Impact of Parity on Gestational Diabetes Mellitus: A Population-Based Cohort Study with Stratified Analyses by Body Mass Index and Maternal Age

Technical Summary: Impact of Parity on Gestational Diabetes Mellitus

Problem Statement
Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication with significant adverse maternal and neonatal outcomes, including an increased risk of type 2 diabetes and cardiovascular disease later in life. While established risk factors such as advanced maternal age and high pre-pregnancy body mass index (BMI) are well-documented, the role of parity (the number of previous live births) remains controversial. Previous epidemiological studies have yielded inconsistent findings, ranging from positive associations (higher parity increases risk) to null or inverse associations. The authors posit that these discrepancies likely stem from inadequate adjustment for confounding variables—specifically maternal age and BMI, which are strongly correlated with parity—and a lack of exploration into effect modification (interaction) by these factors.

Methodology
This study employed a large-scale, population-based retrospective cohort design utilizing data from the SINA Electronic Health Record (EHR) system, the integrated maternal health registry of Mashhad University of Medical Sciences, Iran.

• Study Population: The initial dataset included 556,346 delivery records from May 2018 to May 2025. After excluding women with pre-existing diabetes, multiple gestations, and missing data, the final analysis included 423,273 pregnant women.
• Exposure and Outcome: Parity was categorized into three groups: nulliparous (0), one previous birth (1), and two or more previous births (≥2). The primary outcome was GDM, diagnosed according to International Association of Diabetes and Pregnancy Study Groups (IADPSG)/WHO criteria using a 75-g oral glucose tolerance test (OGTT).
• Statistical Analysis: Multivariable logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). The analysis progressed through four models:
  • Model 1: Adjusted for maternal age, education, and residence.
  • Model 2: Further adjusted for pre-pregnancy BMI and gravidity.
  • Model 3: Further adjusted for smoking and hypertensive disorders of pregnancy.
  • Model 4: Fully adjusted, including infant sex.
  • Stratified analyses and interaction tests were conducted to assess effect modification by maternal age and pre-pregnancy BMI.

Key Results

• Crude vs. Adjusted Associations: The crude prevalence of GDM increased with parity (3.4% for parity 0, 4.2% for parity 1, and 5.7% for parity ≥2; P < 0.001). In partially adjusted models (Model 1), higher parity appeared to increase GDM risk. However, after full adjustment for maternal age, BMI, and other covariates (Model 4), the direction of the association reversed. Higher parity was associated with a reduced risk of GDM compared to nulliparous women (Parity 1: OR 0.85, 95% CI 0.80–0.91; Parity ≥2: OR 0.81, 95% CI 0.75–0.87).
• Effect Modification: Significant interactions were observed for both maternal age and pre-pregnancy BMI (P for interaction < 0.001).
  • BMI Stratification: The inverse association between parity and GDM was primarily observed in overweight and obese women (BMI ≥ 25 kg/m²). No significant associations were found in underweight or normal-weight women.
  • Age Stratification: The protective effect of higher parity was strongest among women aged ≥35 years (Parity ≥2: OR 0.72, 95% CI 0.64–0.80), though the association remained inverse across most age strata.

Key Contributions

• Clarification of Confounding: The study demonstrates that the apparent positive association between parity and GDM in unadjusted analyses is largely an artifact of confounding by maternal age and pre-pregnancy BMI. Women with higher parity in this cohort were systematically older and had higher BMIs, both of which are independent risk factors for GDM.
• Identification of Subgroup Effects: By employing stratified analyses, the study reveals that the relationship between parity and GDM is not uniform. The protective association of multiparity is specific to women with elevated pre-pregnancy BMI and is most pronounced in older maternal age groups.
• Large-Scale Evidence: Utilizing a dataset of over 420,000 women, this research addresses limitations of previous studies regarding sample size and the depth of clinical data, providing robust evidence on the interplay between reproductive history and metabolic risk.

Significance and Claims
The authors conclude that parity should not be viewed as a direct, independent risk factor for GDM in isolation. Instead, the study claims that the apparent risk associated with higher parity is driven by the underlying metabolic profile (age and adiposity) of the population. Once these factors are accounted for, higher parity is associated with a reduced risk of GDM, particularly in overweight/obese women.

The paper emphasizes that relying solely on parity as a predictor for GDM may be misleading in heterogeneous populations. The findings suggest that risk assessment models must incorporate the interaction between reproductive history, maternal age, and BMI. Clinically, this highlights the importance of targeted screening, particularly for nulliparous women of advanced maternal age who may represent a higher-risk group. The authors note that while their findings offer a clearer epidemiological picture, they are limited by the retrospective nature of the data, potential misclassification in clinical records, and the lack of detailed lifestyle data (e.g., physical activity, diet, family history).