Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.

Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).

Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs).

Cervical ripening at home or in hospital during induction of labour: the CHOICE prospective cohort study, process evaluation and economic analysis.

Background: Around one in three pregnant women undergoes induction of labour in the United Kingdom, usually preceded by in-hospital cervical ripening to soften and open the cervix.

Objectives: This study set out to determine whether cervical ripening at home is within an acceptable safety margin of cervical ripening in hospital, is effective, acceptable and cost-effective from both National Health Service and service user perspectives.

Design: The CHOICE study comprised a prospective multicentre observational cohort study using routinely collected data (CHOICE cohort), a process evaluation comprising a survey and nested case studies (qCHOICE) and a cost-effectiveness analysis.

A multi-ancestry genome-wide association study identifies novel candidate loci in the RARB gene associated with hypertensive disorders of pregnancy.

Genetic factors related to pregnancy-related traits are understudied, especially in ancestrally diverse cohorts. To assess maternal contributions to hypertensive disorders of pregnancy (HDP), we performed a multi-ancestry genome-wide association study (GWAS) of HDP in data from the North Carolina-based Personalized Environment and Genes Study (PEGS) cohort with validation in the UK Biobank (UKBB). The GWAS revealed two maternal loci associated with HDP at the genome-wide significance level.

Association between maternal hemoglobin concentration and educational attainment in mid-childhood in a high-resource obstetric setting: a prospective cohort study.

Background: Although maternal hemoglobin levels during pregnancy are commonly associated with perinatal outcomes, their link to childhood neurodevelopment remains uncertain.

Objective: This study aimed to examine the associations between maternal hemoglobin in early and late pregnancy and the educational attainment of offspring mid-childhood in a high-resource obstetric setting.

Study Design: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012, N=3285) were linked to mid-childhood educational outcomes (Department for Education, United Kingdom).

Predicting and preventing stillbirth at term.

Stillbirth at term affects ∼1 per 1000 pregnancies at term in high income countries. A range of maternal characteristics are associated with stillbirth risk. However, given the low a priori risk of stillbirth, the vast majority of women with clinical risk factors would not experience a stillbirth in the absence of intervention.

Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants.

Streptococcus agalactiae (Group B Streptococcus; GBS) is a common cause of sepsis in neonates. Previous work detected GBS DNA in the placenta in ~5% of women before the onset of labour, but the clinical significance of this finding is unknown. Here we re-analysed this dataset as a case control study of neonatal unit (NNU) admission.

Prediction of spontaneous preterm birth using supervised machine learning on metabolomic data: A case-cohort study.

Objectives: To identify and internally validate metabolites predictive of spontaneous preterm birth (sPTB) using multiple machine learning methods and sequential maternal serum samples, and to predict spontaneous early term birth (sETB) using these metabolites.

Design: Case-cohort design within a prospective cohort study.

Setting: Cambridge, UK.

Association between adverse pregnancy outcome and placental biomarkers in the first trimester: A prospective cohort study.

Objective: To determine the inter-relationships between five first-trimester biomarkers (pregnancy associated plasma protein A [PAPP-A], alpha-fetoprotein [AFP], beta human chorionic gonadotrophin [beta-hCG], placenta growth factor [PlGF] and soluble fms-like tyrosine kinase receptor-1 [sFlt-1]) and a range of adverse pregnancy outcomes (APOs).

Design: Prospective cohort study of nulliparous singleton pregnancy.

Setting: Cambridge, UK.

Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcomes.

Background: In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes.

Methods: We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age.

The human placenta exhibits a unique transcriptomic void.

The human placenta exhibits a unique genomic architecture with an unexpectedly high mutation burden and many uniquely expressed genes. The aim of this study is to identify transcripts that are uniquely absent or depleted in the placenta. Here, we show that 40 of 46 of the other organs have no selectively depleted transcripts and that, of the remaining six, the liver has the largest number, with 26.

Group B Streptococcus and the risk of perinatal morbidity and mortality following term labor.

Streptococcus agalactiae (group B Streptococcus) colonizes the genital tract of approximately 20% of pregnant women. In the absence of intervention, approximately 1% of infants born to colonized mothers exhibit a clinical infection. This has led to implementation of screening and intervention in the form of intrapartum antibiotic prophylaxis in many countries, including the United States.

Physiologically relevant culture medium Plasmax improves human placental trophoblast stem cell function.

Human trophoblast cultures provide powerful tools to model key processes of placental development. In vitro trophoblast studies to date have relied on commercial media that contains nonphysiological levels of nutrients, and the impact of these conditions on trophoblast metabolism and function is unknown. Here, we show that the physiological medium (Plasmax) with nutrient and metabolite concentrations recapitulating human plasma improves human trophoblast stem cell (hTSC) proliferation and differentiation compared with standard medium (DMEM-F12).

Association of birthweight centiles and early childhood development of singleton infants born from 37 weeks of gestation in Scotland: A population-based cohort study.

Background: Birthweight centiles beyond the traditional thresholds for small or large babies are associated with adverse perinatal outcomes but there is a paucity of data about the relationship between birthweight centiles and childhood development among children born from 37 weeks of gestation. This study aims to establish the association between birthweight centiles across the whole distribution and early childhood development among children born from 37 weeks of gestation.

Methods And Findings: This is a population-based cohort study of 686,284 singleton infants born from 37 weeks of gestation.

Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction.

Background: Preeclampsia and fetal growth restriction (FGR) are both associated with an increased ratio of sFLT1 (soluble fms-like tyrosine kinase-1) to PlGF (placenta growth factor) in maternal serum. In preeclampsia, it is assumed that increased placental release of sFLT1 results in PlGF being bound and inactivated. However, direct evidence for this model is incomplete, and it is unclear whether the same applies in FGR.

Placental sex-dependent spermine synthesis regulates trophoblast gene expression through acetyl-coA metabolism and histone acetylation.

Placental function and dysfunction differ by sex but the mechanisms are unknown. Here we show that sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding spermine synthase (SMS). Female placental trophoblasts demonstrate biallelic SMS expression, associated with increased SMS mRNA and enzyme activity.

Mode of delivery of twins at term.

Observational epidemiological analyses demonstrated a decreased risk of death and severe morbidity associated with caesarean delivery at term but an increased risk at preterm gestational age. A multicentre international randomized controlled compared planned caesarean section with vaginal birth and observed no difference in outcome; however, the trial included preterm and term births in approximately similar proportions. A subsequent re-analysis of the trial demonstrated that planned caesarean section was associated with an increased risk of adverse neonatal outcome at preterm gestational ages, but reduced the risk of perinatal complications at term, consistent with the epidemiological studies.

Metabolomic Identification of a Novel, Externally Validated Predictive Test for Gestational Diabetes Mellitus.

Context: Undiagnosed gestational diabetes mellitus (GDM) is a major preventable cause of stillbirth. In the United Kingdom, women are selected for diagnostic testing for GDM based on risk factors, including body mass index (BMI) > 30 kg/m2.

Objective: To improve the prediction of GDM using metabolomics.

Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes.

Background: Hypertensive disorders of pregnancy are common pregnancy complications that are associated with greater cardiovascular disease risk for mothers. However, risk of cardiovascular disease subtypes associated with gestational hypertension or pre-eclampsia is unclear. The present study aims to compare the risk of cardiovascular disease outcomes for women with and without a history of gestational hypertension and pre-eclampsia using national hospital admissions data.