The Research Snippets are extracts from a monthly service called the Journal Article Summary Service. It is a service that summarises new articles in obstetrics and gynaecology published over the preceding month. If you would like to have information on how to subscribe, please email the editor Athol Kent at email@example.com or visit the website www.getjass.com.
The remaining sections of Insights from outside BJOG are written by Shona Kirtley, Research Information Specialist, Centre for Statistics in Medicine, Botnar Research Centre, Oxford, UK.
This Insights from outside BJOG was edited by Patrick Chien, Consultant Obstetrician and Gynaecologist, Ninewells Hospital, Dundee, UK.
While the developing world tries to provide contraception for population control, women in developed countries are delaying their childbearing. This may seem ideal for those with the privilege of education and choice but on closer inspection there are personal, social and medical challenges waiting for women who choose to delay starting a family (Daly and Bewley Reprod Biomed Online 2013;27:722–32).
Four decades ago the mean age of women giving birth was 25 in Europe but this has risen to 30 years in recent times. This means that the age of a woman's first delivery is 29 years and half of all deliveries are to women over 30 years old.
People are living longer and fewer babies are being born. Senior citizens live off pensions provided by funds that rely heavily on flourishing economies contributed to by a shrinking pool of young adults. In the UK half of all government spending is on welfare and the NHS.
For populations to remain stable the total fertility rate must be 2.1 children per woman but in countries like Germany and Spain it is 1.4 so unless there is net immigration they are looking at smaller numbers of people, many of whom do not contribute financially.
These demographic consequences are not lost on governments who can dissuade or encourage childbearing by policy. These can be ‘quantum’ effects like gender equality in the public and private sectors, which have long-term consequences, or ‘tempo’ effects like baby bonuses and parental leave, which have shorter-term outcomes. In France and Sweden these appear to be working with resultant fertility rates of just under 2, but without positive immigration policies total population numbers will continue to fall.
Socially, young couples wish to enjoy their youth and have their smaller families at a time to suit themselves. The sociological ramifications of ‘precious’ children with ‘helicopter’ (ever-hovering) parents are yet to be played out but there may well be psychological consequences like entitlement and narcissistic trends.
Individual decisions as to when to start a family are also determined by socio-economic constraints. Tertiary education is seen as desirable and careers are less attractive than moving from job to job as ‘high-voltage’ employees while childcare by grandparents is less common.
These educational, economic and social chronological issues do not tick synchronously with a woman's biological clock (Figs 1 and 2).
Contraceptive methods do not usually affect fecundity when discontinued but age does. Older women have higher rates of infertility, chromosomal abnormalities, ectopic pregnancies and miscarriages. All these factors have J-shaped graphs that reflect the natural attrition of primordial follicles, oocyte quality, tubal factors and gamete integrity, all of which climb steeply over the age of 35 years.
Assisted reproductive treatment, most prominently in vitro fertilisation can assist with low sperm counts or tubal blockage but not oocytes degeneration. In vitro success rates drop with egg age and assisted reproductive treatment cannot compensate for age and is not a significant factor in population regulation. Women must not be seduced into thinking that they can put off conceiving and be rescued by medical science.
Spontaneous miscarriage rates are about 20% up to the age of 35 years but climb dramatically thereafter, reaching 90% at 45 years. The causes are genetic in the main but also may include tubal factors with longer potential exposure to infective processes and endometrial receptivity coming into play.
All pregnancy-related complications rise with age, for example pre-eclampsia, caesarean section rates, gestational diabetes, stillbirths and neonatal deaths—so more resources need to be provided for antenatal, intrapartum and postpartum care. Complicated pregnancies are expensive in terms of technology, skills and person-power with half of women over the age of 35 years finding themselves in this ‘complex’ category. The statistics reflect the risk of maternal mortality, showing that at 40 years it is double the population average and soars thereafter.
Older age is also associated with multiple pregnancies, as is in vitro fertilisation so maternal co-morbidities may be confounded by multifetal complications.
