data are disaggregated, analysed and presented by sex and gender

The Sex and Gender Sensitive Research Call to Action Group

To the Editor: We read with interest the recent publication by Rowe and colleagues.1 The authors reported low influenza vaccine coverage (39%) among pregnant women in Victoria from 2015 to 2017. Individual‐level factors associated with this finding included greater maternal age, primigravidity, early antenatal care and GP‐led antenatal care.1 As the authors accurately concluded, integrating vaccine delivery into antenatal care pathways is important to improve pregnant women's vaccination coverage.1 Our team reported on this previously, with coverage approximating 90% achieved by introducing standing orders for midwives.2 In collaboration with key stakeholders from six Victorian maternity services, a Monash University‐led project funded by Better Care Victoria is currently underway to implement integrated vaccination strategies and measure the cost and magnitude of improvement in maternal immunisation coverage in Victoria,3 the results of which will be available by the end of 2019. One of the key findings in the article by Rowe and colleagues1 is higher odds of influenza vaccination in women who gave birth after 37 weeks' gestation compared with women who gave birth before 28 weeks (adjusted odds ratio [aOR], 4.74; 95% CI, 3.54–6.35). A similar finding was reported for women who gave birth between 28 and 36 weeks gestation (aOR, 4.13; 95% CI, 3.07–5.56).1 This finding has two important implications. Firstly, it may indicate a potential beneficial effect of influenza vaccine received by pregnant women in reducing pre‐term birth (< 37 weeks' gestation). This is consistent with a recent systematic review and meta‐analysis that reported inactivated influenza vaccine to have a protective effect against pre‐term birth and low birth weight.4 Secondly, this finding may serve as an opportunity to emphasise the safety and benefits of influenza vaccines on perinatal outcomes. As the authors alluded to in their discussion, pregnant women tend to view influenza as primarily a health risk for themselves rather than for their infants.1 Given the importance of health care providers' recommendations in encouraging influenza vaccination among pregnant women, timely dissemination of the potential benefit in lowering the chance of pre‐term birth could further empower health care providers to recommend influenza vaccines to pregnant women.5

Khai Lin Kong · Michelle L Giles · Euan M Wallace

To the Editor: I thank Whitfield and colleagues for their article about hyperemesis gravidarum and abnormal liver function in pregnancy.1 In a 15‐month prospective study in South West Wales, abnormalities of liver function were present in 3% of pregnancies.2 In managing pregnant women with hepatic dysfunction, it is important to consider uncommon causes of liver disease that may be associated with serious maternal and fetal morbidity and mortality if untreated. Addison disease is a rare but potentially life‐threatening condition that may imitate hyperemesis gravidarum in presenting with vomiting, weight loss, postural hypotension and hyponatraemia.3,4 Addison disease has also been associated with elevated hepatic transaminases in 16 published cases, reversing with glucocorticoid replacement.5 In excluding Addison disease, the physiological rise in cortisol during pregnancy must be considered using trimester‐specific reference ranges for short synacthen testing.6 In the pregnant woman with unexplained liver disease and fever, acyclovir should be administered empirically, given the absence of cutaneous vesicles in up to 80% of affected patients and the extreme maternal and fetal mortality associated with untreated herpes simplex virus hepatitis.7 Budd–Chiari syndrome should be considered with abnormal liver function in pregnancy with abdominal pain, hepatomegaly and ascites. Additionally, the use of herbal and over‐the‐counter medications should be sought in pregnant women with abnormal liver function, given the high rates of complementary and alternative medicine use in pregnancy and their potential to cause liver injury.8 Investigations need to be interpreted with regard to gestational physiological changes, as copper, ceruloplasmin, α‐1 antitrypsin and alkaline phosphatase levels rise significantly in pregnancy. Serum lipase levels are commonly elevated in hyperemesis gravidarum — levels up to ten times normal have been reported in the absence of pancreatitis.9 Antithrombin III levels may be useful to distinguish acute fatty liver of pregnancy from pre‐eclampsia with haemolysis, elevated liver enzymes and low platelets.10 Bile acid levels are not specific for intrahepatic cholestasis of pregnancy, being elevated in many hepatic disorders including non‐alcoholic fatty liver disease. Twenty per cent of women with pruritus typical of intrahepatic cholestasis of pregnancy have normal bile acids and liver function at presentation, and symptoms may precede abnormal biochemistry by up to 6 weeks.11 In addition to ondansetron and glucocorticoids, mirtazapine has been effective in the management of hyperemesis gravidarum in case reports.12

