孕妇吸烟与儿童孤独症谱系障碍关系队列研究的Meta分析

Cohort studies on the association between maternal smoking during pregnancy and autism spectrum disorders of children:a Meta-analysis

目的通过Meta分析定量评价孕妇吸烟与儿童孤独症谱系障碍(ASD)的关系。方法检索PubMed、Embase、Web of Science、Cochrane Library、中国知网、万方数据知识服务平台等数据库于2000年1月至2019年7月发表的国内外队列研究文献,提取原始研究中RR值(95%CI)。用Stata 15.1软件进行Meta分析。根据异质性检验结果用随机效应模型合并RR值,通过亚组分析和Meta回归探索异质性来源,并对纳入的文献进行发表偏倚检验和敏感性分析。结果共11项队列研究纳入分析,累计1631618例样本和9276例ASD病例。结果显示孕妇吸烟可增加儿童ASD的发病风险(RR=1.16,95%CI:1.02~1.32);亚组分析发现,前瞻性队列研究(RR=1.16,95%CI:1.10~1.23)合并RR值高于回顾性队列研究(RR=0.92,95%CI:0.83~1.06);调整变量研究(RR=1.13,95%CI:1.04~1.23)的合并RR值高于未调整变量的研究(RR=1.12,95%CI:1.04~1.20);分娩前评估吸烟状态的研究异质性高于分娩后评估的研究。Meta回归提示样本量和吸烟评估时间为可能的异质性来源。本研究无明显发表偏倚,结果稳定性较好。结论孕妇吸烟会增加儿童ASD的发病风险,但现有研究的合并效应值较低。未来应开展高质量的大样本、前瞻性队列研究,在矫正潜在混杂因素的基础上深入分析两者之间的因果关系。

Objective To examine the association between maternal smoking during pregnancy and autism spectrum disorders(ASD)of children through Meta-analysis.Methods We searched data on relative risk(RR)and 95%confidence interval(CI)on cohort studies published between January 2000 and July 2019 from PubMed,Embase,Web of Science,Cochrane Library,China National Knowledge Infrastructure,and Wanfang database.We used Stata software 15.1 to perform the Meta analysis with random effect model applied to pool RRs according to the results of heterogeneity test through subgroup analysis and Meta regression analysis to explore the potential heterogeneity,publication bias and sensitivity.Results A total of eleven cohort studies involving 1631618 samples and 9276 ASD cases were included in this Meta-analysis.Results showed that maternal smoking was associated with the increased risk of autism spectrum disorder(RR=1.16,95%CI:1.02-1.32).For subgroup analysis,the pooled RR for prospective studies(RR=1.16,95%CI:1.10-1.23)appeared higher than that in the retrospective studies(RR=0.92,95%CI:0.83-1.06).The pooled RR for studies with adjusted confounding factors(RR=1.13,95%CI:1.04-1.23)was higher than that without(RR=1.12,95%CI:1.04-1.20).In studies that exposure to smoking assessed before delivery,inter-study heterogeneity appeared higher than those after delivery.Sample size and time of assessment on smoking seemed the sources of heterogeneity.No significant publication bias was observed in this study,and the results were quite stable.Conclusions Maternal smoking was associated with the increased risk of autism spectrum disorder.However,value of the combined effect seemed low.High-quality,large-sample,and prospective cohort studies should be conducted to further verify the causal relationship,based on the correction of potential confounding factors.