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

Abstract

Introduction We identified risk factors and outcomes associated with SARS‐CoV‐2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS‐CoV‐2 during pregnancy in national health registers in Denmark. Material and methods Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS‐CoV‐2 test during pregnancy with non‐infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID‐19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS‐CoV‐2 diagnosis in pregnancy in the registers. Results SARS‐CoV‐2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28–2.07). Risk factors for severe COVID‐19 disease requiring hospital admission were high 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 the time of infection (gestational age 28–36 vs < 22: RR 3.53, 95% CI 1.75–7.10). SARS‐CoV‐2‐infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04–1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00–1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01–5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01–2.19) and small‐for‐gestational age children (aHR 1.28, 95% CI 1.05–1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS‐CoV‐2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9–100.0) and a positive predictive value of 82.1 (95% CI 80.4–83.7). Conclusions Women infected with SARS‐CoV‐2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS‐CoV‐2 infection during pregnancy.

Severe COVID‐19 during pregnancy in Sweden, Norway, and Denmark

“…The Norwegian Patient Registry was subsequently used to identify the women that had been specifically admitted to ICU for COVID‐19 as indicated by having a registration of either International Classification of Diseases 10 th revision (ICD‐10) codes U07.1, U07.2, U09, or U10 as the primary diagnoses. In Denmark, pregnant women admitted to ICU because of COVID‐19 were identified through the Danish COVID‐19 in pregnancy database (DCOD) 12 . Women admitted to ICU were included during the same study period as for all birthing women in each country, except for Denmark, where end of follow up for those admitted to ICU was February 28, 2022.…”

SARS‐CoV‐2 placentitis and severe pregnancy outcome after maternal infection: A Danish case series

“…All the women that were included were covered by an overall approval for “the Danish nationwide prospective population‐based study investigating the association between SARS‐CoV‐2 infection in pregnancy and clinical characteristics and maternal, delivery, and neonatal outcomes” by Aabakke et al 16 , 20 The approval was granted by the Danish Patient Safety Authority on April 24, 2020 (reg. no.…”

Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection

“…In the third trimester of pregnancy, the following indicators should serve as warning signs for exacerbation of the condition and for possible severe illness: progressive exacerbation of hypoxemia or respiratory distress; exacerbation of tissue oxygenation indicators (e.g., fingertip oxygen saturation, oxygenation index) or progressive elevation of lactate; progressive decrease of peripheral blood lymphocyte count, or progressive elevation of inflammatory factors, such as interleukin 6, C-reactive protein, and ferritin; and significant elevation of coagulation-related indicators, such as d -dimer 16 …”