Maternal Pre-Pregnancy BMI and Pregnancy Weight Gain in Relation to Autism Spectrum Disorder (ASD) in Offspring

Background: A handful of studies have examined the relationship of maternal pre-pregnancy weight or body mass index (BMI) and weight gain during pregnancy to ASD in offspring, producing inconsistent results. Further examination is important for distinguishing associations and teasing apart potential mechanisms.

Objectives: Examine the relationship of maternal pre-pregnancy BMI and weight gain during pregnancy, as well as their combination, with a diagnosis of ASD in the offspring.

Methods: The Study to Explore Early Development (SEED) is a multi-site, case-control study of children born in 2003-2006 designed to characterize ASD and examine a variety of risk factors.  Children were enrolled at ages 2-5 and classified based on pre-study diagnosis, a maternal screening questionnaire (SCQ), and in-person developmental evaluations of the child, into three study groups; 1) children with ASD (n=696), 2) children with other developmental delays (DD) (n=987), and 3) a population-based control group selected from birth certificates (POP) (n=887). Maternal height, pre-pregnancy weight, and gestational weight gain were obtained from maternal interview conducted 2-5 years post-partum, as measured weights were not available. Three primary weight “exposures” were examined: 1) Pre-pregnancy BMI classified as underweight (<18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥30 kg/m²). Weight gain assessed by 2) comparing upper and lower deciles to the middle 60%, and by 3) a combined variable using IOM/ACOG weight-gain-by-initial BMI recommendations, which are categorized as “Below”, “Meets” or “Exceeds” recommendations. Chi-square values were used to assess the distributions across the study groups. Odds ratios adjusting (AOR) for maternal age, race/ethnicity, education, and parity were calculated by multivariable logistic regression models for these weight variables separately, comparing the ASD or DD groups to the POP group.

Results: The distribution of all three maternal weight variables varied significantly across study groups; about 19% of mothers of children with ASD or DD were obese pre-pregnancy, compared to 13% of POP mothers (p<0.001), and more mothers of children with ASD exceeded IOM weight gain recommendations (47%) than DD or POP mothers (42%), while more mothers of DD children gained below recommendations (21% vs. 16% of ASD or POP) (p=0.006). After adjustment, associations for ASD vs. POP were not significant for maternal obesity (AOR 1.29, 95%CI 0.95-1.74), but were for weight gain in the upper decile (≥55 lbs.; AOR=1.57, 95%CI 1.10-2.24) and in the Exceeds IOM-recommended weight gain (AOR=1.27, 95%CI=1.01-1.61). Examining DD (vs. POP), maternal overweight and obesity were significantly associated after adjustment (AORs =1.37, 95%CI 1.08-1.73 and 1.50, 95%CI 1.14-1.98, respectively), but neither weight gain variable was significantly associated.

Conclusions: To our knowledge, ours is the first study of ASD to examine pregnancy weight gain categories taking pre-pregnancy BMI into account. Results indicate ASD was associated with such weight gain measures, but only marginally associated with maternal obesity, while DD was associated with both maternal obesity and overweight but not weight gain. Additional sensitivity analyses will determine whether differences persist. They might yield clues to the influence of timing of excess weight, which may affect neurodevelopment via metabolic/hormonal or immunologic pathways.