An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women

Kalafat, Erkan
Prasad, Smriti
Birol, Pinar
Tekin, Arzu Bilge
Kunt, Atilla
Di Fabrizio, Carolina
Alatas, Cengiz
Celik, Ebru
Bagci, Helin
Binder, Julia
Le Doare, Kirsty
Magee, Laura A
Mutlu, Memis Ali
Yassa, Murat
Tug, Niyazi
Sahin, Orhan
Krokos, Panagiotis
O'brien, Pat
von Dadelszen, Peter
Palmrich, Pilar
Papaioannou, George
Ayaz, Reyhan
Ladhani, Shamez N
Kalantaridou, Sophia
Mihmanli, Veli
Khalil, Asma
Background: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts 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 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The 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. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves. Results Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The ‘mini-COvid Maternal Intensive Therapy’ model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07–1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06–1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78–8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The ‘full-COvid Maternal Intensive Therapy’ model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07–1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81–21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36–1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15–1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). 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 comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.
American Journal of Obstetrics and Gynecology


COVID-19 vaccination during pregnancy: coverage and safety
Blakeway, Helena; Prasad, Smriti; Kalafat, Erkan; Heath, Paul T.; Ladhani, Shamez N.; Le Doare, Kirsty; Magee, Laura A.; O'Brien, Pat; Rezvani, Arezou; von Dadelszen, Peter; Khalil, Asma (2021-01-01)
Background: Concerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom; limited data exist on its uptake and safety. Objective: This study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women. Study Design: This was a cohort study of pregnant women ...
Predictive accuracy of Southwest Thames Obstetric Research Collaborative (STORK) chorionicity-specific twin growth charts for stillbirth: a validation study
Kalafat, E.; Sebghati, M.; Thilaganathan, B.; Khalil, A. (2019-02-01)
Objective Twin pregnancy is associated with a 2-3-fold increased risk of stillbirth compared with singleton pregnancy. Despite the fact that the growth pattern in twins has been shown to be different from that in singletons, it is controversial whether twin-specific growth charts should be used routinely. A major goal of prenatal ultrasound is to identify fetuses with growth restriction at risk of stillbirth. The main aim of this study was to compare the performance of chorionicity-specific twin charts with...
The role of aspirin in prevention of preeclampsia in twin pregnancies: does the dose matter?
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Objective The use of aspirin in twin pregnancies for the prevention of preeclampsia is a controversial topic, and evidence on the required dose of aspirin is scarce. We aimed to assess the efficacy of 75 mg/day vs 150 mg/day aspirin for the prevention of preeclampsia in twin pregnancies. Study Design This is a retrospective cohort study of twin pregnancies managed at St George’s University Hospital between 2012 and 2019. The National Institute for Health and Care Excellence guideline published in 2010 has...
Incidence of postpartum hypertension within 2 years of a pregnancy complicated by pre-eclampsia: a systematic review and meta-analysis
Giorgione, V; Ridder, A.; Kalafat, E.; Khalil, A.; Thilaganathan, B. (Wiley, 2020-10-01)
Background Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long-term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth. Objectives This review aims to estimate the incidence of hypertension in the first 2 years after HDP. Search strategy MEDLINE, Embase and Cochrane databases were systematically searched in October 2019. Selection criteria Observational studies comparing hypertension rate following H...
Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension
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Background: Women with chronic hypertension are at increased risk for adverse maternal and perinatal outcomes. Maternal serum angiogenic markers, such as soluble fms-like tyrosine kinase 1 and placental growth factor, can be used to triage women with suspected preeclampsia. However, data about these markers in pregnant women with chronic hypertension are scarce. Objective: We aimed to evaluate the predictive accuracy of maternal serum levels of soluble fms-like tyrosine kinase 1, placental growth factor, an...
Citation Formats
E. Kalafat et al., “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, 2021, Accessed: 00, 2021. [Online]. Available: