Shireen Meher

Management of pre-eclampsia.

Pre-eclampsia is part of a spectrum of conditions known as the hypertensive disorders of pregnancy (box 1).1 A multisystem disorder usually associated with raised blood pressure and proteinuria, pre-eclampsia is relatively common, affecting 2-8% of pregnancies. Although outcome is often good, pre-eclampsia can be devastating and life threatening for both mother and baby (box 2), particularly in developing countries.2 It may also lead to an increased risk of cardiovascular disease in later life. Although the cause is not fully understood, factors thought to have a role include genes, the placenta, the immune response, and maternal vascular disease.3 Inadequate blood supply to the placenta leads to endothelial dysfunction, which accounts for the secondary changes in maternal target systems (such as platelet aggregation and vasoconstriction) responsible for the signs and symptoms of pre-eclampsia (box 3). Effective care includes identification and referral of women at high risk, prompt diagnosis with prevention and treatment of complications, and timely delivery (the only definitive cure). This review summarises current evidence on management of pre-eclampsia. We searched The Cochrane Database of Systematic Reviews , the trials register of the Cochrane Pregnancy and Childbirth Group, CENTRAL and EMBASE for systematic reviews and randomised trials. Searches were updated in November 2005. Details of the search strategy are summarised on bmj.com. We also identified systematic reviews of studies assessing risk factors for pre-eclampsia. References for trials and reviews are on bmj.com.w1-w28 Assessment usually begins when a woman presents to a general practitioner or midwife requesting antenatal care (box 4). Women at high risk are then offered further visits and testing, with referral for specialist care.4 Screening of low risk women is based primarily on blood pressure measurement and urine analysis. The search for additional tests continues.5 Despite initial optimism for uterine artery …

Choice of primary outcomes in randomised trials and systematic reviews evaluating interventions for preterm birth prevention: a systematic review

The inappropriate and inconsistent selection of primary outcomes (POs) in randomised controlled trials (RCTs) and systematic reviews (SRs) can make evidence difficult to interpret, limiting its usefulness to inform clinical practice.

A core outcome set for evaluation of interventions to prevent preterm birth.

OBJECTIVE: To develop a consensus on a set of key clinical outcomes for the evaluation of preventive interventions for preterm birth in asymptomatic pregnant women. METHODS: A two-stage web-based Delphi survey and a face-to-face meeting of key stakeholders were used to develop a consensus on a set of critical and important outcomes. We approached five stakeholder groups (parents, midwives, obstetricians, neonatologists, and researchers) from middle- and high-income countries. Outcomes subjected to the Delphi survey were identified by systematic literature review and stakeholder input. Survey participants scored each outcome on a 9-point Likert scale anchored between 1 (limited importance) and 9 (critical importance). They had the opportunity to reflect on total and stakeholder subgroup feedback between survey stages. For consensus, defined a priori, outcomes required at least 70% of participants of each stakeholder group to score them as “critical” and less than 15% as “limited.” RESULTS: A total of 228 participants from five stakeholder groups from three lower middle-income countries, seven upper middle-income countries, and 17 high-income countries were asked to score 31 outcomes. Of these participants, 195 completed the first survey and 174 the second. Consensus was reached on 13 core outcomes: four were related to pregnant women: maternal mortality, maternal infection or inflammation, prelabor rupture of membranes, and harm to mother from intervention. Nine were related to offspring: gestational age at birth, offspring mortality, birth weight, early neurodevelopmental morbidity, late neurodevelopmental morbidity, gastrointestinal morbidity, infection, respiratory morbidity, and harm to offspring from intervention. CONCLUSION: This core outcome set for studies that evaluate prevention of preterm birth developed with an international multidisciplinary perspective will ensure that data from trials that assess prevention of preterm birth can be compared and combined. DATABASE REGISTRATION: COMET Initiative, http://www.comet-initiative.org/studies/details/603, Registration Number: 603.

Antiplatelet therapy before or after 16 weeks' gestation for preventing preeclampsia: an individual participant data meta-analysis.

