Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG)

Objective: To assess risk factors for and pregnancy outcomes after SARS-CoV-2 infection in pregnancy by disease severity (hospital admission status) and to validate identification of SARS-CoV-2 infection during pregnancy in Danish national registers. Methods: Nationwide cohort including all pregnancies in Denmark from March 1, 2020 to February 28, 2021, comparing SARS-CoV-2-infected with non-infected pregnant women. Risk factors and pregnancy outcomes were analyzed using Poisson and Cox regression, stratified by hospital admission reason (COVID-19 symptoms or other). Predictive values for identifying infection during pregnancy in registers were calculated using medical record data. Results: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (RR 1.63, 95% CI 1.28-2.07). Risk factors for severe COVID-19 requiring hospital admission included higher body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at infection (GA 28-36 vs <22 weeks: RR 3.53, 95% CI 1.75-7.10). Infected women more frequently had hypertensive disorders of pregnancy (aHR 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), extremely preterm delivery before GA 28 (aHR 2.31, 95% CI 1.01-5.26) and iatrogenic preterm delivery before GA 37 (aHR 1.49, 95% CI 1.01-2.19). Offspring were more often small for gestational age (SGA) <10th percentile (aHR 1.28, 95% CI 1.05-1.54); SGA <2.3rd percentile aHR 1.24 (95% CI 0.89-1.72). Infected women admitted for any reason had higher risks of hypertensive disorders (aHR 4.38, 95% CI 2.66-7.21), SGA (<10th percentile: aHR 2.96, 95% CI 1.76-4.97; <2.3rd percentile: aHR 2.75, 95% CI 1.21-6.24), preterm delivery <37 weeks (aHR 5.16, 95% CI 2.90-9.20), induction of labor (aHR 2.45, 95% CI 1.71-3.52) and intensive care unit admission (aHR 15.96, 95% CI 6.45-39.48). The positive predictive value for identifying a positive SARS-CoV-2 test during pregnancy in registers was 82.1% (95% CI 80.4-83.7) and the negative predictive value was 99.9% (95% CI 99.9-100.0). Conclusions: SARS-CoV-2 infection in pregnancy increased risks of hypertensive disorders, early pregnancy loss, preterm birth and SGA; Danish registers showed acceptable validity for identification of SARS-CoV-2 during pregnancy.