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An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women
American Journal of Obstetrics and Gynecology  (IF8.661),  Pub Date : 2021-09-25, DOI: 10.1016/j.ajog.2021.09.024
Erkan Kalafat, Smriti Prasad, Pinar Birol, Arzu Bilge Tekin, Atilla Kunt, Carolina Di Fabrizio, Cengiz Alatas, Ebru Celik, Helin Bagci, Julia Binder, Kirsty Le Doare, Laura A. Magee, Memis Ali Mutlu, Murat Yassa, Niyazi Tug, Orhan Sahin, Panagiotis Drokos, Pat O’Brien, Asma Khalil

Background

Pregnant women are at increased risk of mortality and morbidity due to coronavirus disease 2019 (COVID-19). Many studies reported on the association of COVID-19 with pregnancy specific adverse outcomes but prediction models utilizing large cohort of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events.

Objective

The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection.

Study design

This was a multicenter retrospective cohort study including eight hospitals from four countries (UK, Austria, Greece and Turkey). Data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth), reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. Secondary outcomes included maternal death, preeclampsia and stillbirth. The association between the primary outcome and 12 candidate predictors with known association with severe COVID-19 in pregnancy, was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios (aRR). All potential predictors were evaluated in one model and only baseline factors in another. Predictive accuracy were assessed by the area under the receiver operating characteristic curves (AUROC).

Results

Of 793 pregnant women positive for SARS-CoV-2 and symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The ‘mini-COvid Maternal Intensive Therapy’ model included demographic and clinical variables available at disease onset: maternal age (aRR: 1.45, 95% CI: 1.07–1.95, P=0.015); body-mass index (aRR: 1.34, 95% CI: 1.06–1.66, P=0.010); and diagnosis in the third trimester of pregnancy (aRR: 3.64, 95% CI: 1.78–8.46, P=0.001). The optimism-adjusted AUROC was 0.73. The ‘full-COvid Maternal Intensive Therapy’ model included body-mass index (aRR: 1.39, 95% CI: 1.07–1.95, P=0.015), lower respiratory symptoms (aRR: 5.11, 95% CI: 1.81–21.4, P=0.007), neutrophil/lymphocyte ratio (aRR: 1.62, 95% CI: 1.36–1.89, P<0.001); and serum C-reactive protein (aRR: 1.30, 95% CI: 1.15–1.44, P<0.001), with an optimism-adjusted AUROC 0.85. Neither model showed signs of poor fit (P>0.05). Categorization as high risk by either model was associated with a shorter diagnosis to ICU admission interval (log-rank test P<0.001, both), higher maternal death (5.2% vs. 0.2%; P<0.0001) and preeclampsia (5.7% vs. 1.0%; P=0.0003). A spreadsheet calculator is available for risk estimation.

Conclusion

At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity, and should further emphasize that even in the absence of other co-morbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programmes to quickly protect those at highest risk of critical and fatal COVID-19.