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The article discusses the guidelines on the care of pregnant women with obesity. Topics include the information on the risks of obesity during pregnancy and childbirth, the nutritional supplements to be recommended, the measurement of weight, height and body mass index and the factors to be considered in screening, diagnosing and managing maternal disease in obese pregnant women.

Objective To investigate the impact of maternal body mass index ( BMI, kg/m2) on clinical complications, inpatient admissions, and additional short-term costs to the National Health Service ( NHS) in Scotland. Design Retrospective cohort study using an unselected population database. Setting Obstetric units in Scotland, 2003-2010. Population A total of 124 280 singleton deliveries in 109 592 women with a maternal BMI recorded prior to 16 weeks of gestation. Methods Population-based retrospective cohort study of singleton deliveries, with multivariable analysis used to assess short-term morbidity and health service costs. Main outcome measures Maternal and offspring outcomes, number and duration of hospital admissions, and healthcare costs. Results Using multivariable analysis, in comparison with women of normal weight, women who were overweight, obese, or severely obese had an increased risk of essential hypertension [1.87 (1.18-2.96), 11.90 (7.18-19.72), and 36.10 (18.33-71.10)], pregnancy-induced hypertension [1.76 (1.60-1.95), 2.98 (2.65-3.36), and 4.48 (3.57-5.63)], gestational diabetes [3.39 (2.30-4.99), 11.90 (7.54-18.79), and 67.40 (37.84-120.03)], emergency caesarean section [1.94 (1.71-2.21), 3.40 (2.91-3.96), and 14.34 (9.38-21.94)], and elective caesarean section [2.06 (1.84-2.30), 4.61 (4.06-5.24), and 17.92 (13.20-24.34)]. Compared with women of normal weight, women who were underweight, overweight, obese, or severely obese were associated with an 8, 16, 45, and 88% increase in the number of admissions, respectively, and women who were overweight, obese, or severely obese were associated with a 4, 9, and 12% increase in the duration of stay (all P < 0.001). The additional maternity costs [mean (95% CI), adjusted analyses] for women who were underweight, overweight, obese, or severely obese were £102.27 (£48.49-156.06), £59.89 (£41.61-78.17), £202.46 (£178.61-226.31), and £350.75 (£284.82-416.69), respectively. Conclusions Maternal BMI influences maternal and neonatal morbidity, the number and duration of maternal and neonatal admissions, and health service costs. [ABSTRACT FROM AUTHOR]

Cytokines such as monocyte chemotactic peptide-1 (MCP-1), interleukin-8 (IL-8), RANTES (Regulated on Activation and Normally T-cells Expressed and presumably Secreted) and interleukin-10 (IL-10) are thought to play pivotal roles in immune recognition, acceptance of the fetal allograft, maintenance of pregnancy and parturition. Their secretion and regulation within the third trimester uterus is, however, less well defined. We therefore investigated the release of these cytokines by third trimester amnion, chorion, placenta and decidua, and studied the influence of prostaglandin E2 (PGE2) infusion on their release in a dynamic placental cotyledon perfusion system. MCP-1 was released predominately by the chorion (78.2 ± 7.3 pg/mg wet tissue weight; mean ± SEM), decidua (112.4 ± 5.2 pg/ml) and placenta (101.8 ± 5.0 pg/mg) with low amounts from the amnion (1.3 ± 0.4 pg/ml). High concentrations of IL-8 were released by the amnion (39.9 ± 5.3 pg/mg), chorion (52.8 ± 1.9 pg/mg), decidua (42.2 ± 1.5 pg/mg) and placenta (45 ± 1.3 pg/mg). Release of RANTES was not detectable from the amnion but was detected in moderate amounts from the chorion (6.0 ± 1.2 pg/mg), decidua (15.2 ± 1.4 pg/mg) and placenta (26.9 ± 1.6 pg/mg). Low concentrations of IL-10 were secreted by the chorion (6.8 ± 0.8 pg/mg), decidua (9.0 ± 0.9 pg/mg) and placenta (3.3 ± 0.3 pg/mg) with none detectable from the amnion. MCP-1, IL-8, RANTES and IL-10 were all released by perfused placental cotyledons. PGE2 stimulated release of MCP-1, IL-8 and IL-10 into the maternal and of MCP-1 and IL-8 into the fetal circulation of the placenta but had no effect on RANTES release. It is suggested that MCP-1 and IL-8 may be involved in the inflammatory process of parturition and IL-10 in the protection of the fetal allograft. In addition, PGE2 may have an important immunomodulatory role within the uterus at term. [ABSTRACT FROM PUBLISHER]

Monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) are important chemokines which effect the chemotaxis of monocytes and neutrophils, respectively. There is increasing evidence that such chemokines play an integral role in the control and maintenance of a normal pregnancy from implantation to parturition. However, little is known about the sites of secretion and function of MCP-1 and IL-8 in particular with respect to establishment of the placenta and membranes during first trimester. The aim of this study was therefore to investigate the concentrations and localization of MCP-1 and IL-8 in amniotic fluid and extra-embryonic coelomic fluid (EECF) collected by ultrasound-guided needle aspiration and maternal serum during the first trimester of pregnancy. Using specific enzyme-linked immunosorbent assays, MCP-1 was present at high concentrations in the EECF, significantly higher than those in amniotic fluid and maternal serum. IL-8 was also present predominantly in the EECF with concentrations being significantly higher than the low values detected in maternal serum and the very low amounts found in amniotic fluid. This strict compartmentalization of these cytokines in the fluid compartments of early pregnancy may be important for establishment and development of a viable pregnancy. [ABSTRACT FROM AUTHOR]

In March 2020, the World Health Organisation named the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2), which causes corona virus disease 2019 (COVID -19), as a pandemic. Pregnant women were considered at increased risk of developing severe COVID-19 after viral infection. In response maternity services reduced face-to-face consultations with high-risk pregnant women by supplying blood pressure monitors for supported self-monitoring. This paper explores the experiences of patients and clinicians of the rapid roll-out of supported self-monitoring programme in Scotland during the first and second wave of the COVID-19 pandemic. We conducted semi-structured telephone interviews with high-risk women and healthcare professionals who were using supported self-monitoring of blood pressure (BP) In four case studies during the COVID-19 pandemic. 20 women, 15 midwives and 4 obstetricians took part in the interviews. Interviews with healthcare professionals showed that while implementation occurred at pace and at scale across the National Health Service (NHS) in Scotland, implementation differed locally, resulting in mixed experiences. Study Participants observed several barriers and facilitators to implementation. Women value the simplicity of use and convenience of the digital communications platforms while health professionals were more interested in their impact on reducing workload for both women and health professionals largely found self-monitoring acceptable, with only a few exceptions. These results show that rapid change can occur in the NHS at a national level when there is a shared motivation. While self-monitoring is acceptable to most women, decisions regarding self-monitoring should be made jointly and on an individual basis., Competing Interests: BM has a paid consultancy with the Scottish Government to provide advice on the implementation of remote health monitoring. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Paterson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Using a cohort study design, we analysed 17 diagnoses and 9 interventions (including critical care admission) as a composite measure of severe maternal morbidity for pregnancies recorded over 14 years in Scotland. There were 762,918 pregnancies, of which 7947 (10 in 1000 pregnancies) recorded 9345 severe maternal morbidity events, 2802 episodes of puerperal sepsis being the most common (30%). Severe maternal morbidity incidence increased from 9 in 1000 pregnancies in 2012 to 17 in 1000 pregnancies in 2018, due in part to puerperal sepsis recording. The odds ratio (95%CI) for severe maternal morbidity was higher for: older women, for instance 1.22 (1.13-1.33) for women aged 35-39 years and 1.44 (1.27-1.63) for women aged > 40 years compared with those aged 25-29 years; obese women, for instance 1.13 (1.06-1.21) for BMI 30-40 kg.m -2 and 1.32 (1.15-1.51) for BMI > 40 kg.m -2 compared with BMI 18.5-24.9 kg.m -2 ; multiple pregnancy, 2.39 (2.09-2.74); and previous caesarean delivery, 1.52 (1.40-1.65). The median (IQR [range]) hospital stay was 3 (2-5 [1-8]) days with severe maternal morbidity and 2 (1-3 [1-5]) days without. Forty-one women died during pregnancy or up to 42 days after delivery, representing mortality rates per 100,000 pregnancies of about 365 with severe maternal morbidity and 1.6 without. There were 1449 women admitted to critical care, 807 (58%) for mechanical ventilation or support of at least two organs. We recorded an incidence of severe maternal morbidity higher than previously published, possibly because sepsis was coded inaccurately in our databases. Further research may determine the value of this composite measure of severe maternal morbidity., (© 2022 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure in utero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) in utero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child's behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.

Introduction: Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised., Methods: We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9)., Results: After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA., Discussion: There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Study Objectives: To determine the prevalence of obstructive sleep apnea (OSA) in a cohort of women with class III obesity, and a comparator lean group, in the second and third trimesters of pregnancy. Secondary objectives were to compare characteristics of women with obesity with and without OSA and to assess factors that were predictive of OSA., Methods: We performed a prospective cohort study involving 33 women with class III obesity (mean body mass index 43.5 ± 3.9 kg/m 2 ) and 39 lean women (body mass index 22.0 ± 1.7 kg/m 2 ) with singleton pregnancies. Participants completed 2 level 3 sleep studies between 12-22 weeks and 32-38 weeks gestation. OSA was defined as a respiratory event index ≥ 5 events/h (≥ 3% desaturation criteria). Levels of interleukin-6, glucose, and C-peptide were quantified in maternal blood. Logistic regression analysis was performed to determine predictors of OSA., Results: OSA was identified in 12 (37.5%) and 14 (50.0%) women with obesity and in 1 (2.6%) and 3 (9.1%) lean women in the second and third trimesters, respectively. Women with obesity with OSA were older than those with no OSA but otherwise had similar characteristics. In unadjusted analysis of women with obesity, increased age, body mass index, homeostatic model assessment of insulin resistance, and history of nonsmoking were associated with increased odds of OSA. In multivariable analysis, only increased age remained significantly associated with OSA., Conclusions: OSA is highly prevalent in pregnant women with class III obesity. Further research is required to establish effective management strategies for the growing number of women in this high-risk group., Citation: Johns EC, Hill EA, Williams S, et al. High prevalence of obstructive sleep apnea in pregnant women with class III obesity: a prospective cohort study. J Clin Sleep Med . 2022;18(2):423-432., (© 2022 American Academy of Sleep Medicine.)

