Women's health

To the Editor: Pregnancy following aorto-iliac bypass or replacement grafting is uncommon, as most patients requiring this operation are beyond childbearing age. However, conditions may occur at earlier ages that necessitate such a procedure and, as the case described here illustrates, the surgery is no bar to pregnancy. In 1982, a 13-year-old girl presented to hospital after two episodes of abdominal pain. Ultrasound examination showed a large dumbbell-shaped retroperitoneal tumour widely separating the aorta and vena cava. Laparotomy revealed a large tumour firmly adherent to the inferior vena cava and completely surrounding the aorta. Biopsy showed it to be a ganglioneuroma. It was possible to separate the tumour from the vena cava but not the aorta, as no plane could be defined, and during the dissection a hole was made in the vessel. The involved aorta was resected and the tumour was able to be completely removed. The removed segment was replaced with a 10 mm woven dacron tube graft (compatible with the host aorta) from the infrarenal level to the aortic bifurcation. Five years later, the aortic graft thrombosed. Exploration showed no evidence of recurrence of the tumour, and the previous graft was replaced with a 14 × 7 mm gelatin-impregnated, knitted dacron bifurcated prosthesis from the infrarenal aorta to each common iliac artery. The patient had regular follow-up, including ultrasound and magnetic resonance imaging scans. In June 2007, after I had retired from vascular surgery, I was contacted by the patient (now aged 39 years), who was seeking information about her previous operations because she was 14 weeks pregnant and her obstetrician was concerned about the uterine blood supply. She had approached the hospital, but was told that her records had been destroyed. Fortunately, I still had my personal records of her previous surgery. The patient had required in-vitro fertilisation for conception because her uterine tubes were blocked. The pregnancy proceeded normally until the 36th week, when signs of eclampsia developed. Caesarian section was performed at 37 weeks and a healthy infant was delivered. A review of the literature revealed six other reported cases of pregnancy occurring in patients who had had previous aortic grafting for aneurysmal or atherosclerotic disease.1-6 Two patients had caesarean section and the others were delivered vaginally; all infants were viable. Possible concerns expressed by clinicians in cases such as this include compromise of the pelvic circulation, affecting foetal development; compression of the graft by the fetal head during delivery; uterine contractions contributing to graft occlusion; reduction of blood flow through the graft because of the patient’s position during labour; and false aneurysm formation at the anastomotic sites, with an increased risk of rupture. With adequate assessment and supervision by obstetric and vascular surgical teams, the outcome of pregnancy in women with a history of aortic grafting should be favourable.

H Reginald Magee

To the Editor: The advent of midurethral slings (MUSs) has revolutionised surgery for female stress urinary incontinence. An MUS is a narrow, synthetic (usually polypropylene) tape that is surgically placed beneath the middle part of the urethra, traversing either the retropubic space or the obturator foramina to provide dynamic support in order to restore urinary continence. Medicare Australia data from 1994 to 2008 (Box) show that there was a 75% increase in surgery for stress urinary incontinence over this period, from 4000 to nearly 7000 cases a year, reflecting the increasing popularity of MUSs as a result of lower morbidity and shorter hospitalisation (day surgery). The rapid uptake of MUSs since 1999 has been matched with a rapid decline, since 2001, in use of the Burch colposuspension procedure. Colposuspension is an open abdominal or laparoscopic procedure in which the bladder neck is supported by elevating the paravaginal fascia using sutures to the ipsilateral iliopectineal ligament on both sides. This operation is done via an abdominal incision or through operative laparoscopy. There has also been a decline in the use of pubovaginal fascial slings and a small increase in urethral bulking procedures. Very few needle suspensions are performed in Australia. There has been a significant increase in the number of urodynamic procedures performed (including uroflow, cystometry and urethral pressure profiles), which may also be a reflection of an increased number of women presenting for treatment. It should be noted that these Medicare data reflect trends within the private sector only, and our data are not age- or sex-specific. Nor do they distinguish between the specialties of gynaecology or urology in their use of MUSs or between different midurethral slings used in Australia. Although Burch colposuspension and autologous pubovaginal slings were for many years considered the “gold standard” operations for stress incontinence,1 recent systematic reviews have shown MUSs to be just as efficacious2,3 and possibly more cost-effective.4 Regardless of debate about which operation may be best,5 MUS surgery has become the most common operation performed for stress urinary incontinence in Australia. Data from the National Health Service in the United Kingdom show a similar trend.6 However, changes in MUS use in Australia and internationally have not always been driven by good science. The remarkable popularity of the newer single-incision slings in the United States, despite very limited availability of clinical evaluation information, is of concern. Their popularity has been attributed anecdotally to the fact that insertion of a single-incision sling is an “office” procedure that attracts greater insurance reimbursement than procedures that are performed under anaesthesia or require hospital stays. Surgery for stress urinary incontinence has moved rapidly towards a minimally invasive approach, making it more appealing to all patients, especially those who are older or medically unfit. At present, new devices to treat stress incontinence and other pelvic floor problems are being introduced and extensively used without adequate clinical evaluation by good prospective randomised trials.7 Changes in surgical practice should be driven by good scientific evidence of safety and effectiveness, rather than commercial interests or government budgets. Trends in surgery for stress urinary incontinence (SUI), based on Medicare Australia data, January 1994 to December 2008 BCS = Burch colposuspension (item no. 37044). MUS = midurethral sling (item no. 35599). * Item nos. 35602, 37042. † Item no. 37043. ‡ Item no. 37339.

Joseph K Lee · Peter L Dwyer

To the Editor: Two recent publications have described programs of carrier testing for cystic fibrosis (CF) gene mutations.1,2 The authors conclude that CF carrier testing of women in early pregnancy and their partners, as well as couples contemplating pregnancy, can successfully identify those who are at risk of having a child with CF and provide them with reproductive choices. The authors use these proof-of-concept studies, in the absence of Australian economic data, to call for all couples to be offered CF carrier testing that is supported by government funding. Although reproductive choice is clearly an individual’s right, what obligation does the community have regarding government funding of specific services to generate information that might assist such couples? Genetic screening policies have often been determined on the basis of technological capability, rather than through a rigorous evidence-based review process.3 Decision making should also take into account evidence of clinically effective screening programs, ethical principles, and opportunity costs, given the limited resources available in the health sector. A simple economic analysis of these publications highlights some issues that need to be addressed. Massie and colleagues identified nine carrier couples by screening 3200 individuals (3000 females) before conception or during early pregnancy (CF carrier frequency, one in 30). Two of the nine carrier couples had affected pregnancies, which equates to a cost of $300 000 per CF case. In Christie and colleagues’ dataset of 1000 individuals, 73% had no family history of CF; 27 of these individuals carried CF mutations, and two carrier couples but no affected pregnancies were identified. Based on population gene frequency statistics (CF carrier frequency, one in 25; 75% of CF gene mutations being p. F508del),1 Massie et al’s screening model2 would, on average, require 3585 women to be screened to detect one affected pregnancy, costing about $740 000. Christie et al’s expanded one-step model1 would require about 3763 couples to be screened to detect one affected pregnancy, at a cost of more than $430 000. Among the 270 individuals with a family history of CF who were screened in the latter model, 126 were carriers of CF mutations (carrier frequency, one in two). It is clear that cascade screening of those with a family history would be a more effective strategy. There is an ethical argument that projected economic benefits from the termination of affected fetuses should not play a role in decisions to offer testing.4 Nevertheless, technological capability needs to be considered together with evidence of cost-effectiveness and community acceptance before public funding of community CF carrier screening can be justified.