The blessings of prosperity, choice, independence and technology are there to be enjoyed but biology has its own pace and waits for no woman.
Preventing venous thromboembolism recurrence
More people die from cardiovascular disease than anything else. After myocardial infarction and stroke comes venous thromboembolism (VTE) in the conditions causing death or morbidity and it is in the field of VTE treatment that major advances are being reported. The classical management for VTE has been low-molecular-weight heparin followed by warfarin carefully monitored for 3–6 months or longer. The balance has to be struck between preventing recurrence of VTE and the patient developing a bleeding disorder once the initial heparin treatment has been completed.
The difficulty with vitamin K antagonists like warfarin is the need for tight control by laboratory methods to ensure that dosages are adjusted to keep bleeding times within the therapeutic range. Various factor X inhibitors have proved promising alternatives to warfarin and now a clinical trial shows that edoxaban is at least as effective as warfarin in preventing recurrence of VTEs with significantly less risk of bleeding. It comes in the form of a once-a-day 60-mg tablet and does not require monitoring (Hokusai, VTE investigators. N Engl J Med 2013;369:1406–15).
The trial accepted patients with a broad spectrum of VTEs with or without pulmonary embolism in real-world circumstances so it seems that edoxaban is set to join the growing range of anticoagulants that outperform warfarin. Is it time to hear from your local haematologist?
Should women take calcium and vitamin D supplements?
Should healthy postmenopausal women take calcium supplements? If a woman has a mixed diet that contains fruit, vegetables and dairy products is extra calcium justified to prevent osteoporosis and fractures and are there possible side effects?
These are reasonable questions to which Bauer supplies the answers (N Engl J Med 2013;369:1537–43). Calcium is constantly laid down and absorbed from bone, it plays a vital role in skeletal integrity and calcium-deficient women and men are at increased risk of fractures. To maintain adequate intake dairy products, yoghurt, grains (especially fortified) and some fish need to be regular ingredients of a person's diet.
Milk, cheese and yoghurts provide 75% of all dietary calcium and the recommended allowance is between 1000 and 2000 mg per day. If this is achieved then additional elemental calcium is not necessary and a daily limit of 2500 mg should not be exceeded. Supplements should only be recommended in those unable to meet the daily requirements through their diet.
The side effects of calcium supplements are few but include minor constipation or dyspepsia; there are rarer events like nephrolithiasis or possibly cardiac events but evidence for the latter is equivocal. On balance it is wiser to encourage increased dietary calcium intake than the routine use of supplements.
Is the ingestion of ‘extra’ vitamin D justified in healthy women to prevent osteoporosis? The short answer is no—according to a systematic review and meta-analysis published in The Lancet (Reid et al. Lancet 2013;pii:S0140–6736(13)61647–5).
Like almost all studies in all journals about all supplements, adding extra vitamins, minerals or other substances to a mixed diet does not improve health. Deficiency states are different, for example where people are unable to be outside in the sunlight vitamin D may be required or if geographical areas are trace-substance deficient but otherwise supplements ‘for better health’ are just a con.
The results of consanguineous unions are seldom reported because of social sensitivities. This does not help medical science and there is little evidence on which advice can be based for couples who marry ‘within the family’, usually cousins.
The exception is the ‘Born in Bradford’ study by Sheridan et al. (Lancet 2013;382:1350–9) that tracked the outcomes of pregnancies of unions between related Pakistani parents and unrelated British parents in a low socio-economic region of the UK. They found that where there was consanguinity in the Pakistani community, the rate of congenital abnormalities doubled compared with the background incidence, even after adjustment for deprivation. They also found raised risks of anomalies in the least educated sections of the population.
According to Bittles (Lancet 2013;382:1316–17) exome sequencing could be helpful in identifying deleterious gene variants and establishing appropriate disease registries to guide communities where consanguinity is socially acceptable or even desirable.
