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.

The prevalence of obesity in pregnancy is rising exponentially; about 15–20% of pregnant women now enter pregnancy with a BMI which would define them as obese. This paper provides a review of the strong links between obesity and adverse pregnancy outcome which operate across a range of pregnancy complications. For example, obesity is associated with an increased risk of maternal mortality, gestational diabetes mellitus, thromboembolism, pre-eclampsia and postpartum haemorrhage. Obesity also complicates operative delivery; it makes operative delivery more difficult, increases complications and paradoxically increases the need for operative delivery. The risk of the majority of these complications is amplified by excess weight gain in pregnancy and increases in proportion to the degree of obesity, for example, women with extreme obesity have OR of 7·89 for gestational diabetes and 3·84 for postpartum haemorrhage compared to their lean counterparts. The consequences of maternal obesity do not stop once the baby is born. Maternal obesity programmes a variety of long-term adverse outcomes, including obesity in the offspring at adulthood. Such an effect is mediated at least in part via high birthweight; a recent study has suggested that the odds of adult obesity are two-fold greater in babies weighing more than 4 kg at birth. The mechanism by which obesity causes adverse pregnancy outcome is uncertain. This paper reviews the emerging evidence that hyperglycaemia and insulin resistance may both play a role: the links between hyperglycaemia in pregnancy and both increased birthweight and insulin resistance have been demonstrated in two large studies. Lastly, we discuss the nature and rationale for possible intervention strategies in obese pregnant women.

Objectives: Preterm birth contributes to a range of healthcare problems amongst infants surmounting to sizeable healthcare costs. Twin pregnancies are at particular risk of preterm birth. The objective of this study was to assess the cost-effectiveness of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies.

Methods: An economic evaluation was conducted alongside a randomized placebo controlled trial (the STOPPIT trial) of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. Five hundred women were recruited from nine maternity hospitals in the United Kingdom. The outcomes of the economic evaluation were presented in terms of net benefit statistics, cost-effectiveness acceptability curves, generated using the nonparametric bootstrap method, and the expected value of perfect information.

Results: Mean health service costs between the period of randomization and discharge for mother and infant were £28,031 in the progesterone group and £25,972 in the placebo group, generating a mean nonsignificant cost difference of £2,059 (bootstrap mean cost difference £2,334; 95 percent confidence interval: −£5,023, £9,142; p = .33). The probability of progesterone being cost-effective was 20 percent at a willingness to pay threshold of £30,000 per preterm birth prevented. There is little economic justification for conducting further research into the use of vaginal progesterone gel in twin pregnancies for the prevention of preterm birth.

Conclusions: Further studies of preventive interventions for preterm birth more generally are required given the scale of the clinical and economic burden of this condition. These studies should be sufficiently powered for economic endpoints and extend beyond hospital discharge.

Since the discovery of the structure and function of steroids over 60 years ago, it has long been recognized that synthetic antagonists of the natural hormones would have potential therapeutic uses. Antagonists of mineralocorticoids, androgens and oestrogens, for example spironolactine, cyproterone, flutamide and tamoxifen, have already found a place in the management of hormone dependent conditions. In 1982, chemists at Roussel UCLAF announced that they had synthesized mifepristone (RU486) 17β-hydroxy-11(p-(dimethylamino)phenyl)-17-(1-propynyl) estra-411, 9-dien-3-one) a derivative of norethindrone which had potent antiprogestogenic as well as antiglucocorticoid activity. Although it was immediately realised that this compound would potentially have wide clinical application, its development in the last 10 years has been dominated by its abortifacient action. In the original clinical report by Herrman and colleagues it was shown that bleeding occurred when it was given to female volunteers in the second half of the menstrual cycle. In addition, complete abortion occurred in eight of 11 women who took the drug in the early weeks of pregnancy. These findings, which demonstrated that mifepristone could be used as the basis of a medical method of inducing abortion, were immediately made the focus of groups opposed to abortion on moral grounds. Experience over the last 10 years has confirmed the promise of these early studies and mifepristone, in combination with a suitable prostaglandin, is now licensed in France, UK and Sweden for use as a medical method of inducing abortion in early pregnancy.