Ewelina Rogozinska

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence

Objective To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. Design Systematic review and meta-analysis. Data sources Major databases from inception to January 2012 without language restrictions. Study selection Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. Data synthesis Results summarised as relative risks for dichotomous data and mean differences for continuous data. Results We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference −50 g, −100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference −60 g, −120 to −10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. Conclusions Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.

Interventions to Reduce or Prevent Obesity in Pregnant Women: A Systematic Review

BACKGROUND Around 50% of women of childbearing age are either overweight [body mass index (BMI) 25-29.9 kg/m(2)] or obese (BMI ≥ 30 kg/m(2)). The antenatal period provides an opportunity to manage weight in pregnancy. This has the potential to reduce maternal and fetal complications associated with excess weight gain and obesity. OBJECTIVES To evaluate the effectiveness of dietary and lifestyle interventions in reducing or preventing obesity in pregnancy and to assess the beneficial and adverse effects of the interventions on obstetric, fetal and neonatal outcomes. DATA SOURCES Major electronic databases including MEDLINE, EMBASE, BIOSIS and Science Citation Index were searched (1950 until March 2011) to identify relevant citations. Language restrictions were not applied. REVIEW METHODS Systematic reviews of the effectiveness and harm of the interventions were carried out using a methodology in line with current recommendations. Studies that evaluated any dietary, physical activity or mixed approach intervention with the potential to influence weight change in pregnancy were included. The quality of the studies was assessed using accepted contemporary standards. Results were summarised as pooled relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous data. Continuous data were summarised as mean difference (MD) with standard deviation. The quality of the overall evidence synthesised for each outcome was summarised using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and reported graphically as a two-dimensional chart. RESULTS A total of 88 studies (40 randomised and 48 non-randomised and observational studies, involving 182,139 women) evaluated the effect of weight management interventions in pregnancy on maternal and fetal outcomes. Twenty-six studies involving 468,858 women reported the adverse effect of the interventions. Meta-analysis of 30 RCTs (4503 women) showed a reduction in weight gain in the intervention group of 0.97 kg compared with the control group (95% CI -1.60 kg to -0.34 kg; p = 0.003). Weight management interventions overall in pregnancy resulted in a significant reduction in the incidence of pre-eclampsia (RR 0.74, 95% CI 0.59 to 0.92; p = 0.008) and shoulder dystocia (RR 0.39, 95% CI 0.22 to 0.70; p = 0.02). Dietary interventions in pregnancy resulted in a significant decrease in the risk of pre-eclampsia (RR 0.67, 95% CI 0.53 to 0.85; p = 0.0009), gestational hypertension (RR 0.30, 95% CI 0.10 to 0.88; p = 0.03) and preterm birth (RR 0.68, 95% CI 0.48 to 0.96; p = 0.03) and showed a trend in reducing the incidence of gestational diabetes (RR 0.52, 95% CI 0.27 to 1.03). There were no differences in the incidence of small-for-gestational-age infants between the groups (RR 0.99, 95% CI 0.76 to 1.29). There were no significant maternal or fetal adverse effects observed for the interventions in the included trials. The overall strength of evidence for weight gain in pregnancy and birthweight was moderate for all interventions considered together. There was high-quality evidence for small-for-gestational-age infants as an outcome. The quality of evidence for all interventions on pregnancy outcomes was very low to moderate. The quality of evidence for all adverse outcomes was very low. LIMITATIONS The included studies varied in the reporting of population, intensity, type and frequency of intervention and patient complience, limiting the interpretation of the findings. There was significant heterogeneity for the beneficial effect of diet on gestational weight gain. CONCLUSIONS Interventions in pregnancy to manage weight result in a significant reduction in weight gain in pregnancy (evidence quality was moderate). Dietary interventions are the most effective type of intervention in pregnancy in reducing gestational weight gain and the risks of pre-eclampsia, gestational hypertension and shoulder dystocia. There is no evidence of harm as a result of the dietary and physical activity-based interventions in pregnancy. Individual patient data meta-analysis is needed to provide robust evidence on the differential effect of intervention in various groups based on BMI, age, parity, socioeconomic status and medical conditions in pregnancy.

