National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

SummaryBackgroundPregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes.MethodsIn this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527.FindingsBetween March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most...

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BACKGROUNDProgesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODSWe conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twicedaily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. RESULTSA total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, −4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. CONCLUSIONSProgesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages.

Abstract-Prospective contemporaneous data on the outcome of pregnancies in women with chronic hypertension are sparse. Indices of maternal and perinatal morbidity and mortality were determined in 822 women with chronic hypertension with data prospectively collected and rigorously validated. The incidence of superimposed preeclampsia was 22% (nϭ180) with early-onset preeclampsia (Յ34 weeks gestation) accounting for nearly half of these cases. Delivery at Ͻ37 weeks gestation occurred in 51% of those with superimposed preeclampsia (98% of these iatrogenic) and 15% without (66% iatrogenic) (RR 3.52; 95% CI 2.79 to 4.45). Using multiple logistic regression, black ethnic origin, raised body mass index, present smoking, booking systolic blood pressure of 130 to 139 mm Hg, and diastolic blood pressure of 80 to 89 mm Hg, a previous history of preeclampsia or eclampsia and chronic renal disease were identified as risk factors for superimposed preeclampsia. Adverse maternal and perinatal outcomes occur in women with chronic hypertension; the prevalence of infants born small for gestational age and preterm is considerably higher than background rates, and is increased further in women with superimposed preeclampsia. Use of customized birthweight centiles provides more accurate determination of fetal growth restriction and highlights the need for greater fetal surveillance in these women. Paradoxically, smoking is an independent risk factor for superimposed preeclampsia in chronic hypertension, in contrast to the protective effect in low-risk pregnant women. Key Words: hypertension Ⅲ pregnancy Ⅲ preeclampsia Ⅲ maternal morbidity Ⅲ fetal morbidity Ⅲ risk factors P reeclampsia is estimated to affect 8 370 000 women worldwide every year. In the UK, it complicates approximately 4% to 6% of all pregnancies (approximately 33 500 per annum) and remains a major cause of maternal, fetal, and neonatal morbidity and mortality, contributing a significant healthcare economic burden. 1 The disease not only affects pregnancy outcome, but also predisposes mother and child to long-term health complications such as cardiovascular disease. 2 Currently, chronic hypertension is estimated to complicate between 1 and 5 percent of pregnancies; however the increase in maternal age and obesity and the changing ethnic profile of women in their reproductive years is likely to increase prevalence as these factors all impact on the hypertensive disease process. A small number of studies, mostly retrospective and from women investigated 1 to 2 decades ago, have documented the increased risk of adverse maternal and perinatal outcomes in pregnant women with chronic hypertension, 3,4,5 but high quality recent prospective data are sparse. Information from contemporaneous cohorts is needed to provide an evidence base for the management of affected pregnant women and to inform future research.Our group recently undertook a large prospective interventional study in women at increased risk of preeclampsia, 6 for which chronic hypertension was an entry criterion. ...

Objective-Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention in obese pregnant women associated with improved maternal diet and reduced gestational weight gain leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum.Subjects and Methods-We conducted a planned postnatal follow up of a randomised controlled trial (UPBEAT) of a complex behavioural intervention targeting maternal diet (glycemic load and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire.Results-698 (45.9%) infants (342 intervention, 356 standard antenatal care) were followed up at mean age 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs. standard care arms (difference -0.14 SD, 95% CI -0.38 to 0.10, p=0.246), but subscapular skinfold thickness z-score was 0.26 SD (-0.49 to -0.02; p=0.03) lower in the intervention arm. Maternal dietary glycemic load (-35.34; -48.0 to -22.67; p<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; p<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was mediated by changes in antenatal maternal diet and gestational weight gain rather than postnatal diet.Conclusion-This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.