Differential Effects of Gestational Diabetes Mellitus on Preterm Birth between Nullipara and Multipara: A Population-Based Cohort Study

Abstract

Background: The differential effect of gestational diabetes mellitus (GDM) on preterm birth according to parity has not been fully addressed. Herein we conducted a city-wide population-based cohort study aiming to determine the association between maternal GDM and offspring prematurity stratified by parity. Methods: We conducted a cohort study of all pregnant women in Qingdao during August 1, 2018, to June 30, 2020. Multivariate logistic regression analysis and propensity score (PS) matching analyses were performed to balance confounding bias in estimation of the GDM effect on  premature birth. Odds ratio (OR) of matched samples was calculated from conditional logistic regression. Association between maternal GDM and premature birth was examined using stratified analyses based on parity status. Findings: A total of 105768 mother-child pairs were included in our analysis. Overall, more than 98.72% of the women with GDM during pregnancy were successfully matched, resulting in 16613 equal-sized cohort pairs. In the PS adjusted analysis, multiparous mothers with current and previous GDM were at a significantly higher risk of giving a premature birth than those without GDM (OR= 1.78, 95% confidence interval [CI]: 1.19-2.71). However, such association did not hold true for PS matched samples of nullipara (OR= 1.14, 95%CI: 0.90-1.44). The risk estimates for maternal GDM on moderate preterm birth were similar to that of preterm birth. There was an inverse association between GDM and very preterm birth among nullipara in PS matched models (OR= 0.29, 95% CI: 0.08-0.83). While no association between GDM and very preterm birth was observed in multipara (all P >0.05). Interpretation: The effect of maternal GDM on offspring prematurity differed with parity status. For nulliparous mothers, there was no association between GDM and premature birth , while among multiparous mothers with current and previous GDM, an increased risk for  prematurity was observed. There was even a protective effect of GDM against very preterm birth among nulliparous mothers. Pregnancy care should consider parity and GDM for better prediction and intervention of preterm. Funding: The National Natural Science Foundation of China (NSFC), [Grant No.81903335] &China Postdoctoral Science Foundation Funded Project [Grant No.2019M662307]. Declaration of Interest: We declare no competing interests. Ethical Approval: The study was approved by the Institutional Review Board of Qingdao Women and Children’s Hospital Ethics (No. 002-2018-FEKY).