Peter C O’Leary · Susannah J Maxwell · Leanne M Youngs · Kate J Brameld · Ian R Walpole

In reply: Our aims in publishing the outcomes of offering cystic fibrosis (CF) carrier testing to couples were to demonstrate the high acceptability rate and report the reproductive choices made by high-risk couples. Not all decisions resulted in termination. O’Leary and colleagues rightly raise the question of screening costs. Laboratory costs will reduce with economies of scale and centralisation of testing. The recent release of a position paper on population screening for CF by the Human Genetics Society of Australasia1 will influence the demand for testing. It recommends that all couples intending to have children, and women in early pregnancy and their partners, be made aware of the availability of CF carrier testing, and that couples should be offered testing for 10 CF transmembrane conductance regulator gene mutations using an expanded one-step or two-step model. O’Leary and colleagues suggest that cascade testing of those with a family history of CF would be a more effective strategy. However, only 10% of children born with CF have a family history.2 Studies have demonstrated that costs of CF screening are less than the averted medical care costs associated with fewer births of infants with CF.3-5 Although economic considerations are important, these should not form the primary goal of any screening program.

Louise M Christie · Angela J Ingrey · Gillian M Turner · Anne L Proos · Gloria E Watts

Robust evidence, rather than political pressure, should inform decisions about maternity care The status of home birth in Australia has become more contentious than ever with the introduction of legislation which requires that all services provided by registered health professionals be covered by appropriate indemnity insurance. Although never intended to prevent registered midwives from providing care in planned home births, the absence of insurance for home birth has meant that any midwife assisting in a planned home birth appeared to have to forgo midwife registration, or risk penalty. The Maternity Services Review1 recommended that home birth not be supported, but this recommendation was based on the lack of consensus among providers of maternity care that would be required for its safe implementation. The Review remained silent on whether or not home birth should be considered as a safe model of care for the Australian maternity system. Previously published Australian evidence shows that planned home birth in Australia is associated with a higher risk of intrapartum perinatal mortality.2-5 An article by Kennare and colleagues in this issue of the Journal reviews the outcomes of all planned home births in South Australia from 1991 to 2006, and confirms previous findings.6 Although women with recognised risk factors such as nulliparity, Indigenous status, lower occupational status and residence outside metropolitan areas were less likely to plan home birth, planned home birth was associated with a sevenfold increase in risk of intrapartum perinatal mortality compared with planned hospital birth, and a 27-fold higher risk of death due to intrapartum asphyxia.6 These differences were significant despite a sample size of only 1141 home births. Overall perinatal mortality standardised for gestation and birthweight was more than double that of planned hospital births, but because of low numbers these differences were not statistically significant. Of course, not all severe adverse perinatal outcomes in labour can be avoided, but they are better avoided, statistically speaking, when birth is planned to take place in a hospital birth unit. Perinatal mortality is not the only relevant outcome, but it is generally accepted as a most important outcome measure. It is also significant that the incidence of intrapartum perinatal mortality due to asphyxia had halved in South Australian hospital births during 1991–2006 compared with the outcomes recorded for 1976–1987, but hardly improved for planned home birth.2,6 Rates of interventions such as caesarean section and instrumental delivery were lower in the planned home birth group in Kennare et al’s study, but, as there was no adjustment for risk, it is unclear to what extent this is due to the model of care, and to what extent it is due to the fact that hospitals care for higher-risk pregnancies.6 There were no measurable increases in rate of postpartum haemorrhage,6 and it appears that the adoption of oxytocin into home birth practice has resulted in improvement in this outcome compared with data from previous studies in Australia.5 Notwithstanding Australian data, calls for integration of planned home birth into mainstream maternity services continue, based on international evidence of comparative safety.7-9 Advocates argue that the poorer outcomes measured in Australian studies are due to inappropriate inclusion of high-risk pregnancies that will have poorer outcomes in home birth and, if restricted to low-risk pregnancies cared for by accredited practitioners, planned home birth outcomes would be comparable or superior to hospital birth outcomes . Home birth models of care have been adopted by a small number of maternity units within the state hospital systems. The federal Minister for Health and Ageing, Nicola Roxon, has been under much pressure to move beyond the recommendations of the Maternity Services Review and provide indemnity insurance and funding for planned home birth. The decision to exempt registered midwives from the indemnity insurance requirements but not extend further support is a political compromise. It is consistent with evidence that current planned home birth practice in Australia increases the risk of perinatal mortality, but recognises that a small minority of women will continue to choose to give birth at home and that it is safer for these women to be cared for by registered midwives, rather than give birth unassisted. As with most compromises, it angers both home birth advocates, who want indemnity and funding provided, and opponents, who argue that a different professional standard is being applied for the benefit of a noisy minority. The decision essentially maintains the status quo. Uninsured midwives can continue to provide care for women planning to give birth at home without risk of professional sanction (as they have since 2002). But, given the accumulated evidence from Australia spanning 30 years, facilitating and funding home birth in an autonomous setting would be contrary to the principles of evidence-based health administration. The outcome is that midwives can continue to provide care for women who have planned home births, but are required to provide full disclosure to their clients that they are not indemnified, and in return must provide data and participate in a safety and quality framework that will be overseen by the Victorian Department of Health. This should ensure a gradual accumulation of data (including statistics on outcomes such as maternal and perinatal morbidity) that can inform future policy direction, and also encourage adherence to proper clinical risk assessment and management to minimise preventable mortality and morbidity. Those who argue that planned home birth in Australia can be safe will have to show this on the basis of accumulated evidence before any further changes can be considered. With time, the gulf between the politics and science of home birth in Australia should narrow, allowing health policymakers to focus on evidence-based decisions, rather than political ones.

Andrew F Pesce MB BS, FRANZCOG

Objective: To examine differences in outcomes between planned home births, occurring at home or in hospital, and planned hospital births.Design and setting: Population-based study using South Australian perinatal data on all births and perinatal deaths during the period 1991–2006. Analysis included logistic regression adjusted for predictor variables and standardised perinatal mortality ratios.Main outcome measures: Perinatal death, intrapartum death, death attributed to intrapartum asphyxia, Apgar score < 7 at 5 minutes, use of specialised neonatal care, operative delivery, perineal injury and postpartum haemorrhage.Results: Planned home births accounted for 0.38% of 300 011 births in South Australia. They had a perinatal mortality rate similar to that for planned hospital births (7.9 v 8.2 per 1000 births), but a sevenfold higher risk of intrapartum death (95% CI, 1.53–35.87) and a 27-fold higher risk of death from intrapartum asphyxia (95% CI, 8.02–88.83). Review of perinatal deaths in the planned home births group identified inappropriate inclusion of women with risk factors for home birth and inadequate fetal surveillance during labour. Low Apgar scores were more frequent among planned home births, and use of specialised neonatal care as well as rates of postpartum haemorrhage and severe perineal tears were lower among planned home births, but these differences were not statistically significant. Planned home births had lower caesarean section and instrumental delivery rates, and a seven times lower episiotomy rate than planned hospital births.Conclusions: Perinatal safety of home births may be improved substantially by better adherence to risk assessment, timely transfer to hospital when needed, and closer fetal surveillance.

