The association between frailty and recurrent pregnancy loss in reproductive-aged women: a cross-sectional study

This study aims to investigate the association between multidimensional frailty phenotypes and recurrent pregnancy loss (RPL) in reproductive-aged women. This cross-sectional study analyzed data from 6,438 reproductive-aged women participating in the National Health and Nutrition Examination Survey from 1999 to 2018. RPL was defined as experiencing two or more pregnancy losses, including elective abortions and stillbirths. Frailty was assessed using a validated 49-item Frailty Index (FI), which encompasses seven domains: cognitive health, physical health, mental health, comorbidities, healthcare utilization, laboratory parameters, and performance metrics. Participants were categorized as robust, pre-frail, or frail. We employed weighted multivariable logistic regression models, hierarchically adjusted for covariates, to evaluate the associations between frailty and RPL. Additionally, sensitivity analyses and subgroup analyses were conducted to confirm the robustness and specificity of our findings. A total of 6,438 reproductive-aged women were included in the analysis, frailty severity demonstrated a dose-dependent association with RPL risk. The overall RPL prevalence was 21.73%, with increasing rates observed across frailty strata: 18.75% (robust, FI < 0.10), 23.08% (pre-frail, 0.10 ≤ FI < 0.25), and 29.03% (frail, FI ≥ 0.25). Multivariable models revealed persistently elevated RPL risks for pre-frail ( OR = 1.23, 95% CI:1.01-1.52) and frail women (OR = 1.51, 95% CI:1.11-2.05) versus robust counterparts after full adjustment for sociodemographic and clinical confounders (p trend < 0.001). Subgroup analyses confirmed robustness across demographic and health strata, except for educational attainment (interaction p = 0.046). Threshold regression identified a nonlinear relationship: below FI = 0.183, each SD increase in frailty index amplified RPL odds exponentially (OR = 67.11, p < 0.001), whereas no significant association emerged beyond this inflection point. This study underscores frailty severity as an independent risk factor for RPL in reproductive-aged women, highlighting the need for standardized frailty screening and early interventions during the pre-frailty stage to mitigate RPL risk.