Introduction: Class III obesity (BMI ≥ 40 kg/m 2 ) during pregnancy predisposes mother and offspring to a range of adverse pregnancy complications and outcomes. Risk profiles vary between pregnancies and are affected by interpregnancy weight gain. We evaluated the risk of adverse outcomes in women with BMI ≥ 40 kg/m 2 in first and second pregnancies, and the impact of interpregnancy weight change on this risk., Materials and Methods: Data were extracted for all women with BMI ≥ 40 kg/m 2 at first antenatal visit, who completed antenatal and delivery care for first and second pregnancies in NHS Lothian between 1/1/2009-31/12/2018. Multiple pregnancies and recipients of bariatric surgery were excluded., Results: 442 pregnancies among 221 women were included. In first pregnancy, median (interquartile range) weight was 117 kg (108.5-126.7), age 28 years (24-31) and BMI 42 kg/m 2 (41.0-44.5), 14.4% had gestational diabetes (GDM), 11.3% had pregnancy-induced hypertension and 44.6% had a post-partum haemorrhage (PPH). 20.8% of babies were large for gestational age (LGA, ≥97% centile at birth). In second pregnancy, women were heavier with a median weight of 119.9 kg (109.0-130.0, p = 0.00) with 19.9% gaining over 10 kg. Women were more likely to develop GDM (21.6%, p = 0.02). Babies were heavier with 40% of babies LGA (p < 0.0001). Interpregnancy weight change had no significant impact on GDM, pregnancy induced hypertension, PPH, perinatal mortality or LGA., Conclusions: In a population of women with BMI ≥ 40 kg/m 2 , pregnancy complications are common and risk is higher in second pregnancy. The interpregnancy period is a critical time to engage women in health improvement and weight loss strategies to maximise outcomes for mother and offspring., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: A negative association between obesity and pregnancy outcomes has been described, as well as between time sedentary and pregnancy outcomes. Most interventions based on physical activity involving obese pregnant women have failed in improving pregnancy outcomes. Exchanging time spent in sedentary activities with time spent in light-intensity activities, performed in a home-based setting, might help morbidly obese pregnant women. We aimed to assess the feasibility of an exercise intervention., Methods: An exercise intervention for morbidly obese pregnant women was designed involving morbidly obese pregnant women. Pregnant women with BMI ≥ 40 kg/m² with 20 or less weeks of gestation were invited to take part in the OPALS Feasibility Study. A home-based approach was employed. Participants were asked to perform the intervention for at least 12 weeks, and to register their performance in an activity diary. After the intervention, participants were asked to return the activity diary and answer a feasibility questionnaire., Results: In the intervention, 28 participants took part. Six women completed the intervention for 12 weeks or more. All declared they intended to keep on doing the intervention. All women reported that the exercises made them feel better., Conclusion: Empowering, and involving morbidly obese pregnant women in taking care of themselves and giving them realistic tasks to do on their own and around their environment helps to increase commitment, as does avoiding the effect of their own weight whilst exercising. A 20% of compliance was observed in this study, which might be explained by the difficulties that pregnancy and excess weight mean. Thus, for future studies, we suggest adding a supervision plan to increase that number.

The SARS-CoV-2 virus is primarily transmitted through virus-laden fluid particles ejected from the mouth of infected people. Face covers can mitigate the risk of virus transmission but their outward effectiveness is not fully ascertained. Objective: by using a background oriented schlieren technique, we aim to investigate the air flow ejected by a person while quietly and heavily breathing, while coughing, and with different face covers. Results: we found that all face covers without an outlet valve reduce the front flow through by at least 63% and perhaps as high as 86% if the unfiltered cough jet distance was resolved to the anticipated maximum distance of 2-3 m. However, surgical and handmade masks, and face shields, generate significant leakage jets that may present major hazards. Conclusions: the effectiveness of the masks should mostly be considered based on the generation of secondary jets rather than on the ability to mitigate the front throughflow., (This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/.)

