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.

Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m(2) or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30-39 vs ≥40 kg/m(2)). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference -0·029, 95% CI -0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3·60, 95% CI 0·74-17·50; p=0·11). Metformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes. The Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research partnership.

Maternal obesity is associated with increased morbidity and mortality for both mother and offspring. The mechanisms underlying the increased risk associated with maternal obesity are not well understood. In non-pregnant populations, many of the complications of obesity are thought to be mediated in part by inflammation and its sequelae. Recent studies suggest that a heightened inflammatory response may also be involved in mediating adverse clinical outcomes during pregnancy. This review summarizes our current knowledge about adipose tissue biology, and its role as an endocrine and inflammatory organ. The evidence for inflammation as a key mediator of adverse pregnancy outcome is also presented, focusing on the role of inflammation in adipose tissue, systemic inflammation, the placenta, and vascular endothelium.

Arterial stiffness and compliance are major predictors of adverse cardiovascular events and are influenced by female sex hormones, including estrogen and progesterone. The aim of this longitudinal study was to evaluate the effect of the menstrual cycle, normal pregnancy, and preeclampsia on central and systemic arterial stiffness. Ten healthy nulliparous women with regular menses were studied in the early and midfollicular, periovulatory, and luteal phases of a single menstrual cycle. Twenty-two primigravida pregnant women were studied throughout pregnancy at 16, 24, 32, and 37 weeks gestation and at 7 weeks postpartum. Fifteen primigravida women with preeclampsia were studied at diagnosis and 7 weeks postpartum. Augmentation index and carotid-radial and carotid-femoral pulse wave velocities were measured using applanation tonometry. Augmentation index fell during the luteal phase of the menstrual cycle (luteal phase versus periovulatory phase; P <0.05). In normal pregnancy, pulse wave velocity and augmentation index increased from 24 weeks over the third trimester ( P ≤0.01 for both). All of the measures were increased in women with preeclampsia ( P ≤0.01), with augmentation index and carotid-femoral pulse wave velocity remaining elevated 7 weeks postpartum ( P ≤0.02). We conclude that systemic arterial stiffness undergoes major changes during the menstrual cycle and pregnancy and that preeclampsia is associated with greater and more prolonged increases in arterial stiffness. These effects may contribute to adverse cardiovascular outcomes of pregnancy and preeclampsia.

Perinatal depression is strikingly common with a prevalence of 10–15 %. The adverse effects of perinatal depression on maternal and child health are profound with considerable costs. Despite this, few women seek medical attention. E-health, providing healthcare via the Internet is an accessible and effective solution for the treatment of depression in the general population. We aimed to conduct a systematic review of web-based interventions for the prevention and treatment of mood disorders in the perinatal period, defined as the start of pregnancy to 1 year post-partum. Six databases were searched until 26th March 2015. Two researchers independently screened articles for eligibility. Of the 547 screened articles, four met the inclusion criteria. These included three randomised-controlled trials and one feasibility trial, with total data from 1274 participants. MOOSE and PRISMA guidelines were adhered to for the conduct and reporting of the systematic review. All studies were conducted in the post-partum period. All reported an improvement in maternal mood following intervention. A significant improvement in depressive symptoms was measured using validated rating scales, such as the Edinburgh Postnatal Depression Scale (EPDS), either at post-treatment or follow-up which ranged from 3 to 12 months post study completion. For the two RCTs utilising the EPDS, the EPDS score reductions were (mean ± SEM) 8.52 ± 0.22 (Range 19.46 to10.94) and 9.19 ± 0.63 (Range, 20.24 to 11.05) for treatment groups and 5.16 ± 0.25 (Range 19.44 to 14.28) and 6.81 ± 0.71 (Range 21.07 to 14.26) for comparator groups. However attrition within studies ranged from 13 to 61 %. One study was rated as ‘good’ quality. Preliminary data suggests web-based therapies for perinatal depression delivered in the post-partum period may play a role in improving maternalmood but more studies are needed, particularly with interventions delivered antenatally. Further research is needed to address the limitations of the existing evidence base.