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Background The vast majority of systematic reviews are planned retrospectively, once most eligible trials have completed and reported, and are based on aggregate data that can be extracted from publications. Prior knowledge of trial results can introduce bias into both review and meta-analysis methods, and the omission of unpublished data can lead to reporting biases. We present a collaborative framework for prospective, adaptive meta-analysis (FAME) of aggregate data to provide results that are less prone to bias. Also, with FAME, we monitor how evidence from trials is accumulating, to anticipate the earliest opportunity for a potentially definitive meta-analysis. Methodology We developed and piloted FAME alongside 4 systematic reviews in prostate cancer, which allowed us to refine the key principles. These are to: (1) start the systematic review process early, while trials are ongoing or yet to report; (2) liaise with trial investigators to develop a detailed picture of all eligible trials; (3) prospectively assess the earliest possible timing for reliable meta-analysis based on the accumulating aggregate data; (4) develop and register (or publish) the systematic review protocol before trials produce results and seek appropriate aggregate data; (5) interpret meta-analysis results taking account of both available and unavailable data; and (6) assess the value of updating the systematic review and meta-analysis. These principles are illustrated via a hypothetical review and their application to 3 published systematic reviews. Conclusions FAME can reduce the potential for bias, and produce more timely, thorough and reliable systematic reviews of aggregate data., Author(s): Jayne F. Tierney *, David J. Fisher, Claire L. Vale, Sarah Burdett, Larysa H. Rydzewska, Ewelina Rogozinska, Peter J. Godolphin, Ian R. White, Mahesh K. B. Parmar Background The [...]

Contexte : L'induction du travail est fréquente et l'accouchement par césarienne est considéré comme sa principale complication. Nous avons procédé à une revue systématique et à une méta-analyse pour vérifier si le risque d'accouchement par césarienne est plus ou moins élevé après l'induction du travail comparativement à une approche attentiste. Méthodes : Nous avons interrogé 6 bases de données électroniques pour y recenser les articles pertinents publiés jusqu'en avril 2012 et portant sur des essais randomisés et contrôlés (ERC) au cours desquels l'induction du travail était comparée à un placebo ou à une approche attentiste chez des femmes présentant une grossesse monofœtale viable. Nous avons évalué le risque de biais et extrait les données sur les taux d'accouchement par césarienne. Nous avons utilisé des techniques d'analyse de régression pour explorer l'effet des caractéristiques des patientes, des méthodes d'induction et de la qualité des études sur le risque d'accouchement par césarienne. Résultats : Nous avons recensé 157 ERC admissibles (n = 31 085). Globalement, le risque d'accouchement par césarienne a été de 12 % moindre avec l'induction du travail que dans le cas d'une approche attentiste (risque relatif [RR] regroupé 0,88; intervalle de confiance [IC] de 95 % 0,84-0,93; I² = 0 %). L'effet a été significatif pour les grossesses à terme et prolongées, mais non pour les accouchements prématurés. L'analyse de métarégression a révélé que le score cervical initial, l'indication de l'induction et le mode d'induction n'ont pas modifié le paramètre principal. On a noté un risque moindre de mortalité foetale (RR 0,50; IC de 95 % 0,25-0,99; I² - 0 %) et d'admission aux soins intensifs néonataux (RR 0,86; IC de 95 % 0,79-0,94) et on n'a observé aucun impact sur la mortalité maternelle (RR 1,00; IC de 95 % 0,10-9,57; I² = 0 %) dans les cas d'induction du travail. Interprétation : Le risque d'accouchement par césarienne a été moindre chez les femmes dont le travail a été induit que chez celles qui ont été soumises à une approche attentiste pour les grossesses à terme et prolongées. On a noté des avantages pour le foetus et on n'a noté aucune augmentation du risque de mortalité maternelle. [ABSTRACT FROM AUTHOR]

Importance: Randomized clinical trials have found that antenatal lifestyle interventions optimize gestational weight gain (GWG) and pregnancy outcomes. However, key components of successful interventions for implementation have not been systematically identified., Objective: To evaluate intervention components using the Template for Intervention Description and Replication (TIDieR) framework to inform implementation of antenatal lifestyle interventions in routine antenatal care., Data Sources: Included studies were drawn from a recently published systematic review on the efficacy of antenatal lifestyle interventions for optimizing GWG. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, MEDLINE, and Embase were searched from January 1990 to May 2020., Study Selection: Randomized clinical trials examining efficacy of antenatal lifestyle interventions in optimizing GWG were included., Data Extraction and Synthesis: Random effects meta-analyses were used to evaluate the association of intervention characteristics with efficacy of antenatal lifestyle interventions in optimizing GWG. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Data extraction was performed by 2 independent reviewers., Main Outcomes and Measures: The main outcome was mean GWG. Measures included characteristics of antenatal lifestyle interventions comprising domains related to theoretical framework, material, procedure, facilitator (allied health staff, medical staff, or researcher), delivery format (individual or group), mode, location, gestational age at commencement (<20 wk or ≥20 wk), number of sessions (low [1-5 sessions], moderate [6-20 sessions], and high [≥21 sessions]), duration (low [1-12 wk], moderate [13-20 wk], and high [≥21 wk]), tailoring, attrition, and adherence. For all mean differences (MDs), the reference group was the control group (ie, usual care)., Results: Overall, 99 studies with 34 546 pregnant individuals were included with differential effective intervention components found according to intervention type. Broadly, interventions delivered by an allied health professional were associated with a greater decrease in GWG compared with those delivered by other facilitators (MD, -1.36 kg; 95% CI, -1.71 to -1.02 kg; P < .001). Compared with corresponding subgroups, dietary interventions with an individual delivery format (MD, -3.91 kg; 95% CI -5.82 to -2.01 kg; P = .002) and moderate number of sessions (MD, -4.35 kg; 95% CI -5.80 to -2.89 kg; P < .001) were associated with the greatest decrease in GWG. Physical activity and mixed behavioral interventions had attenuated associations with GWG. These interventions may benefit from an earlier commencement and a longer duration for more effective optimization of GWG., Conclusions and Relevance: These findings suggest that pragmatic research may be needed to test and evaluate effective intervention components to inform implementation of interventions in routine antenatal care for broad public health benefit.

