Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with Covid-19 in pregnancy: The INTERCOVID Study.
Eskenazi B., Rauch S., Iurlaro E., Gunier RB., Rego A., Gravett MG., Cavoretto PI., Deruelle P., García-May PK., Mhatre M., Usman MA., Elbahnasawy M., Etuk Fwacs S., Napolitano R., Deantoni S., Liu B., Prefumo F., Savasi V., Marques PF., Baafi E., Zainab G., Nieto R., Serrano B., Aminu MB., Cardona-Perez JA., Craik R., Winsey A., Tavchioska G., Bako B., Oros D., Benski C., Galadanci H., Savorani M., Oberto M., Sentilhes L., Risso M., Takahashi K., Vecciarelli C., Ikenoue S., Pandey AK., Soto Conti CP., Cetin I., Nachinab VB., Ernawati E., Duro EA., Kholin A., Firlit ML., Easter SR., Sichitiu J., John-Akinola Y., Casale R., Cena H., Agyeman-Duah J., Roggero P., Langer A., Bhutta ZA., Kennedy SH., Villar J., Papageorghiou AT.
BACKGROUND: Among non-pregnant individuals, diabetes mellitus (DM) and high body mass index (BMI) increase the risk of Covid-19 and its severity. OBJECTIVE: To determine whether DM and high BMI are risk factors for Covid-19 in pregnancy and whether gestational diabetes mellitus (GDM) is also associated with covid-19 diagnosis. STUDY DESIGN: INTERCOVID was a multinational study, conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women ≥18 years; 2071 were included in these analyses. For each woman diagnosed with Covid-19, two non-diagnosed women delivering or initiating antenatal care at the same institution were also enrolled. Main exposures were pre-existing DM or high BMI (overweight/obesity defined as ≥25 kg/m2), and GDM in pregnancy. Main outcome was a confirmed diagnosis of Covid-19 based on an RT-PCR test, antigen test, antibody test, radiological pulmonary findings, or ≥2 predefined Covid-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and Covid-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. We also conducted sensitivity analyses: 1) restricted to those with an RT-PCR or antigen test in the last week of pregnancy; 2) restricted to those with an RT-PCR or antigen test during the entire pregnancy; 3) generating values for missing data using multiple imputation; and 4) analyses controlling for month of enrollment. In addition, among those who were diagnosed with Covid-19, we examined whether having GDM, DM, or high BMI, increased risk for having symptomatic vs. asymptomatic Covid-19. RESULTS: Covid-19 was associated with preexisting DM (RR=1.94, 95% CI=1.55, 2.42), overweight/obesity (RR=1.20; 95% CI=1.06, 1.37), and GDM (RR=1.21; 95% CI=0.99, 1.46). The GDM association was specifically among women requiring insulin, whether they were of normal-weight (RR=1.79, 95% CI=1.06, 3.01) or overweight/obese (RR=1.77, 95% CI=1.28, 2.45). A somewhat stronger association with Covid-19 diagnosis was observed among women with pre-existing DM, whether they were of normal weight (RR=1.93, 95% CI=1.18, 3.17) or overweight/obese (RR=2.32, 95% CI=1.82, 2.97). When the sample was restricted to those with a RT-PCR or antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation, or controlling for month of enrollment, the observed associations were comparable. CONCLUSION: DM and overweight/obesity are risk factors for Covid-19 diagnosis in pregnancy, and insulin-dependent GDM is also associated with the disease. It is therefore essential that those women with these co-morbidities are vaccinated.