Are there sex differences in fetal growth strategies and in the long-term effects of pregnancy complications on cognitive functioning?

Abstract

Males and females have been proposed to have different prenatal growth strategies, whereby males invest more in fetal growth and less in placental development, leaving them more susceptible to early-life adversity. We tested predictions of this hypothesis using data from the National Collaborative Perinatal Project. Male newborns were heavier than females, but there was no difference in placental weight, adjusting for birthweight. Among infants born prior to 33 weeks, the difference in birthweight between males and females was greater among those who did not survive than among those who did, potentially reflecting a strategy whereby males maintained growth in the face of prenatal insults, while females adjusted growth. However, there was no significant difference in mortality between the sexes. Being born small-for-gestational age or very preterm (prior to 33 weeks) was associated with significantly reduced performance for most of the cognitive traits examined at 7 years, although maternal preeclampsia was associated with reduced performance in fewer traits. Generally, these effects of early-life adversity (poor fetal growth, prematurity, and preeclampsia) did not differ between the sexes. However, analyzing the sexes separately (rather than testing the interaction between sex and adversity) resulted in numerous spurious sex-specific effects, whereby the effect of early-life adversity appeared to be significant in one sex but not the other. Overall, we found little support for the hypothesis that males prioritize growth more than females, and that this makes them more susceptible to early-life adversity. Furthermore, our results show that analyzing the sexes separately, rather than testing the adversity by sex interaction, can be highly misleading.

Sex-based disparities in DNA methylation and gene expression in late-gestation mouse placentas

“…These findings align with existing evidence-primarily based on meta-analyses of human pregnanciesconsistently indicating that male fetuses have higher susceptibility to pregnancy complications such as gestational diabetes, premature membrane rupture, preterm birth, and macrosomia (8)(9)(10)(11)(12)(13)(14). Males also exhibit a higher prevalence of neurodevelopmental disorders, including dyslexia and attention deficit hyperactivity disorder.…”

“…Recent studies demonstrate that the placenta has sex-specific responses to certain stimuli or perturbations, which influence their impacts on the embryo (6–8). These findings align with existing evidence—primarily based on meta-analyses of human pregnancies—consistently indicating that male fetuses have higher susceptibility to pregnancy complications such as gestational diabetes, premature membrane rupture, preterm birth, and macrosomia (8–14). Males also exhibit a higher prevalence of neurodevelopmental disorders, including dyslexia and attention deficit hyperactivity disorder, which may be influenced by placental dysfunction and adaptations to diverse pregnancy conditions (6).…”

In the pandemic from the womb. Prenatal exposure, maternal psychological stress and mental health in association with infant negative affect at 6 months of life

“…All associations in the model were controlled for the confounding effects of gestational age at t0 (Rouse & Goodman, 2014), maternal age and family socioeconomic status (e.g., family income; Hendry et al, 2022). Regression on the infant negative affect variable also controlled for the child's sex (Christians & Chow, 2022).…”

Gastrulation‐stage alcohol exposure induces similar rates of craniofacial malformations in male and female C57BL/6J mice

“…Similar effects have been observed in humans. While males are often heavier than females at birth in healthy human pregnancies (Christians & Chow, 2022), the growth difference between male and female infants is exacerbated in response to prenatal or perinatal insults, with females demonstrating reduced growth rates compared to the males, (Christians & Chow, 2022). This effect is similar to what has been reported in children with FASD: females exhibit reduced growth rates and physical symptoms of FASD, while males show greater neurodevelopmental impairments during childhood (Flannigan et al, 2023; Philip A May et al, 2017a, 2017b).…”