Robyn M Kennare RM, DipApplSc(Nursing), GradDipPH · Marc J N C Keirse MD, DPhil, FRANZCOG · Graeme R Tucker BSc · Annabelle C Chan MB BS, DPH, FAFPHM

A history of the ‘unfortunate experiment’ at National Women’s Hospital. Linda Bryder. Auckland: Auckland University Press, 2009 (vi + 250 pp). ISBN 978 1 86940 435 2. The so-called “unfortunate experiment” of this book triggered the 1987 New Zealand Cartwright Inquiry into cervical cancer treatment. Consultant gynaecologist Herbert Green of the Auckland National Women’s Hospital was the main target of a long and complex legal process hinging on allegations that he had prospectively studied two groups of women referred to the hospital with positive cervical cytology. One large group received treatment, following which most had no further problems (although some later developed invasive cancer). The second group, it was said, had no treatment but, despite positive cytology, were followed for years so that the natural history of what are now called high-grade epithelial abnormalities (formerly carcinoma-in-situ) could be studied; these women were 25 times more likely than the first group to develop invasive cancer, from which some of them died. Green was accused of callously disregarding the health of these women to satisfy his own scientific curiosity, and condemnation of his actions was central to the findings of the inquiry. However, as Linda Bryder painstakingly demonstrates, there was no such “experiment”. The two groups were a statistical construction in a 1984 paper by four of Green’s colleagues.1 Both groups had been treated but when positive cytology persisted, women were (unsurprisingly) more likely to develop invasive cancer. Green himself certainly advocated a less interventionist approach to the management of cervical pre-malignancy, which in the 1960s tended toward hysterectomy and in the 1970s to cone biopsy. A more low-key approach, now that we understand the role of human papillomavirus and have LLETZ (large loop excision of the transformation zone) procedures available, is universally practised — but, as I’ve observed over my own 30 years of gynaecological practice, it has required a great deal of clinical and scientific effort, much of it by people like Green, to reach this point. Bryder’s book is meticulously referenced and even-handed — although she does not conceal criticism of the feminist health activists who instigated the inquiry. Undoubtedly, the book will arouse much comment from those still able to recall these events, but as a work of medical history it will be a valuable and lasting resource.

Caroline M de Costa

Incorrect order of authors: In “ASID (HICSIG) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (H1N1) influenza 2009, in Australian health care facilities” published online on 21 September 2009 and in the 19 October 2009 issue of the Journal (Med J Aust 2009; 191: 454-458), John K Ferguson was incorrectly listed as the first author of the article. The correct order of authors is: Rhonda L Stuart, Allen C Cheng, Caroline L Marshall and John K Ferguson.

Rhonda L Stuart FRACP, PhD · Allen C Cheng FRACP, MPH, PhD · Caroline L Marshall FRACP, PhD, GradDipClinEpi · John K Ferguson FRACP, FRCPA, DTMH

Some years ago, a woman in her late 30s was referred to me for consideration for an amniocentesis on the basis of advanced maternal age. She had had three previous pregnancies, all resulting in healthy babies. An ultrasound confirmed a single, viable intrauterine pregnancy, and a fetal size consistent with dates. The amniocentesis was performed without complications. However, the results of the chromosome culture showed there was a balanced 2 on 17 translocation (Box). This was of concern to me — if this was a new mutation, there would be a significant risk that the fetus could have a neurological disorder, ranging from mild cerebral dysfunction, through to severe intellectual disability. However, most cases that I see with a translocation are not new mutations; they are a reflection of the chromosome makeup of one of the parents. I contacted the patient, and told her of the result, and requested that her blood and her husband’s blood be analysed for evidence of a translocation. After 72 hours, the laboratory issued the report showing that neither the patient nor her husband had the translocation. This did alarm me, but when I told the patient about the results, she asked whether it would be reasonable for her boyfriend to have chromosome analysis done as well. I assured her that this would be very useful, and contacted her boyfriend. He supplied blood and, sure enough, it showed that he had a balanced 2 on 17 translocation. I explained to the patient that, under these circumstances, the fetus was very unlikely to have an intellectual disability, and she seemed quite relaxed about this information. I discussed the result further with the patient’s boyfriend, pointing out to him that it may be possible that his siblings could also have a balanced translocation. If he or his siblings had any further children, these children could be affected. The patient’s boyfriend told me categorically that he was not going to be having any more children. He had a sister who had three children, and she was not going to have any further pregnancies. Nevertheless, his sister agreed to have a chromosome analysis done, which confirmed that she had a normal chromosome complement. The boyfriend also told me that he had a brother who lived on a farm. When I asked if it was likely that he would have children, he said that his brother was 28 years old and had been damaged by obstetric forceps during a difficult delivery, leaving him with an intellectual disability. This brother agreed to have chromosome analysis, and surprise, surprise, it showed that he had an unbalanced translocation. This then would explain his intellectual disability. I doubt very much whether the obstetric forceps played any role in his condition. When my patient’s baby was born, a physical examination showed that the baby was normal. I recount this history to reinforce that sometimes the obvious is not as clear cut as one may first think. The country general practitioner who delivered the boyfriend’s brother 28 years ago has probably laboured under the weight of blame being ascribed to him for the poor outcome in this young man. Chromosome translocations If two chromosomes break, genetic material can be exchanged between the chromosomes. This is called a translocation. If the person with the translocation has lost or gained no genetic material, and is phenotypically normal, the rearrangement of the genetic material is said to be balanced — a balanced translocation. If the person has an excessive or decreased amount of genetic material after the breakage, the rearrangement of the genetic material is said to be unbalanced — an unbalanced translocation.

Francis V Carmody FRCOG, FRANZCOG, DDU

To the Editor: In their national analysis, Robson and colleagues found less favourable outcomes among term singleton babies born in public hospitals than in private hospitals.1 Most health services research is non-randomised, and it is unrealistic to expect studies such as this to be as internally valid as a randomised controlled trial.2 As noted by others,3,4 in the absence of randomisation, it is difficult to untangle the myriad differences between mothers, babies, and the care provided in private and public hospitals (ie, the results might be subject to confounding). Robson et al statistically accounted for the potential confounding effect of maternal smoking (although these data were only available for about half the mothers), age, Indigenous status, parity, diabetes, hypertension, rurality and method of birth. We replicated their analysis using the Queensland Perinatal Data Collection (July 2005 – December 2007), which included virtually complete data on maternal smoking. Our analysis of 124 300 term singleton babies gave an adjusted odds ratio (AOR) for perinatal mortality of 2.0 (95% CI, 1.4–2.7), which is similar to that reported by Robson et al. Using more detailed data from the Queensland dataset, we statistically adjusted for other potential confounders — including pre-existing and gestational diabetes, pre-existing and pregnancy-induced hypertension, pre-eclampsia, eclampsia, antepartum haemorrhage, anaemia, depression, urinary tract infection, low birthweight (< 2500 g), socioeconomic status (based on area of usual residence5), alcohol and drug misuse, and artificial reproductive technology — and obtained an AOR of 2.1 (95% CI, 1.5–2.9). We are not implying that adding more and more variables to a statistical model is an appropriate way to account for confounding. Our aim is simply to show that Robson et al’s result is robust to statistical adjustment using the available data; this is not the same as saying the analysis is robust to confounding. We found that the higher perinatal mortality in public hospitals was greater for neonatal deaths (AOR, 3.1; 95% CI, 1.8–5.6) than for stillbirths (AOR, 1.6; 95% CI, 1.0–2.4). Excluding lethal congenital anomalies4 did not materially change the result (AOR, 1.9; 95% CI, 1.3–2.8). We also stratified our analysis by level of hospital — tertiary referral (neonatal intensive care unit), base (special care nursery), and community — and obtained a similar twofold mortality excess in each stratum. Although perinatal mortality is uncommon among term singleton babies (1 in 1000 in private hospitals versus 2 in 1000 in public hospitals), any excess risk should be investigated and the reasons for it understood. The results from Robson et al’s article might be due to confounding, but they should not be dismissed and should be investigated with more detailed clinical data. Even if all the excess risk is due to confounding, explicit confirmation of this would be extremely useful. To this end, the Statewide Maternity and Neonatal Clinical Network in Queensland Health will undertake clinical review and classification of term singleton deaths according to national guidelines6 and collaborate with the Australian Maternity Outcomes Surveillance System (AMOSS)7 to enhance prospective monitoring of late gestation perinatal deaths nationally.

