Sex-specific associations between prenatal negative life events and birth outcomes

Maternal psychosocial stress can negatively impact gestational length and development of the fetus. These effects may be sex-specific but have not been extensively studied. The objective of this study was to examine the associations between prenatal maternal stress and birth outcomes and whether effects are modified by sex. Prenatal maternal stress was indexed by a maternal negative life events (NLEs) score ascertained in 527 urban mothers; a higher NLE score indicates greater stress. Birth outcomes included gestational age, preterm birth (PTB) (<37 weeks), and birthweight for gestational age z-scores. Modified Poisson regression and linear models were used to evaluate associations of prenatal NLE scores with birth outcomes. Sex differences were assessed by inclusion of an interaction term for sex by NLE score and in sex-stratified analyses. In analyses adjusted for maternal age, education, race/ethnicity, and pre-pregnancy body mass index (BMI), increasing prenatal stress was associated with shortened gestational age (days) (β = -0.63, [95% CI -1.20, -0.06]). This effect was sex specific, with increasing prenatal stress associated with shortened gestational age, as well as increased risk of PTB, in male infants (β = -1.35 [95% CI -2.17, -0.54] and RR = 1.18 [95% CI 0.99, 1.42], respectively) but not female infants (β = 0.15 [95%CI -0.63, 0.94] and RR = 0.85, [95%CI 0.65, 1.11], respectively). Prenatal stress was not associated with birthweight z-scores. Our results support the importance of psychosocial stress as a programming factor that may have sex-specific effects for adverse fetal outcomes. Understanding sex-specific effects of prenatal stress on birth outcomes may inform prevention strategies. LAY SUMMARY Higher stress experienced by mothers in pregnancy was associated with shorter length of pregnancy and the effect was stronger in male infants when compared to female infants.