Insights from outside BJOG


  • Athol Kent,

  • Shona Kirtley,

  • Patrick Chien

  • These snippets are extracts from a monthly service called the Journal Article Summary Service. It is a service that summarises all that is new in obstetrics and gynaecology over the preceding month. If you would like to know the details of how to subscribe, please email the editor Athol Kent at or visit the website
  • Shona Kirtley, Research Information Specialist, Centre for Statistics in Medicine, Botnar Research Centre, Oxford, UK and Patrick Chien, Consultant Obstetrician and Gynaecologist, Ninewells Hospital, Dundee, UK.

The term ‘Term’

Gestational age is widely defined as the duration of pregnancy since the onset of the last menstrual period. For statistical and research purposes it is important to have accepted terminology as to what constitutes preterm, term and post-term. Further subdivisions of these stages of pregnancy have been adopted for preterm with delivery before 28 weeks called extreme preterm, 28 weeks 0 days–31 weeks 6 days called very preterm and 32 weeks 0 days–36 weeks 6 days called late preterm (Born too soon: The Global Action Report on Preterm Birth. Geneva: WHO, 2012).

Now the nomenclature for term is being subdivided into the following stages:

  • 37 weeks 0 days–38 weeks 6 days = early term.
  • 39 weeks 0 days–40 weeks 6 days = full term.
  • 41 weeks 0 days–41 weeks 6 days = late term.

This is an American proposal in concert with the World Health Organization (WHO) to aid definitions when comparing results and to guide clinical decisions as there is a U-shaped curve of adverse outcomes for neonates with its nadir from 39 weeks 0 days–40 weeks 6 days (Spong JAMA 2013;309:2445–6).

The experts who drew up these recommendations do not favour first-trimester ultrasound measurements for gestational ageing if the date of the last menstrual period is known but concur with the 20 week scan being sufficient to confirm dating. The clinical implication is that non-urgent inductions or elective caesarean sections should not be scheduled before full term.

Delivery by caesarean section for a clinical indication, either primary or repeat, or at maternal request needs to be timed to coincide with optimal neonatal outcomes, which are most likely to be achieved at full term. If an untoward situation is to be avoided then a time after 39 weeks is optimal.

Data suggest that one-fifth of obstetricians would choose a caesarean section on request for themselves or their partner, which the Americans are calling caesarean delivery on maternal request (Ecker JAMA 2013;309:1930–6). This figure rises to half if urogynaecologists are asked their opinion, so the moral high-ground about caesarean section without maternal or fetal indications needs careful reflection.


Source: Drawn from Spong JAMA 2013;309: 2445–6.

Maternal obesity and risk factors

Two factors are inexorably increasing in obstetrics—they are caesarean section rates and obesity.

Both are products of the modern age, having only arisen as concerns in the last 30 years, both unforeseeably, both as a result of lifestyle and personal decisions taken and neither has plateaued.

Both are perversely unwanted. Apart from those who believe that an abdominal delivery protects the pelvic floor, a caesarean section is a costly, artificial and risky method of giving birth that can hardly be deemed first choice any more than the perils, stigmata and costs of obesity could be considered medically or socially desirable. Both cause debate, morbidity and mortality, and stir up strong feelings without any real evidence to show how they can be decreased.

Data from Ireland reveal associations between obesity and caesarean section rates that are more related to body mass index than ethnicity and, in addition have a correlation with induction of labour (O'Dwyer et al. J Obstet Gynaecol 2013;33:466–70). The authors link obesity to economic prosperity as well as to increased rates of induction, which in turn lead to higher caesarean section rates with about half being precipitated by ‘fetal distress’. So a cycle is built up with obese women being at higher maternal risk of gestational hypertension (10% versus 5%), pre-eclampsia (3% versus 2%) and gestational diabetes (6% versus 2%), while their fetuses are more likely to be born early, be overweight, suffer fetal distress and be admitted to neonatal intensive care units. With a high-risk maternal/fetal combination, interventions like induction to prevent postdatism are common, which is associated with high primary caesarean section rates, which then result in repeat caesarean sections, thus fuelling the cycle.

One of the strongest associations of obesity is socio-economic disadvantage. Low levels of education and income plus other factors such as a higher parity, smoking, advanced maternal age and minimal breast feeding are all associated with women who are unwilling or unable to respond defensively to the ‘abnormal environment of plenty’ that has arrived with low-cost, high-calorie food and drink.

