Fetal sex modifies the effect of maternal macronutrient intake on the incidence of small-for-gestational-age births: a prospective observational cohort study.

Background: Maternal macronutrient intake is likely to play a pivotal role in fetoplacental growth. Male fetuses grow faster and their growth is more responsive to maternal size. Objective: We assessed the role of fetal sex in modifying the effect of maternal macronutrient intake on the risk of small-for-gestational-age (SGA) birth. Design: This was a prospective, observational cohort study of 2035 births from an urban South Asian Indian population. Maternal intakes of total energy and macronutrients were recorded by validated food-frequency questionnaires. The interaction of trimester 1 macronutrient intake with fetal sex was tested on the outcome of SGA births. Results: The prevalence of SGA was 28%. Trimester 1 macronutrient composition was high in carbohydrate and low in fat (means ± SDs-carbohydrate: 64.6% ± 5.1%; protein: 11.5% ± 1.1%; and fat: 23.9% ± 4.4% of energy). Higher carbohydrate and lower fat consumption were each associated with an increased risk of SGA [adjusted OR (AOR) per 5% of energy (95% CI): carbohydrate: 1.15 (1.01, 1.32); fat: 0.83 (0.71, 0.97)] specifically among male births (males: n = 1047; females: n = 988). Dietary intake of >70% of energy from carbohydrate was also associated with increased risk (AOR: 1.67; 95% CI: 1.00, 2.78), whereas >25% of energy from fat intake was associated with decreased risk (AOR: 0.61; 95% CI: 0.41, 0.90) of SGA in male births. Conclusions: Higher carbohydrate and lower fat intakes early in pregnancy were associated with increased risk of male SGA births. Therefore, we speculate that fetal sex acts as a modifier of the role of maternal periconceptional nutrition in optimal fetoplacental growth.