Maternal Consumption of Artificially Sweetened Beverages in Pregnancies and Biomarkers of Fecundity in Adult Sons

Introduction: Maternal intake of artificial sweeteners in beverages (ASB) during pregnancy may have a programming effect on offspring health, including biomarkers of male fecundity. Objective: We investigated whether maternal intake of ASB during pregnancy was associated with biomarkers of male fecundity in adult sons. Materials and methods: In this cohort study, 880 young men from the Fetal Programming of Semen Quality cohort, nested within the Danish National Birth Cohort, were included. Information on maternal intake of ASB was collected via a food frequency questionnaire around gestational week 25 and categorized as: never, <1 serving/week, 1–<7 servings/week, and ≥1 serving/day. Outcomes included semen characteristics, average testicular volume, and reproductive hormone levels, collected at ages 18–21 years. A negative binomial regression model was applied to estimate relative differences (%) with 95% CIs in biomarkers by maternal ASB intake. Sensitivity, mediation, substitution, and dose-response analyses tested robustness and explored potential pathways. Results: We observed no consistent associations between maternal ASB intake and most biomarkers of male fecundity. Sons of mothers consuming ≥1 serving/day showed higher levels of spermatozoa with immature chromatin structure (18.1%; 95% CI: 3.8, 34.3) and a tendency toward higher DNA fragmentation (6.8%; 95% CI: −5.4, 20.5) compared with unexposed sons. Maternal ASB intake was not associated with testes volume or reproductive hormone levels. Conclusion: Our results showed subtle adverse tendencies in specific biomarkers of male fecundity in adult sons of mothers who consumed artificially sweetened beverages during pregnancy. These include lower sperm concentration, lower proportion of normal sperm morphology, and higher proportions of spermatozoa with immature chromatin structure and DNA fragmentation, showing some of the same tendencies as observed in animal studies, suggesting sweeteners may affect sperm DNA. However, findings are uncertain and do not indicate clear adverse effects.