Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy.

OBJECTIVES: 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, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women 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 (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) 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: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-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 partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. CONCLUSIONS: 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.

Prediction of gestational diabetes in obese pregnant women from the UK Pregnancies Better Eating and Activity (UPBEAT) pilot trial.

AIM: To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester. METHODS: A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity were studied. Blood samples were obtained at recruitment (15⁺°-17⁺6 weeks' gestation) and demographic, clinical history and anthropometric measures recorded. The biomarkers analysed were plasma lipids (HDL cholesterol, LDL cholesterol, triglycerides), high-sensitivity C-reactive protein, alanine transaminase, aspartate transaminase, ferritin, fructosamine, insulin, adiponectin, tissue plasminogen activator, interleukin-6, visfatin and leptin. Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver-operating curve was calculated for the model. RESULTS: Of the 106 participants included in the analysis, 29 (27.4%) developed gestational diabetes. Participants with gestational diabetes were older (P = 0.002), more often of parity ≥ 2, had higher systolic (P = 0.02) and diastolic blood pressure (P = 0.02) and were more likely to be black (P = 0.009). Amongst the blood biomarkers measured, plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models (P = 0.002). The area under the receiver-operating curve for clinical factors alone (0.760) increased significantly (area under the curve 0.834, chi-square statistic (1) = 4.00, P = 0.046) with the addition of adiponectin. CONCLUSIONS: A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes. Validation in a large prospective study is required to determine the usefulness of this algorithm in clinical practice.

Clinical and geographical variation in prophylactic and therapeutic treatments for pre-eclampsia in the UK.

OBJECTIVE: To evaluate the clinical and geographical variation in the use of aspirin in women at high risk of pre-eclampsia, and in the use of antihypertensive drugs and magnesium sulphate in women with established pre-eclampsia. DESIGN: Analysis of vitamins in pre-eclampsia (VIP) trial database. SAMPLE: A total of 2399 women at increased risk of pre-eclampsia in 25 UK hospitals. METHODS: An analysis of a large prospectively validated database of high-risk women in the UK was undertaken to assess aspirin use across different risk groups and to evaluate the use of antihypertensives and magnesium sulphate in 370 women who developed pre-eclampsia. Logistic regression was employed to compare drug use between region and by recognised clinical indicators. MAIN OUTCOME MEASURES: Usage of aspirin, antihypertensive drugs and magnesium sulphate. RESULTS: Of the women with known risk factors at trial entry, 24% (569/2399) received low-dose aspirin. Aspirin usage varied widely between risk groups [from 5% (19/378) in women with multiple pregnancy to 94% (50/53) in women with antiphospholipid syndrome] and between geographical regions [from 8% (20/248) to 49% (95/193)]. Three hundred and seventy women developed pre-eclampsia, 52% (n = 193) of whom received new or additional antihypertensives after 20 weeks of gestation; 34% (77/224) with a maximum recorded systolic blood pressure of >OR=160 mmHg in the second half of pregnancy did not receive antihypertensive treatment; 17% (62/370) of women with pre-eclampsia received magnesium sulphate prophylactically. CONCLUSIONS: Prophylactic and treatment regimes for pre-eclampsia in the UK vary by region and risk group.

Fetal fibronectin as a predictor of spontaneous preterm labour in asymptomatic women with a cervical cerclage.

OBJECTIVE: To assess the accuracy of fetal fibronectin (fFN) testing for prediction of preterm labour in asymptomatic high-risk women with a cervical cerclage. DESIGN: Retrospective observational study. SETTING: United Kingdom. POPULATION: Nine hundred and ten asymptomatic women at high-risk of Preterm birth referred to specialist antenatal clinics and undergoing fFN testing between November 1997 and December 2007. METHODS: Women had fFN tests taken between 23(+0) and 27(+6) weeks' gestation, on one or more occasions. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive values and negative predictive values of fFN testing for predicting delivery <30 and <37 weeks were compared in those with and without cerclage. RESULTS: For delivery <30 weeks' gestation, the specificity of fFN testing was significantly lower in women with cervical cerclage (77% vs 90%; P < or = 0.00001). The sensitivity of the test was similar between the groups (78.6 (no-cerclage) vs 60% (cerclage); P > 0.4). The negative predictive value of the fFN test for delivery <30 weeks was high in both groups (>98%). CONCLUSIONS: Asymptomatic high-risk women with cerclage in situ are more likely to have a false positive fFN test. The negative predictive value is similar.

Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.

BACKGROUND: Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors. METHODS: We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 . FINDINGS: Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]). INTERPRETATION: Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.

BACKGROUND: Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. METHODS: 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. FINDINGS: Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002). INTERPRETATION: Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.