This report, published by the United Nations Population Fund (UNFPA), examines the underlying causes of pregnancy in girls under the age of 18, discusses the pressures that young girls face from many different directions and levels, proposes methods to tackle adolescent pregnancy and considers the key benefits of addressing this issue. The report states that there are 20 000 girls under the age of 18 years giving birth per day in developing countries and girls under the age of 15 years account for 2 million out of the 7.3 million births that occur every year in developing countries to adolescent girls under 18 years old. Adolescent pregnancy has a huge impact on a girl's health, education and productivity and the report includes quotes from young girls who have experienced adolescent pregnancy, highlighting the effect that this has had on their lives. Underlying causes listed in the report include: poverty; gender inequality; sexual violence and coercion; child marriage; national policies restricting access to contraception, age-appropriate sexuality education; lack of access to education and reproductive health services and underinvestment in adolescent girls' human capital. Eight ways to address this issue are proposed: preventative interventions for girls aged 10–14 years; ending the practice of child marriage and preventing sexual violence and coercion; introducing multi-level approaches to ensure that girls remain healthy and have safe life trajectories; protecting rights to education, health, security and freedom from poverty; encouraging schooling for girls and helping those who are already schooling to stay enrolled longer; engaging men and boys to help them to play a part in the solution; ensuring access to both age-appropriate sexual education and adolescent health services; building a post-Millennium Development Goal framework based on human rights, equality and sustainability.
This report, published by the UK National Audit Office, focuses particularly on whether the UK Department of Health is achieving value for money in its current provision of maternity services. The report provides a detailed overview of both the performance and management of maternity service provision in England. The report states that in 2012 there were 694 241 live births in England and that the cost of providing maternity care services in 2012–13 was £2.6 billion, equivalent to approximately £3,700 per birth. The number of births in the UK is said to have increased by almost a quarter in the last 10 years with increasing demands being placed on NHS maternity services and a higher proportion of births are now classed as ‘complex’, which increases the risks of childbirth. Key findings include: overall women's experiences are positive but experiences related to continuity of care are mixed; level of consultant presence on labour wards has improved substantially; the number of midwives has increased but the NHS is not meeting a widely recognised benchmark for midwife staffing levels; the number of midwifery-led units has increased, and more women now live within a 30-minute drive of both an obstetric unit or a midwifery-led unit; there is substantial variation between trusts in the costs of delivering maternity care. Where the demand for maternity services might outstrip capacity, some trusts are restricting access through pre-emptive caps on numbers or reactive short-term closures of maternity units in order to safeguard the quality and safety of care. Twenty-eight per cent of units reported that they were closed for half a day or more between April and September 2012. The report also highlights that within the UK NHS maternity care accounted for a third of the clinical negligence bill in 2012–13 and that the number of claims increased by 80% (to 1146 clinical negligence claims) in the 5 years to 2012–13. A total of £482 million is reported as having been spent covering the costs of maternity clinical negligence cover in 2012–13. The most common reasons for maternity claims being made are said to be mistakes in the management of labour and relating to caesarean sections, and also errors that lead to the development of cerebral palsy. The report states that the increase in litigation highlights the need for improved risk management and ensuring improvements in safety and care. There is also significant variation in the cost and efficiency (in terms of length of stay and bed occupancy) of delivering maternity care.
This report, produced by the Overseas Development Institute, aims to investigate the reasons why Nepal has managed to reduce its maternal mortality rate (MMR) so significantly within a 10-year period and to highlight lessons learned that could help other countries striving to reduce their MMRs. Between 1996 and 2006 the Nepal Demographic and Health Survey (NDHS) reported that the maternal mortality rate dropped by 47% (from 539 to 229 per 100 000 live births). Data sources informing this report included analysis of primary sources, a comprehensive literature review, interviews with experts, visits to three Nepalese districts (Dolakha, Lalitpur and Rupandehi) and a stakeholder workshop. Comprehensive statistics are provided including for variation in MMR by ethnicity, the under-5, infant and neonatal mortality rates from 1975 to 2011 and health expenditure per capita. The key factors driving this change in Nepal are reported as: the prioritisation of maternal health by various Nepali governments, improving access to health services and behavioural changes at the household level. Six lessons learned have been highlighted: engagement of a well-connected policy advocacy movement; integration of maternal health and family planning services; more extensive and informed use of evidence based data; working at a multisectoral manner to improve maternal health; reducing barriers to maternity services and addressing demand constraints on such services; creation of awareness of pregnancy of risk at the community level.
