Abstract
OBJECTIVE
To investigate the independent and joint effects of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on adverse pregnancy outcomes, evaluate their potential interaction, and explore the nonlinear dose-response relationships between blood glucose and blood pressure levels and composite adverse outcomes using a restricted cubic spline (RCS) model.
METHODS
This retrospective cohort study included 240 women who delivered at Dongyang Maternal and Child Health Hospital between January 2020 and December 2024. Participants were categorized into four groups according to the presence of GDM and/or HDP: control, GDM only, HDP only, and comorbid GDM + HDP. The primary outcome was a composite of adverse pregnancy outcomes, including preterm birth, Apgar score < 7, neonatal intensive care unit (NICU) admission, and fetal growth abnormalities. Multivariable logistic regression models were applied to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Additive interaction indices-relative excess risk due to interaction (RERI) and attributable proportion (AP)-were calculated to assess synergistic effects. Nonlinear dose-response associations between mean fasting glucose, systolic blood pressure (SBP).
RESULTS
Compared with the control group, HDP was independently associated with a higher risk of composite adverse outcomes (aOR = 3.30, 95% CI: 1.41-7.70, P = 0.006), while comorbid GDM + HDP showed a substantially elevated risk (aOR = 9.25, 95% CI: 2.63-32.45, P < 0.001). Additive interaction analysis demonstrated a significant positive interaction between GDM and HDP (RERI = 5.62; AP = 0.61), suggesting that over half of the excess risk was attributable to their joint effect. Specifically, the risks of preterm birth and small-for-gestational-age infants increased markedly in the HDP and comorbid groups, whereas GDM alone was primarily associated with large-for-gestational-age outcomes. RCS analysis revealed a nonlinear positive relationship between mean SBP and composite adverse outcomes, with the risk increasing sharply beyond approximately 135 mmHg and accelerating above 160 mmHg.
CONCLUSION
Both GDM and HDP independently increase the risk of adverse pregnancy outcomes, and their coexistence exerts a synergistic effect that amplifies maternal and neonatal risk. The nonlinear dose-response pattern between SBP and adverse outcomes highlights that even mild elevations in blood pressure can have detrimental effects.