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Maternal infection requiring hospitalization during pregnancy and attention-deficit hyperactivity disorder in offspring: a quasi-experimental family-based study
Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet, Stockholm, Sweden; Indiana University, Bloomington IN, USA.
Indiana University, Bloomington IN, USA.
University of Illinois, Chicago IL, USA.
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2019 (English)In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 60, no 2, p. 160-168Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Maternal infection during pregnancy (IDP) has been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. However, infection is associated with social adversity, poor living conditions and other background familial factors. As such, there is a need to rule out whether the observed association between maternal IDP and ADHD might be attributed to such confounding.

METHODS: This nationwide population-based cohort study using a family-based, quasi-experimental design included 1,066,956 individuals born in Sweden between 1992 and 2002. Data on maternal IDP (bacterial or viral) requiring hospitalization and ADHD diagnosis in offspring were gathered from Swedish National Registers, with individuals followed up through the end of 2009. Ordinary and stratified Cox regression models were used for estimation of hazard ratios (HRs) and several measured covariates were considered. Cousin- and sibling-comparisons accounted for unmeasured genetic and environmental factors shared by cousins and siblings.

RESULTS: In the entire population, maternal IDP was associated with ADHD in offspring (HR = 2.31, 95% CI = 2.04-2.61). This association was attenuated when accounting for measured covariates (HR = 1.86, 95% CI = 1.65-2.10). The association was further attenuated when adjusting for unmeasured factors shared between cousins (HR = 1.52, 95% CI = 1.12-2.07). Finally, the association was fully attenuated in sibling comparisons (HR = 1.03, 95% CI = 0.76-1.41).

CONCLUSIONS: This study suggests that the association between maternal IDP and offspring ADHD is largely due to unmeasured familial confounding. Our results underscore the importance of adjusting for unobserved familial risk factors when exploring risk factors for ADHD.

Place, publisher, year, edition, pages
Blackwell Publishing, 2019. Vol. 60, no 2, p. 160-168
Keywords [en]
Maternal infection during pregnancy, attention-deficit/hyperactivity disorder, cousin comparisons, familial confounding, quasi-experimental, sibling comparisons
National Category
Psychiatry Obstetrics, Gynecology and Reproductive Medicine Occupational Health and Environmental Health
Identifiers
URN: urn:nbn:se:oru:diva-68597DOI: 10.1111/jcpp.12959ISI: 000456605900005PubMedID: 30136726Scopus ID: 2-s2.0-85052396814OAI: oai:DiVA.org:oru-68597DiVA, id: diva2:1242071
Funder
Stockholm County CouncilThe Karolinska Institutet's Research FoundationSwedish Research Council
Note

Funding Agency:

Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM)  340-2013-5867

Available from: 2018-08-27 Created: 2018-08-27 Last updated: 2019-02-07Bibliographically approved

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Larsson, Henrik

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