Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with COVID-19 in pregnancy: the INTERCOVID study

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity.OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is 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 aged >= 18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index >= 25 kg/m(2)), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction 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. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an 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 women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19.RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an 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: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated

Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures

Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, setting, and participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main outcomes and measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures

Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with Covid-19 in pregnancy: The INTERCOVID Study.

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