Gestational diabetes in multifetal versus singleton pregnancies: A multicenter cohort study

Gestational diabetes mellitus (GDM) is associated with increased neonatal morbidity in singleton pregnancies, but evidence in multifetal pregnancies is limited. Current diagnostic thresholds are largely extrapolated from singleton data; It remains unclear whether plurality modifies GDM-associated neonatal and long-term offspring outcomes. We wanted to evaluate neonatal complications and long-term offspring healthcare utilization associated with GDM in multifetal versus singleton pregnancies, and to assess effect modification by plurality and the impact of gestational age at delivery.

This multicenter retrospective cohort study utilized electronic medical records across six university-affiliated medical centers in Israel (1/1/2010-6/30/2024). All live births at 22 weeks' gestation or later or with birthweight of >500 g were included. Four exposure groups were defined by plurality and GDM status (ICD-9 code 648.8x): singleton without GDM, singleton with GDM, multifetal without GDM, and multifetal with GDM. Short-term neonatal complications (neonatal hypoglycemia, neonatal ICU admission, respiratory distress, intraventricular hemorrhage, and growth abnormalities) and long-term offspring outcomes were assessed by hospital-based health-care utilization (e.g., neurology, ophthalmology, cardiology). Multivariable Firth logistic and ordinary least squares regression models were adjusted for maternal age, body mass index, parity, and fertility treatment. Additional models adjusted for gestational age were performed. False discovery rate correction and GDM-by-plurality interaction terms were applied.

Of 134 517 pregnancies (136 579 live-born offspring) to 104 023 mothers, 10 605 singleton (7.9%) and 256 multifetal (0.2%) pregnancies were complicated by GDM. In multifetal pregnancies, GDM was not associated with increased short-term neonatal complications nor with lower adjusted odds of neonatal hypoglycemia (adjusted odds ratio [aOR], 0.30; 95% CI: 0.18-0.49), neurologic (aOR, 0.37; 95% CI: 0.24-0.59), or ophthalmologic (aOR, 0.49; 95% CI: 0.31-0.77) health-care utilization. Adjustment for gestational age attenuated associations for neonatal intensive care unit admission but did not fully explain interactions for hypoglycemia or selected long-term outcomes. Conversely, GDM in singleton pregnancies was associated with increased neonatal morbidity.

Associations between GDM and neonatal and offspring outcomes differ by plurality. Risk stratification strategies derived from singleton pregnancies may not fully capture risk profiles in multifetal pregnancies.