Use of labour induction and risk of cesarean delivery: a systematic review and meta-analysis

Background: Induction of labour is common, and cesarean delivery is regarded as its major complication. We conducted a systematic review and meta-analysis to investigate whether the risk of cesarean delivery is higher or lower following labour induction compared with expectant management. Methods: We searched 6 electronic databases for relevant articles published through April 2012 to identify randomized controlled trials (RCTs) in which labour induction was compared with placebo or expectant management among women with a viable singleton pregnancy. We assessed risk of bias and obtained data on rates of cesarean delivery. We used regression analysis techniques to explore the effect of patient characteristics, induction methods and study quality on risk of cesarean delivery. Results: We identified 157 eligible RCTs (n = 31 085). Overall, the risk of cesarean delivery was 12% lower with labour induction than with expectant management (pooled relative risk [RR] 0.88, 95% confidence interval [CI] 0.84–0.93; I2 = 0%). The effect was significant in term and post-term gestations but not in preterm gestations. Meta-regression analysis showed that initial cervical score, indication for induction and method of induction did not alter the main result. There was a reduced risk of fetal death (RR 0.50, 95% CI 0.25–0.99; I2 = 0%) and admission to a neonatal intensive care unit (RR 0.86, 95% CI 0.79–0.94), and no impact on maternal death (RR 1.00, 95% CI 0.10–9.57; I2 = 0%) with labour induction. Interpretation: The risk of cesarean delivery was lower among women whose labour was induced than among those managed expectantly in term and post-term gestations. There were benefits for the fetus and no increased risk of maternal death.

Nutritional Manipulation for the Primary Prevention of Gestational Diabetes Mellitus: A Meta-Analysis of Randomised Studies

Introduction The rise in gestational diabetes (GDM), defined as first onset or diagnosis of diabetes in pregnancy, is a global problem. GDM is often associated with unhealthy diet and is a major contributor to adverse outcomes maternal and fetal outcomes. Manipulation of nutrition has the potential to prevent GDM. Methods We assessed the effects of nutritional manipulation in pregnancy on GDM and relevant maternal and fetal outcomes by a systematic review of the literature. We searched MEDLINE, EMBASE, and Cochrane Database from inception to March 2014 without any language restrictions. Randomised controlled trials (RCT) of nutritional manipulation to prevent GDM were included. We summarised dichotomous data as relative risk (RR) and continuous data as standardised mean difference (SMD) with 95% confidence interval (CI). Results From 1761 citations, 20 RCTs (6,444 women) met the inclusion criteria. We identified the following interventions: diet-based (n = 6), mixed approach (diet and lifestyle) interventions (n = 13), and nutritional supplements (myo-inositol n = 1, diet with probiotics n = 1). Diet based interventions reduced the risk of GDM by 33% (RR 0.67; 95% CI 0.39, 1.15). Mixed approach interventions based on diet and lifestyle had no effect on GDM (RR 0.95; 95% CI 0.89, 1.22). Nutritional supplements probiotics combined with diet (RR 0.40; 95% CI 0.20, 0.78) and myo-inositol (RR 0.40; 95% CI 0.16, 0.99) were assessed in one trial each and showed a beneficial effect. We observed a significant interaction between the groups based on BMI for diet-based intervention. The risk of GDM was reduced in obese and overweight pregnant women for GDM (RR 0.40, 95% CI 0.18, 0.86). Conclusions Nutritional manipulation in pregnancy based on diet or mixed approach do not appear to reduce the risk of GDM. Nutritional supplements show potential as agents for primary prevention of GDM.

Abnormal blood biomarkers in early pregnancy are associated with preeclampsia: a meta-analysis.

OBJECTIVE Our aim was to evaluate the strength of association between abnormal levels of first trimester maternal blood biomarkers and the risk of preeclampsia. STUDY DESIGN We searched MEDLINE, EMBASE and Cochrane databases from inception until April 2013. Studies that assessed the association between any abnormal maternal blood biomarker in the first trimester and preeclampsia were included. Two independent reviewers selected studies, extracted data and assessed the quality. Results were summarized as pooled odds ratios with 95% confidence intervals. RESULTS From 1071 citations, we identified 30 studies (65,538 women) for inclusion. Twenty four studies assessed preeclampsia of any onset, 10 studied early onset preeclampsia and seven evaluated late onset preeclampsia (after 34 weeks of gestation). The biomarkers PAPP-A (OR 2.1, 95% CI 1.6, 2.6), PP13 (OR 4.4, 95% CI 2.9, 6.8), sFlt-1 (OR 1.3, 95% CI 2.9, 6.8), pentraxin (OR 5.3, 95% CI 1.9, 15.0) and inhibin-A (OR 3.6, 95% CI 1.7, 7.6) were significantly associated with any preeclampsia. The odds of early onset preeclampsia were significantly increased when the biomarkers PlGF (OR 3.4, 95% CI 1.6, 7.2), PAPP-A (OR 4.8, 95% CI 2.5, 22.5), PP13 (OR 7.5, 95% CI 2.5, 22.5), soluble endoglin (OR 18.5, 95% CI 8.4, 41.0) and inhibin-A (OR 4.1, 95% CI 1.9, 8.8) were abnormal. Two biomarkers, soluble endoglin (OR 2.1, 95% CI 1.9, 2.4) and inhibin-A (OR 1.9, 95% CI 1.4, 2.8) were significantly associated with late onset preeclampsia. CONCLUSION Abnormal maternal blood biomarkers in early pregnancy are significantly associated with preeclampsia, particularly early onset disease.

