Nonlinear association between first-trimester plasma aldosterone concentration and risk of hypertensive disorders of pregnancy: a multicenter prospective cohort study.

BACKGROUND

Hypertensive disorders of pregnancy (HDP) threaten maternal and fetal health, and the etiology remains unclear. Previous studies have reported lower plasma aldosterone concentration (PAC) in patients with HDP, but this association remains controversial. The primary objective of this study was to determine the relationship between first-trimester PAC and the risk of HDP.

METHODS

This prospective, multicenter cohort study recruited eligible pregnant women in their first-trimester from six hospitals in China between May 1, 2023, and December 31, 2024. Inclusion criteria comprised naturally conceived singleton pregnancy with a gestational age of less than 14 weeks. The primary exposure was the baseline PAC measured at first-trimester pregnancy registration. The primary outcome was a clinical diagnosis of HDP. The association was assessed using multivariable logistic regression, adjusting for potential confounders. Potential nonlinearity was explored with restricted cubic splines (RCS), and threshold effects were evaluated using piecewise regression. Sensitivity analyses were conducted to test the robustness of the findings. Statistical analyses were performed using R software (version 4.2.2) and SPSS (version 26.0). A two-sided P-value < 0.050 was considered statistically significant.

RESULTS

A total of 1,486 women were included in the final analysis, of whom 145 (9.8%) developed HDP. Women with HDP had significantly lower first-trimester PAC than those without (median: 18.85 vs. 22.96 ng/dL, P < 0.001). The RCS analysis revealed a significant nonlinear relationship between PAC and HDP risk (P for nonlinearity = 0.005). Piecewise regression identified a threshold at 39.30 ng/dL: below it, each 1 ng/dL increase in PAC was associated with a 3.8% reduction in the odds of HDP (adjusted odds ratio [OR], 0.962, 95% confidence interval [CI]: 0.939-0.985, P = 0.001); at or above it, the association was positive but not significant (adjusted OR, 1.027, 95% CI: 0.995-1.060, P = 0.098). These findings remained consistent across multiple sensitivity analyses.

CONCLUSION

First-trimester PAC exhibited a nonlinear association with HDP risk, with an inflection point at 39.30 ng/dL. Below this threshold, higher PAC was significantly associated with a lower risk of HDP. At or above this level, the association was positive but not statistically significant.