Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS)

Abstract

Background: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking.

Objective: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19.

Study design: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints.

Results: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m² increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight.

Conclusion: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m² were a particularly vulnerable group in the case of COVID-19.

Keywords: SARS-CoV-2; diabetes mellitus; invasive ventilation; large for gestational age; maternal pregnancy outcomes; morbidity; obesity; pregnancy.

Figure 1

Flowchart showing the CRONOS participants being eligible for analysis CRONOS, COVID-19–Related Obstetric and Neonatal Outcome Study; GDM, gestational diabetes mellitus; ICU, intensive care unit; NICU, neonatal intensive care unit. Kleinwechter. Gestational diabetes mellitus and COVID-19: COVID-19–Related Obstetric and Neonatal Outcome Study registry results. Am J Obstet Gynecol 2022.

Figure 2

Associations between plasma glucose concentrations from OGTT and primary endpoints Data are presented as aOR (95% CI) using logistic regression analyses for combined primary maternal and fetal and neonatal endpoints (yes or no) as the dependent variable (separate model for each) per 1 mg/dL increase in venous plasma glucose concentrations from OGTT (continuous variables, all included in the same model). Adjusted for week of gestation at the onset of COVID-19 symptoms (or at PCR-positive test result), multiples (yes or no), maternal age at positive COVID-19 test result, language competence (communication possible with or without problems), parity (0 or ≥1), maternal BMI category before or at the beginning of pregnancy (BMI, <25 or ≥25 kg/m²), hypertensive disorders in pregnancy (yes or no), and type of GDM therapy (diet or insulin). The model with combined primary fetal and neonatal endpoint was additionally adjusted for nicotine or smoking during pregnancy (yes or no) as a quasi-complete separation of data points was observed with this potential confounding variable. The asterisk represents P<.05. aOR, adjusted odds ratio; BMI, body mass index; CI, confidence interval; OGTT, oral glucose tolerance test; PCR, polymerase chain reaction. Kleinwechter. Gestational diabetes mellitus and COVID-19: COVID-19–Related Obstetric and Neonatal Outcome Study registry results. Am J Obstet Gynecol 2022.