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BackgroundRecent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries. Advanced maternal age has been associated with several adverse maternal and perinatal outcomes. Although there are many studies on this topic, data from large contemporary population-based cohorts that controls for demographic variables known to influence perinatal outcomes is limited.MethodsWe performed a population-based cohort study using data on all singleton births in 2004–2008 from the North Western Perinatal Survey based at The University of Manchester, UK. We compared pregnancy outcomes in women aged 30–34, 35–39 and ≥40 years with women aged 20–29 years using log-linear binomial regression. Models were adjusted for parity, ethnicity, social deprivation score and body mass index.ResultsThe final study cohort consisted of 215,344 births; 122,307 mothers (54.19%) were aged 20–29 years, 62,371(27.63%) were aged 30–34 years, 33,966(15.05%) were aged 35–39 years and 7,066(3.13%) were aged ≥40 years. Women aged 40+ at delivery were at increased risk of stillbirth (RR = 1.83, [95% CI 1.37–2.43]), pre-term (RR = 1.25, [95% CI: 1.14–1.36]) and very pre-term birth (RR = 1.29, [95% CI:1.08–1.55]), Macrosomia (RR = 1.31, [95% CI: 1.12–1.54]), extremely large for gestational age (RR = 1.40, [95% CI: 1.25–1.58]) and Caesarean delivery (RR = 1.83, [95% CI: 1.77–1.90]).ConclusionsAdvanced maternal age is associated with a range of adverse pregnancy outcomes. These risks are independent of parity and remain after adjusting for the ameliorating effects of higher socioeconomic status. The data from this large contemporary cohort will be of interest to healthcare providers and women and will facilitate evidence based counselling of older expectant mothers.

Objectives To develop a predictive model for preeclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated. Design Prospective multicentre cohort. Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland. Participants 3572 "healthy" nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%). Main outcome measure Pre-eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks' gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37 +0 weeks' gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia. Results Of the 3529 women, 186 (5.3%) developed preeclampsia, including 47 (1.3%) with preterm preeclampsia. Clinical risk factors at 14-16 weeks' gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors.Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop preeclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively. Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia ( P <0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

Our population-based study suggests that severe stress to a mother during the first trimester may alter the risk of schizophrenia in offspring. This finding is consistent with ecological evidence from whole populations exposed to severe stressors and suggests that environment may influence neurodevelopment at the feto-placental-maternal interface.

These recommendations from the ISSHP are based upon available literature and expert opinion. It is intended that this be a 'living' document, to be updated when needed as more research becomes available to influence good clinical practice. Unfortunately there is a relative lack of high quality randomised trials in the field of Hypertension in Pregnancy compared with studies in essential hypertension outside of pregnancy and ISSHP encourages greater funding and uptake of collaborative research in this field. Accordingly, the quality of evidence for the recommendations in this document has not been graded, though relevant references and explanations are provided for each recommendation. The document will be a 'living' guideline and we hope to be able to grade recommendations in the future.Guidelines and recommendations for management of hypertension in pregnancy are typically written for implementation in an ideal setting. It is acknowledged that in many parts of the world, it will not be possible to adopt all of these recommendations; for this reason, options for management in less-resourced settings are discussed separately in relation to diagnosis, evaluation, and treatment. This document has been endorsed by the International Society of Obstetric Medicine (ISOM) and the Japanese Society for the Study of Hypertension in Pregnancy (JSSHP). 5 KEY POINTS: All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes.The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies. Classification1. Hypertension in pregnancy may be chronic (pre-dating pregnancy or diagnosed before 20 weeks of pregnancy) or de novo (either pre-eclampsia or gestational hypertension).2. Chronic hypertension is associated with adverse maternal and fetal outcomes and is best managed by tightly controlling maternal blood pressure (BP 110-140/85 mmHg), monitoring fetal growth and repeatedly assessing for the development of pre-eclampsia and maternal complications. This can be done in an outpatient setting.3. White-coat hypertension refers to elevated office/ clinic (≥140/90mmHg) blood pressure but normal blood pressure measured at home or work (<135/85mmHg); it is not an entirely benign condition and conveys an increased risk for pre-eclampsia. 6 4. Masked hypertension is another form of hypertension, more difficult to diagnose, characterised by blood pressure that is normal at a clinic or office visit but elevated at other times, most typically diagnosed by 24 hour ambulatory BP monitoring (ABPM) or automated home blood pressure monitoring (HBPM). 5.Gestational hypertension is hypertension arising de novo after 20 weeks' gestation in the absence of proteinuria and without biochemical or haematological abnormalities. It...

Obesity is one of the biggest challenges facing global reproductive health. Women in the UK and USA are today more likely to be obese or overweight at booking than normal weight, and many low-and middle-income countries (LMICs) seem destined to follow suit (Poston et al. Lancet Diabetes Endocrinol 2016;4:1025-36). Understanding how, and to what extent, maternal body mass index (BMI) and weight gain during pregnancy contribute to adverse outcomes for mothers and their offspring is therefore vital to informing future health policy.In an individual participant data meta-analysis of over 265 000 births, Santos et al. (BJOG 2019;126:984-95) confirm strong correlations between pre-pregnancy maternal BMI and the risks of gestational hypertension, preeclampsia and gestational diabetes. Over one-third of such complications in the study population were considered attributable to maternal overweight and obesity. The risk of large size for gestational age (LGA) at birth increased similarly across all categories of pre-pregnancy BMI and gestational weight gain, although these data should be interpreted in the context of a continuing debate regarding the customisation of fetal growth charts. It remains uncertain how maternal height and weight influence fetal growth potential, and whether LGA babies born to mothers who are obese or mothers with excessive weight gain carry the same short-and long-term health risks as LGA babies born to mothers who are normal weight. Preterm birth was also more common among women who are obese and past literature has suggested that this association is strongest for extremely preterm delivery (Cnattingius et al. JAMA 2013;309:2362-70), whether spontaneous or iatrogenic.Whereas women who are obese or have high weight gain are consistently shown to be at greatest risk, there is clear evidence of a continuum of risk across the full BMI range, which is emphasised by the authors' use of population attributable risk (PAR). Notably, the overall burden of pregnancy complications is similar in overweight and obese groups (PAR 11.4 and 12.5%, respectively). This calls into question traditional models of care targeting women with a booking BMI above 30 kg/m 2 or even higher thresholds. Minimising gestational weight gain in these women ameliorates but does not remove the excess risk, and ultimately may have less impact on outcomes at a population level than previously hoped.The authors acknowledge that the data were derived from cohorts who were largely white; however, comparable findings have been reported in LMICs with varied ethnic populations (Rahman et al. Obes Rev 2015;16:758-70).Being healthy entails more than just not being obese, and the study also draws important attention to the risks of small size for gestational age and preterm birth, particularly amongst underweight women with inadequate weight gain during pregnancy. These findings strengthen the argument for novel public health approaches to optimise maternal health with a shift in focus towards pre-conception and interpregnancy intervent...

BackgroundMaternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.Methods and findingsWe conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.ConclusionsIn this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large po...