Michael D Coory · Guan T Koh · Vicki Flenady · Maarten Kamp

To the Editor: Robson and colleagues found higher crude odds of perinatal death in public hospitals — an unsurprising finding, given the maternal demographics in the public system.1 However, after taking into account known risk factors for poor perinatal outcome by “adjusting for the potentially confounding variables available in the NPDC [National Perinatal Data Collection]”, the authors found that the odds ratio actually went up — implying that the pregnancies of mothers in the private system are higher risk. This is implausible. There are a number of problems with the analysis. The possibility that potentially important maternal information was not included has been acknowledged.1,2 Of greater concern is the omission of a history of low birthweight from the regression model. Since intrauterine growth retardation is a very strong risk factor for perinatal death,3 and since the rate of low birthweight in the public hospitals was double that in the private hospitals, this omission is puzzling. Furthermore, while the authors’ stated aim was to assess the effect of the private model of obstetrician-led interventional care on perinatal outcomes, they included the method of birth and hospital type as independent explanatory variables. Since the interventional nature of obstetric care is, as acknowledged by the authors, a key component of the model of care provided in a private hospital, adjusting for this variable will lessen the usefulness of the study in assessing the impact of private hospital care on perinatal outcomes. Put another way, in deciding what is best for her baby, a mother who is considering giving birth in the private system cannot cherry-pick only the non-interventional side of the obstetrician-led model of care — she must adopt the entire package. Including method of birth as a separate explanatory variable artificially inflates the apparent “riskiness” of the pregnancies of mothers presenting to private hospitals to give birth. These mothers had a 75% increased incidence of caesarean section; however, most of these procedures would be elective rather than emergency. Since this distinction was not made, the women in private hospitals appear high risk despite having had a caesarean section for a low-risk pregnancy. This will have the effect of making perinatal outcomes in private hospitals appear more favourable than they actually are. As currently analysed, the data are of little value to prospective mums and dads in making the first, and one of the most emotive, of the many decisions they need to make as parents.

Daniel C Chambers

To the Editor: Of the many problems with the study by Robson and colleagues,1 the one that concerns us most is the outcome of perinatal death. The headline that this is twice as high in public hospitals has the potential to scare those who have no choice about where they give birth. Both the public and the medical community have a right to expect that this outcome is rigorously and accurately represented. We do not believe this to be the case. The perinatal death rate is made up of stillbirths and neonatal deaths in the first 28 days of life. Stillbirths will comprise 70% of all perinatal deaths, and more than 90% of stillbirths after 37 weeks’ gestation will occur before the onset of labour.2,3 It cannot be excluded that this relates to model of care but, because less than 10% of these stillbirths will have occurred during delivery, it is most certainly not related to the type of birth hospital or the interventions performed during labour. Most likely, it reflects differences in intrinsic risk that have not been controlled for by Robson et al.1 The neonatal death component of this statistic is probably confounded by ascertainment bias. Most neonatal deaths after 37 weeks’ gestation occur for two reasons: intrapartum hypoxia–ischaemia and severe congenital abnormalities. When the latter are diagnosed antenatally, the mothers will often be transferred to tertiary public hospitals for a second opinion and further management. Babies with undiagnosed lethal abnormalities or severe intrapartum hypoxia will invariably be transferred postnatally to a tertiary public hospital neonatal intensive care unit, where death often occurs after withdrawal of intensive care. The midwives data collection form is filled in at the birth hospital, and the baby is categorised as “discharged”, “transferred” or “died”. The 2006 national perinatal data collection report specifically cautions: Ascertainment of neonatal deaths within 28 days of birth is likely to be incomplete. In particular, deaths occurring among babies transferred to another hospital, readmitted to hospital or dying at home may not be known to midwives who collect these data or staff who compile state and territory data.2 Thus, it is unlikely that the difference in perinatal mortality described by Robson et al1 has anything to do with the birth hospital. To represent it as such in the public arena is irresponsible. Further, for the MJA to misrepresent “perinatal mortality” as “neonatal mortality” in the media release about this article defies belief.

Nick Evans · Girvan Malcolm · Adrienne Gordon

To the Editor: The study by Robson and colleagues1 predictably produced alarming media headlines. However, we feel the study contains potential inaccuracies that seriously undermine the conclusion that the baby toll is lower in private hospitals. Did the authors ascertain the true impact of fetal abnormality or conditions requiring transfer to tertiary care? Women with threatened preterm labour often transfer to the public system and subsequently remain under the care of public high-risk teams. Babies with a known congenital anomaly detected antenatally by private obstetricians may be similarly transferred. This highest level of care is only available in public hospitals, usually those with dedicated subspecialist services in maternal–fetal medicine, neonatology or neonatal surgery. When babies who have been transferred from private hospitals to the public neonatal intensive care system subsequently die within 28 days of birth, this may be recorded as a public hospital death. The authors stated that the “major adverse outcome associated with social disadvantage is low birthweight” but that assessment of the effect of social disadvantage was beyond the scope of their study. Not accounting for the effect of low birthweight is unacceptable. The National Perinatal Data Collection records birthweight accurately and is easily used to remove the bias of low birthweight. An internationally accepted indicator of optimal perineal outcome is the rate of intact perineum. This is known to be lower in private hospitals but was curiously not reported. Further, a prospective data audit in a tertiary hospital revealed that where episiotomy extends to third- or fourth-degree tear, this is only reported as episiotomy.2 Thus, with twice the rate of episiotomy in private hospitals,3 and its association with severe perineal trauma, this outcome could be seriously under-reported in Robson et al’s study. The authors identify the significantly higher rate of caesarean sections in private hospitals as one of the measurable benefits of this model of care and dismiss any concerns as “orthodoxy”. They have overlooked the significant morbidity and mortality among term neonates associated with the rise in caesarean rates, both elective and following labour. Research using detailed Australian and New Zealand Neonatal Network data to ascertain admission rates of babies of ‘‘low-risk’’ women to neonatal intensive care units and special care nurseries not only found higher rates of admission across each gestational age group after elective caesarean section but also reported the death of two infants.4 Such morbidity and mortality is arguably the most important differential of care experienced by women who give birth in private or public hospitals.