There are many unknowns for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. Clinical experience of pregnancies complicated with infection by other coronaviruses e.g., Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome, has led to pregnant woman being considered potentially vulnerable to severe SARS-CoV-2 infection. Physiological changes during pregnancy have a significant impact on the immune system, respiratory system, cardiovascular function, and coagulation. These may have positive or negative effects on COVID-19 disease progression. The impact of SARS-CoV-2 in pregnancy remains to be determined, and a concerted, global effort is required to determine the effects on implantation, fetal growth and development, labor, and neonatal health. Asymptomatic infection presents a further challenge regarding service provision, prevention, and management. Besides the direct impacts of the disease, a plethora of indirect consequences of the pandemic adversely affect maternal health, including reduced access to reproductive health services, increased mental health strain, and increased socioeconomic deprivation. In this review, we explore the current knowledge of COVID-19 in pregnancy and highlight areas for further research to minimize its impact for women and their children.

Sleep disordered breathing (SDB) is a common obesity-related co-morbidity with strong associations to cardiometabolic disease. The risk of SDB is increased during pregnancy, particularly among obese pregnant women. Accumulating evidence suggests that an association exists between maternal SDB and the development of adverse pregnancy outcomes, particularly gestational diabetes and hypertensive disorders of pregnancy. Intermittent hypoxia, a central characteristic of SDB, has been shown in animal and clinical studies to dysregulate several biological pathways. This includes the promotion of oxidative stress, increased inflammation, activation of the hypothalamic-pituitary-adrenal axis, increased sympathetic activity and impaired glucose and insulin metabolism. This review considers how, during pregnancy, these pathophysiological processes are plausible mechanisms through which SDB may contribute to an increased risk of adverse outcomes, for the mother and perhaps also the offspring. However, a lack of robust evidence specific to the pregnant population, including limited evaluation of the placental function in affected pregnancies, limits our ability to draw definite conclusions on mechanisms contributing to adverse pregnancy outcomes and, indeed, the strength of association between SDB and certain pregnancy complications., (© 2020 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Maternal obesity is the most common metabolic disturbance in pregnancy affecting >1 in 5 women in some countries. Babies born to obese women are heavier with more adiposity at birth, and are vulnerable to obesity and metabolic disease across the lifespan suggesting offspring health is 'programmed' by fetal exposure to an obese intra-uterine environment. The placenta plays a major role in dictating the impact of maternal health on prenatal development. Maternal obesity impacts the function of integral placental receptors and transporters for glucocorticoids and nutrients, key drivers of fetal growth, though mechanisms remain poorly understood. This review aims to summarise current knowledge in this area, and considers the impact of obesity on the epigenetic machinery of the placenta at this vital juncture in offspring development. Further research is required to advance understanding of these areas in the hope that the trans-generational cycle of obesity can be alleviated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Endometriosis is defined by the presence of endometrial-like tissue (lesions) outside the uterus, commonly on the pelvic peritoneum. It affects 6-10% of women and is associated with debilitating pelvic pain. Current management options are often unsatisfactory. Omega-3 polyunsaturated fatty acids (O-PUFA) have the potential to reduce the painful symptoms associated with endometriosis, reduce lesion size, preserve the patient's ability to conceive, and have minimal side effects. We performed a two-arm, parallel double-blinded randomised controlled trial to inform the planning of a future multicentre randomised controlled trial to evaluate the efficacy of O-PUFA for endometriosis-associated pain., Objectives: The primary objectives of the trial were to assess recruitment and retention rates. The secondary objectives were to determine the acceptability to women of the proposed methods of recruitment, randomisation, treatments and questionnaires, to estimate the variability in the proposed primary endpoints to inform the sample size calculation and to refine the research methodology for the future definitive trial., Methods: We recruited women with endometriosis from June 2016 to June 2017 and randomised them to eight weeks of treatment with O-PUFA or olive oil. Pain scores and quality of life questionnaires were collected at baseline and eight weeks. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to eight weeks. Acceptability questionnaires were used to evaluate women's experiences of the trial., Results: The proportion of eligible participants who were randomised was 45.2% (33/73) and 81.8% (27/33) completed the study. The majority of participants described their overall trial experience favourably and there were no adverse events in either group., Conclusion: Our pilot trial supports the feasibility of a future larger trial to definitively evaluate the efficacy of O-PUFA for endometriosis-associated pain., Trial Registration: The trial was registered on the ISRCTN registry (registration number ISRCTN44202346)., Competing Interests: AH is Past Chair of ESHRE Special Interest Group Endometriosis/Endometrium, was Lead of James Lind Alliance Priority Setting Partnership for Endometriosis, was a Member of NICE Endometriosis Guideline Group, was a Member of the ESHRE Endometriosis Guideline Group, is a Trustee and Medical Advisor to Endometriosis UK, is a Medical Advisor to the Pelvic Pain Support Network and is Deputy Editor of Human Reproduction Open. He receives grant funding from NIHR, MRC, Wellcome Trust, CSO, Wellbeing of Women, Ferring and Roche. He has received consultancy fees from AbbVie, Nordic Pharma, Ferring and Roche Diagnostics.None of the other authors have declared any potential conflicts of interest. This does not alter his adherence to PLOS ONE policies on sharing data and materials.

