Association between preeclampsia and autism spectrum disorder: a population-based study

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Date
2019-09-17
Authors
Maher, Gillian M.
O'Keeffe, Gerard W.
Dalman, Christina
Kearney, Patricia M.
McCarthy, Fergus P.
Kenny, Louise C.
Khashan, Ali S.
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John Wiley & Sons Ltd.
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Abstract
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.
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Keywords
Autism spectrum disorder , Preeclampsia , Epidemiology
Citation
Maher, G. M., O'Keeffe, G. W., Dalman, C., Kearney, P. M., McCarthy, F. P., Kenny, L. C. and Khashan, A. S. (2019) 'Association between preeclampsia and autism spectrum disorder: a population-based study', Journal of Child Psychology and Psychiatry. doi: 10.1111/jcpp.13127
Copyright
© 2019, Association for Child and Adolescent Mental Health. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Maher, G. M., O'Keeffe, G. W., Dalman, C., Kearney, P. M., McCarthy, F. P., Kenny, L. C. and Khashan, A. S. (2019) 'Association between preeclampsia and autism spectrum disorder: a population-based study', Journal of Child Psychology and Psychiatry, doi: 10.1111/jcpp.13127, which has been published in final form at https://doi.org/10.1111/jcpp.13127. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.