Maternal Testosterone and Offspring Birth Weight: A Mendelian Randomization Study

Abstract

Background Evidence showed maternal androgen levels in both healthy/general population and populations with hyperandrogenic disorders were inversely associated with offspring’s birth weight. We aimed to investigate the causal effect of maternal testosterone levels in general population on offspring’s birth weight and preterm delivery risk using two-sample Mendelian randomization (MR) method. Methods We obtained independent genetic instruments from a sex-specific genome wide association study with up to 230,454 females of European descent from UK biobank. Genetic instruments with consistent testosterone effects but no aggregate effect on sex-hormone binding globulin were used to perform the main analysis. Summary-level data of offspring’s birth weight with offspring's genotype adjusted was obtained from a study with 210,406 females of European descent. Summary-level data of preterm delivery was obtained from the FinnGen study (6,736 cases and 116,219 controls). Results MR analysis showed per standard deviation (0.62 nmol/L) increase in testosterone levels could reduce offspring's birth weight by 37.26 g (95% confidence interval = 19.59 g to 54.94 g, p = 3.62×10 -5). Per standard deviation increase in testosterone levels was also associated with an increased risk of preterm delivery (odds ratio = 1.329, 95% confidence interval = 1.161 to 1.520, p = 3.57×10 -5). Similar results were found in different MR methods and multivariable MR analyses. Conclusion This two-sample MR study showed genetically determined higher circulating testosterone levels in females from the general population were associated with low birth weight of offspring and increased risk of preterm delivery.

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Prenatal Cadmium Exposure and Maternal Sex Steroid Hormone Concentrations across Pregnancy

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