Maternal body mass index in early pregnancy and autism in offspring: a population-based cohort study in Sweden and Denmark

BACKGROUND: Elevated maternal pre-pregnancy body mass index (BMI) has been suggested to increase risk of offspring autism spectrum disorder (ASD) but evidence is mixed across heterogeneous studies and robust estimates spanning the full BMI range are lacking. This study examined the association between maternal BMI and offspring ASD in a harmonized, two-nation study and across the full BMI range. METHODS: We included all singleton children born in Denmark 2004-2018 and Sweden 1998-2019 to parents of Nordic origin (n = 2,072,445), with follow-up from age 2 until 31 December 2021, or 2022, respectively. Maternal BMI recorded at the first antenatal visit was obtained from the Swedish and Danish Medical Birth Registers and was analyzed as a continuous variable and in World Health Organization-defined categories of underweight (BMI < 18.5), normal weight (18.5-24.9), overweight (25-29.9), obese class I (30-34.9), and obese class II-III (≥ 35). The relative risk of ASD was estimated as hazard ratios (HR) from Cox regression models, adjusted for birth year and parental age, educational level, income, and psychiatric history at time of childbirth, using data from national health and population registers. Both country-specific and pooled analyses were conducted. Subgroup and sensitivity analyses, including a sibling comparison, were performed to address the specificity and robustness of findings. RESULTS: A total of 58,416 (2.8%) children were diagnosed with ASD during follow-up. The risk of ASD exhibited a J-shaped association with BMI, which gradually increased for mothers with both lower and higher BMI compared to BMI 22 (mid-normal range) (HR = 1.16 95% CI 1.06-1.27 for BMI 15, and HR = 1.50 95% CI 1.46-1.53 for BMI 30 in the fully adjusted model). Adjustment for familial factors in a sibling comparison attenuated associations. CONCLUSIONS: Both high and low maternal BMI are associated with an increased risk of ASD in the offspring. Familial factors, including genetic and environmental components consistent between siblings, may explain part of the association.