1. Fetal sex effects on maternal health can now be tested via randomization: A first-in-class illustration in cows on glucoregulatory outcomes.
- Author
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Suarez-Trujillo A, Vorland CJ, Nicholls GT, Chusyd DE, Parker C, Golzarri-Arroyo L, Swann S, Funnell BJ, Stewart KR, and Allison DB
- Subjects
- Animals, Cattle physiology, Female, Pregnancy, Male, Insulin blood, Glucose Tolerance Test veterinary, Random Allocation, Maternal Health, Fetus physiology, Blood Glucose
- Abstract
Background: The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship., Objective: To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes., Methods: Holstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose tolerance test was performed 30 days before the expected calving day. The primary outcome was insulin area under the curve (AUC), and secondary outcomes were clearance rate, half-life, and AUC for glucose, insulin, and non-esterified fatty acid concentrations. An intention-to-treat (ITT) approach using multiple imputation was employed for primary analysis, and an as-treated (AT) approach was used for secondary analysis., Results: We demonstrated that we could successfully randomize the assignment of fetal sex to dams and test for causal effects of fetal sex on glucoregulatory outcomes using dairy cows as a model. Insulin AUC was not statistically different between groups (ITT p = 0.857, AT p = 0.874), and other outcomes were also not statistically different (p > 0.05)., Conclusion: We demonstrated that causal effects of fetal sex on maternal outcomes can be causally tested in dairy cows. Our study did not provide statistical evidence to support an effect of fetal sex on maternal glucose-related outcomes., Competing Interests: Declaration of competing interest In the last thirty-six months, Dr. Allison has received personal payments or promises for same from: Novo Nordisk Fonden; and Zero Longevity Science (as stock options). Donations to a foundation have been made on his behalf by the Northarvest Bean Growers Association. Dr. Allison's institution, Indiana University, and the Indiana University Foundation have received funds or donations to support his research or educational activities from: Eli Lilly and Company; National Cattlemen's Beef Association; Pfizer, Inc.; Soleno Therapeutics; The Morris Animal Foundation; USDA Agricultural Research Service; WW (formerly Weight Watchers); and numerous other for-profit and non-profit organizations to support the work of the School of Public Health and the university more broadly. All other authors report no disclosures in the last 36 months related to the topic of this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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