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

Maher, Gillian M.; O'Keeffe, Gerard W.; Dalman, Christina; Kearney, Patricia M.; McCarthy, Fergus P.; Kenny, Louise C.; Khashan, Ali S.

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

dc.contributor.author	Maher, Gillian M.
dc.contributor.author	O'Keeffe, Gerard W.
dc.contributor.author	Dalman, Christina
dc.contributor.author	Kearney, Patricia M.
dc.contributor.author	McCarthy, Fergus P.
dc.contributor.author	Kenny, Louise C.
dc.contributor.author	Khashan, Ali S.
dc.contributor.funder	Health Research Board	en
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2019-11-12T15:05:39Z
dc.date.available	2019-11-12T15:05:39Z
dc.date.issued	2019-09-17
dc.date.updated	2019-11-12T14:53:48Z
dc.description.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.	en
dc.description.sponsorship	Health Research Board (Grant Number: SPHeRE/2013/1)	en
dc.description.status	Peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.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	en
dc.identifier.doi	10.1111/jcpp.13127	en
dc.identifier.eissn	1469-7610
dc.identifier.issn	0021-9630
dc.identifier.journaltitle	Journal of Child Psychology and Psychiatry	en
dc.identifier.uri	https://hdl.handle.net/10468/8992
dc.language.iso	en	en
dc.publisher	John Wiley & Sons Ltd.	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2272/IE/Irish Centre for Fetal and Neonatal Translational Research (INFANT)/	en
dc.relation.uri	https://onlinelibrary.wiley.com/doi/abs/10.1111/jcpp.13127
dc.rights	© 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.	en
dc.subject	Autism spectrum disorder	en
dc.subject	Preeclampsia	en
dc.subject	Epidemiology	en
dc.title	Association between preeclampsia and autism spectrum disorder: a population-based study	en
dc.type	Article (peer-reviewed)	en