Background: Retained placenta following vaginal delivery is a major cause of postpartum haemorrhage. Currently, the only effective treatments for a retained placenta are the surgical procedures of manual removal of placenta (MROP) and uterine curettage, which are not universally available, particularly in low- and middle-income countries. The objective of the trial was to determine whether sublingual nitroglycerin spray was clinically effective and cost-effective for medical treatment of retained placenta following vaginal delivery., Methods and Findings: A randomised, placebo-controlled, double-blind trial was undertaken between October 2014 and July 2017 at 29 delivery units in the UK (Edinburgh, Glasgow, Manchester, Newcastle, Preston, Warrington, Chesterfield, Crewe, Durham, West Middlesex, Aylesbury, Furness, Southampton, Bolton, Sunderland, Oxford, Nottingham [2 units], Burnley, Chertsey, Stockton-on-Tees, Middlesborough, Chester, Darlington, York, Reading, Milton Keynes, Telford, Frimley). In total, 1,107 women with retained placenta following vaginal delivery were recruited. The intervention was self-administered 2 puffs of sublingual nitroglycerin (800 μg; intervention, N = 543) or placebo spray (control, N = 564). The primary clinical outcome was the need for MROP, assessed at 15 minutes following administration of the intervention. Analysis was based on the intention-to-treat principle. The primary safety outcome was measured blood loss between study drug administration and transfer to the postnatal ward or other clinical area. The primary patient-sided outcomes were satisfaction with treatment and side-effect profile, assessed by questionnaires pre-discharge and 6 weeks post-delivery. Secondary clinical outcomes were measured at 5 and 15 minutes after study drug administration and prior to hospital discharge. There was no statistically significant or clinically meaningful difference in need for MROP by 15 minutes (primary clinical outcome, 505 [93.3%] for nitroglycerin versus 518 [92.0%] for placebo, odds ratio [OR] 1.01 [95% CI 0.98-1.04], p = 0.393) or blood loss (<500 ml: nitroglycerin, 238 [44.3%], versus placebo, 249 [44.5%]; 500 ml-1,000 ml: nitroglycerin, 180 [33.5%], versus placebo, 224 [40.0%]; >1,000 ml: nitroglycerin, 119 [22.2%], versus placebo, 87 [15.5%]; ordinal OR 1.14 [95% CI 0.88-1.48], p = 0.314) or satisfaction with treatment (nitroglycerin, 288 [75.4%], versus placebo, 303 [78.1%]; OR 0.87 [95% CI 0.62-1.22], p = 0.411) or health service costs (mean difference [£] 55.3 [95% CI -199.20 to 309.79]). Palpitations following drug administration were reported more often in the nitroglycerin group (36 [9.8%] versus 15 [4.0%], OR 2.60 [95% CI 1.40-4.84], p = 0.003). There were 52 serious adverse events during the trial, with no statistically significant difference in likelihood between groups (nitroglycerin, 27 [5.0%], versus placebo, 26 [4.6%]; OR 1.13 [95% CI 0.54-2.38], p = 0.747). The main limitation of our study was the low return rate for the 6-week postnatal questionnaire. There were, however, no differences in questionnaire return rates between study groups or between women who did and did not have MROP, with the patient-reported use of outpatient and primary care services at 6 weeks accounting for only a small proportion (approximately 5%) of overall health service costs., Conclusions: In this study, we found that nitroglycerin is neither clinically effective nor cost-effective as a medical treatment for retained placenta, and has increased side effects, suggesting it should not be used. Further research is required to identify an effective medical treatment for retained placenta to reduce the morbidity caused by this condition, particularly in low- and middle-income countries where surgical management is not available., Trial Registration: ISRCTN.com ISRCTN88609453 ClinicalTrials.gov NCT02085213., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: FCD is named as Principal Investigator on government and charitable research grants to their institution which aim to improve pregnancy outcome. JEN is named as Principal Investigator on government and charitable research grants to their institution which aim to improve pregnancy outcome. In the last three years JEN has provided consultancy to pharma companies GSK and Dilafor; my institution was renumerated for this. JEN's institution has received travel and subsistence expenses from Merck to facilitate them speaking at a Merck sponsored symposium on metformin. JEN is on Subpanel A1 for REF, and on a Wellcome Trust Science interview panel, and receive personal renumeration for each. KFC is named as CoInvestigator on a charitable research grant about coronary syndrome. None of the other co-authors have declared any competing interests.

