Adverse perinatal outcomes in gestational diabetes mellitus with and without SARS-CoV-2 infection during pregnancy: results from two nationwide registries in Germany

Abstract

Introduction: Pregnancy is a known independent risk factor for a severe course of COVID-19. The relationship of SARS-CoV-2 infection and gestational diabetes mellitus (GDM) on neonatal outcomes is unclear. Our aim was to determine if SARS-CoV-2 infection represents an independent risk factor for adverse perinatal outcomes in pregnancy with GDM.

Research design and methods: We compared data from two German registries including pregnant women with GDM, established during the SARS-CoV-2 pandemic (COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study) and already existing before the pandemic (German registry of pregnant women with GDM; GestDiab). In total, 409 participants with GDM and SARS-CoV-2 infection and 4598 participants with GDM, registered 2018-2019, were eligible for analyses. The primary fetal and neonatal outcomes were defined as: (1) combined: admission to neonatal intensive care unit, stillbirth, and/or neonatal death, and (2) preterm birth before 37+0 weeks of gestation. Large and small for gestational age, maternal insulin therapy, birth weight >4500 g and cesarean delivery were considered as secondary outcomes.

Results: Women with SARS-CoV-2 infection were younger (32 vs 33 years) and had a higher median body mass index (28 vs 27 kg/m²). In CRONOS, more neonates developed the primary outcome (adjusted OR (aOR) 1.48, 95% CI 1.11 to 1.97) and were born preterm (aOR 1.50, 95% CI 1.07 to 2.10). Fasting glucose was higher in women in CRONOS versus GestDiab (5.4 vs 5.3 mmol/L) considering each 0.1 mmol/L increase was independently associated with a 5% higher risk of preterm birth among women in CRONOS only (aOR 1.05, 95% CI 1.01 to 1.09).

Conclusions: GDM with SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse fetal and neonatal outcomes as compared with GDM without SARS-CoV-2 infection.

Keywords: COVID-19; Diabetes, Gestational; Pregnancy Outcome.

Figure 1

Flow chart showing the CRONOS and GestDiab participants being eligible for analysis.BMI, body mass index; CRONOS, COVID-19-Related Obstetric and Neonatal Outcome Study; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test.

Figure 2

Comparison of the odds for primary adverse neonatal outcomes between women with gestational diabetes mellitus (GDM) with (COVID-19-Related Obstetric and Neonatal Outcome Study, CRONOS) and without (GestDiab) SARS-CoV-2 infection. Data are presented as adjusted OR (aOR) (95% CI) using logistic regression analyses for the two primary neonatal outcomes: combined neonatal outcome (admission to neonatal intensive care unit, stillbirth, and/or neonatal death) and preterm birth (yes or no) as the dependent variable (separate model for each). *P<0.05. †Holm-Bonferroni corrected for multiple testing. ¹CRONOS/GestDiab. ²Adjusted for maternal body mass index (BMI), maternal age, gestation week of GDM diagnosis, insulin therapy, and fasting blood glucose concentration. OGTT, oral glucose tolerance test.

Figure 3

Comparison of adjusted oral glucose tolerance test (OGTT) results between women with gestational diabetes mellitus (GDM) with (COVID-19-Related Obstetric and Neonatal Outcome Study, CRONOS) and without (GestDiab) SARS-CoV-2 infection. Data are presented as mean [SEM], adjusted for maternal body mass index (BMI), maternal age, week of gestation of GDM diagnosis, and insulin therapy. *To convert to mg/dL multiply mmol/L with 18.02. OGTT, oral glucose tolerance test.