BACKGROUND:Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. OBJECTIVES:To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. SEARCH STRATEGY:Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. SELECTION CRITERIA:RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. DATA COLLECTION AND ANALYSIS:One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. MAIN RESULTS:Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design-outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. CONCLUSION:None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. SYSTEMATIC REVIEW REGISTRATION:This study is registered with PROSPERO, registration number CRD42015015941.

译文

背景:对产前酒精暴露影响的系统评价通常仅包括常规观察性研究。但是,此类研究的估计值容易造成混淆和其他偏见。
目的:使用替代分析方法改善因果推理,系统地回顾随机对照试验(RCT)和观察性设计对产前酒精暴露影响的证据。
搜索策略:从成立到2018年6月21日,包括Medline,Embase,Web of Science,PsychINFO。手动检索已检索论文的参考文献清单。
选择标准:使用替代分析方法(准实验研究,例如孟德尔随机试验和自然实验,阴性对照比较)来确定妊娠期饮酒停止/减少干预措施的RCT,以确定产前饮酒对怀孕和更长寿的因果关系人类研究中的足月后代结局。
数据收集和分析:一位审阅者提取了数据,另一名检查了提取的数据。使用定制的偏见风险工具评估了偏见风险。对结果进行叙述性综合,并对一项结果进行荟萃分析。
主要结果:包括23项研究,代表五种研究设计类型,包括1项RCT,9项孟德尔随机和7项自然实验研究,并报告了30多种结果。一种研究设计-结果组合包括足够的独立结果以进行荟萃分析。基于多项研究的证据,我们发现产前饮酒对认知结局可能具有因果关系,而低出生体重的作用证据却较弱。
结论:所有纳入研究均未被判定在所有领域的偏倚风险均较低,因此应谨慎解释结果。
系统评价注册:本研究已在PROSPERO注册,注册号CRD42015015941。

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