Turner and Layte (Am J Obstet Gynecol 2013;209:124e1–7) have demonstrated these associations at 9 months postpartum, identifying target populations in whom behavioural modifications are most likely to be of benefit. These are difficult and costly challenges with high stakes:

  • Ongoing medical problems that are lifelong and serious, like the metabolic syndrome, hypertension, cancer risk, joint and skeletal problems.
  • Increased healthcare costs estimated at $50 billion annually in the USA plus $60 billion in weight-loss programmes and products (Rodgers & Collins JAMA 2012; 308:1095–6) and projected to reach £2 billion in the UK in less than two decades.
  • Direct obstetric risks to mother and fetus.
  • Intergenerational effects.
  • Socio-economic and cultural stigmatisation.

Until the medical profession is prepared to confront obesity the way it has tackled smoking—as a direct harm to health that can be reversed by supportive interventions—then the problem will remain. It is an uncomfortable topic that doctors need the courage to take on in a positive manner.

Screening mammography

The debate for and against mammography screening has been ratcheting up for some time with strong feelings being expressed by the protagonists and opponents. There are numerous arguments about the harms and benefits with the distilled wisdom being ‘informed discussion’ between the doctor and the patient. If the medical opinion was unambiguous then professionals could guide the discussion in an erudite manner. Unfortunately there is no consensus as to whether routine screening mammography results in more harms than benefits or the other way round.

The Marmot report from the UK (Lancet 2012;380:1778–86), which was supposed to settle the issue has not been placatory and more data are emerging that give cause for concern. How clinicians respond to patients’ queries depends on their information derived partly from journals and these have been interesting of late.

Three major issues are overdiagnosis, cost-effectiveness and ‘lives saved’.


Those opposed to screening hold that it leads to overdiagnosis and hence to overtreatment—in other words the treatment of women who would otherwise be untroubled by their condition, which is non-progressive. If the treatment involved were a harmless process carrying no risks, then overdiagnosis would not be a major issue, but this is not the case.

Any woman facing surgery to her breast(s), be it lumpectomy or mastectomy, experiences a physical, medical and psychological assault that resonates through her entire life and that of her family. The addition of radiotherapy and chemotherapy also carry repercussions to her body and psyche with radiotherapy being deleterious to her heart. Radiation can result in cardiac disease, both ischaemic and valvular, from therapeutic procedures with resultant morbidity and mortality (Darby et al. N Engl J Med 2013;368: 987–8, Little et al. N Engl J Med 2013;368: 2523–4, Toutouzas et al. N Engl J Med 2013; 368:2524–5).

These radiation data were gathered from protocols that were in use some time ago, when it was less sophisticated than it is today; more skilful planning, patient positioning and intraoperative radiation will hopefully result in less collateral damage. However, calculations evaluating the harms and benefits of screening mammography should take all-cause mortality into account when a balance is being concluded.

If screening saves lives, the many it saves must be weighed against the mortality rates of overtreatment.

Cost effectiveness

In the UK all women aged 50–69 years are offered screening mammography through the health service. Questions have been raised as to its value and more specifically the cost effectiveness offered in terms of additional quality-adjusted life-years (QALYs).

The calculations are complex and depend on what is considered good value for money, which is nationally set at £20,000 per QALY gained. The sums have been done and the answer is delightfully ambiguous. The researchers showed that the programme is ‘moderately likely’ to be cost effective (Pharoah et al. BMJ 2013;346:f2618). This must be the ultimate fudge of terminology.

How does one explain to a woman whether ‘moderately likely’ effectiveness is good for her or not? If the statisticians cannot put a definitive value on the investigation, the logical conclusion is that it cannot be worked out mathematically for the population, never mind for the individual, given our present data. This hardly tilts the balance in favour of a test that is riddled with non sequiturs.

Millions of women around the world have to pay for mammograms themselves and are sent reminders to re-attend once they have embarked on a programme. Is spending money on a dubious investigation with such a probability of cost-effectiveness worthwhile?

Lives saved

A study from Oxford has shown that routine mammography for breast cancer in the last few decades has not reduced deaths rates (Mukhtar et al. J Roy Soc Med 2013;106:234–42). The researchers looked at all-cause mortality and conclude that death rates started falling 3 years before the introduction of the national screening programme in 1988 and since then ‘Mortality statistics do not show an effect of mammographic screening on population-based breast cancer mortality in England.’ They also contend that some of the data informing last year's Marmot report were obsolete.

The controversy continues.