Background: Retained placenta is associated with postpartum haemorrhage and can lead to significant maternal morbidity if untreated. The only effective treatment is the surgical procedure of manual removal of placenta, which is costly, requires skilled staff, requires an operative environment and is unpleasant for women. Small studies suggest that glyceryl trinitrate may be an effective medical alternative., Objective: To determine the clinical effectiveness and cost-effectiveness of sublingual glyceryl trinitrate spray compared with placebo in reducing the need for manual removal of placenta in women with retained placenta after vaginal delivery following the failure of current management., Design: A group-sequential randomised double-blind placebo-controlled trial with a cost-effectiveness analysis., Setting: There were 29 obstetric units in the UK involved in the study., Participants: There were 1107 women (glyceryl trinitrate group, n  = 543; placebo group, n  = 564) randomised between October 2014 and July 2017., Interventions: Glyceryl trinitrate spray was administered to 541 women in the intervention group, and a placebo was administered to 563 women in the control group., Main Outcome Measures: Four primary outcomes were defined: (1) clinical - the need for manual removal of placenta, (2) safety - measured blood loss, (3) patient sided - satisfaction with treatment and side effects and (4) economic - cost-effectiveness of both treatments using the UK NHS perspective. Secondary clinical outcomes included a > 15% decrease in haemoglobin level, time from randomisation to delivery of placenta in theatre, the need for earlier manual removal of placenta than planned, increase in heart rate or decrease in blood pressure, requirement for blood transfusion, requirement for general anaesthesia, maternal pyrexia, and sustained uterine relaxation requiring additional uterotonics., Results: No difference was observed between the glyceryl trinitrate group and the control group for the placenta remaining undelivered within 15 minutes of study treatment (93.3% vs. 92%; odds ratio 1.01, 95% confidence interval 0.98 to 1.04; p  = 0.393). There was no difference in blood loss of > 1000 ml between the glyceryl trinitrate group and the control group (22.2% vs. 15.5%; odds ratio 1.14, 95% confidence interval 0.88 to 1.48; p  = 0.314). Palpitations were more common in the glyceryl trinitrate group than in the control group after taking the study drug (9.8% vs. 4.0%; odds ratio 2.60, 95% confidence interval 1.40 to 4.84; p  = 0.003). There was no difference in any other measures of patient satisfaction between the groups. There was no difference in costs to the health service between groups (mean difference £55.30, 95% confidence interval -£199.20 to £309.79). Secondary outcomes revealed that a fall in systolic or diastolic blood pressure, or an increase in heart rate, was more common in the glyceryl trinitrate group than in the control group (odds ratio 4.9, 95% confidence interval 3.7 to 6.4; p  < 0.001). The need for a blood transfusion was also more common in the glyceryl trinitrate group than in the control group (odds ratio 1.53, 95% confidence interval 1.04 to 2.25; p  = 0.033)., Conclusions: Glyceryl trinitrate spray did not increase the delivery of retained placenta within 15 minutes of administration when compared with the placebo, and was not cost-effective for medical management of retained placenta. More participants reported palpitations and required a blood transfusion in the glyceryl trinitrate group. Further research into alternative methods of medical management of retained placenta is required., Trial Registration: Current Controlled Trials ISRCTN88609453., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 70. See the NIHR Journals Library website for further project information., Competing Interests: Fiona C Denison has received funding from Dilafor AB (Solna, Sweden) outside the submitted work. Jane E Norman has received funding from Dilafor AB and GlaxoSmithKline plc (Middlesex, UK) outside the submitted work and declares membership of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Maternal Newborn and Child Health Panel. Jane Norman was a member of the HTA and Efficacy and Mechanism Evaluation (EME) Editorial Board. John Norrie declares grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and membership of the following NIHR boards: Cardiopulmonary Resuscitation Decision-making Committee, HTA Commissioning Board, HTA Commissioning Sub-Board (Expression of Interest), HTA Funding Boards Policy Group, HTA General Board, HTA post-board funding teleconference, NIHR Clinical Trials Unit Standing Advisory Committee, NIHR HTA and EME Editorial Board and Pre-exposure Prophylaxis Impact Review Panel. Julia Lawton declares membership of the HTA General Board.

Background: The prevalence of sleep problems among pregnant women is over 50%, and daytime sleepiness is among the most common sleep problems. Previous studies have associated antenatal sleep problems with adverse maternal health and neonatal outcomes, but the consequences of antenatal sleep problems and particularly daytime sleepiness on child psychological development have not been assessed prospectively., Methods: In this prospective cohort study including 111 mother-child dyads, we examined the associations of maternal daytime sleepiness during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth Sleepiness Scale, with child neuropsychiatric problems and neuropsychological development, assessed with mother-rated questionnaires and individually administered neuropsychological tests, at child age 2.6-5.7 years (mean = 4.3 years)., Results: Independently of sociodemographic and perinatal covariates and maternal depressive and anxiety symptoms during and/or after pregnancy, maternal antenatal daytime sleepiness was associated with increased total [unstandardized regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence interval (CI) 0.01-0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01-0.49) psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04-0.50) in children, and with poorer executive function, particularly in the areas of attention, working memory and inhibitory control (B = -0.39 s.d.s: 95% CI -0.69 to -0.10)., Conclusions: Maternal antenatal daytime sleepiness carries adverse consequences for offspring psychological development. The assessment of sleep problems may be an important addition to standard antenatal care.

