Association between preeclampsia and autism spectrum disorder: a population-based study
Association between preeclampsia and autism spectrum disorder: a population-based study
复制标题
DOI：
10.1111/jcpp.13127
复制
发表时间：
2019-09-17
影响因子：
7.6
通讯作者：
Khashan, Ali S.
中科院分区：
文献类型：
--
作者：
Maher, Gillian M.;O'Keeffe, Gerard W.;Khashan, Ali S.
自闭症谱系障碍（ASD）的环境贡献约为17%-50%，这突出了调查可能导致其发展的因素以及更好地了解ASD周围发病机制的重要性。本研究的目的是使用基于人群的队列研究来检查先兆子痫和ASD之间的关联。方法使用瑞典国家登记处的数据，纳入1982年至2010年瑞典所有单胎活产婴儿。利益风险包括：（a）先兆子痫（根据ICD-8、ICD-9和ICD-10分类）和（B）先兆子痫和小于胎龄儿（SGA）组合，用作先兆子痫伴胎盘功能障碍的代表。ASD状态基于ICD-9和ICD-10。该队列包括2，842，230名儿童，其中54，071例ASD病例。随访从孩子的第一个生日开始，数据在首次诊断ASD、死亡、迁移或研究期结束（2016年12月31日）时删失。我们进行了多变量考克斯比例风险回归分析，调整了几个围产期和社会人口因素，选择了先验。我们进一步控制了共享的遗传和家族混杂使用同胞匹配分析。结果在校正的考克斯比例风险回归分析中，与未暴露于先兆子痫的患者相比，先兆子痫与ASD的可能性增加25%相关（风险比（HR）：1.25，95%CI：1.19，1.30），而在同胞匹配分析中，HR为1.17（95%CI：1.06，1.28）。在校正的考克斯模型中，先兆子痫和SGA合并的HR为1.66（95% CI：1.49，1.85），在同胞匹配分析中为1.95（95% CI：1.53，2.48）。结论先兆子痫或先兆子痫/SGA（即SGA婴儿暴露于先兆子痫）与ASD相关。与先兆子痫/SGA的关联比单独的先兆子痫更强，表明胎盘病理可能是ASD可能性增加的机制。
Background The environmental contribution of autism spectrum disorder (ASD) is approximately 17%-50%, highlighting the importance of investigating factors potentially contributing to the likelihood of its development, and of gaining a greater understanding of the pathogenesis surrounding ASD. The objective of this study was to examine the association between preeclampsia and ASD using a population-based cohort study. Methods All singleton live births in Sweden from 1982 to 2010 were included, using data from Swedish National Registers. Exposures of interest included: (a) preeclampsia (classified according to ICD-8, ICD-9 and ICD-10) and (b) preeclampsia and small for gestational age (SGA) combined, used as a proxy for preeclampsia with placental dysfunction. ASD status was based on ICD-9 and ICD-10. The cohort consisted of 2,842,230 children, with 54,071 cases of ASD. Follow-up began from the child's first birthday, and data were censored at first diagnosis of ASD, death, migration or end of study period (31st December 2016). We conducted multivariate Cox proportional hazards regression analysis, adjusting for several perinatal and sociodemographic factors, selected a priori. We further controlled for shared genetic and familial confounding using sibling-matched analysis. Results In the adjusted Cox proportional hazards regression analysis, preeclampsia was associated with a 25% increase in the likelihood of ASD (Hazard Ratio (HR): 1.25, 95% CI:1.19, 1.30) compared with those unexposed to preeclampsia, while in the sibling-matched analysis the HR was 1.17 (95% CI: 1.06, 1.28). The HR for preeclampsia and SGA combined was 1.66 (95% CI: 1.49, 1.85) in the adjusted Cox model and 1.95 (95% CI: 1.53, 2.48) in the sibling-matched analysis. Conclusions Exposure to preeclampsia or preeclampsia/SGA (i.e. SGA baby exposed to preeclampsia) was associated with ASD. The stronger association with preeclampsia/SGA than preeclampsia alone suggests that placental pathology may be a mechanism for the increased likelihood of ASD.