Associations between parity, age at childbirth, and later-life mortality in postmenopausal women mediated by premature menopause.

Abstract

We aimed to examine the long-term effects of parity, age at first childbirth, and age at last childbirth on mortality in postmenopausal women. The data were from the Women's Health Initiative involving 106,760 postmenopausal women. We used propensity score matching to create matched samples, where each exposure group was matched with a reference group based on their propensity scores. We employed multilevel Cox proportional hazard models to estimate hazard ratios and 95% confidence intervals to examine the associations of parity and age at childbirth with mortality. We conducted multiple mediation analyses to estimate the effects of potential mediators on the associations. Compared to parity of 2, the hazard ratios (95% confidence intervals) for the association of all-cause mortality with parity of 0, 1, 3, 4, and 5+ were 1.09 (1.05-1.13), 1.11 (1.06-1.16), 1.01 (0.99-1.04), 1.00 (0.97-1.03), and 1.00 (0.96-1.03), respectively. Age at first childbirth of <20, age at last childbirth of <25, and age at last childbirth ≥40 years were associated with increased mortality risks, with the corresponding hazard ratios (95% confidence intervals) of 1.14 (1.09-1.19), 1.06 (1.02-1.11), and 1.07 (1.00-1.15), respectively. Women with parity of 0, 4+, or age at first childbirth <25 years had shorter lifespans than the reference groups. Premature menopause was a pivotal mediator in the associations of parity and age at first childbirth with mortality. We found long-term adverse impacts of nulliparity and young age at first childbirth on women's mortality risk and lifespan. Premature menopause may operate as a critical intermediate between childbirth and later-life mortality, underscoring the importance to identify at-risk women early.