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

Autoři: Martina Persson aff001;  Signe Opdahl aff005;  Kari Risnes aff006;  Raz Gross aff008;  Eero Kajantie aff006;  Abraham Reichenberg aff003;  Mika Gissler aff013;  Sven Sandin aff001
Působiště autorů: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden aff001;  Department of Clinical Science and Education, Division of Pediatrics, Karolinska Institutet, Stockholm, Sweden aff002;  Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States of America aff003;  Seaver Autism Center for Research and Treatment at Mount Sinai, New York, United States of America aff004;  Department of Public Health and Nursing, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway aff005;  Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway aff006;  Department of Research and Development, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway aff007;  Division of Psychiatry, The Chaim Sheba Medical Center, Tel Hashomer, Israel aff008;  Department of Epidemiology and Preventive Medicine, Department of Psychiatry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel aff009;  Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki and Oulu, Finland aff010;  PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland aff011;  Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland aff012;  THL Finnish Institute for Health and Welfare, Information Services Department, Helsinki, Finland aff013;  University of Turku, Research Centre for Child Psychiatry, Turku, Finland aff014;  Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden aff015;  Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region aff016
Vyšlo v časopise: Gestational age and the risk of autism spectrum disorder in Sweden, Finland, and Norway: A cohort study. PLoS Med 17(9): e32767. doi:10.1371/journal.pmed.1003207
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003207



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.


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.

Author summary

Klíčová slova:

Autism spectrum disorder – Birth – Finland – Labor and delivery – Medical risk factors – Norway – Preterm birth – Sweden


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PLOS Medicine

2020 Číslo 9

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