Objectives: To identify if maternal educational attainment is a prognostic factor for gestational weight gain (GWG), and to determine the differential effects of lifestyle interventions (diet based, physical activity based or mixed approach) on GWG, stratified by educational attainment., Design: Individual participant data meta-analysis using the previously established International Weight Management in Pregnancy (i-WIP) Collaborative Group database (https://iwipgroup.wixsite.com/collaboration). Preferred Reporting Items for Systematic reviews and Meta-Analysis of Individual Participant Data Statement guidelines were followed., Data Sources: Major electronic databases, from inception to February 2017., Eligibility Criteria: Randomised controlled trials on diet and physical activity-based interventions in pregnancy. Maternal educational attainment was required for inclusion and was categorised as higher education (≥tertiary) or lower education (≤secondary)., Risk of Bias: Cochrane risk of bias tool was used., Data Synthesis: Principle measures of effect were OR and regression coefficient., Results: Of the 36 randomised controlled trials in the i-WIP database, 21 trials and 5183 pregnant women were included. Women with lower educational attainment had an increased risk of excessive (OR 1.182; 95% CI 1.008 to 1.385, p =0.039) and inadequate weight gain (OR 1.284; 95% CI 1.045 to 1.577, p =0.017). Among women with lower education, diet basedinterventions reduced risk of excessive weight gain (OR 0.515; 95% CI 0.339 to 0.785, p = 0.002) and inadequate weight gain (OR 0.504; 95% CI 0.288 to 0.884, p=0.017), and reduced kg/week gain (B -0.055; 95% CI -0.098 to -0.012, p=0.012). Mixed interventions reduced risk of excessive weight gain for women with lower education (OR 0.735; 95% CI 0.561 to 0.963, p=0.026). Among women with high education, diet based interventions reduced risk of excessive weight gain (OR 0.609; 95% CI 0.437 to 0.849, p=0.003), and mixed interventions reduced kg/week gain (B -0.053; 95% CI -0.069 to -0.037,p<0.001). Physical activity based interventions did not impact GWG when stratified by education., Conclusions: Pregnant women with lower education are at an increased risk of excessive and inadequate GWG. Diet based interventions seem the most appropriate choice for these women, and additional support through mixed interventions may also be beneficial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Pre-eclampsia, a condition with raised blood pressure and proteinuria is associated with an increased risk of maternal and offspring mortality and morbidity. Early identification of mothers at risk is needed to target management., Methods/design: We aim to systematically review the existing literature to identify prediction models for pre-eclampsia. We have established the International Prediction of Pregnancy Complication Network (IPPIC), made up of 72 researchers from 21 countries who have carried out relevant primary studies or have access to existing registry databases, and collectively possess data from more than two million patients. We will use the individual participant data (IPD) from these studies to externally validate these existing prediction models and summarise model performance across studies using random-effects meta-analysis for any, late (after 34 weeks) and early (before 34 weeks) onset pre-eclampsia. If none of the models perform well, we will recalibrate (update), or develop and validate new prediction models using the IPD. We will assess the differential accuracy of the models in various settings and subgroups according to the risk status. We will also validate or develop prediction models based on clinical characteristics only; clinical and biochemical markers; clinical and ultrasound parameters; and clinical, biochemical and ultrasound tests., Discussion: Numerous systematic reviews with aggregate data meta-analysis have evaluated various risk factors separately or in combination for predicting pre-eclampsia, but these are affected by many limitations. Our large-scale collaborative IPD approach encourages consensus towards well developed, and validated prognostic models, rather than a number of competing non-validated ones. The large sample size from our IPD will also allow development and validation of multivariable prediction model for the relatively rare outcome of early onset pre-eclampsia., Trial Registration: The project was registered on Prospero on the 27 November 2015 with ID: CRD42015029349., Competing Interests: Not applicableNot applicableKM is Editor-in-Chief and KS is an associate editor for BMC Diagnostic and Prognostic Research. The other authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Pregnant 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/design: Randomised 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 Registration: PROSPERO 2013: CRD42013003804.

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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)