Parental ancestry and risk of early pregnancy loss at high altitude.

High altitude pregnancy is associated with increased frequency of low birth weight infants and neonatal complications, the risks of which are higher in women of low-altitude ancestry. Does ancestry also influence the risk of miscarriage (pregnancy loss <20 weeks) in high-altitude pregnancy? To answer this, 5386 women from La Paz, Bolivia (3300-4150 m) with ≥1 live-born infant were identified. Data were extracted from medical records including maternal and paternal ancestry, demographic factors, and reproductive history. The risk of miscarriage by ancestry was assessed using multivariate logistic regression, adjusting for parity, and maternal age. Andean women experienced first live-births younger than Mestizo or European women (21.7 ± 4.6 vs 23.4 ± 8.0 vs 24.1 ± 5.1, P < .001). Andeans experienced more pregnancies per year of reproductive life (P < .001) and had significantly higher ratios of live-births to miscarriages than women of Mestizo or European ancestry (P < .001). Andean women were 24% less likely to have ever experienced a miscarriage compared to European women (OR:0.76; CI:0.62-0.90, P < .001). The woman's partner's ancestry wasn't a significant independent predictor of miscarriage. In conclusion, the risk of miscarriage at high altitude is lower in Andean women. The lack of a paternal ancestry effect suggests underlying mechanisms relate more to differential maternal adaptation in early pregnancy than fetal genetics.

Approaches to screening for hyperglycaemia in pregnant women during and after the COVID-19 pandemic.

AIM: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA1c , during the COVID-19 pandemic. METHODS: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004-2008; 826 consecutive gestational diabetes pregnancies, 2014-2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA1c performance. RESULTS: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79-0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65-0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85-0.98)] and HbA1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75-0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77-0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2-5.4 mmol/l (sensitivity 18-41%; specificity 97-98%). CONCLUSIONS: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.

Barriers to completing oral glucose tolerance testing in women at risk of gestational diabetes.

AIM: Complications of gestational diabetes (GDM) can be mitigated if the diagnosis is recognized. However, some at-risk women do not complete antenatal diagnostic oral glucose tolerance testing (OGTT). We aimed to understand reasons contributing to non-completion, particularly to identify modifiable factors. METHODS: Some 1906 women attending a tertiary UK obstetrics centre (2018-2019) were invited for OGTT based on risk-factor assessment. Demographic information, test results and reasons for non-completion were collected from the medical record. Logistic regression was used to analyse factors associated with non-completion. RESULTS: Some 242 women (12.3%) did not complete at least one OGTT, of whom 32.2% (n = 78) never completed testing. In adjusted analysis, any non-completion was associated with younger maternal age [≤ 30 years; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6-3.4; P < 0.001], Black African ethnicity (OR 2.7, 95% CI 1.2-5.5; P = 0.011), lower socio-economic status (OR 0.9, 95% CI 0.8-1.0; P = 0.021) and higher parity (≥ 2; OR 1.8, 95% CI 1.1-2.8; P = 0.013). Non-completion was more likely if testing indications included BMI ≥ 30 kg/m2 (OR 1.7, 95% CI 1.1-2.4; P = 0.009) or family history of diabetes (OR 2.2, 95% CI 1.5-3.3; P < 0.001) and less likely if the indication was an ultrasound finding (OR 0.4, 95% CI 0.2-0.9; P = 0.035). We identified a common overlapping cluster of reasons for non-completion, including inability to tolerate test protocol (21%), social/mental health issues (22%), and difficulty keeping track of multiple antenatal appointments (15%). CONCLUSIONS: There is a need to investigate methods of testing that are easier for high-risk groups to schedule and tolerate, with fuller explanation of test indications and additional support for vulnerable groups.

Seasonal variations in incidence and maternal-fetal outcomes of gestational diabetes.

