Gestational diabetes mellitus and vascular malperfusion lesions in the placenta: A systematic review and meta-analysis

Background: Gestational diabetes mellitus (GDM) can result in increased placental lesions related to high maternal blood glucose, but these relationships are not well understood. Objective: To examine the relationship between GDM and placental vascular malperfusion lesions: accelerated villous maturation, increased syncytial knots, delayed villous maturation, and increased fibrin deposition. Search Strategy: PubMed, BIOSIS, and Web of Science databases were systematically searched for full-text articles in English from inception until August 21, 2024. Selection Criteria: Our inclusion criteria were randomized controlled trials, case–control, cohort, and cross-sectional studies that examined the relationship between GDM and selected placental vascular malperfusion lesions. The outcome must have been reported as a total proportion. Data Collection and Analysis: We included all eligible studies in narrative synthesis. If an outcome of interest was in at least three studies, we calculated the odds ratios (ORs) by GDM diagnosis, with 95% confidence intervals (CIs), using mixed-effects logistic regression with random study effects. We evaluated the risk of bias with the Newcastle-Ottawa Scale. Main Results: We screened 151 studies, of which eight were included (n = 1291), and six met the criteria for meta-analysis (n = 561). Unadjusted odds (95% CI) of delayed villous maturation were six-fold higher (OR: 6.37 [3.28–12.37]) in pregnancies with GDM than in those without GDM. The narrative synthesis of the literature found higher proportions of increased syncytial knots, delayed villous maturation, and increased fibrin deposition, but not accelerated villous maturation, in pregnancies with versus without GDM. Conclusions: GDM was associated with a higher risk of three placental malperfusion lesions, although there is a small number of studies in this area. Future investigations should examine if these vascular malperfusions are associated with adverse pregnancy outcomes often linked with GDM.