Exercise During the First Trimester and Infant Size at Birth: Targeted Maximum Likelihood Estimation of the Causal Risk Difference

This cohort study sought to estimate the differences in risk of delivering infants who were small or large for gestational age (SGA or LGA, respectively) according to exercise during the first trimester of pregnancy (vs. no exercise) among 2,286 women receiving care at Kaiser Permanente Northern California in 2013-2017. Exercise was assessed by questionnaire. SGA and LGA were determined by the sex- and gestational-age-specific birthweight distributions of the 2017 US Natality file. Risk differences were estimated by targeted maximum likelihood estimation, with and without data-adaptive prediction (machine learning). Analyses were also stratified by prepregnancy weight status. Overall, exercise at the cohort-specific 75th percentile was associated with an increased risk of SGA of 4.5 (95% CI: 2.1, 6.8) per 100 births, and decreased risk of LGA of 2.8 (95% CI: 0.5, 5.1) per 100 births; similar findings were observed among the underweight and normal-weight women, but no associations were found among those with overweight or obesity. Meeting Physical Activity Guidelines was associated with increased risk of SGA and decreased risk of LGA but only among underweight and normal-weight women. Any vigorous exercise reduced the risk of LGA in underweight and normal-weight women only and was not associated with SGA risk.