BACKGROUND: The optimum time for commencing antiplatelet therapy for the prevention of preeclampsia and its complications is unclear. Aggregate data meta‐analyses suggest that aspirin is more effective if given prior to 16 weeks’ gestation, but data are limited because of an inability to place women in the correct gestational age subgroup from relevant trials. OBJECTIVE: The objective of the study was to use the large existing individual participant data set from the Perinatal Antiplatelet Review of International Studies Collaboration to assess whether the treatment effects of antiplatelet agents on preeclampsia and its complications vary based on whether treatment is started before or after 16 weeks’ gestation. STUDY DESIGN: A meta‐analysis of individual participant data including 32,217 women and 32,819 babies recruited to 31 randomized trials comparing low‐dose aspirin or other antiplatelet agents with placebo or no treatment for the prevention of preeclampsia has been published previously. Using this existing data set, we performed a prespecified subgroup analysis based on gestation at randomization to antiplatelet agents before 16 weeks, compared with at or after 16 weeks, for 4 of the main outcomes prespecified in the Perinatal Antiplatelet Review of International Studies protocol: preeclampsia, death of baby, preterm birth before 34 weeks, and small‐for‐gestational‐age baby. Individual participant data for the subgroups were combined in a meta‐analysis using RevMan software. Heterogeneity was assessed with the I2 statistic. The χ2 test for interaction was used to assess statistically significant (P < .05) differences in treatment effect between subgroups. RESULTS: There was no significant difference in the effects of antiplatelet therapy for women randomized before 16 weeks’ gestation compared with those randomized at or after 16 weeks for any of the 4 prespecified outcomes: preeclampsia, relative risk, 0.90, (95% confidence interval, 0.79–1.03; 17 trials, 9241 women) for <16 weeks and relative risk, 0.90 (95% confidence interval, 0.83–0.98; 22 trials, 21,429 women) for ≥16 weeks (interaction test, P = .98); death of baby, relative risk, 0.89 (95% confidence interval, 0.73–1.09; 15 trials, 8626 women) for <16 weeks and relative risk, 0.92 (95% confidence interval, 0.79–1.07; 21 trials, 22,336 women) for ≥16 weeks (interaction test, P = .80); preterm birth prior to 34 weeks, relative risk, 0.90 (95% confidence interval, 0.77–1.04; 19 trials, 9155 women) for <16 weeks and relative risk, 0.91 (95% confidence interval, 0.82–1.00; 25 trials, 22,117 women) for ≥16 weeks (interaction test, P = .91); and small‐for‐gestational‐age baby, relative risk, 0.76 (95% confidence interval, 0.61–0.94; 13 trials, 6393 women) for <16 weeks and relative risk, 0.95 (95% confidence interval, 0.84–1.08; 18 trials, 14,996 women) for ≥16 weeks (interaction test, P = .08). CONCLUSION: The effect of low‐dose aspirin and other antiplatelet agents on preeclampsia and its complications is consistent, regardless of whether treatment is started before or after 16 weeks’ gestation. Women at an increased risk of preeclampsia should be offered antiplatelet therapy, regardless of whether they are first seen before or after 16 weeks’ gestation.

Pathway Analysis of Genetic Factors Associated with Spontaneous Preterm Birth and Pre-Labor Preterm Rupture of Membranes

Background Pre-term birth (PTB) remains the leading cause of infant mortality and morbidity. Its etiology is multifactorial, with a strong genetic component. Genetic predisposition for the two subtypes, spontaneous PTB with intact membranes (sPTB) and preterm prelabor rapture of membranes (PPROM), and differences between them, have not yet been systematically summarised. Methods and findings Our literature search identified 15 association studies conducted in 3,600 women on 2175 SNPs in 274 genes. We used Ingenuity software to impute gene pathways and networks related to sPTB and PPROM. Detailed insight in the defined functional ontologies clearly separated integrated datasets for sPTB and PPROM. Our analysis of upstream regulators of genes suggests that glucocorticoid receptor (NR3C1), peroxisome proliferator activated receptor γ (PPARG) and interferon regulating factor 3 (IRF3) may be sPTB specific. PPROM-specific genes may be regulated by estrogen receptor2 (ESR2) and signal transducer and activator of transcription (STAT1). The inflammatory transcription factor NFκB is linked to both sPTB and PPROM, however, their inflammatory response is distinctly different. Conclusions Based on our analyses, we propose an autoimmune/hormonal regulation axis for sPTB, whilst pathways implicated in the etiology of PPROM include hematologic/coagulation function disorder, collagen metabolism, matrix degradation and local inflammation. Our hypothesis generating study has identified new candidate genes in the pathogenesis of PPROM and sPTB, which should be validated in large cohorts.

Postpartum haemorrhage: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

University of Liverpool, UK University of Washington, WA, USA Gynuity Health Projects, NY, USA Mowbray Maternity Hospital, South Africa Government Medical College and Hospital Nagpur, India University of Adelaide, Australia St George’s University of London, UK Barts and The London School of Medicine and Dentistry, UK Busitema University, Mbale Regional Referral Hospital, Uganda Global Healthcare Consulting, India

Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study

To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of postpartum haemorrhage (PPH), and recommendations on how to report the COS.

Core outcomes set for studies on primary prevention of preterm birth

Materials and methods Between May and November 2014 we went through the process of identification and selection of outcomes. All possible outcomes were drawn from systematic reviews, interviews and questionnaires. From this initial list, a selection process was performed using an online 2-round Delphic survey and a consultation meeting. Target stakeholders were approached to contribute in this selection (parents, midwives, obstetricians, neonatologists and methodologists) through purposive sampling in relevant networks: patient organisations, midwife networks, Global Obstetrics Network (GONet), the Cochrane collaboration and journal editors from the Core Outcomes in Women’s health (CROWN) initiative.