Introduction: The optimal surgical approach for caesarean section is uncertain in women with very severe obesity (body mass index (BMI) >40kg/m2). We aimed to assess maternal and surgical predictors of surgical site skin infection (SSSI) in very severely obese women and to undertake an exploratory evaluation of clinical outcomes in women with a supra-panniculus transverse compared to an infra-panniculus transverse skin incision., Material and Methods: Using a retrospective cohort design, case-records were reviewed of very severely obese women with a singleton pregnancy delivered by caesarean between August 2011 and December 2015 (n = 453) in two maternity hospitals in Scotland. Logistic regression analysis was used to determine predictors for SSSI. Outcomes were compared between women who had a supra-panniculus transverse compared to infra-panniculus transverse skin incision., Results: Lower maternal age was predictive of SSSI, with current smoking status and longer wound open times being marginally significant. Maternal BMI, suture method and material demonstrated univariate associations with SSSI but were not independent predictors. Women with a supra-panniculus transverse skin incision were older (32.9 (4.4), vs. 30.6 (5.7), p = 0.002), had higher BMI (49.2 (7.1), vs. 43.3 (3.3), p<0.001), shorter gestation at delivery (days) (267.7 (14.9), vs. 274.8 (14.5), p<0.001) and higher prevalence of gestational diabetes mellitus (42.6% vs. 21.9%, p = 0.002). SSSI rates did not differ between supra-panniculus transverse (13/47; 27.7%) and infra-panniculus transverse (90/406; 22.2%; p = 0.395) skin incisions., Conclusion: SSSI rates are high in very severely obese women following caesarean section, regardless of location of skin incision., Competing Interests: The authors have declared that no competing interests exist.

Group B streptococcus (GBS) is the most common cause of early-onset neonatal sepsis in many countries and responsible for significant perinatal morbidity and mortality worldwide. Intrapartum antibiotic prophylaxis has been the mainstay of efforts to prevent early-onset GBS disease in recent decades, however it is unclear if women should be targeted based on the presence of clinical risk factors or by screening for GBS colonisation during pregnancy. Universal bacteriological screening of women in late pregnancy has been widely adopted but questions remain regarding its benefits and potential harms. Newer approaches to screening based on rapid point-of-care testing require further evaluation in randomised controlled trials to inform evidence-based practice. Given current preventive strategies do not protect against late onset disease and other sequelae of infection, maternal vaccination against GBS may present the best opportunity to reduce the global burden of invasive GBS disease in the future., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy. The prevalence is rising and correlates with the increase in maternal obesity over recent decades. The etiology of GDM is complex, with genetic and environmental factors implicated in mechanistic and epidemiological studies. GDM begets important short- and long-term health risks for the mother, developing fetus, and offspring. This includes the high likelihood of subsequent maternal type 2 diabetes (T2DM), and possible adverse cardiometabolic phenotypes in the offspring. The most clinically and cost-effective methods of screening for GDM remain uncertain. Whilst treatments with lifestyle and pharmacological interventions have demonstrated short-term benefits, the long-term impact for the offspring of intrauterine exposure to antidiabetic medication remains unclear., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: Evidence suggests that screening for gestational diabetes (GDM) occurs too late in pregnancy, when changes in glucose metabolism and fetal growth rates can already be detected. In August 2016 NHS Lothian began screening women with risk factors for GDM during early pregnancy (11-13 weeks). We hypothesised that an earlier identification and treatment of dysglycaemia would improve pregnancy outcomes compared to previous standard care., Methods: We compared management and outcomes for singleton pregnancies with GDM delivering at Royal Infirmary Edinburgh, UK, diagnosed through routine or early screening from 01/01/2015-31/10/2017 (routine screening n = 335, early screening n = 241)., Results: Early screening increased the proportion of women diagnosed before 24 weeks' gestation (n = 59/335, 17.6% vs n = 103/241, 42.7%, p < 0.001) but did not change the average monthly rate of diagnosis. Early screening increased the median duration of GDM during pregnancy (71 vs 93 days of gestation, p < 0.001) with no significant changes in the pharmacological management. Early screening improved the primary composite outcome (emergency caesarean section, neonatal hypoglycaemia and macrosomia; n = 138/335, 41.2% vs n = 73/241, 30.3%, adjusted Odds Ratio [95% confidence interval] 0.62 [0.43-0.91]., Conclusions: There is a role for early screening and management of GDM however it is unclear whether this represents a cost-effective intervention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Interventions to increase physical activity in pregnancy are challenging for morbidly obese women. Targeting sedentary behaviors may be a suitable alternative to increase energy expenditure. We aimed to determine total energy expenditure, and energy expended in sedentary activities in morbidly obese and lean pregnant women. We administered the Pregnancy Physical Activity Questionnaire (nonobjective) and the Actical accelerometer (objective) to morbidly obese (BMI ≥ 40 kg/m²) and lean (BMI ≤ 25 Kg/m²) pregnant women recruited in early (<24 weeks), and late (≥24 weeks) gestation. Data are mean (SD). Morbidly obese pregnant women reported expending significantly more energy per day in early (n = 140 vs 109; 3198.4 (1847.1) vs 1972.3 (10284.8) Kcal/d, P < .0001) and late (n = 104 vs 64; 3078.2 (1356.5) vs 1947.5 (652.0) Kcal/d, P < .0001) pregnancy, and expended significantly more energy in sedentary activities, in early (816.1 (423.5) vs 540.1 (244.9) Kcal/d, P < .0001) and late (881.6 (455.4) vs 581.1 (248.5) Kcal/d, P < .0001) pregnancy, than lean pregnant women. No differences were observed in the proportion of energy expended sedentary between lean and morbidly obese pregnant women. The greater total energy expenditure in morbidly obese pregnant women was corroborated by Actical accelerometer in early (n = 14 per group, obese 1167.7 (313.6) Kcal; lean 781.1 (210.1) Kcal, P < .05), and in late (n = 14 per group, obese 1223.6 (351.5) Kcal; lean 893.7 (175.9) Kcal, P < .05) pregnancy. In conclusion, non-objective and objective measures showed morbidly obese pregnant women expended more energy per day than lean pregnant. Further studies are needed to determine whether sedentary behaviors are a suitable target for intervention in morbidly obese pregnancy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This article reviews existing clinical practices and sensor research undertaken to monitor fetal well-being during labour. Current clinical practices that include fetal heart rate monitoring and fetal scalp blood sampling are shown to be either inadequate or time-consuming. Monitoring of lactate in blood is identified as a potential alternative for intrapartum fetal monitoring due to its ability to distinguish between different types of acidosis. A literature review from a medical and technical perspective is presented to identify the current advancements in the field of lactate sensors for this application. It is concluded that a less invasive and a more continuous monitoring device is required to fulfill the clinical needs of intrapartum fetal monitoring. Potential specifications for such a system are also presented in this paper.

