Department of Pediatrics, University of California San Diego, La Jolla, California.
Alcohol Res. 2023 Mar 16;43(1):01. doi: 10.35946/arcr.v43.1.01. eCollection 2023.
Although abstinence is recommended in pregnancy, many pregnancies are exposed to alcohol. Observational studies of the effects of low to moderate prenatal alcohol exposure (PAE) and neurodevelopmental outcomes have yielded inconsistent results, with some studies finding an increased risk of adverse neurobehavioral and cognitive outcomes, and other studies finding no changes or reduced risk of the same outcomes. The purpose of this narrative review is to summarize these inconsistencies and apply a methodological framework to discuss how different parameters contribute to the findings. The authors also provide recommendations on how to advance future research in this area.
The PubMed, Web of Science, and Embase databases were searched, along with reference lists of selected systematic reviews and meta-analyses. Search terms used were (infant or child or children or adolescent or offspring) AND (low or light or mild or moderate or low-to-moderate) AND (drinking or alcohol or drinks) AND (pregnancy or prenatal or fetal) AND (neurodevelopment or behavioral or psychological or cognitive or developmental) NOT (mice or rat or fish or animal) NOT (meta-analysis or review). Peer-reviewed original research studies were included if they analyzed associations between an exposure defined and characterized as low/light or moderate PAE with offspring neurodevelopmental outcomes. Animal studies, studies that did not provide clear cutoff points to classify PAE categories, studies lacking an abstinence control group, and studies that did not present a multivariable-adjusted measure of association were excluded.
The searches identified 2,422 papers, with 36 papers meeting eligibility criteria. These studies were carried out across nine countries and included samples ranging from approximately 500 to 40,000 participants. Cognitive, academic, socioemotional, and behavioral outcomes were assessed from infancy through age 19.
When the findings from the selected articles were summarized by geographic region, exposure definition, or neurodevelopmental outcome, no consistent observations or patterns emerged between low to moderate PAE and offspring outcomes. Although some studies found positive (i.e., beneficial) associations between low to moderate PAE and outcomes (primarily outcomes related to cognition) and others found negative (i.e., detrimental) associations (primarily for behavioral outcomes), most findings were null (i.e., showed no effect of PAE). The heterogeneity in study results is likely due to methodological issues, including residual confounding, effect measure modification, and exposure misclassification that make synthesis of studies difficult. Alternative study designs, including longitudinal trajectory analysis, sibling design, negative controls, and instrumental variable analyses, may reduce biases and are discussed. To date, the consequences of light to moderate levels of PAE on neurodevelopment remain unresolved; studies that advance methodological rigor will be important contributions to the field.
尽管建议孕妇戒酒，但仍有许多孕妇会接触到酒精。观察性研究表明，低至中度产前酒精暴露（PAE）与神经发育结局之间存在关联，但结果不一致，一些研究发现不良神经行为和认知结局的风险增加，而其他研究则发现相同结局的风险没有变化或降低。本叙述性综述的目的是总结这些不一致之处，并应用方法学框架讨论不同参数如何影响研究结果。作者还就如何推进该领域的未来研究提出了建议。
检索了 PubMed、Web of Science 和 Embase 数据库，以及选定的系统评价和荟萃分析的参考文献列表。使用的检索词是（婴儿或儿童或儿童或青少年或后代）和（低或轻或温和或中度或低至中度）和（饮酒或酒精或饮料）和（妊娠或产前或胎儿）和（神经发育或行为或心理或认知或发育）而非（老鼠或大鼠或鱼或动物）而非（荟萃分析或综述）。如果原始研究分析了低/轻或中度 PAE 与后代神经发育结局之间的关联，且符合纳入标准，则纳入研究。排除了动物研究、未提供明确分类 PAE 类别的截止点的研究、缺乏戒酒对照组的研究以及未呈现多变量调整关联测量的研究。
搜索共确定了 2422 篇论文，其中 36 篇符合入选标准。这些研究在九个国家进行，样本量从大约 500 到 40000 名参与者不等。从婴儿期到 19 岁，评估了认知、学业、社会情感和行为结果。
当按地理位置、暴露定义或神经发育结果对所选文章的发现进行总结时，低至中度 PAE 与后代结局之间没有出现一致的观察结果或模式。尽管一些研究发现低至中度 PAE 与认知相关的结局（主要是认知结局）之间存在正相关（即有益），而另一些研究则发现与行为结局相关的负相关（即有害），但大多数研究结果为中性（即没有 PAE 的影响）。研究结果的异质性可能是由于方法学问题，包括残余混杂、效应量修正和暴露错误分类，使得研究综合变得困难。讨论了替代研究设计，包括纵向轨迹分析、兄弟姐妹设计、阴性对照和工具变量分析，这些设计可能会减少偏倚。迄今为止，轻度至中度 PAE 对神经发育的后果仍未得到解决；提高方法学严谨性的研究将是该领域的重要贡献。
