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

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

Author Information

Gillian M Maher: INFANT Research Centre, Cork, Ireland.
Gerard W O'Keeffe: INFANT Research Centre, Cork, Ireland.
Christina Dalman: Department of Public Health Sciences, Division of Public Health Epidemiology, Karolinska Institutet, Stockholm, Sweden.
Patricia M Kearney: School of Public Health, Western Gateway Building, University College Cork, Cork, Ireland.
Fergus P McCarthy: INFANT Research Centre, Cork, Ireland.
Louise C Kenny: Department of Women's and Children's Health, Institute of Translational Medicine, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Ali S Khashan: INFANT Research Centre, Cork, Ireland.

PMID: 31531876 DOI: 10.1111/jcpp.13127

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.

Autism spectrum disorder epidemiology preeclampsia

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Adolescent

Adult

Autism Spectrum Disorder

Child

Child, Preschool

Female

Follow-Up Studies

Humans

Infant

Infant, Newborn

Infant, Small for Gestational Age

Male

Placenta Diseases

Pre-Eclampsia

Pregnancy

Proportional Hazards Models

Sweden

Young Adult

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