Larger differences in parental age were associated with increased risk of spontaneous abortion: A population-based retrospective cohort study among 11 million Chinese planned pregnancies.

OBJECTIVE

To assess the association between parental age differences (PAD) and the risk of spontaneous abortion (SAB).

METHODS

A large-scale population-based retrospective cohort study was conducted on women aged 20-49 years who participated in the National Free Pre-pregnancy Check-ups Project and became pregnant during 2010-2018. PAD was defined as paternal age minus maternal age. To overcome the perfect collinearity between PAD and parental ages, we employed a two-stage instrumental variable approach. In the first stage, county-level average paternal and maternal ages were used as instruments to predict individual parental ages. In the second stage, inverse probability weighting based on generalized linear mixed models (GLMM) with county-level random intercepts was employed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for SAB associated with PAD, adjusting for the predicted parental ages and a comprehensive set of covariates. Generalized additive mixed models (GAMM) with penalized splines were used to explore nonlinear exposure-response relationship.

RESULTS

The overall incidence of SAB was 2.60%. Compared with couples with no age difference (PAD=0 years), the ORs for SAB were 1.93 (95% CI: 1.68-2.21) for a PAD of < -10 years, 1.27 (1.20-1.33) for -10 to -6 years, 1.07 (1.05-1.08) for -5 to -1 years, 1.00 (1.00-1.01) for 1 to 5 years, 1.05 (1.03-1.06) for 6 to 10 years, and 1.12 (1.09-1.16) for > 10 years. A V-shaped nonlinear relationship was observed between PAD and the risk of SAB (Pnon-linear <0.001), with a steeper increase in risk when the female partner was older than the male partner.

CONCLUSION

Larger PAD was associated with an increased risk of SAB, especially in couples where the mother was older than the father.