Maternal body mass index during early pregnancy, gestational weight gain, and risk of autism spectrum disorders: Results from a Swedish total population and discordant sibling study

Background: Prenatal environmental factors such as maternal adiposity may influence the risk of offspring autism spectrum disorders (ASD), though current evidence is inconsistent. The objective of this study was to assess the relationship of parental BMI and gestational weight gain (GWG) with risk of offspring ASD in a population-based cohort study using family-based study designs. Methods: The cohort was based in Stockholm County, Sweden, including 333 057 individuals born 1984-2007, of whom 6420 were diagnosed with an ASD. We evaluated maternal body mass index (BMI) at first antenatal visit, GWG and paternal BMI at the time of conscription into the Swedish military as exposures using general estimating equation (GEE) models with logit link. Results: At the population level, maternal overweight/obesity was associated with increased risk of offspring ASD [odds ratio (OR)_{25 ≤ BMI < 30} 1.31, 95% confidence interval =1.21-1.41; OR_{BMI ≥ 30} 1.94, 1.72-2.17], as was paternal underweight (OR_{BMI < 18.5}, 1.19, 1.06-1.33) and obesity (OR_{BMI ≥ 30} 1.47, 1.12-1.92) in mutually adjusted models. However, in matched sibling analyses, the relationship between elevated maternal BMI and ASD risk was not apparent. GWG had a U-shaped association with offspring ASD at the population level (OR_insufficient 1.22, 1.07-1.40; OR_excessive 1.23, 1.08-1.40). Matched sibling analyses were suggestive of elevated risk with excessive GWG (OR_insufficient 1.12, 0.68-1.84; OR_excessive 1.48, 0.93-2.38). Conclusions: Whereas population-level results suggested that maternal BMI was associated with ASD, sibling analyses and paternal BMI analyses indicate that maternal BMI may also be a proxy marker for other familial risk factors. Evidence is stronger for a direct link between GWG and ASD risk.