Summary: The risk of ASD may increase slightly for every week a child is born before or after 40 weeks gestation.
A study of more than 3.5 million Nordic children suggests that the risk of autism spectrum disorder (ASD) may increase slightly for each week a child is born before or after 40 weeks of gestation. Martina Persson of the Karolinska Institutet in Stockholm, Sweden and colleagues present these findings in the open-access journal PLOS Medicine.
The causes of ASD are complex and remain unresolved, but they likely involve both genetic and environmental factors. Some previous research suggests that children born before or after their due dates (40 weeks of gestation) may have an elevated risk of ASD. However, most of those studies have been limited in scope and have not accounted for sex and birth weight.
To better understand potential links between gestational age and risk of ASD, Persson and colleagues analyzed medical registry data on more than 3.5 million children born in Sweden, Finland, or Norway between 1995 to 2015. Within that cohort, 1.44 percent of the children were diagnosed with ASD, and 4.7 percent were born pre-term — before 37 weeks of gestation.
The analysis, which covered gestational ages at birth ranging from 22 to 44 weeks, showed that overall risk of ASD was low for every age, especially for girls born post-term (after 42 weeks of gestation). However, the relative risk of ASD increased for each week of gestational age below or above 40 weeks.
Of the children born at term — in weeks 37 to 42 — 0.83 percent were diagnosed with ASD. The percentage was 1.67 for those born in weeks 22 to 31, 1.08 percent for weeks 32 to 36, and 1.74 for weeks 43 to 44. These differences in risk were independent of sex and birth weight for gestational age.
These findings provide new insights into the potential links between risk of ASD and gestational age at birth — which is potentially modifiable. More research will be needed to clarify these links and investigate whether they could lead to strategies to lower risk by addressing pre-term birth.
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Gestational age and the risk of autism spectrum disorder in Sweden, Finland, and Norway: A cohort study
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.