Addiction Medicine Fellowship Program, Department of Family and Community Medicine, University of New Mexico, Albuquerque.
Honors College, University of New Mexico, Albuquerque.
JAMA Netw Open. 2020 Mar 2;3(3):e201195. doi: 10.1001/jamanetworkopen.2020.1195.
The number of children with prenatal opioid exposure to medication for addiction treatment (MAT) with methadone and buprenorphine for maternal opioid use disorder is increasing, but the associations of this exposure with cognitive outcomes are not well understood.
To examine the strength and consistency of findings in the medical literature regarding the association of prenatal exposure to MAT with early childhood cognitive development, particularly when accounting for variables outside MAT exposure.
A search strategy obtained publications from PubMed, CINAHL, PsycINFO, Web of Science, and Embase from January 1972 to June 2019. Reference lists from identified articles were searched.
Inclusion criteria were cohort studies, studies including children aged 1 to 60 months with at least 2 months of prenatal MAT exposure, studies using standardized direct-observation testing scales, and studies reporting means and SDs. Case reports, case series, historical controls, and reviews were excluded.
Two authors independently selected studies for inclusion, extracted data, and assessed study quality. Data extracted included demographic characteristics, covariates, sources of bias, and effect estimates. Meta-analysis was performed using random-effects models. This study was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Data extraction and synthesis were conducted between January 2018 and August 2019.
Cognitive test scores and demographic variability between exposed and unexposed groups.
A total of 16 unique cohorts, described in 27 articles and including 1086 children (485 [44.7%] with MAT exposure), were included in a quantitative synthesis. On meta-analysis, MAT exposure was associated with lower cognitive development scores (pooled standardized mean difference, -0.57; 95% CI, -0.93 to -0.21; I2 = 81%). Multiple subanalyses on demographic characteristics (ie, maternal education, race/ethnicity, socioeconomic status, prenatal tobacco exposure, infant sex) were conducted. In the subanalysis of studies with comparable prenatal exposure to tobacco smoke, the association of MAT exposure with cognitive scores was no longer statistically significant and became homogeneous (standardized mean difference, -0.11; 95% CI, -0.42 to 0.20; I2 = 0%).
In this study, predefined subanalyses demonstrated how poor recruitment, particularly imbalances in maternal tobacco use, could contribute to a negative overall association of cognitive development test scores with prenatal MAT exposure. Promoting tobacco cessation for pregnant women with opioid use disorder should be prioritized in this high-risk population.
接受美沙酮和丁丙诺啡药物治疗（MAT）治疗母亲阿片类药物使用障碍的产前阿片类药物暴露的儿童数量不断增加，但这种暴露与认知结果的关联尚不清楚。
研究医学文献中关于产前暴露于 MAT 与幼儿认知发展之间关联的研究结果的强度和一致性，特别是在考虑 MAT 暴露以外的变量时。
从 1972 年 1 月至 2019 年 6 月，通过 PubMed、CINAHL、PsycINFO、Web of Science 和 Embase 的搜索策略获取文献。从确定的文章的参考文献列表中搜索。
纳入标准为队列研究，研究对象为至少接受 2 个月产前 MAT 暴露的 1 至 60 个月龄儿童，使用标准化直接观察测试量表的研究，以及报告均值和标准差的研究。排除病例报告、病例系列、历史对照和综述。
两名作者独立选择纳入的研究，提取数据并评估研究质量。提取的数据包括人口统计学特征、协变量、偏倚来源和效应估计值。使用随机效应模型进行荟萃分析。这项研究是根据观察性研究的荟萃分析流行病学（MOOSE）指南和系统评价和荟萃分析的首选报告项目（PRISMA）声明进行的。数据提取和综合于 2018 年 1 月至 2019 年 8 月进行。
暴露组和未暴露组之间的认知测试分数和人口统计学差异。
共有 16 个独特的队列，在 27 篇文章中描述，包括 1086 名儿童（485 [44.7%] 接受 MAT 暴露），纳入了定量综合分析。荟萃分析显示，MAT 暴露与认知发展评分较低相关（合并标准化均数差，-0.57；95%CI，-0.93 至 -0.21；I2=81%）。对人口统计学特征（即母亲教育程度、种族/民族、社会经济地位、产前烟草暴露、婴儿性别）进行了多项亚分析。在与产前接触烟草烟雾相似的研究亚分析中，MAT 暴露与认知评分的关联不再具有统计学意义且变得同质（标准化均数差，-0.11；95%CI，-0.42 至 0.20；I2=0%）。
在这项研究中，预先设定的亚分析表明，招募不足，特别是孕妇吸烟的不平衡，可能导致认知发展测试分数与产前 MAT 暴露之间的总体负面关联。在这个高危人群中，应优先促进孕妇戒烟。
