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Association of Maternal Autoimmune Diseases with Risk of Mental Disorders in Offspring in Denmark

Association of Maternal Autoimmune Diseases with Risk of Mental Disorders in Offspring in Denmark

Title: Association of Maternal Autoimmune Diseases with Risk of Mental Disorders in Offspring in Denmark
Author: He, Hua
Yu, Yongfu
Liew, Zeyan
Gissler, Mika
László, Krisztina D.
Valdimarsdóttir, Unnur Anna
Zhang, Jun
Li, Fei
Li, Jiong
Date: 2022-04-01
Language: English
Scope: 1157034
Department: Faculty of Medicine
Series: JAMA network open; 5(4)
ISSN: 2574-3805
DOI: 10.1001/jamanetworkopen.2022.7503
Subject: Adolescent; Adult; Arthritis, Rheumatoid/complications; Attention Deficit Disorder with Hyperactivity/epidemiology; Child, Preschool; Cohort Studies; Denmark/epidemiology; Diabetes Mellitus, Type 1/complications; Female; Humans; Infant; Male; Mothers; Pregnancy; Prenatal Exposure Delayed Effects/epidemiology; Medicine (all)
URI: https://hdl.handle.net/20.500.11815/3887

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He , H , Yu , Y , Liew , Z , Gissler , M , László , K D , Valdimarsdóttir , U A , Zhang , J , Li , F & Li , J 2022 , ' Association of Maternal Autoimmune Diseases with Risk of Mental Disorders in Offspring in Denmark ' , JAMA network open , vol. 5 , no. 4 , pp. E227503 . https://doi.org/10.1001/jamanetworkopen.2022.7503


Importance: Maternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood. Objective: To investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood. Design, Setting, and Participants: This population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021. Exposures: Maternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register. Main Outcomes and Measures: The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders. Results: Of the 2254234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05-1.36]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-1.21), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08-1.36] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]). Conclusions and Relevance: In this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.


Funding Information: László); grants 19410713500 and 2018SHZDZX01 from the Science and Technology Commission of Shanghai Municipality (Dr F. Li); grants GWV-10.1-XK07, 2020CXJQ01, and 2018YJRC03 from the Shanghai Municipal Commission of Health and Family Planning (Dr F Li); and grant 2018B030335001 from the Guangdong Key Project (Dr F Li) . Funding Information: Funding/Support: This study was supported by grant NNF18OC0052029 from the Novo Nordisk Foundation (Dr J. Li) ; grants DFF-6110-00019B, DFF-9039-00010B, and DFF-1030-00012B from the Danish Council for Independent Research (Dr J. Li); grant R275-A15770 from the Nordic Cancer Union (Dr J. Li); grant 2016 from the Karen Elise Jensens Fond (Dr J. Li); grants 81761128035, 81930095, and 82125032 (Dr F. Li) and grant 82073570 (Dr J. Li) from the National Natural Science Foundation of China; grant 20180306 from the Swedish Heart and Lung Foundation (Dr László); grant 2015-00837 from the Swedish Council for Working Life and Social Research (Dr Publisher Copyright: © 2022 American Medical Association. All rights reserved.

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