AIMS: To determine whether the neonatal and delivery outcomes of gestational diabetes vary seasonally in the context of a relatively cool temperate climate. METHODS: A retrospect cohort of 23 735 women consecutively delivering singleton, live-born term infants in a single tertiary obstetrics centre in the UK (2004-2008) was identified. A total of 985 (4.1%) met the diagnostic criteria for gestational diabetes. Additive dynamic regression models, adjusted for maternal age, BMI, parity and ethnicity, were used to compare gestational diabetes incidence and outcomes over annual cycles. Outcomes included: random plasma glucose at booking; gestational diabetes diagnosis; birth weight centile; and delivery mode. RESULTS: The incidence of gestational diabetes varied by 30% from peak incidence (October births) to lowest incidence (March births; P=0.031). Ambient temperature at time of testing (28 weeks) was strongly positively associated with diagnosis (P<0.001). Significant seasonal variation was evident in birth weight in gestational diabetes-affected pregnancies (average 54th centile June to September; average 60th centile December to March; P=0.027). Emergency Caesarean rates also showed significant seasonal variation of up to 50% (P=0.038), which was closely temporally correlated with increased birth weights. CONCLUSIONS: There is substantial seasonal variation in gestational diabetes incidence and maternal-fetal outcomes, even in a relatively cool temperate climate. The highest average birth weight and greatest risk of emergency Caesarean delivery occurs in women delivering during the spring months. Recognizing seasonal variation in neonatal and delivery outcomes provides new opportunity for individualizing approaches to managing gestational diabetes.

Improving outcomes in gestational diabetes: does gestational weight gain matter?

AIM: Excessive gestational weight gain increases risk of gestational diabetes mellitus (GDM) but it remains unclear whether weight control after GDM diagnosis improves outcomes. We assessed whether: (1) total gestational weight gain during pregnancy (0-36 weeks); (2) early gestational weight gain (0-28 weeks, before GDM diagnosis); or (3) late gestational weight gain (28-36 weeks, after diagnosis) are associated with maternal-fetal outcomes. METHODS: Some 546 women with GDM who delivered viable singleton infants at a single UK obstetric centre (October 2014 to March 2017) were included in this retrospective observational study. RESULTS: Higher total gestational weight gain was associated with Caesarean section [n = 376; odds ratio (OR) 1.05; confidence intervals (CI) 1.02-1.08, P < 0.001] and large for gestational age (OR 1.08; CI 1.03-1.12, P < 0.001). Higher late gestational weight gain (28-36 weeks; n = 144) was associated with large for gestational age (OR 1.17; CI 1.01-1.37, P < 0.05), instrumental deliveries (OR 1.26; CI 1.03-1.55, P < 0.01), higher total daily insulin doses (36 weeks; beta coefficient 4.37; CI 1.92-6.82, P < 0.001), and higher post-partum 2-h oral glucose tolerance test concentrations (beta coefficient 0.12; CI 0.01-0.22, P < 0.05). Women who avoided substantial weight gain after GDM diagnosis had 0.7 mmol/l lower postnatal 2-h glucose and needed half the amount of insulin/day at 36 weeks compared with women with substantial weight gain after diagnosis. There were no significant associations between early gestational weight gain (0-28 weeks) and pregnancy outcomes. CONCLUSIONS: These findings suggest that controlling gestational weight gain should be a priority following GDM diagnosis to optimize pregnancy outcomes and improve maternal postnatal glucose homeostasis. The period after diagnosis of GDM (often 28 weeks gestation) is not too late to offer lifestyle advice or intervention to improve weight management and pregnancy outcomes.

Early life environment influences the trajectory of post-partum weight loss in adult female rats.