Adam Morton

To the Editor: In their article, De Costa and colleagues1 clearly demonstrate the importance of making mifepristone freely available for prescription to all registered Australian medical practitioners, and they emphasise that the current need for special registration discourages general practitioners to become involved in medical abortion provision. We conducted a cross‐sectional study of 39 GPs and 30 primary health care nurses from regional or rural Victoria and identified additional uptake barriers.2 Most study participants showed important gaps in medical abortion knowledge, despite their overall positive stance on abortion and extensive experience with women with unplanned pregnancies, and only a few indicated to be current medical abortion providers. Although nearly all health practitioners indicated they would support a colleague in providing abortions, fewer GPs than nurses were interested in medical abortion training. The main reported uptake barriers to medical abortion provision included a lack of training opportunities as well as the absence of local support services required in Australia for the recommended pre‐abortion ultrasound and for surgical back‐up in the case of complications. Participants additionally worried about the legality of providing abortions, and some indicated that their practices would not allow the provision of this service. Abortion access for Australian women in regional and rural regions is still very restricted. By moving early medical abortion provision into the primary health care setting of underserved regions, and particularly in general practice, this situation can be considerably improved. However, the uptake among GPs remains low.3 In addition to addressing uptake barriers, alternative solutions to improve abortion access in underserved areas should be further explored as well, such as the use of telemedicine (until recently provided by the Tabbot Foundation) and the inclusion of primary health care nurses in the abortion provision process — an evidence‐based practice that is already extensively implemented in a range of high income countries.4,5 A nurse‐led model approach not only addresses the shortage of physicians but also the time‐intensive aspect of the medical abortion process, and it provides women with choice and flexibility, which is indispensable to their reproductive autonomy and, thus, to their overall welfare.

Caroline Moel‐Mandel · Melissa Graham

Many questions need to be discussed before 3D-mammography is adopted for standard screening

Meagan E Brennan

There is no strong evidence that first-line therapy with intravenous iron is superior to oral administration

Alaa Qassim · Rosalie M Grivell · Amanda Henry · Giselle Kidson‐Gerber · Antonia Shand · Luke E Grzeskowiak

To the Editor: The authors of a recent Guttmacher–Lancet Commission article1 point out that Australia is a signatory to the United Nations Sustainable Development Goals, which nominate sexual and reproductive health as rights. The key focus of the article on the Guttmacher–Lancet Commission is around human immunodeficiency virus and sexually transmitted infections, unintended pregnancy, contraception, abortion, and sexual violence.1 These are all important reproductive health rights to address. While the Guttmacher–Lancet Commission also includes maternal and newborn health, there is no mention of reproductive carrier screening. Reproductive carrier screening involves testing prospective parents — before pregnancy, ideally, or in the early stage of pregnancy — for carrier status for autosomal recessive and X‐linked recessive disorders, and giving reproductive choices to people at increased risk of having an affected child. These choices include pre‐implantation genetic diagnosis, prenatal diagnosis by chorionic villus sampling or amniocentesis, donor gametes or embryos, adoption, having no children, or ignoring the risks. Most couples with or at risk of having an affected child have no family history, which is typical for recessively inherited diseases. Reproductive carrier screening is available in Australia, although only through a fee‐for‐service mechanism, but most couples are unaware of its availability. Currently, screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy is available,2 and in the future we may be able to screen for a vastly expanded number of diseases. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists has recently released a position statement to recommend that all women, either before pregnancy or in the first trimester, should be offered carrier screening for inherited conditions.3 Reproductive carrier screening should be a routine part of pregnancy care and should be considered a health care right.

R John Massie · Martin B Delatycki

The two-dose schedule currently recommended in Australia provides better protection than a one-dose regimen

Scott W White · Janice C Cheng · Blagica Penova‐Veselinovic · Carol Wang · Melanie White · Bernie Ingleby · Christine Arnold · Craig E Pennell