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.

Dietary interventions in overweight and obese pregnant women: a systematic review of the content, delivery, and outcomes of randomized controlled trials.

CONTEXT Interventions targeting maternal obesity are a healthcare and public health priority. OBJECTIVE The objective of this review was to evaluate the adequacy and effectiveness of the methodological designs implemented in dietary intervention trials for obesity in pregnancy. DATA SOURCES A systematic review of the literature, consistent with PRISMA guidelines, was performed as part of the International Weight Management in Pregnancy collaboration. STUDY SELECTION Thirteen randomized controlled trials, which aimed to modify diet and physical activity in overweight and obese pregnant women, were identified. DATA SYNTHESIS There was significant variability in the content, delivery, and dietary assessment methods of the dietary interventions examined. A number of studies demonstrated improved dietary behavior in response to diet and/or lifestyle interventions. Nine studies reduced gestational weight gain. CONCLUSION This review reveals large methodological variability in dietary interventions to control gestational weight gain and improve clinical outcomes in overweight and obese pregnant women. This lack of consensus limits the ability to develop clinical guidelines and apply the evidence in clinical practice.

Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies

OBJECTIVE Preterm birth continues to be the one of the leading causes of infant deaths worldwide. There is a need for effective, easily available, safe and acceptable interventions to prevent preterm delivery, especially before 34 weeks of gestation. Omega-3 fatty acids such as EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) are available as over the counter nutritional supplements, and are taken by women to improve pregnancy outcomes, without any clear recommendations. We undertook a systematic review to assess the effects of omega-3 fatty acids on early (<34 weeks) and any (<37 weeks) preterm delivery. METHODS We searched MEDLINE, EMBASE and Cochrane Library from inception to 2014 without any language restrictions. Study selection, quality assessment and data extraction were done by two independent reviewers. Results were summarized as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences for continuous outcomes. RESULTS Of the nine included trials (5980 women), six (4193 women) evaluated the effects of omega-3 fatty acids on early preterm delivery. The risk of early preterm delivery was reduced by 58% (RR 0.42; 95% CI 0.27-0.66; I(2)=0%; p=0.0002) and any preterm delivery by 17% (RR 0.83; 95% CI 0.70-0.98; I(2)=0%; p=0.03) with the intervention. There was a significant increase in the mean gestational age by 1.95 weeks (95% CI 0.42-3.48 weeks; I(2)=0.47; p=0.01) and mean birth weight by 122.1g (95% CI 47.4-196.8; I(2)=0.84; p=0.001) in the intervention group compared to the controls. Subgroup analysis showed no significant differences in the effects between the groups according to the risk status, dose and timing of the intervention. CONCLUSION Omega-3 fatty acids are effective in preventing early and any preterm delivery. The intervention is simple and easily available and has the potential to influence population based strategies in the prevention of preterm birth.

Sentinel lymph node biopsy in vulval cancer: systematic review and meta-analysis.

Background:The purpose of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy with technetium 99 (99mTc) and/or blue dye-enhanced lymphoscintigraphy in vulval cancer.Methods:Sensitive searches of databases were performed upto October 2013. Studies with at least 75% of women with FIGO stage IB or II vulval cancer evaluating SLN biopsy with 99mTc, blue dye or both with reference standard of inguinofemoral lymphadenectomy (IFL) or clinical follow-up were included. Meta-analyses were performed using Meta-Disc version 1.4.Results:Of the 2950 references, 29 studies (1779 women) were included; most of them evaluated 99mTc combined with blue dye. Of these, 24 studies reported results for SLN followed by IFL, and 5 reported clinical follow-up only for SLN negatives. Pooling of all studies was inappropriate because of heterogeneity. Mean SLN detection rates were 94.0% for 99mTc, 68.7% for blue dye and 97.7% for both. SLN biopsy had pooled sensitivity of 95% (95% CI 92–98%) with negative predictive value (NPV) of 97.9% in studies using 99mTc/blue dye, ultrastaging and immunohistochemistry with IFL as reference. Pooled sensitivity for SLN with clinical follow-up for SLN-negatives was 91% (85–95%) with NPV 95.6%. Patients undergoing SLN biopsy experienced less morbidity than those undergoing IFL.Conclusions:Sentinel lymph node biopsy using 99mTC, blue dye and ultrastaging with immunohistochemistry is highly accurate when restricted to carefully selected patients, within a rigorous protocol, with close follow-up and where sufficient numbers for learning curve optimisation exist. Patients must make an informed choice between the slightly higher groin recurrence rates of SLN biopsy vs the greater morbidity of IFL.

Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes-individual patient data (IPD) meta-analysis and health economic evaluation

BackgroundPregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.Methods/designRandomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.Systematic review registrationPROSPERO 2013:CRD42013003804