New reports and guidelines

Family planning advocacy toolkit


This comprehensive web-based toolkit, produced by K4Health, the Health Policy Project, World Vision, United Nations (UN) Foundation, Christian Connections for International Health, Marie Stopes International and the US Agency for International Development (USAID), aims to ensure that national, community and international advocacy groups and individuals have access to the information and resources that they need to make the case for improving access to voluntary family planning services. K4Health state that unmet need for family planning services remains high and that the UN and the Guttmacher Institute have estimated that 222 million women would like to avoid pregnancy but have no access to family planning methods to allow them to do so. The toolkit contains links to a wealth of resources, including multimedia resources, on topics such as policy, family planning development, guidance and tools for developing an advocacy strategy, communication tools, data and evidence, monitoring and evaluation, individual country case studies, evidence briefs and fact sheets on family planning. Links to detailed contraceptive option toolkits are also provided covering condom use, implants, injectables, intrauterine device, lactational amenorrhoea method, oral contraceptives, standard days or rhythm method and 2-day method which is a fertility awareness-based method that uses cervical secretions to indicate fertility. The resources included in/linked to the toolkit are published by organisations such as the USAID-funded Measure Demographic and Health Surveys, Guttmacher Institute, Pathfinder International, the International Planned Parenthood Federation and Advance Family Planning. K4Health welcome resource suggestions for inclusion in the toolkit and would like to hear from people willing to share their experiences of advocating for family planning services.

Available online at

Responding to intimate partner violence and sexual violence against women: WHO clinical and policy guidelines


These guidelines, produced by the Department of Reproductive Health and Research at the World Health Organization (WHO), are aimed at healthcare providers who are often the first professional that women who experience intimate partner violence or sexual violence have contact with. The guidelines aim to provide health professionals with up-to-date evidence-based guidance regarding clinical care and emotional support and hope to raise awareness about appropriate healthcare responses to violence against women among health providers and policy makers and for those developing training curricula in the fields of nursing, medicine and public health. Development of the guideline began following an expert meeting on health sector responses to violence against women held in March 2009 and the guideline is based on systematic reviews of clinical care for sexual assault and intimate partner violence, training relating to violence against women and policies and programmes relating to service delivery and reporting of such violence. A comparison of different models of delivering care to women who have experienced violence is provided, as are a set of minimum requirements for health sector responses to violence against women. Summary recommendations are highlighted for six key areas: women-centred care; identification and care for survivors of intimate partner violence; clinical care for survivors of sexual assault; training for healthcare providers on intimate partner violence and sexual assault; healthcare policy and provision and mandatory reporting of intimate partner violence. Information and advice is provided on the dissemination, implementation, monitoring and evaluation of the guidelines and identified knowledge gaps and research implications are discussed. It is hoped that the standards outlined in this guideline can form the basis for countries to incorporate into national policies and guidelines.

Available online at

US selected practice recommendations for contraceptive use, 2013


These US guidelines, published by the Centers for Disease Control and Prevention (CDC), provide comprehensive guidance on the initiation, management and follow-up of women using contraception with a focus on the different methods of contraception, and how best to use them, for all women (including adolescents). New guidance is highlighted on the use of the combined contraceptive patch and the vaginal ring. Four new topic areas are also discussed: how to start regular contraception after taking emergency contraceptive pills; management of bleeding irregularities among women using extended or continuous combined hormonal contraceptives (including pills, the patch and the ring); when women can rely on female sterilisation for contraception; when women can stop using contraceptives and not be at risk for unintended pregnancy. The guidelines have been adapted from the WHO Selected Practice Recommendations for Contraceptive Use, 2nd edition with four key changes made by the CDC: changes to the length of the grace period for depot medroxyprogesterone acetate re-injection; differences in some of the examinations and tests recommended before contraceptive method initiation; differences in some of the recommendations for management of bleeding irregularities because of new data and drug availability in the USA; a modified missed pill algorithm to respond to concerns of the CDC expert group and other reviewers that simplified algorithms are preferable.

