Prenatal famine, birthweight, reproductive performance and age at menopause: the Dutch hunger winter families study.

STUDY QUESTION: Is there an association between acute prenatal famine exposure or birthweight and subsequent reproductive performance and age at menopause? SUMMARY ANSWER: No association was found between intrauterine famine exposure and reproductive performance, but survival analysis showed that women exposed in utero were 24% more likely to experience menopause at any age. WHAT IS KNOWN ALREADY: Associations between prenatal famine and subsequent reproductive performance have been examined previously with inconsistent results. Evidence for the effects of famine exposure on age at natural menopause is limited to one study of post-natal exposure. STUDY DESIGN, SIZE, DURATION: This cohort study included men and women born around the time of the Dutch famine of 1944-1945. The study participants (n = 1070) underwent standardized interviews on reproductive parameters at a mean age of 59 years. PARTICIPANTS/MATERIALS, SETTING,
METHODS: The participants were grouped as men and women with prenatal famine exposure (n = 407), their same-sex siblings (family controls, n = 319) or other men and women born before or after the famine period (time controls, n = 344). Associations of famine exposure with reproductive performance and menopause were analysed using logistic regression and survival analysis with competing risk, after controlling for family clustering. MAIN RESULTS AND THE ROLE OF CHANCE: Gestational famine exposure was not associated with nulliparity, age at birth of first child, difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At any given age, women were more likely to experience menopause after gestational exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was not attenuated with an additional control for a woman's birthweight. In this study, there was no association between birthweight and age at menopause after adjustment for gestational famine exposure. LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. The study power to examine associations with specific gestational periods of famine exposure and reproductive function was limited. WIDER IMPLICATIONS OF THE
FINDINGS: Our findings support previous results that prenatal famine exposure is not related to reproductive performance in adult life. However, natural menopause occurs earlier after prenatal famine exposure, suggesting that early life events can affect organ function even at the ovarian level. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the NHLBI/NIH (R01 HL-067914). TRIAL REGISTRATION NUMBER: Not applicable.