This US Center for Disease Control and Prevention (CDC) National Health Statistics Report presents national estimates (part of the National Survey of Family Growth [NSFG]) of the use of family planning and related medical services among US women aged 15–44 years between the years 2006 and 2010. The report is based on 12 279 face-to-face interviews (78% response rate) with women aged between 15 and 44 years in the household population of the USA. The data are presented by key demographic characteristics including age, Hispanic origin and race, marital status, parity, metropolitan residence, health insurance and poverty level. The report estimated that, 43 million of the 62 million US women aged 15–44 years between the study period received a family planning or related medical service in the 12 months before the interview was held. The most common services accessed included pelvic examinations, birth control methods or a prescription, check-up or test related to the use of contraception, or a cervical Papanicolaou smear test. Users of family planning and related services are stated as being more likely to be married or cohabiting than nonusers and users were more likely than nonusers to have been treated for a sexually transmitted disease in the past year and were more likely to have engaged in any sexual or drug-related HIV risk behaviour in the past year.
US 2013296447 (A1) Method of preventing neurodevelopmental damage due to prenatal exposure to environmental toxins. This patent application outlines methods for assessing the risk of a woman having a child with neurocognitive development disabilities due to exposure to environmental toxins such as organophosphate pesticides, endocrine disruptors and xenoestrogens. Specifically, the patent relates to a noninvasive method of measuring concentrations of such toxins and an evaluation of deficiency in paraoxonase 1 (PON1) activity from a urine sample obtained from the woman.
This application claims the benefit of Provisional Application Ser. No. 61/610,921 filed on 14 March 2012, the entirety of which is hereby incorporated herein by reference.
Bralley III, JA. 7 November 2013.
EP2658545 (A1) Treatment of pain associated with dislocation of basal endometrium.. This patent application relates to a method for reducing the pain associated with endometriosis or adenomyosis and a method for reducing or halting menstrual bleeding in women with endometriosis or adenomyosis. Specifically, this method relates to the administration of a daily dose of 7–12 mg ulipristal (formerly known as CDB-2914) which is 17α-acetoxy-11β-[4-N,N-dimethylamino-phenyl)-19-norpregna-4,9-diene-3, 20-dione.
Loumaye E, Bestel E, Osterloh I. 6 November 2013.
WO2013165256 (A1) Postpartum uterus model. This patent application discusses the development of a postpartum uterus model or simulator to aid the training of health professionals in manoeuvres associated with the treatment of postpartum haemorrhage due to uterine atony such as bimanual uterine compression, manual removal of retained placenta and insertion of intrauterine balloon tamponade and the immediate postpartum intrauterine device insertion especially in developing countries due to difficulties with patient follow up following child birth. The simulator consists of a realistic model of an immediate postpartum uterus (24 hour immediately following delivery of the infant and placenta) cervix and vagina.
Garvik TI, Quinonez P. 7 November 2013.
GB2502238 (A) Compositions and methods for diagnosing ovarian cancer. This patent application proposes methods and compositions for differentiating ovarian cancer from a benign pelvic mass, particularly in women with increased serum CA125 levels. The presence of two or more of the following biomarkers interleukin-6 (IL-6), matrix metallopeptidase 9 (MMP9), tissue plasminogen activator (tPA), insulin-like growth factor binding protein 2 (IGFBP2), matrix metallopeptidase 7 (MMP7), Tenascin, nucleosome assembly protein 2 (NAP2), glycodelin, MCSF, matrix metallopeptidase 2 (MMP2), Inhibin A, Urokinase-type plasminogen activator receptor (uPAR), and epidermal growth factor receptor (EGFR) will be assessed.
