G Huang1, S A Aroner2, C P Bay3, S E Gilman4,5, A Ghassabian6, E B Loucks7, S L Buka7, R J Handa8,9, B L Lasley10,11,12, S Bhasin13, J M Goldstein2,14. 1. Section of Men's Health, Aging and Metabolism, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ghuang7@bwh.harvard.edu. 2. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3. Center for Clinical Investigation, Brigham and Women's Hospital, Boston, MA, USA. 4. Social and Behavioral Sciences Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD, USA. 5. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 6. Departments of Pediatrics, Environmental Medicine, and Population Health, New York University School of Medicine, New York, NY, USA. 7. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA. 8. Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. 9. Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, USA. 10. Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, CA, USA. 11. Department of Obstetrics and Gynecology, School of Medicine, Center for Health and the Environment, University of California Davis, Davis, CA, USA. 12. Center for Health and the Environment, University of California, Davis, CA, USA. 13. Section of Men's Health, Aging and Metabolism, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 14. Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract
CONTEXT: In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN: We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS: Higher maternal androgen levels associated with lower BMIz at birth (β = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (β = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION: Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.
CONTEXT: In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN: We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS: Higher maternal androgen levels associated with lower BMIz at birth (β = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (β = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION: Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.
Entities:
Keywords:
Androgens; Body mass index; Childhood; Prenatal; Sex; Weight growth trajectory
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