Available online at

Guideline: calcium supplementation in pregnant women


This evidence-based guideline has been published by the WHO in response to a request from Member States for guidance on the efficacy and safety of providing calcium supplementation to pregnant women as a public health measure which could help in their efforts to achieve Millennium Development Goals (MDGs) 4 and 5 and meet global targets on the maternal, infant and young child nutrition comprehensive implementation plan. The evidence for the development of this guideline was derived from two Cochrane systematic reviews including the findings of 21 randomised controlled trials, involving more than 19 000 pregnant women from both developed and developing countries in all continents. These trials compared calcium supplementation with receiving a placebo or no intervention in addition to regular antenatal care. Calcium supplementation is said to potentially reduce adverse gestational outcomes, particularly in respect to decreasing the risk of pre-eclampsia (relative risk [RR] 0.48, 95% confidence interval [CI] 0.34–0.67, 15 trials, 16 490 women) and hypertensive disorders developing during pregnancy in low-risk woman (RR 0.59, 95% CI 0.42–0.82, ten trials, 15 903 women) and high-risk women (RR 0.22, 95% CI 0.12–0.42, five trials, 587 women). A significant increase in the risk ratio for HELLP (haemolysis, elevated liver enzymes, low platelet counts) syndrome was observed in women who received calcium supplementation compared with those who received placebo (RR 2.67, 95% CI 1.05–6.82, two trials, 12 901 women). There was no effect on reducing the risk of maternal death and preterm birth. The guideline states that in populations where calcium intake is low, calcium supplementation during pregnancy should be recommended at a dose of 1.5–2.0 g elemental calcium/day divided into three doses preferably taken at meal times from 20 weeks gestation until the end of pregnancy for the prevention of pre-eclampsia among those at risk of developing hypertension. Annexes 1 and 2 provide detailed information about the evidence-base underpinning this recommendation. This guideline is aimed at policy makers, programme and technical staff, and others who are involved in public health programmes addressing nutrition.

Available online at

Clinical guidelines updates

Royal College of Obstetricians and Gynaecologists (RCOG).

The following guideline is now available online at

Sex Steroid Treatment for Pubertal Induction and Replacement in the Adolescent Girl, No. 40, June 2013.

Innovations and patents

Patent applications

The following patents can be found online at

Means and methods for the detection of a predisposition of a female subject to recurrent pregnancy loss (RPL), pre-eclampsia (PE) and/or fetal growth restriction (FGR) EP2609110 (A1). This patent application outlines a method and kit for detecting or diagnosing a woman's predisposition to developing pre-eclampsia or suffering from recurrent pregnancy loss or fetal growth restriction. Specifically, the invention involves the examination of the human annexin A5 (ANXA5) promoter in a blood sample obtained from the biological father to detect the following nucleotide exchanges: G to A at a position which corresponds to nucleotide 186 of SEQ ID No. 2; A to C at a position which corresponds to nucleotide 203 of SEQ ID No. 2; T to C at a position which corresponds to nucleotide 229 of SEQ ID No. 2; G to A at a position which corresponds to nucleotide 276 of SEQ ID No. 2. The presence of nucleotide exchanges is said to indicate a predisposition of the female to the above pregnancy complications.

Markov, A., Bogdanova, N., Gerke, V. 3 July 2013.

Methylation biomarkers for ovarian cancer WO2013096661 (A1). This patent application discusses the identification of biological markers that are indicative of ovarian cancer, and outlines methods for identifying differentially methylated genomic CpG dinucleotide sequences that are associated with ovarian cancer in women. Identification involves measuring the level of methylation in a biological sample (either blood or tissue) obtained from the woman suspected of having ovarian cancer at a CpG dinucleotide sequence in one or more genomic targets of SEQ ID NOs: 1–300 and comparing the level of methylation at one or more CpG dinucleotide sequences in the sample to a reference level of methylation in a normal sample. The difference in methylation levels between the sample and the reference level is said to indicate the presence of ovarian cancer.

The present application claims priority to US provisional patent application serial no. 61/579,537 filed 22 December 2011, which is incorporated herein by reference in its entirety.

Fan, J-B., Bibikova, M., Royce, T., Chien, JR., Hartmann, L., Shridhar, V. 27 June 2013.

Method of in vitro fertilization with delay of embryo transfer and use of peripheral blood mononuclear cells US2013172666 (A1). This patent application outlines a method combining in vitro fertilisation techniques for women who have reduced fertility as a result of autoimmune disease. Specifically, this method comprises intrauterine injections of peripheral blood mononuclear cells obtained from the woman and then after a predetermined delay (of at least two menstrual or ovulation cycles but preferable 3–12 menstrual cycles), the transfer of at least one embryo into the uterus following initiation of in vitro fertilisation. The inventors state that the delay should decrease autoimmune rejection of the embryo with an increased chance of successful pregnancy rate and/or decreased risk of an autoimmune response in the woman.