Sally K Tracy · Alec W Welsh · Hannah G Dahlen · Mark B Tracy

To the Editor: More than 30 years ago, I was employed by the Commonwealth Government’s Maternal Mortality Committee to identify and evaluate factors contributing to maternal and infant mortality among Aboriginal Queenslanders. At that time, government policy was to transfer all pregnant Aboriginal women from their rural communities or missions to Cairns Base Hospital at 32 weeks’ gestation until 7–10 days after birth. Findings I presented in a report to Queensland Health in 19771 and at the Australian College of Paediatrics Annual Meeting in 19792 included: Babies of women who were compulsorily transferred at 32 weeks’ gestation to Cairns Hospital had lower neonatal death rates. It was assumed that — as Aboriginal women had unreliable gestational age assessments, antenatal care was irregular, and birthweights were lower than for other races3 — the risk of premature deliveries could be avoided by early transfer. There was a lower rate of breastfeeding among mothers transferred to Cairns, largely because if they opted to bottle-feed they could return home after 3–4 days (rather than waiting 7–10 days in Cairns to ensure breastfeeding was established).1 Growth failure was common in the month after weaning.4 Bottle-fed babies experienced slower weight gain and higher rates of illness.5 Suboptimal growth in bottle-fed babies during the early postnatal months predisposed babies to poor growth patterns during infancy6 and increased death rates.7 Women returning to their communities took with them infections acquired during the hospital stay in Cairns. Separation anxiety or maternal deprivation was common among children left in their communities. There was decreased family bonding (eg, between the father and the new child) and sibling resentment at maternal separation. There was unquantifiable resentment at having babies born away from the ancestral lands. Women delayed admitting their pregnancies in an attempt to remain in their communities, resulting in fewer antenatal visits. The antenatal transfer policy has been in effect for 30 years, despite conflict between those who were predominantly concerned with maternal and perinatal mortality (who favoured compulsory delivery in Cairns Base Hospital), and those (myself included) who were concerned about the effects on children’s growth and development. During this time, I have observed weakening family and community bonds, increasing alcohol and substance misuse and sexual abuse, low school attendance, poor employment records and domestic violence. My studies of Aboriginal and non-Aboriginal children born in Cunnamulla in western Queensland followed the same cohort of children from birth8 for 20 years.9 The presence of a father who was employed at the time of the child’s birth acted as a role model for the future and was more effective than all other social interventions with respect to the child’s successful education or employment 20 years later, irrespective of race or subsequent social support or interventions offered to the child during school years.9,10 Arnold and colleagues’ recent article in the Journal records a situation almost unchanged from 30 years ago, with the exception that antenatal ultrasounds have allowed transfer to occur at 36 weeks’ instead of 32 weeks’ gestation.11 Enormous resources of goodwill, effort and money have been spent in these communities over 30 years, yet the family disruption, unemployment and abuse statistics remain at variance with the Queensland norm. Perhaps the time has come to allow low-risk births to occur in selected towns, where the mother can be surrounded by her friends and relations, and be in closer contact with her ancestral land. I endorse the article by Arnold et al and hope they are more successful in implementing change than I have been.

John W Cox

Excessive maternal weight adversely affects all aspects of pregnancy and childbirth Weight and weight gain in pregnancy used to be an obstetric obsession, if not an oppression. Belief that weight restriction could prevent pre-eclampsia made scales the most feared instruments in antenatal clinics,1 causing some women to resort to fasting before their next appointment. Nearly 20 years ago, the routine use of scales started to diminish, in the same way as it had begun — without good evidence.1 Attention shifted to the weight of the offspring, and achieving birthweights within the 3000–4000 g bracket, which are associated with better perinatal outcomes.2 Evaluations of the resulting guidelines for weight gain in pregnancy2 (recently revised)3 also centred on birthweight, with less attention to more substantive perinatal and infant outcomes.4 The evaluations also showed that only a minority of women achieve an ideal weight gain;4 many gain more than is recommended, and excessive gain is most frequent in those who are overweight already.4 In the meantime, the childbearing population has changed considerably: growing in age, growing in weight, and growing in the expectation that none of this matters too much. In this issue of the Journal, two articles address different aspects of weight and pregnancy. Callaway and colleagues surveyed women about the preconception weight management advice they received, their self-perception of weight before pregnancy and their success with weight reduction.5 Jeffries and colleagues conducted a randomised controlled trial of an intervention to limit maternal weight gain during pregnancy.6 Callaway et al found that many women enter pregnancy blissfully unaware of their excessive adipose tissue,5 and presumably also of its effects on pregnancy. The study by Jeffries et al revealed that regular self-measurement of weight was effective in reducing pregnancy weight gain only in women who were overweight, but not obese, at the start of pregnancy.6 While it is disappointing that Callaway et al found that pre-pregnancy medical advice to lose weight was rare,5 one wonders how often doctors are rebuked for not acknowledging that “big is beautiful”. Alternatively, they may be constrained in their advice by their own body mass, or by simply not knowing how to translate weight reduction advice into meaningful action for their patients. Despite being innovative, the medical profession is often not an avant-garde movement known for tackling issues that do not fit within the routine framework of history, examination, diagnosis and treatment. It was only after obstetricians turned away from maternal weight control that fertility specialists turned to it,7 although their concern was more with achieving conception than with pregnancy and infant outcomes. Undoubtedly, the obesity pandemic has hit women of reproductive age particularly hard.8 The critical mass needed to initiate the menarche now comes earlier, but anything thereafter — from conception to pregnancy, childbirth, and perinatal outcome — up to the health of the next generation, is a different matter.9 An extensive body of literature, already overweight itself, testifies to the deleterious effects of excessive weight on conception rates (natural and assisted), pregnancy complications (mostly, gestational diabetes, pre-eclampsia and operative delivery, but also others), and fetal wellbeing (with increased rates of miscarriage, congenital malformations, stillbirth and perinatal death). Yet, the issue is not only the increased frequency of so wide a range of problems. It is also the weight-dependent increase in the challenges of diagnosis and management, not to mention the inherent complications of treatments, all of which add further fuel to the fire. Increased risks of fetal malformations are accompanied by greater difficulties of visualisation on ultrasound. Increased rates of late fetal death are compounded by reduced perception of fetal movements and the inadequacy of clinical examinations, including ultrasound and cardiotocography, in oversized individuals. Increased caesarean section rates are accompanied by greater challenges in gaining access to airways and the epidural space; increased operating times; greater blood loss; and a range of postoperative complications, including excessive bleeding, thromboembolism, impaired wound healing, wound dehiscence, urinary tract infection, and longer time to recovery. None of these ameliorate what is already common in obese mothers postpartum: failure to initiate and sustain breastfeeding, and postpartum depression, which have their own effects on giving infants who have survived earlier assaults a healthy start in life. Motivation on the part of pregnant women to protect their baby from unhealthy lifestyles and not to transmit these across generations is rarely lacking, but this is often an underutilised window of opportunity. It suffers from two main problems. First, and contrary to the wealth of evidence on the effects of obesity on pregnancy from its inception to its aftermath, there is remarkably little evidence on what can be done about it, as Jeffries et al noted.6 Second, the 9 months of pregnancy is too short a time for much to be achieved, especially for those at greatest need. Weight loss during pregnancy is not recommended. Recycling adipose tissue provides energy but few building blocks for fetal development, while the resulting ketoacidosis may harm the fetus. Re-introducing the terror of the scales (although worth considering for women who are unaware of their weight5) is probably not a solution. First, its effectiveness is limited, as Jeffries et al found.6 Second, although it reduces rates of fetal macrosomia and postpartum weight retention,4 it is too little too late for almost anything else. Third, it has the potential of adding insult to injury, victimising those who need ongoing support and assistance rather than repetitive lectures. Attention certainly needs to shift to preconception care, but further than preconception and fertility clinics.5,7 Too few attend them;5 half of all pregnancies are unplanned;5 and, when planned, there is usually too little time to produce substantial change. Contraception care may be better if it includes the question “what about afterwards?” and anticipatory guidance on the importance of weight, folic acid supplementation and planned pregnancy before instead of after stopping contraception. Like other pandemics that have hit maternity care in the past few decades, such as advanced maternal age and caesarean section rates, the obesity pandemic has roots that are deeper and longer than the 9 months of pregnancy.7,10 Digging them up will require more innovative strategies than we have witnessed thus far.

