Sex-specific associations between second-trimester maternal cortisol and neonatal outcomes in island and mainland populations.

BACKGROUND

Maternal psychosocial stress during pregnancy has been associated with long-term developmental and metabolic consequences in offspring. Cortisol, a primary stress hormone, plays a central role in this process, and its levels may be influenced by environmental factors, such as geographic isolation. The aim of this study was to investigate the association between place of residence (islands or mainland) and newborn-sex on maternal cortisol levels (as a physiological indicator of stress) and neonatal anthropometry in the first Croatian Islands' Birth Cohort Study (CRIBS).

METHODS

A total of N = 337 pregnant women from the CRIBS cohort were included: N = 188 residing on islands and N = 149 residing on the mainland. Maternal plasma cortisol levels were measured during the second trimester using High performance liquid chromatography (HPLC). Anthropometry and cortisol data were analyzed using appropriate parametric and non-parametric tests, two-way ANOVA or ANCOVA for group comparisons, and mixed-effects modeling for repeated measures.

RESULTS

Pre- and post- pregnancy BMI values were elevated in women residing on the islands in comparison to women residing on the mainland. Cortisol levels, birth weight, birth length, and head circumference were influenced by newborn sex. Mothers carrying female offspring had higher cortisol levels and their offspring lower developmental outcomes, with greater differences observed among island residents for birth weight and length.

CONCLUSION

Fetal sex and environmental context (mainland vs. island) influence maternal HPA axis regulation and early developmental outcomes, suggesting that island residents may experience unique stressors related to their environment. Sex-specific associations in maternal cortisol and neonatal growth highlight the importance of considering fetal sex in studies of prenatal stress biology. Future work should clarify how geographic isolation influences prenatal stress biology and identify actionable risks to improve maternal and child health.