Zhang Z and Chan DW. 20 November 2013.
Germany: third gender option on birth certificates
Germany recently became the first country in Europe to allow the parents of children born of physically indeterminate gender to register the child as neither male nor female on their birth certificate. A third box titled ‘X’ has been included alongside ‘M’ and ‘F’ on the form that all parents must complete to register their child. Previously, parents were given one week to decide whether their intersex child was male or female before they were required to register them. The German government has stated that the introduction of this third box does not mean that an official third gender has been legally recognised but simply that it provides children with the right to take time to decide whether they will live as a male or female in the future.
Lesbian egg donor granted parental rights by Florida Supreme Court
The Florida Supreme Court has recently formally recognised the parental rights of nonbirth biological mothers in same-sex relationships after a case involving a dispute over the legal status of a nonbirth mother who provided the eggs for the couple, and her partner who gave birth to the child. After the relationship ended the biological mother wished joint custody of the child but the Assisted Reproductive Technology Statute in Florida excludes egg or sperm donors from obtaining parental rights of any resulting child except in the case of a commissioning couple. Initially, the trial court granted the birth mother parental rights but on appeal this decision was reversed in favour of the biological mother by the Florida Supreme Court.
This multicentre observational study aims to determine the safety and tolerability of the addition of bevacizumab (Avastin) to standard chemotherapy in Greek women with stage IIIb, IIIC or IV epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma.
Primary: Number of participants with adverse events.
Secondary: Number of participants with response rate; percentage of women with progression-free survival.
Various locations, Greece.
Anticipated study end date: March 2015
Quantitative ultrasound assessment of gastric volume in pregnant women at term
This randomised study aims to develop a mathematical model that can be used to predict clear fluid volume in the stomach of nonlabouring pregnant women. Women will fast overnight and will then be randomised to either of the following groups: empty or various volumes of fluid (50, 100, 200, 300 or 400 ml of apple juice administered before ultrasound scanning). Their gastric contents will then be assessed by an anaesthesiologist.
Primary: Correlation between ingested volume and ultrasonically measured cross-sectional area (CSA) in the gastric antrum.
Secondary: Not specified.
Anticipated study end date: June 2014
Barbed suture in single-port laparoscopic myomectomy
This multicentre randomised controlled trial aims to investigate whether using unidirectional knotless barbed suture in single-port laparoscopic myomectomy using V-Loc™ suture material could assist with the suture of uterine wall defect after myoma enucleation when compared with conventional multi-port laparoscopic myomectomy using V-Loc™ suture material.
Primary: Suturing time.
Secondary: Cosmetic satisfaction.
Various locations, Republic of Korea.
Anticipated study end date: November 2015
Prediction of growth-restricted fetuses using femur length to mid-thigh circumference ratio: a case–control study (IUGR)
This observational case–control study aims to investigate the usefulness of antenatal measurement of the fetal femur length to mid-thigh circumference ratio by ultrasound as a method of predicting intrauterine growth restriction in a fetus.
Primary: Femur length to mid-thigh circumference ratio.
Secondary: Not specified.
Anticipated study end date: September 2014
Effects of analgesic techniques on duration of spontaneously laboring patients
This randomised trial aims to determine if there are any differences in the duration of the first stage of labour in nulliparous women in spontaneous labour who receive analgesia maintained with a combined spinal epidural (CSE) technique compared with nulliparous women in spontaneous labour who receive an epidural de novo technique. It is hypothesised that that the duration of the first stage of labour, in nulliparous women who receive either intrathecal 25 μg fentanyl alone or intrathecal 15 μg fentanyl and 2.5 ml of 0.5% bupivacaine as part of a CSE technique, will be no different but that the duration of the first stage of labour will be shorter in labouring women receiving intrathecal analgesia (as part of a CSE technique) compared with those who receive an epidural de novo technique with 100 μg fentanyl and 10–20 ml in divided doses of 0.125% bupivacaine.
Primary: Duration of first stage of labour.
Secondary: Presence or absence of fetal heart rate decelerations.