Marc J N C Keirse MD, DPhil, FRANZCOG

Objective: To investigate the issues that confront women when addressing overweight and obesity before conception.Design: Questionnaire-based study of 412 unselected women in early pregnancy.Setting and participants: 255 women who attended a public, antenatal “first visit” clinic at a major urban obstetric hospital in Brisbane and 157 women who presented to a private obstetrician in Brisbane for a routine ultrasound scan during a 6-week period in 2006 were surveyed.Main outcome measures: Preconception health activities, prepregnancy body mass index (BMI), self-reported weight category, attempts to lose weight before pregnancy, and weight loss advice received before pregnancy.Results: Folic acid supplementation was reported by 56% of participants, and 53% attended a preconception health check. Of women who provided details of height and prepregnancy weight, 30% were overweight or obese before pregnancy. However, 23 of 65 women with a BMI in the overweight range categorised themselves as normal weight (36%), and only 8 of 50 women with a BMI in the obese range categorised themselves as obese (16%). As BMI increased, more women reported trying to lose weight (P < 0.001) and reported receiving advice regarding weight loss (P < 0.001). Prepregnancy weight loss was reported by 52 of 115 overweight and obese women (45%).Conclusions: Potential barriers to addressing overweight and obesity before pregnancy include poor uptake of routine prepregnancy health activities, inaccurate self-categorisation of weight, unsuccessful weight loss attempts and inadequate advice regarding prepregnancy weight loss.

Leonie K Callaway MB BS(Hons), FRACP, PhD · Michael J O’Callaghan FRACP · H David McIntyre FRACP

Objective: To determine if regular weight measurement throughout pregnancy can reduce excessive gestational weight gain.Design: A randomised controlled trial.Setting: A tertiary obstetric hospital in Melbourne, between July 2007 and May 2008.Participants: 236 pregnant women recruited at ≤ 14 weeks’ gestation.Intervention: Women allocated to the intervention group were given a personalised weight measurement card, advised of their optimal gestational weight gain (based on their body mass index at the time of recruitment and the United States Institute of Medicine guidelines), and instructed to record their weight at 16, 20, 24, 28, 30, 32 and 34 weeks’ gestation. The control group were weighed at recruitment, but were not given instructions about regular weight measurement. All participants were blinded to the purpose of the study.Main outcome measure: Weight gain from recruitment to follow-up at 36 weeks’ gestation.Results: In the study population, there was a trend to less weight gain in the intervention group. The women in the intervention group experienced a mean (SD) per-week weight gain of 0.44 (0.173) kg compared with those in the control group, who gained 0.46 (0.156) kg/week (mean difference, 0.02 kg/week; 95% CI, − 0.02 to 0.07 kg/week). The intervention significantly reduced gestational weight gain in the group of women who were overweight but not obese at recruitment: those in the intervention group (20 women) gained a mean (SD) of 0.42 (0.153) kg/week and the control group (18 women) gained 0.54 (0.123) kg/week (mean difference, 0.12 kg/week; 95% CI, 0.03 to 0.22 kg/week; P = 0.01).Conclusion: Regular weight measurement in pregnancy was not found to be effective in reducing weight gain, except among women who were overweight but not obese before pregnancy.Trial registration: Australian Clinical Trials Registry ACTRN12607000272493

Kirby Jeffries · Alexis Shub MB BS, FRANZCOG, PhD · Susan P Walker MB BS, FRANZCOG, MD · Richard Hiscock FANZCA, GradDipMedStat · Michael Permezel MB BS, FRCP, FRANZCOG

Standard and Droplet Precautions are considered adequate to control the transmission of influenza in most health care situations. Vaccination of health care staff, carers and vulnerable patients against seasonal and, eventually, pandemic influenza strains is an essential protective strategy. Management principles include: performance of hand hygiene before and after every patient contact or contact with the patient environment, in accord with the national 5 Moments for Hand Hygiene Standard; disinfection of the patient environment; early identification and isolation of patients with suspected or proven influenza; adoption of a greater minimum distance of patient separation (2 metres) than previously recommended; use of a surgical mask and eye protection for personal protection on entry to infectious areas or within 2 metres of an infectious patient; contact tracing for patient and health care staff and restriction of prophylactic antivirals mainly to those at high risk of severe disease; in high aerosol-risk settings, use of particulate mask, eye protection, impervious long-sleeved gown, and gloves donned in that sequence and removed in reverse sequence, avoiding self-contamination; exclusion of symptomatic staff from the workplace until criteria for non-infectious status are met; reserving negative-pressure ventilation rooms (if available) for intensive care patients, especially those receiving non-invasive ventilation; ensuring that infectious postpartum women wear surgical masks when caring for their newborn infants and practise strict hand hygiene; and implementation of special arrangements for potentially infected newborns who require nursery or intensive care.

Rhonda L Stuart FRACP, PhD · Allen C Cheng FRACP, MPH, PhD · Caroline L Marshall FRACP, PhD, GradDipClinEpi · John K Ferguson FRACP, FRCPA, DTMH

Pregnancy and delivery are critical times for women with bleeding disorders, with mothers, and possibly their affected infants, being exposed to a variety of haemostatic challenges. Management of women with bleeding disorders during pregnancy involves a multidisciplinary team including, but not limited to, an obstetrician, an anaesthetist and a haematologist. This consensus document from the Australian Haemophilia Centre Directors’ Organisation (AHCDO) provides practical information for clinicians managing women with bleeding disorders during pregnancy. Included are: the expected physiological response in pregnancy in such women; management of pregnancy, labour and delivery, as well as obstetric anaesthesia issues, postpartum care, and reducing and treating postpartum haemorrhage; and management of infants at risk of a bleeding disorder and of bleeding in neonates. The guidelines were developed after extensive consultation, face-to-face meetings and revisions. The final document represents a consensus opinion of all AHCDO members. Where evidence is lacking, recommendations are based on clinical experience and consensus opinion.

on behalf of the Australian Haemophilia Centre Directors’ Organisation

Objective: To determine whether a surveillance program including clinical breast examination (CBE) and three screening modalities (magnetic resonance imaging [MRI], high-resolution ultrasound [U/S] and mammographic x-ray [MMX]) was feasible, and whether it could improve detection of pathological lesions in young women at high risk of developing breast cancer.Design, setting and participants: Western Australian women aged 50 years or under at high risk of developing breast cancer were recruited to our study. For a 2-year period, they were offered breast MRI and U/S scans in addition to their annual MMX and CBE. Our study was conducted between June 2002 and October 2005.Main outcome measures: Number and type of cancerous or precancerous lesions; recall rates after screening; comparative sensitivity of screening modalities.Results: Of 102 women approached, 72 agreed to participate. Fifteen lesions were detected, of which three were significant: a metastatic papillary cancer in an axillary lymph node, a borderline lesion (multiple papillomatosis with atypia), and a papilloma. All 15 lesions were visible on MRI, and four were detected by MRI only. Only one lesion was visible on all three imaging modalities. Nothing significant was detected by CBE. The recall rate after MRI scans fell from 9/72 (12.5%) in the first year to 5/67 (7.5%) in the second year.Conclusion: Our study gave valuable experience in a team approach to screening MRI, and showed that MRI can detect more lesions than MMX or U/S in women at high risk of developing breast cancer. Screening U/S may not add value to MMX and MRI screening, and we suggest a single oblique-view MMX may be used in some cases.

