INFANT Research Centre, Cork, Ireland.
School of Public Health, Western Gateway Building, University College Cork, Cork, Ireland.
J Child Psychol Psychiatry. 2020 Feb;61(2):131-139. doi: 10.1111/jcpp.13127. Epub 2019 Sep 17.
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.
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.
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.
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.
自闭症谱系障碍（ASD）的环境贡献约为 17%-50%，这突出表明有必要调查可能导致其发病的因素，并深入了解 ASD 的发病机制。本研究的目的是使用基于人群的队列研究来检验子痫前期与 ASD 之间的关联。
本研究纳入了 1982 年至 2010 年期间瑞典所有的单胎活产儿，数据来源于瑞典国家登记处。感兴趣的暴露因素包括：（a）子痫前期（根据 ICD-8、ICD-9 和 ICD-10 分类）和（b）子痫前期和胎儿生长受限（SGA）联合，用作胎盘功能障碍性子痫前期的替代指标。ASD 状态基于 ICD-9 和 ICD-10。该队列由 2842230 名儿童组成，其中 54071 例 ASD。随访从儿童一岁生日开始，数据在首次诊断为 ASD、死亡、迁移或研究期结束（2016 年 12 月 31 日）时截止。我们进行了多变量 Cox 比例风险回归分析，根据预先选择的几项围产期和社会人口统计学因素进行了调整。我们还使用同胞匹配分析进一步控制了共同遗传和家族混杂因素。
在调整后的 Cox 比例风险回归分析中，与未暴露于子痫前期的儿童相比，子痫前期使 ASD 的发病可能性增加了 25%（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）。在调整后的 Cox 模型中，子痫前期和 SGA 联合的 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）。
暴露于子痫前期或子痫前期/胎儿生长受限（即患有子痫前期的 SGA 婴儿）与 ASD 相关。与子痫前期相比，子痫前期/胎儿生长受限与 ASD 的关联更强，这表明胎盘病理可能是 ASD 发病可能性增加的机制。
