Am J Epidemiol. 2022 Mar 24;191(5):775-786. doi: 10.1093/aje/kwab301.
Suboptimal pregnancy conditions may affect ovarian development in the fetus and be associated with early natural menopause (ENM) for offspring. A total of 106,633 premenopausal participants in Nurses' Health Study II who provided data on their own prenatal characteristics, including diethylstilbestrol (DES) exposure, maternal cigarette smoking exposure, multiplicity, prematurity, and birth weight, were followed from 1989 to 2017. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of in utero exposures with ENM. During 1.6 million person-years of follow-up, 2,579 participants experienced ENM. In multivariable models, women with prenatal DES exposure had higher risk of ENM compared with those without it (HR = 1.33, 95% CI: 1.06, 1.67). Increased risk of ENM was observed for those with low (<5.5 pounds (<2.5 kg)) versus normal (7.0-8.4 pounds (3.2-3.8 kg)) birth weight (HR = 1.21, 95% CI: 1.01, 1.45). Decreasing risk was observed per 1-pound (0.45-kg) increase in birth weight (HR = 0.93, 95% CI: 0.90, 0.97). Prenatal smoking exposure, being part of a multiple birth, and prematurity were not associated with ENM. In this large cohort study, lower birth weight and prenatal DES exposure were associated with higher risk of ENM. Our results support a need for future research to examine in utero exposures that may affect offspring reproductive health.
不良的妊娠条件可能会影响胎儿的卵巢发育，并与后代的早期自然绝经（ENM）有关。共有 106633 名参加护士健康研究 II 的绝经前参与者提供了自己的产前特征数据，包括己烯雌酚（DES）暴露、母亲吸烟暴露、多胎、早产和出生体重，并在 1989 年至 2017 年期间进行了随访。使用 Cox 回归模型来估计宫内暴露与 ENM 相关的风险比（HR）和 95%置信区间（CI）。在 160 万人年的随访期间，2579 名参与者经历了 ENM。在多变量模型中，与未暴露于 DES 的女性相比，产前暴露于 DES 的女性发生 ENM 的风险更高（HR=1.33，95%CI：1.06，1.67）。与出生体重正常（7.0-8.4 磅（3.2-3.8 千克））相比，出生体重低（<5.5 磅（<2.5 千克））的女性发生 ENM 的风险增加（HR=1.21，95%CI：1.01，1.45）。每增加 1 磅（0.45 千克）体重，风险就会降低（HR=0.93，95%CI：0.90，0.97）。产前吸烟暴露、多胎妊娠和早产与 ENM 无关。在这项大型队列研究中，较低的出生体重和产前 DES 暴露与更高的 ENM 风险相关。我们的研究结果支持未来需要研究可能影响后代生殖健康的宫内暴露。
