University of Oulu

Persson M, Opdahl S, Risnes K, Gross R,Kajantie E, Reichenberg A, et al. (2020) Gestational age and the risk of autism spectrum disorder in Sweden, Finland, and Norway: A cohort study. PLoS Med 17(9):e1003207.

Gestational age and the risk of autism spectrum disorder in Sweden, Finland, and Norway : a cohort study

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Author: Persson, Martina1,2,3,4; Opdahl, Signe5; Risnes, Kari6,7;
Organizations: 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
2Department of Clinical Science and Education, Division of Pediatrics, Karolinska Institutet, Stockholm, Sweden
3Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States of America
4Seaver Autism Center for Research and Treatment at Mount Sinai, New York, United States of America
5Department of Public Health and Nursing, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway
6Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway
7Department of Research and Development, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
8Division of Psychiatry, The Chaim Sheba Medical Center, Tel Hashomer, Israel
9Department of Epidemiology and Preventive Medicine, Department of Psychiatry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
10Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki and Oulu, Finland
11PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
12Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
13THL Finnish Institute for Health and Welfare, Information Services Department, Helsinki, Finland
14University of Turku, Research Centre for Child Psychiatry, Turku, Finland
15Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
16Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Public Library of Science, 2020
Publish Date: 2020-12-03


Introduction: The complex etiology of autism spectrum disorder (ASD) is still unresolved. Preterm birth (<37 weeks of gestation) and its complications are the leading cause of death of babies in the world, and those who survive often have long-term health problems. Length of gestation, including preterm birth, has been linked to ASD risk, but robust estimates for the whole range of gestational ages (GAs) are lacking. The primary objective of this study was to provide a detailed and robust description of ASD risk across the entire range of GAs while adjusting for sex and size for GA.

Methods and findings: Our study had a multinational cohort design, using population-based data from medical registries in three Nordic countries: Sweden, Finland, and Norway. GA was estimated in whole weeks based on ultrasound. Children were prospectively followed from birth for clinical diagnosis of ASD. Relative risk (RR) of ASD was estimated using log-binomial regression. Analyses were also stratified by sex and by size for GA. The study included 3,526,174 singletons born 1995 to 2015, including 50,816 (1.44%) individuals with ASD. In the whole cohort, 165,845 (4.7%) were born preterm. RR of ASD increased by GA, from 40 to 24 weeks and from 40 to 44 weeks of gestation. The RR of ASD in children born in weeks 22–31, 32–36, and 43–44 compared to weeks 37–42 were estimated at 2.31 (95% confidence interval [CI] 2.15–2.48; 1.67% vs 0.83%; p-value < 0.001), 1.35 (95% CI 1.30–1.40; 1.08% vs 0.83%; p-value < 0.001), and 1.37 (95% CI 1.21–1.54; 1.74% vs 0.83%; p-value < 0.001), respectively. The main limitation of this study is the lack of data on potential causes of pre- or postterm birth. Also, the possibility of residual confounding should be considered.

Conclusion: In the current study, we observed that the RR of ASD increased weekly as the date of delivery diverged from 40 weeks, both pre- and postterm, independently of sex and size for GA. Given the unknown etiology of ASD and the lifelong consequences of the disorder, identifying groups of increased risk associated with a potentially modifiable risk factor is important.

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Series: PLoS medicine
ISSN: 1549-1277
ISSN-E: 1549-1676
ISSN-L: 1549-1277
Volume: 17
Issue: 9
Article number: e1003207
DOI: 10.1371/journal.pmed.1003207
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Copyright information: © 2020 Persson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,provided the original author and source are credited.