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. 2025 Jul:107:61-67.
doi: 10.1016/j.annepidem.2025.05.011. Epub 2025 May 24.

Association of preconception maternal glucocorticoid concentrations with sex ratio at birth: Evidence from a prospective cohort study

Mihret Melaku  1 , Diana L Juvinao-Quintero  2 , Sixto E Sanchez  3 , Marta B Rondon  4 , Clemens Kirschbaum  5 , Michelle A Williams  6 , Bizu Gelaye  7
Affiliations

Association of preconception maternal glucocorticoid concentrations with sex ratio at birth: Evidence from a prospective cohort study

Mihret Melaku et al. Ann Epidemiol. 2025 Jul.

Abstract

Purpose: To examine the association between maternal preconception glucocorticoid concentrations and the sex ratio at birth (SRB).

Methods: We analyzed data from 1106 pregnant women in a birth cohort study in Lima, Peru, focusing on singleton live births with complete data for preconception glucocorticoids, newborn sex, and covariates. Hair samples of 6 cm were collected in the first trimester and analyzed using LC-MS/MS to extract cortisol (HCC) and cortisone concentrations (HCNC) from the 3-6 cm hair segment. Baseline maternal characteristics were described using descriptive statistics. Unadjusted and adjusted Poisson regressions assessed associations between preconception glucocorticoids and newborn sex.

Results: Most of the samples were Mestizos, multiparous, and married women. The observed SRB was 0.52 (576 males out of 1106 total births). Adjusted regressions revealed an association between higher preconception HCC and an 8 % reduction in male births (95 % CI = 0.85, 0.99). Quartile comparisons showed a 13 % decline in male births in the highest versus the lowest quartile of preconception HCC, with similar trends seen for HCNC.

Conclusion: The observed SRB aligns with global averages, and the inverse relationship between preconception cortisol levels and male births supports prior evidence linking maternal stress to SRB variation. This study underscores the potential role of maternal stress and hypothalamic-pituitary-adrenal axis function in influencing reproductive outcomes.

Keywords: Hair glucocorticoids; Maternal stress; Pregnancy; Reproductive outcomes; Sex ratio at birth.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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