RESEARCH QUESTION: The physiological processes of pregnancy and lactation require profound changes in maternal metabolism and energy balance. The timescale of metabolic reversion after pregnancy, in particular post-partum weight loss, is highly variable between individuals. Currently, mechanisms influencing post-partum metabolic recovery are not well understood. The hypothesis tested here is that, in common with other metabolic and obesity-related outcomes, capacity for post-partum weight loss is influenced by developmental programming. DESIGN: Adult female Wistar rats exposed to a maternal low-protein diet in utero then weaned onto a control diet post-natally (recuperated group) were compared with controls. Adult females from both groups underwent pregnancy at 3 months of age. Weight changes and metabolic parameters during pregnancy and lactation were compared between control and recuperated groups, and also with non-pregnant littermates. RESULTS: Pregnancy weight gain was not different between the control and recuperated groups, but post-partum recuperated animals remained significantly heavier than both post-partum control animals (P<0.05) and their non-pregnant recuperated littermates (P<0.05) at the end of lactation. Post-partum recuperated animals had more intra-abdominal fat mass (P<0.05) and higher serum triglyceride concentrations (P<0.01) than controls. Post-partum recuperated animals also had increased expression of IL6, NRF2 and ALOX12 (key regulators of inflammation and lipoxygenase activity) in the intra-abdominal adipose tissue compared with control groups. CONCLUSIONS: Mothers who themselves have been exposed to adverse early life environments are likely to have slower metabolic recovery from pregnancy than controls. Failure to return to pre-pregnancy weight after delivery predisposes to persisting sequential inter-pregnancy weight gain, which can represent a significant metabolic burden across a life course involving several pregnancies.

Contraceptive method preferences and provision after termination of pregnancy: a population-based analysis of women obtaining care with the British Pregnancy Advisory Service.

OBJECTIVE: To examine contraceptive choices among women seeking termination of pregnancy (TOP) and the provision of the chosen methods. DESIGN: Population-based study. SETTING: British Pregnancy Advisory Service (BPAS) clinics in England and Wales. POPULATION: Between 1 January 2011 and 31 December 2014, 211 215 women had a TOP at BPAS, were offered contraceptive counselling, and were eligible to obtain contraception at no cost. METHODS: We examined electronic records from BPAS and assessed the proportions of women who accepted contraceptive counselling and chose a contraceptive method, as well as the distributions of methods chosen, analysed by provider and by TOP type. We calculated the proportions receiving their chosen method and the methods chosen by women using no method at conception. We used logistic regression to examine the factors associated with choice of an intrauterine contraceptive (IUC) or implant. MAIN OUTCOME MEASURES: Post-TOP contraceptive method choice. Receipt of chosen method post-TOP. RESULTS: Eighty-five per cent of women accepted contraceptive counselling and 51% chose to obtain a method from BPAS rather than from a GP or contraception and sexual health clinic post-TOP. [correction added on 25 November 2016 after first online publication: 51% has been inserted in the preceding sentence.] Among those who wanted to receive contraception from BPAS, 51% chose an IUC or implant and 19% chose oral contraceptives. Ninety-one per cent of women who obtained contraception from BPAS received their chosen method. Women were more likely to choose an IUC or implant if they obtained contraception from BPAS, had a surgical TOP, were parous, young, white, or had one or more previous TOPs. CONCLUSIONS: The standards set for patient-centred TOP care should emphasise the need for a full range of contraceptive options to be offered and provided post-TOP. TWEETABLE ABSTRACT: Uptake targets for long-acting reversible methods do not reflect women's post-TOP contraceptive preferences.

Evaluation of urogynaecology care of an elderly population in a specialist urogynaecology centre.

The ageing population of the UK means that demand for urogynaecology services is expected to increase substantially, particularly in patients aged over 65 years. To assess service provision and predict future needs, we reviewed the demographic profile and service requirements of elderly patients referred to our urogynaecology service. We performed a retrospective review of case notes of 125 patients over 65 years of age who attended our urogynaecology clinic within a 6 month period, including comorbidity scoring using a validated instrument. A substantial proportion (56%) of patients did not require hospital-based management, and none of the patients had an adult comorbidity evaluation (ACE-27) score >2. Hence, we recommend assessing patients using the ACE-27 score and not on chronological age alone. A restructuring of urogynaecology services towards better access to community-based clinics is required to reflect the treatment needs of the patient population. This would be in line with national continence care guidance.

