Association between self-reported caffeine intake during pregnancy and social responsiveness scores in childhood: The EARLI and HOME studies

Abstract

Maternal nutrition during gestation has been investigated for its role in child neurodevelopment. However, little is known about the potential impact of gestational caffeine exposure on child autistic behaviors. Here, we assess the relation between maternal caffeine intake during pregnancy and children's behavioral traits related to Autism Spectrum Disorder (ASD). We harmonized data from two pregnancy cohorts, Early Autism Risk Longitudinal Investigation (EARLI) (n = 120), an enriched-risk cohort of mothers who previously had a child with ASD, from Pennsylvania, Maryland, and Northern California (2009-2012), and the Health Outcomes and Measures of the Environment (HOME) Study (n = 269), a general population cohort from Cincinnati, Ohio (2003-2006). Mothers self-reported caffeine intake twice during pregnancy. Caregivers reported child behavioral traits related to ASD using the Social Responsiveness Scale (SRS) when children were aged 3-8 years. Higher scores indicate more ASD-related behaviors. We estimated covariate-adjusted differences in continuous SRS T-scores per interquartile range increase in caffeine intake. Self-reported caffeine intake during pregnancy was positively associated with SRS T-scores among children in EARLI (β: 2.0; 95% CI -0.1, 4.0), but to a lesser extent in HOME (β: 0.6; 95% CI -0.5, 1.6). In HOME, pre-pregnancy body mass index (BMI) modified the association between caffeine intake and SRS T-scores, where more positive associations were observed among women with higher BMIs. Our findings suggest gestational caffeine intake may represent a marker of vulnerability to childhood ASD-related behaviors. Additional studies are warranted to extend these findings.

Fig 1. Adjusted mean child SRS total T-scores at ages three to eight by maternal self-reported caffeine intake during pregnancy, derived from a natural spline: The EARLI and HOME studies.

SRS: Social Responsiveness Scale, EARLI: Early Autism Longitudinal Investigation, HOME: Health Outcomes and Measures of the Environment. Adjusted for maternal age (continuous), maternal race (white vs non-white), income (<$30,000 vs $30,000-$75,000, ≥$75,000), parity (continuous), and log10 –transformed urine/serum cotinine concentrations (continuous). Note cotinine concentrations were ascertained from maternal urine in EARLI and serum in HOME. Bands are the 95% confidence intervals.

Fig 2. Adjusted differences in children’s SRS T-score at ages three to eight per IQR increase in self-reported caffeine intake during pregnancy stratified by maternal pre-pregnancy BMI category: The EARLI and HOME studies.

SRS: Social Responsiveness Scale, EARLI: Early Autism Longitudinal Investigation, HOME: Health Outcomes and Measures of the Environment, IQR: Interquartile Range, BMI: Body mass index. Adjusted for maternal age (continuous), maternal race (white vs non-white), income (<$30,000 vs $30,000-$75,000, ≥$75,000), parity (continuous), and log10 –transformed urine/serum cotinine concentrations (continuous). Note cotinine concentrations were ascertained from maternal urine in EARLI and serum in HOME. Positive coefficients for SRS indicate that maternal caffeine intake is associated with more deficits in social responsiveness traits. Normal/Underweight: BMI <25, Overweight: BMI ≥25<30, and Obese BMI ≥30.