Prepregnancy obesity, adverse pregnancy outcome patterns, and early postpartum cardiometabolic risk: a mediation analysis identified by latent class analysis
L Zuo, Y Fang, X Wang, R Zhang, H Shi, J Li, J Yang, J Chen, B Zhang, Q Yang, X ZhouAbstract
Background
Prepregnancy obesity is a well-established risk factor for adverse pregnancy outcomes (APOs) and future cardiovascular metabolic disease. However, previous studies often focused on isolated APOs or surrogate markers rather than confirmed clinical endpoints. Furthermore, APOs rarely occur in isolation but manifest as complex clinical clusters. The nature of these distinct APO patterns and their specific mediating role in the pathway from obesity to clinical outcomes remain poorly defined. We aimed to quantify these associations and determine the mediating contribution of distinct APO patterns versus individual APOs.
Methods
This retrospective study analyzed data from a Medical Data Platform (2015-2023). Participants were categorized by prepregnancy body mass index (BMI) levels into underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<24 kg/m2), overweight (24≤BMI<28 kg/m2), and obese (BMI≥28 kg/m2). The outcomes including diabetes mellitus (DM), cardiometabolic comorbidities (CMC, composite of DM, hypertension, and dyslipidemia) and stage-4 cardiovascular-kidney-metabolic (CKM) syndrome. Missing data were handled via multiple imputation. Latent Class Analysis (LCA) identified APO patterns based on mediators including gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), preterm, small for gestational age (SGA), large for gestational age (LGA), pregnancy loss, antepartum infection. Cox proportional hazards models and causal mediation analyses were employed to estimate hazard ratios (HR) and the proportion mediated (PM).
Results
Among 555,591 individuals (mean age 29.5 years), 5.8% were obese and 18.3% were overweight. During a median follow-up of 5.8 years, incidence rate were 1.3% for DM, 4.9% for CMC and 3.1% for stage-4 CKM. LCA identified five distinct APO patterns: low burden (85.3%), term non-SGA (4.6%, characterized by GDM/LGA), Term SGA (6.8%), preterm non-SGA (2.5%), and high-burden (0.8%, characterized by HDP/preterm/SGA). Compared with normal weight, obesity significantly increased the risk of DM (HR 4.10, 95%CI 3.83-4.32), CMC (HR 2.36, 95%CI 2.29-2.47) and stage-4 CKM (HR 1.19, 95%CI 1.12-1.27). Mediation analysis revealed distinct pathways: the identified APO patterns mediated 27.3% of the association with DM, 15.9% with CMC, and 16.6% with stage-4 CKM. Component-specific analysis further highlighted mechanism divergence: GDM was the dominant mediator for DM (PM 30.6% vs. HDP 7.2%), whereas HDP was the dominant mediator for stage-4 CKM (PM 22.5% vs. GDM 8.4%).
Conclusion
The early postpartum health risks of prepregnancy obesity are mediated through divergent APO patterns. We identified a metabolic trajectory driving future DM and a separate vascular/high-burden trajectory predisposing to stage-4 CKM. Recognizing these distinct pathways is crucial for moving beyond generic postpartum advice toward precision prevention strategies tailored to specific APOs.Abstract graph-01Abstract graph-02