This application claims the benefit of previously filed US Provisional Patent Application Ser. No. 61/629,651, filed on 23 November 2011, the subject matter of which is hereby incorporated by reference in its entirety.

Feskov, A., Feskova, I., Zhylkova, I., Zhilkov, S. Method of in vitro fertilization with delay of embryo transfer and use of peripheral blood mononuclear cells. 4 July 2013.

Novel 19-nor-steroids and their use for treating progesterone-dependent conditions AU2011345341 (A1). This patent application relates to the use of 19-norsteroid progesterone receptor modulators to treat progesterone-dependent conditions in women. Specifically, the invention details new steroids possessing potent antiprogestational activity, minimal antiglucocorticoid activity and reduced liver toxicity. The inventors state that these new steroids can be used to treat conditions such as dysmenorrhoea, endometriomas, uterine fibroids, endometriosis, adenomyosis, endocrine hormone-dependent tumours and cancer of the ovary, cervix and breast.

This application claims the benefit of International Application Number PCT/US2010/062068, filed 23 December 2010, the contents of which are hereby incorporated by reference.

Podolski, JS., Wiehle, RD. Novel 19-nor-steroids and their use for treating progesterone-dependent conditions. 4 July 2013.

Legal matters

US supreme court: human DNA is a ‘product of nature’ and cannot be patented

The US Supreme Court has recently rejected various patent claims regarding the isolated forms of two genes, BRCA1 and BRCA2 by Myriad Genetics. Mutations in these genes can significantly increase a person's risk of breast cancer to between 50 and 80% and to between 20 and 50% for ovarian cancer. In its ruling the court stated that ‘a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated’ and that Myriad did not ‘create’ anything to patent as the order of the nucleotides already existed. This judgement means that in the USA human genes or segments of DNA that exist in their natural form are not eligible for patenting but synthesised DNA can be patented.


Clinical trials

Clinicians keen to keep up-to-date regarding clinical studies that are currently recruiting may find the following informative.

Family planning knowledge, attitudes, and practices of postpartum Malawian women
Description This observational study aims to explore the family planning needs of postpartum women from Malawi with a particular focus on long-acting reversible contraception (LARC). The study aims to recruit 630 postpartum Malawian women (210 HIV+ and 420 HIV) who after completing a baseline survey will be followed up at 3, 6 and 12 months postpartum to determine their contraceptive needs and whether they had experienced any barriers to receiving LARC.
Outcome measures Primary: Knowledge about the intrauterine device (IUD) and contraceptive implant.Secondary: Proportion of women using an IUD or contraceptive implant; barriers to receiving an IUD or contraceptive implant.
Study site Lilongwe, Malawi.Anticipated study end date: August 2014.
The effect on risk-reducing salpingectomy in hysterectomy on ovarian reserve
Description It has recently been proposed that risk-reducing salpingectomy at the time of undergoing hysterectomy for benign gynaecological disease can potentially prevent future ovarian cancer. This phase III, randomised controlled trial aims to compare the ovarian reserve by measuring the serum level of anti-Müllerian hormone in women undergoing laparoscopic hysterectomy alone or laparoscopic hysterectomy combined with risk-reducing salpingectomy.
Outcome measures Primary: Ovarian reserve.Secondary: Not specified.
Study site Seoul, Korea.Anticipated study end date: June 2015.
Intervention for postpartum infections following caesarean section (APIPICS)
Description This non-blinded, randomised controlled trial aims to determine the efficacy of negative pressure wound therapy for 4 days when compared with conventional wound treatment between re-operation time and time to re-suturing in women who have had a surgical wound rupture after caesarean section. In the control group the wound will be treated with a hydrofibre or alginate dressing.
Outcome measures Primary: Frequency of re-rupture in each study group.Secondary: Length of hospitalisation; readmission to hospital due to wound complications after the re-operation; number of participants with a decreased health-related quality of life score as a measure of satisfaction and tolerability; the cosmetic outcome as a measure of satisfaction.
Study site Hvidovre and Odense, Denmark.Anticipated study end date: March 2016. 
Factors affecting the prognosis of patients with endometrial cancer
Description This retrospective observational study aims to explore, by reviewing data collected from women with endometrial cancer, factors affecting overall survival and disease-free survival rates.
Outcome measures Primary: Factors affecting overall survival and disease-free survival from endometrial cancer.Secondary: Not specified.
Study site Banqiao, New Taipei, Taiwan.Anticipated study end date: December 2013.