Effects of antenatal diet and physical activity on maternal and fetal outcomes: individual patient data meta-analysis and health economic evaluation.

BACKGROUND: Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes. OBJECTIVES: To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search). REVIEW METHODS: Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions. RESULTS: Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI -0.92 to -0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate -0.10 kg, 95% CI -0.14 to -0.06 kg) and multiparity (summary estimate -0.73 kg, 95% CI -1.24 to -0.23 kg). LIMITATIONS: The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies. CONCLUSION: Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes. FUTURE WORK: The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003804. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cardiovascular risk management after reproductive and pregnancy-related disorders: A Dutch multidisciplinary evidence-based guideline.

BACKGROUND: In the past decades evidence has accumulated that women with reproductive and pregnancy-related disorders are at increased risk of developing cardiovascular disease (CVD) in the future. Up to now there is no standardised follow-up of these women becausee guidelines on cardiovascular risk management for this group are lacking. However, early identification of high-risk populations followed by prevention and treatment of CVD risk factors has the potential to reduce CVD incidence. Therefore, the Dutch Society of Obstetrics and Gynaecology initiated a multidisciplinary working group to develop a guideline for cardiovascular risk management after reproductive and pregnancy-related disorders. METHODS: The guideline addresses the cardiovascular risk consequences of gestational hypertension, preeclampsia, preterm delivery, small-for-gestational-age infant, recurrent miscarriage, polycystic ovary syndrome and premature ovarian insufficiency. The best available evidence on these topics was captured by systematic review. Recommendations for clinical practice were formulated based on the evidence and consensus of expert opinion. The Dutch societies of gynaecologists, cardiologists, vascular internists, radiologists and general practitioners reviewed the guideline to ensure support for implementation in clinical practice. RESULTS: For all reproductive and pregnancy-related disorders a moderate increased relative risk was found for overall CVD, except for preeclampsia (relative risk 2.15, 95% confidence interval 1.76-2.61). CONCLUSION: Based on the current available evidence, follow-up is only recommended for women with a history of preeclampsia. For all reproductive and pregnancy-related disorders optimisation of modifiable cardiovascular risk factors is recommended to reduce the risk of future CVD.

Preventing preterm birth with progesterone: costs and effects of screening low risk women with a singleton pregnancy for short cervical length, the Triple P study.

BACKGROUND: Women with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity. Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity. Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix. However, it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women. METHODS/DESIGN: We plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth. In these women, we will measure cervical length at the standard anomaly scan performed between 18 and 22 weeks. Women with cervical length ≤ 30 mm at two independent measurements will be randomly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks. The primary outcome of this trial is adverse neonatal condition, defined as a composite outcome of neonatal mortality and severe morbidity. Secondary outcomes are time to delivery, preterm birth rate before 32, 34 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We will assess growth, physical condition and neurodevelopmental outcome of the children at two years of age. DISCUSSION: This study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18-22 weeks and subsequent progesterone treatment among low risk women. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR207.

Treatment of valvular heart disease during pregnancy for improving maternal and neonatal outcome.

BACKGROUND: Valvular heart disease constitutes the majority of all causes of heart disease in pregnancy. In the presence of valvular heart disease, the necessary haemodynamic changes of pregnancy might cause heart failure, leading to severe maternal and fetal morbidity and even mortality. Treatment of valvular heart disease is indicated when patients experience a deterioration of symptoms and in case of a severe valvular lesion. Whether medical therapy or interventional therapy is the optimal treatment for both mother and child is unclear. OBJECTIVES: To assess effectiveness and adverse effects of the different treatment modalities of valvular heart disease in pregnancy to improve maternal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), EMBASE (1980 to 23 March 2011) and the reference lists of background review articles. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled and cluster-randomised controlled trials comparing medical therapy with percutaneous or surgical intervention for the treatment of valvular heart disease in pregnancy. DATA COLLECTION AND ANALYSIS: We identified no (randomised) controlled trials to assess the effectiveness and adverse effects of the treatment of valvular heart disease in pregnancy. MAIN RESULTS: There were no randomised controlled trials, quasi-randomised controlled trials or cluster-randomised trials identified from the search strategy. AUTHORS' CONCLUSIONS: There is insufficient evidence to define the most effective treatment of valvular heart disease in pregnancy to improve maternal and neonatal outcomes.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

BACKGROUND: Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. METHODS: We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. FINDINGS: 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. INTERPRETATION: Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. FUNDING: ZonMw.