O-035 Prenatal exposure to parental smoking and infertility in sons and daughters: a cohort study

Study question Is prenatal exposure to parental smoking associated with an increased risk of infertility in adult sons and daughters? Summary answer Preliminary results indicated that prenatal exposure to parental smoking was not associated with an increased risk of infertility in adult sons and daughters. What is known already Intrauterine life seems to represent a particularly vulnerable period, predisposing individuals to diseases through exposure to harmful factors such as parental smoking. Parental smoking has been linked to higher risk of both short- and long-term reproductive outcomes including cryptorchidism, altered pubertal timing, reduced semen quality, miscarriages, and prolonged time-to-pregnancy in adult offspring. This study is the first to examine the potential association between prenatal exposure to parental smoking and infertility in offspring. The prevalence of infertility is notably high, making it an important outcome with major implications for both individuals and society. Study design, size, duration In this cohort study, we utilized data from the Healthy Habits for Two (HH42) birth cohort establish in 1984–1987 as part of a Danish health campaign. A total of 11,980 mothers participated (participation rate = 87%). Participants/materials, setting, methods The HH42 cohort includes 11,144 daughters and sons, representing the final study population. Mothers reported prenatal exposure to parental smoking around gestational week 36. Infertility among sons and daughters was assessed using ICD-10 codes for infertility and records of assisted reproductive technology (ART) usage, obtained from two registers. Associations were analyzed using Cox regression models, accounting for competing risks of infertility. To ensure comprehensive identification of male infertility, we included information on their female partners. Main results and the role of chance Preliminary results suggest that prenatal exposure to maternal smoking, paternal smoking, or parental smoking was not associated with a higher risk of infertility in adult sons and daughters. Adjusted hazard ratios for categorized maternal and paternal smoking, as well as dichotomized concomitant parental smoking, ranged from 0.6 to 1.3, with 95% confidence intervals overlapping 1, indicating results compatible with no association. Furthermore, no indications of dose-response relationships were observed. The analyses are not finalized, and results should be interpreted with caution. Final results will be presented at ESHRE 2025. In sub-analyses, we will restrict the study population to sons and daughters in a registered relationship, assuming that they are more likely to face potential fertility issues and thus be present in the registers. Furthermore, we will exclude sons and daughters who report voluntary childlessness, thereby limiting the analyses to individuals actively pursuing parenthood to enhance the precision of our outcome estimations. Additionally, we will investigate whether a potential social gradient in the use of ART could explain our findings by examining the socioeconomic status of the adult sons and daughters. Limitations, reasons for caution The study findings might be limited by insufficient power. Not all infertility cases might be captured in the registries. Furthermore, our study does not include non-ART treatments (intrauterine inseminations), as the IVF register did not record these types of treatments prior to 2007. Wider implications of the findings Our preliminary results do not align with previous literature suggesting that prenatal exposure to smoking negatively impacts offspring reproductive health. However, the potential for serious adverse effects of smoking during pregnancy underscores the continued recommendation of avoiding smoking. Trial registration number No