The relationship between maternal glucose concentrations, gestational diabetes mellitus, placental weight, and placental vascular malperfusion lesions: A retrospective study of a U.S. pregnancy cohort

PLoS One. 2026 Mar 3;21(3):e0325415. doi: 10.1371/journal.pone.0325415. eCollection 2026.

Abstract

Background: Gestational diabetes mellitus (GDM) is associated with increased placental weight and the presence of placental malperfusion lesions, likely related to high blood glucose. The relationship between high glucose without overt GDM, and placental characteristics is not well understood.

Objective: To examine the relationships between glucose challenge test (GCT) concentrations, GDM, and placental characteristics associated with GDM.

Methods: We conducted a secondary analysis of medical record data from singleton placentas sent to pathology at Northwestern Memorial Hospital (2011-2022; n = 11,585). Placentas were submitted based on standard clinical protocol. Data included maternal demographic variables, GCT concentrations, GDM diagnosis, placental weight, and vascular malperfusion lesions (accelerated villous maturation, increased syncytial knots, delayed villous maturation, and increased perivillous fibrin deposition). We classified GCT <140 mg/dL as pass and ≥140 mg/dL as fail. GDM was classified by diagnosis. We categorized glucose groups into pass GCT/no GDM, fail GCT/no GDM, and GDM. We used linear and Poisson (due to non-convergence of log-binomial) regression models to examine the association between GCT concentrations or groups with placental outcomes, adjusting for maternal age, race and ethnicity, parity, gestational age at delivery, and infant sex.

Results: Of placentas sent to pathology, 17% were in the fail GCT/no GDM group and 5% were in the GDM group. Compared to the pass GCT/no GDM group, the adjusted mean placental weight was heavier by 13.6 grams [95% CI: 8.8, 18.3] in the fail GCT/no GDM and 22.0 grams [13.8, 30.2] in the GDM group. Patients diagnosed with GDM had a 36% [2%, 81%] increased adjusted risk of delayed villous maturation compared to the pass GCT/no GDM. The risk of the other lesions (accelerated villous maturation, increased syncytial knots, and increased perivillous fibrin deposition) was not significantly different between groups.

Conclusion: GDM and high glucose concentrations without GDM were associated with heavier placentas. Patients with GDM had a higher risk of delayed villous maturation, but risk of other placental lesions was similar.

MeSH terms

  • Adult
  • Blood Glucose* / analysis
  • Blood Glucose* / metabolism
  • Diabetes, Gestational* / blood
  • Diabetes, Gestational* / pathology
  • Female
  • Glucose Tolerance Test
  • Humans
  • Organ Size
  • Placenta* / blood supply
  • Placenta* / pathology
  • Pregnancy
  • Retrospective Studies
  • United States

Substances

  • Blood Glucose