Maternal pre-pregnancy BMI and reproductive health in adult sons: a study in the Danish National Birth Cohort.

STUDY QUESTION: Is maternal pre-pregnancy BMI associated with semen quality, testes volume, and reproductive hormone levels in sons? SUMMARY ANSWER: Maternal pre-pregnancy BMI was associated with an altered reproductive hormone profile in young adult sons, characterized by higher levels of oestradiol, LH, and free androgen index (FAI) and lower levels of sex hormone-binding globulin (SHBG) in sons born of mothers with pre-pregnancy overweight and obesity. WHAT IS KNOWN ALREADY: Evidence suggests that maternal pre-pregnancy BMI may influence reproductive health later in life. Only one pilot study has investigated the association between maternal pre-pregnancy BMI and reproductive health outcomes in sons, suggesting that a high BMI was associated with impaired reproductive function in the adult sons. STUDY DESIGN, SIZE, DURATION: A population-based follow-up study of 1058 young men from the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019, was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1058 adult sons (median age 19 years, 2 months), born 1998-2000 by mothers included in the DNBC, participated in FEPOS. At a clinical examination, they provided a semen and blood sample, measured their testes volume, and had height and weight measured. Maternal pre-pregnancy BMI was obtained by self-report in early pregnancy. Semen characteristics, testes volume, and reproductive hormone levels were analysed according to maternal pre-pregnancy BMI categories and as restricted cubic splines using negative binomial and ordinary least square regression models. Mediation analyses examined potential mediation by the sons' birthweight, pubertal timing, fat mass, and BMI. Additional analyses investigated the role of paternal BMI in the potential associations between maternal BMI and reproductive health outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: We found no consistent associations between maternal pre-pregnancy BMI and semen characteristics or testes volume. Sons of mothers with higher pre-pregnancy BMI had higher oestradiol and lower SHBG levels, both in a dose-dependent manner. Sons of mothers with pre-pregnancy obesity (≥30 kg/m2) had higher LH levels and a higher FAI than sons born by mothers with normal pre-pregnancy BMI (18.5-24.9 kg/m2). The mediation analyses suggested that the effect of maternal pre-pregnancy BMI on higher levels of oestrogen, LH, and FAI was partly mediated by the sons' birthweight, in addition to adult fat mass and BMI measured at the clinical examination, whereas most of the effect on lower levels of SHBG was primarily mediated by the sons' own fat mass and BMI. Paternal BMI was not a strong confounder of the associations in this study. LIMITATIONS, REASONS FOR CAUTION: This study was based in a population-based cohort with a low prevalence of overweight and obesity in both mothers and adult sons. Some men (10%) had blood for reproductive hormone assessment drawn in the evening. While several potential confounding factors were accounted for, this study's inherent risk of residual and unmeasured confounding precludes provision of causal estimates. Therefore, caution should be given when interpreting the causal effect of maternal BMI on sons' reproductive health. WIDER IMPLICATIONS OF THE FINDINGS: Given the widespread occurrence of overweight and obesity among pregnant women, it is imperative to thoroughly examine the potential consequences for reproductive hormone levels in adult sons. The potential effects of maternal pre-pregnancy obesity on sons' reproductive hormone profile may potentially be partly avoided by the prevention of overweight and obesity in the sons. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University, Independent Research Fund Denmark (9039-00128B), and the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal alcohol intake in early pregnancy and biomarkers of fecundity in adult sons: A cohort study.

Male fecundity may be largely determined through fetal programming and therefore potentially be sensitive to exposure to maternal alcohol intake during pregnancy. We investigated whether maternal alcohol intake in early pregnancy was associated with biomarkers of fecundity in adult sons. In total, 1058 sons from the Fetal Programming of Semen Quality (FEPOS) cohort nested in the Danish National Birth Cohort (DNBC) provided blood and semen samples at around 19 years of age. Information on maternal weekly average alcohol intake (0 drinks [ref], >0-1 drinks, >1-3 drinks, >3 drinks) and binge drinking episodes (intake of ≥5 drinks on one occasion: (0 [ref], 1-2, ≥3 episodes)) was self-reported at around gestational week 17. Outcomes included semen characteristics, testes volume and reproductive hormones. We found some small tendencies towards lower semen characteristics and an altered hormone level profile in sons of mother who had an intake of > 3 drinks/week in early pregnancy and sons of mother who had ≥ 3 episodes of binge drinking in pregnancy. However, the effect estimates were overall small and inconsistent and with no indication of a dose dependent association. Due to the limited number of mothers with a high weekly alcohol intake, we cannot exclude whether prenatal exposure to higher doses than 4.5 drinks/week of alcohol in early pregnancy might have a detrimental effect on the biomarkers of fecundity in adult sons..