Mother’s stress in pregnancy linked to how her girl plays (Published in Neurotoxicology. January 2014)
Abstract: Previous research on humans and animal models suggests that exposure to prenatal stress not only affects fetal development, but can do so in different ways in males and females. Only one published study has prospectively examined the relationship between exposure to prenatal stress and gender-specific play behavior during childhood, finding masculinized play behavior in girls who experienced high prenatal life events stress, but no associations in boys. Here we examine this question in a second prospective cohort from the Study for Future Families. Pregnant women completed questionnaires on stressful life events during pregnancy, and those who reported one or more events were considered “high stress”. Families were recontacted several years later (mean age of index child: 4.9 years) , and mothers completed a questionnaire including the validated Preschool Activities Inventory (PSAI), which measures sexually dimorphic play behavior. In sex-stratified analyses, after adjusting for child’s age, parental attitudes towards gender-atypical play, age and sex of siblings, and other relevant covariates, girls (n=72) exposed to high prenatal life events stress had higher scores on the PSAI masculine sub-scale (β=3.48, p=0.006) and showed a trend towards higher (more masculine) composite scores (β=2.63, p=0.08). By contrast, in males (n=74), prenatal stress showed a trend towards associated with higher PSAI feminine sub-scale scores (β=2.23, p=0.10), but no association with masculine or composite scores. These data confirm previous findings in humans and animal models suggesting that prenatal stress may have androgenic effects on female fetuses and anti-androgenic effects on male fetuses.
Publication available from Science Direct: http://www.sciencedirect.com/science/article/pii/S0161813X13001927
Fetal exposure to antiandrogens alters androgen-sensitive development in male rodents, resulting in less male-typical behavior. Fetal phthalate exposure is also associated with male reproductive development in humans, but neurodevelopmental outcomes have seldom been examined in relation to phthalate exposure. To assess play behavior in relation to phthalate metabolite concentration in prenatal urine samples, we recontacted participants in the Study for Future Families whose phthalate metabolites had been measured in mid-pregnancy urine samples. Mothers completed a questionnaire including the Preschool Activities Inventory (PSAI), a validated instrument used to assess sexually dimorphic play behavior. We examined play behavior scores (masculine, feminine and composite) in relation to (log10) phthalate metabolite concentrations in mother’s urine separately for boys (N=74) and girls (N=71). Covariates (child’s age, mother’s age and education and parental attitude towards atypical play choices) were controlled using multivariate regression models. Concentrations of dibutyl phthalate (DBP) metabolites, mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP), and their sum, were associated with a decreased (less masculine) composite score in boys (regression coefficients -4.53, -3.61, and -4.20, p=0.01, 0.07 and 0.04 for MnBP, MiBP and their sum, respectively). Concentrations of two urinary metabolites of di(2-ethylhexyl) phthalate (DEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and the sum of these DEHP metabolites plus mono(2-ethylhexyl) phthalate were associated with a decreased masculine score (regression coefficients -3.29, -2.94, and -3.18, p=0.02, 0.04 and 0.04) for MEHHP, MEOHP, and the sum, respectively. No strong associations were seen between behavior and urinary concentrations of any other phthalate metabolites in boys, or between girls’ scores and any metabolites. These data, though based on a small sample, suggest that prenatal exposure to antiandrogenic phthalates may be associated with less male-typical play behavior in boys. Our findings suggest that these ubiquitous environmental chemicals have the potential to alter androgen-responsive brain development in humans.