Christobel M Saunders MB BS, FRCS, FRACS · Gudrun Peters FRANZCR · Glenys Longman RN · Jacqueline Thomson MB ChB, FRANZCR · Donna Taylor MB BS, FRANZCR · Jianmin Hua BSc · Michelle Bennett MB ChB, FRANZCR · Elizabeth Wylie MB BS, FRANZCR · Jack Goldblatt MB BS, MD, FRACP · Arlene Chan MB BS, FRACP, MMed · James Anderson MB BS, FRANZCR

To the Editor: Australia’s world-leading government-funded National Human Papillomavirus (HPV) Vaccination Program for women aged 12–26 years is made up of two components: an ongoing school-based program and a time-limited catch-up program delivered through schools, general practices and community vaccination services. The catch-up program started in April 2007 and was due to finish by July 2009, but has been extended to 31 December 2009 to allow women to complete the three-dose schedule. Assessing the coverage achieved by the National HPV Vaccination Program will be an important measure of the Program’s success, particularly in terms of ensuring equity in vaccine uptake — so that the current gap in cervical cancer incidence and mortality between Indigenous and non-Indigenous women is reduced, not widened.1 Vaccination coverage data are also needed to monitor vaccine effectiveness in preventing cervical lesions and cancer. Accordingly, an integral part of the Program was the establishment, enabled by legislation passed in August 2007, of Australia’s first national adult vaccine register — the National HPV Vaccination Program Register. The Register began collecting data in mid 2008 and is currently uploading notifications of the 5 million doses of HPV vaccine distributed in Australia to date. Initial coverage estimates from the Register will be published by the end of the year, with all notifications from the catch-up program due to be submitted to the Register by March 2010. General practitioner incentive payments of $6 per notification will be available until that time. Interim coverage data provided by various jurisdictions are encouraging; school-based program data for 2007 from New South Wales and Victoria estimate one-dose coverage of more than 80% and three-dose coverage of approximately 70%.2 Unfortunately, there are no routine systems in place to provisionally estimate coverage in women vaccinated outside of schools. In a small population-based telephone survey that was conducted by the Cancer Council Victoria 3 months after the Program commenced, 35 of 90 women aged 18–26 years (39%) had received HPV vaccine. Australian women are taking advantage of Australia’s most expensive vaccination program to date. We encourage vaccination providers to notify the Register3 of doses administered to ensure that this facet of Australian women’s health can be followed into the future. Although we anticipate complete notification of vaccinations given at schools, the accuracy and completeness of total coverage data will depend on GPs notifying the Register.

Julia M L Brotherton · Robyn M Mullins

To the Editor: Over a third of women seeking a termination of pregnancy (TOP) in Melbourne are aged 30 years or over.1 Between 1996 and 2006, there was a 29% increase in the number of women aged 30–50 years having a TOP.2 Possible reasons for this trend are not immediately apparent. We audited the files of 50 consecutive women aged 35 years and over attending a private termination service in metropolitan Melbourne in February 2007 to determine reasons for deciding on a TOP and the women’s prior and intended contraceptive use. Of the 50 women, 38 were working in paid employment, 28 had private health insurance, 39 had at least one child, 22 had had at least one previous TOP, and 43 were in an ongoing relationship. Sixteen separate reasons for TOP were elicited (Box), with nearly three-quarters of the women citing more than three reasons for terminating their pregnancy. Over a third of the women cited financial pressures, a focus on career or studies, having dependent children, or emotional unpreparedness for children as reasons for having a TOP. Contraceptive methods used by the 29 women who indicated their prior contraceptive practice were as follows: none (9), condoms (8), natural family planning (NFP) (4), the combined oral contraceptive pill (COCP) (4), withdrawal (3), and the mini pill (1). After the TOP, contraceptive methods chosen were the COCP (11), vasectomy (10), an intrauterine device (10), condoms (8), the mini pill (5), an etonogestrel implant (4) and NFP (1). Although ours was a small retrospective audit, the contraceptive findings and reasons given for TOP in our study were similar to those of other studies.1-4 However, some of the reasons given for TOP in this age group have not previously been described — for example, having ageing parents to care for, recent migration to Australia, and ambivalence towards parenting. Furthermore, although recent Australian studies have reported a high level of contraceptive use,2,5 women in our study often relied on less effective forms of contraception or no contraception at all. Further qualitative research is needed in women of this age group to explore their understanding of fertility and pregnancy risk, barriers to effective contraceptive use, and additional supports and interventions that could prevent unplanned pregnancy in these women. Reasons for termination of pregnancy among 50 women aged ≥ 35 years Reason Number citing reason Already have dependent children 17 Focus on career or studies 17 Emotionally unprepared for a child 16 Financial pressures 16 Completed family 15 Relationship factors 14 Too old to raise a child 10 Partner factors, including partner not wanting children 9 Physical or psychological health issues 8 Concerns about congenital anomalies 7 Does not want single parenthood 6 Bad timing (recent job change, move home, move to Australia) 4 Uncertain of wanting children or does not want children 4 Exposure to medications or agents that might harm fetus 1 Pregnancy from sexual assault 1 Other factors (other life plans, uncertain paternity, poor social supports, aged dependent parents) 9

Wendy Lee · Danielle Mazza

To the Editor: Although many medicines transfer into breast milk, the amount received by the breastfed infant is usually low, with minimal risk to the infant.1 Because medicines are not tested on breastfeeding women, product information often states that the safety of use during lactation is unknown. This may lead to over-caution in prescribers, who may incorrectly advise women to stop breastfeeding during courses of medication.2 Even brief interruptions to breastfeeding can lead to complications, such as mastitis or breast refusal.1,2 Evidence-based assessments should be made for each mother–baby pair, depending on the baby’s age and the drug’s pharmacokinetics.2 Information about the safety of medicines during breastfeeding is available from books and websites,3 but doctors’ knowledge and use of these resources are not known. We carried out an observational study to describe general practitioners’ current and preferred sources of information about the safety of medicines during breastfeeding. We surveyed the 640 GPs who provided shared maternity care at Victoria’s largest maternity hospital, the Royal Women’s Hospital (RWH), Melbourne. A postal survey to be completed anonymously was sent in November 2007 with a reminder postcard 2 weeks later; a second copy of the survey was sent in February 2008. The study was approved by the human research ethics committees at La Trobe University, University of Melbourne and the RWH. Responses were received from 52% of GPs (335/640); most respondents were women (70%, 233/333), and most had personal experience of breastfeeding for longer than 6 months (68% of participants or their partners, 227/333). Over two-thirds (70%, 233/335) used the Internet during consultations. Eighty-two per cent (270/331) found the Internet helpful. Most participants (73%) obtained information about medicines and breastfeeding from their software program, or from dedicated books (61%; predominantly the RWH’s Drugs and breastfeeding4), and 51% used telephone advice (predominantly from the RWH pharmacy). When asked where they would prefer to access this information, most nominated their software prescribing program (68%) or a reliable Internet database (57%) in their top three preferences (Box). Although most participants (89%, 293/331) felt confident about prescribing for breastfeeding women, the majority were not aware that ibuprofen is considered safe for breastfeeding women; only 31% (102/330) agreed that “there is no problem taking this medicine while breastfeeding”. It appeared that some GPs erroneously believed that pregnancy drug ratings also apply to breastfeeding women. Ibuprofen has a category C pregnancy rating (drugs that have caused or may be suspected of causing harmful effects in the human fetus or neonate without causing malformations), yet the product information from Reckitt Benckiser (Slough, United Kingdom), the manufacturer of Nurofen, states that “no harmful effects are known in breastfed infants”.5 An additional problem is the contradictory advice given by different sources;6 another manufacturer, Abbott, does not recommend ibuprofen for breastfeeding mothers.5 As recommended by researchers in the United States, “We should replace the assumption ‘when in doubt, don’t breast-feed’ with the mandate ‘when in doubt, look it up in a reliable source’”.6 A central accessible source of up-to-date information about individual medications and lactation is urgently needed.7 Most GPs in our study would like this information available on the Internet. Sources of information used by general practitioners when prescribing for breastfeeding women No. of GPs (n = 332) Current sources* Preferred sources† Software prescribing program 242 (73%) 226 (68%) Reliable Internet database 33 (10%) 191 (57%) Dedicated books 203 (61%) 146 (44%) Australian medicines handbook 109 (33%) 125 (38%) Printed guidelines 0 112 (34%) Telephone advice 168 (51%) 106 (32%) Conference/seminars 2 (0.6%) 23 (7%) Journal articles 68 (20%) 19 (6%) One-on-one educational visiting (academic detailing) 0 10 (3%) Printed product information (eg, MIMS) 181 (55%) 3 (0.9%) Therapeutic guidelines 33 (10%) 3 (0.9%) Previous experience 202 (61%) 0 Pharmacist 71 (21%) 0 Colleagues 61 (18%) 0 Other books 3 (0.9%) 0 MIMS = monthly index of medical specialties. * More than one option permitted. † GPs were asked to number their top three preferences.