Transgenerational Developmental Programming of Ovarian Reserve.

Exposure to an adverse early-life environment leads to long-term health problems, many of which are recapitulated in subsequent generations. The female reproductive tract is particularly sensitive to early-life influences, and plays a pivotal role in programming the conceptus. We examine the influence of suboptimal grandmaternal diet on reproductive potential of granddaughters in the absence of any further dietary manipulations in the daughters in a rat low-protein diet model. Exposure to low-protein grand-maternal diet leads to decreased ovarian reserve and increased intra-abdominal fat mass in granddaughters, accompanied by accelerated accumulation of oxidative stress and mtDNA copy number instability in the ovaries. Ovarian telomere length declines more rapidly in the exposed granddaughters, indicating accelerated ageing in the reproductive tract. Thus, we demonstrate that suboptimal grandmaternal diet during pregnancy accelerates reproductive ageing across subsequent generations. These findings have important implications for understanding both individual rates of decline in fertility with age, and the clinical impact of current global trends towards delayed childbearing.

Maternal and fetal outcomes following unplanned conversion to general anesthetic at elective cesarean section.

OBJECTIVE: To investigate risk factors predicting unplanned conversion to general anesthesia during elective cesarean section, and to examine maternal and fetal outcomes associated with unplanned conversion compared with other modes of anesthesia. STUDY DESIGN: A retrospective cohort at a UK center (2008 to 2013). Women (4337) underwent elective cesarean section. Delivery outcomes were compared according to anesthesia type using logistic regression. RESULT: Women (1.6%) underwent unplanned conversion to general anesthetic. Unplanned conversion was associated with higher parity (odds ratio (OR) 3.82, confidence interval (CI; (1.58 to 9.62)) and maternal age ⩾40 (OR 4.40, CI (1.08 to 29.88)). Compared with spinal anesthetic, unplanned conversion was associated with increased likelihood of maternal hemorrhage ⩾1.5 l (OR 5.74, CI (1.90 to 14.01)) and delayed neonatal respiration (OR 4.76, CI (1.76 to 11.05)). Adverse outcomes were not significantly more likely compared with planned general anesthetic. CONCLUSION: Higher parity and maternal age are risk factors for unplanned conversion to general anesthetic. There is no increase in the likelihood of adverse outcomes with unplanned versus planned general anesthetic.

Long-term effects of in utero Doppler ultrasound scanning--a developmental programming perspective.

Ultrasound scanning has been used as a diagnostic and screening tool in obstetric practice for over 50 years. There is no evidence of immediate or long-term harm to the developing fetus from exposure to B mode ultrasound. However, exposure to high levels of Doppler ultrasound during early development is increasingly common, and the full safety implications of this exposure are not clear. Doppler ultrasound exposure in utero gives rise to increased apoptosis in animal models, and there is evidence of the effects of exposure to Doppler ultrasound persisting throughout life, with increased non-right-handedness observed in human epidemiological studies. We consider the idea that there may be long-term developmental implications for fetuses exposed to Doppler ultrasound early in gestation. These effects may be mediated via thermal or mechanical disruption to the developing conceptus, giving rise to free radical damage. Excess free radical exposure early in gestation is a strong candidate for the final common pathway underlying developmental programming effects, and gives rise to concern that fetuses exposed to high levels of ultrasound are at risk of a developmental programming effect. It is suggested that there is a need for animal studies of developmental programming using exposure to Doppler ultrasound scanning as the exposure of interest, and for more observational data to be collected in the clinical setting. While these data are collected, it seems prudent to continue to adhere to the principle of 'as low as reasonably achievable' (ALARA) when exposing first-trimester fetuses to Doppler ultrasound.