Background: Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women., Methods: The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks., Discussion: We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials., Trial Registration: ISRCTN44202346., Competing Interests: Ethical approval has been obtained from the Scotland A Research Ethics Committee (LREC 16/SS/0010). All participants consented and agreed to take part in the study.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Piezoresistive pressure sensors capable of detecting ranges of low compressive stresses have been successfully fabricated and characterised. The 5.5 × 5 × 1.6 mm³ sensors consist of a planar aluminium top electrode and a microstructured bottom electrode containing a two-by-two array of truncated pyramids with a piezoresistive composite layer sandwiched in-between. The responses of two different piezocomposite materials, a Multiwalled Carbon Nanotube (MWCNT)-elastomer composite and a Quantum Tunneling Composite (QTC), have been characterised as a function of applied pressure and effective contact area. The MWCNT piezoresistive composite-based sensor was able to detect pressures as low as 200 kPa. The QTC-based sensor was capable of detecting pressures as low as 50 kPa depending on the contact area of the bottom electrode. Such sensors could find useful applications requiring the detection of small compressive loads such as those encountered in haptic sensing or robotics., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: Metformin is widely used to treat gestational diabetes (GDM), but many women remain hyperglycaemic and require additional therapy. We aimed to determine recruitment rate and participant throughput in a randomised trial of glibenclamide compared with standard therapy insulin (added to maximum tolerated metformin) for treatment of GDM., Methods: We conducted an open label feasibility study in 5 UK antenatal clinics among pregnant women 16 to 36 weeks' gestation with metformin-treated GDM. Women failing to achieve adequate glycaemic control on metformin monotherapy were randomised to additional glibenclamide or insulin. The primary outcome was recruitment rate. We explored feasibility with uptake, retention, adherence, safety, glycaemic control, participant satisfaction and clinical outcomes., Results: Records of 197 women were screened and 23 women randomised to metformin and glibenclamide (n = 13) or metformin and insulin (n = 10). Mean (SD) recruitment rate was 0.39 (0.62) women/centre/month. 9/13 (69.2%, 95%CI 38.6-90.9%) women adhered to glibenclamide and all provided outcome data (100% retention). There were no episodes of severe hypoglycaemia, but metformin and insulin gave superior glycaemic control to metformin and glibenclamide, with fewer blood glucose readings <3.5 mmol/l (median [IQR] difference/woman/week of treatment 0.58 [0.03-1.87])., Conclusions: A large randomised controlled trial comparing glibenclamide or insulin in combination with metformin for women with GDM would be feasible but is unlikely to be worthwhile, given the poorer glycaemic control with glibenclamide and metformin in this pilot study. The combination of metformin and glibenclamide should be reserved for women with GDM with true needle phobia or inability to use insulin therapy., Trial Registration: www.clinicaltrials.gov registration number:NCT02080377 February 11th 2014.