Lisa H Amir · Marie V Pirotta

Could a technique using fetal DNA from the maternal circulation mean the end of invasive prenatal testing? Since the first application of ultrasound to it 50 years ago, the “black box” that is the pregnant uterus has gradually yielded to efforts to gain increasingly precise information about the condition of the fetus. Technological advances in ultrasound and, more recently, magnetic resonance imaging have seen the production of high-resolution displays of fetal anatomy and physiology. Specific information about the fetal genome, however, has until now only been available through the application of invasive techniques. Amniocentesis and chorionic villus sampling have been used to diagnose fetal aneuploidy (such as Down syndrome) and an ever-increasing range of genetic conditions. But these invasive procedures come at a cost — an associated 1% risk of pregnancy loss1 limits their application and causes significant stress for women thinking of undertaking such testing. Screening tests such as ultrasound and maternal serum screening to assess aneuploidy risk have been developed to allow more judicious application of invasive procedures, but of themselves cannot accurately diagnose the fetal condition, and false negatives and positives both occur. Now, the era of non-invasive prenatal diagnosis beckons — offering the ability to obtain specific and accurate genetic information from the fetus without the need for an invasive procedure and its associated risks. The article by Hyland and colleagues in this issue of the Journal reports on the first potential clinical application of non-invasive prenatal diagnosis in an Australian population — the determination of fetal RHD status in Rhesus (Rh) D-negative women.2 About 17% of Australian women are RhD-negative.3 These women are at risk of isoimmunisation, caused by the passage of RhD-positive fetal red blood cells across the placenta during pregnancy and childbirth. The resultant antibodies produced by the mother can cross the placenta and cause fetal anaemia due to haemolysis of fetal red blood cells. Women who are isoimmunised require intensive fetal surveillance, and are at risk for fetal death and neonatal brain injury if timely intervention is not performed. The incidence of isoimmunisation has been dramatically reduced since the introduction of preventive strategies, but these rely on administration of plasma-derived RhD immunoglobulin to all RhD-negative women. The technique employed by Hyland et al involves detecting cell-free fetal DNA (ffDNA) in maternal plasma by real-time polymerase chain reaction (PCR).2 ffDNA constitutes about 4%–6% of all cell-free DNA in the maternal circulation and can be reliably detected as early as 7 weeks after conception.4 The use of ffDNA to detect the RHD gene in RhD-negative pregnant women was first described by Lo and colleagues in 1998.5 Others have since applied the technique, and a recent meta-analysis demonstrated 96.1% sensitivity and 96.5% specificity for correctly determining fetal RHD status.6 To minimise false-negative results, internal controls are used to confirm the presence of fetal DNA. The SRY gene was initially used for this purpose, but as this only detects male fetuses, Hyland and colleagues have also utilised the RASSF1A gene to confirm the presence of fetal DNA from female fetuses.2 Where they were able to determine the fetal RHD status, their predictions showed 100% accuracy when compared with the infants’ serotype determined from cord blood after delivery. In a small number of cases, determination of fetal status could not be achieved. This technique requires further evaluation in larger studies to clarify the true performance characteristics of the test, and to allow algorithms to be developed for dealing with indeterminate results and the RHD gene variants seen in some ethnic groups. However, if these issues can be satisfactorily addressed, the potential applications are significant. In the small group of women with isoimmunised pregnancies, it will allow the determination of fetal RHD status without resorting to invasive tests. In addition to the risk of pregnancy loss, invasive procedures also have the potential to cause further sensitisation and worsen the natural history of the condition. More broadly, this testing has the potential to reduce unnecessary exposure of pregnant women to RhD immunoglobulin. Currently, RhD immunoglobulin is administered for antenatal prophylaxis, potential sensitising events, and postnatally for RhD-positive infants. This regime has been very effective, reducing the incidence of sensitisation during pregnancy by more than 90%.7 However, up to 40% of RhD-negative women receive treatment unnecessarily, as they will be carrying an RhD-negative fetus from a heterozygous partner.8 Routine introduction of non-invasive fetal DNA testing would therefore be likely to have cost implications for delivery of this preventive treatment. Non-invasive detection of fetal RHD status is already being incorporated into clinical practice in Europe, and the feasibility of using this approach to make decisions about prophylaxis has been demonstrated.9 The use of ffDNA can also be applied more broadly than determination of fetal RHD status. Already, reports exist of the non-invasive prenatal diagnosis of Huntington disease,10 cystic fibrosis11 and other conditions. Detection of the SRY gene allows determination of fetal sex in women at risk of carrying a fetus with an X-linked condition.12 The non-invasive diagnosis of Down syndrome and other aneuploidies remains challenging, but newer techniques such as methylation-dependent PCR and digital PCR hold promise.13 As with many technological advances involving reproductive choices, there are ethical concerns associated with this test. Sex determination for social rather than health reasons, for example, could result from unregulated use of such technologies. There is a pressing need for vigorous discussion of these issues. Non-invasive diagnosis of specific fetal gene status using fetal DNA from the maternal circulation without any risk to the pregnancy may be the “holy grail” of prenatal diagnosis. The determination of fetal RHD status is nearing availability as a clinical tool, and is likely to be the first of many applications of non-invasive prenatal testing over the coming decade. Is a future without amniocentesis and chorionic villus sampling dawning? Not quite yet, but at least there is some light on the horizon.

Stephen A Cole MB BS, FRANZCOG, CMFM · Helen F Savoia MB BS, FRCPA

Objective: To evaluate a non-invasive molecular test using free circulating fetal DNA in maternal plasma to predict the fetal RHD type.Design: A prospective cohort study.Participants and setting: Venous blood samples were collected from 140 Rhesus (Rh) D-negative women booked for antenatal care in two tertiary maternity hospitals in Sydney and Brisbane between November 2006 and April 2008. Cell-free DNA, including free maternal and fetal DNA, was extracted from maternal plasma in the tertiary Australian Red Cross Blood Service laboratory, and three exon regions of the RHD gene were amplified.Main outcome measures: Comparison of the predicted fetal RHD status and the infant’s RhD serotype. Secondary analysis involved using SRY and RASSF1A assays as internal controls to confirm the presence of fetal DNA in RHD-negative samples.Results: Of 140 samples tested, results for RHD status were assigned for 135, and all 135 predictions were correct. A result was not assigned in five cases: three did not meet strict threshold criteria for classification, and two were due to RHD variants. Fetal SRY status was correctly predicted in 137 of 140 cases. In 16 samples typed both RHD- and SRY-negative, a positive RASSF1A result verified the presence of fetal DNA.Conclusions: Non-invasive testing of multiple exons provides a robust method of assessing fetal RHD status, and provides a safer alternative to amniocentesis for the management of RhD-negative pregnant women who are isoimmunised.

Catherine A Hyland PhD, MSc · Glenn J Gardener MB BS, DipRACOG, FRANZCOG · Helen Davies BSc, GDPH · Minna Ahvenainen BSc · Robert L Flower PhD, MSc · Darryl Irwin PhD, MIndProp, BAppSc · Jonathan M Morris MB ChB, FRANZCOG, PhD · Christopher M Ward MB ChB, PhD, FRACP · Jonathan A Hyett MB BS, MRCOG, FRANZCOG