key: cord-1022111-4u3v4vyu
authors: Lokken, Erica M.; Huebner, Emily M.; Taylor, G. Gray; Hendrickson, Sarah; Vanderhoeven, Jeroen; Kachikis, Alisa; Coler, Brahm; Walker, Christie L.; Sheng, Jessica S.; al-Haddad, Benjamin J.S.; McCartney, Stephen A.; Kretzer, Nicole M.; Resnick, Rebecca; Barnhart, Nena; Schulte, Vera; Bergam, Brittany; Ma, Kimberly K.; Albright, Catherine; Larios, Valerie; Kelley, Lori; Larios, Victoria; Emhoff, Sharilyn; Rah, Jasmine; Retzlaff, Kristin; Thomas, Chad; Paek, Bettina W.; Hsu, Rita J.; Erickson, Anne; Chang, Andrew; Mitchell, Timothy; Hwang, Joseph K.; Erickson, Stephen; Delaney, Shani; Archabald, Karen; Kline, Carolyn R.; LaCourse, Sylvia M.; Adams Waldorf, Kristina M.
title: Disease Severity, Pregnancy Outcomes and Maternal Deaths among Pregnant Patients with SARS-CoV-2 Infection in Washington State
date: 2021-01-27
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2020.12.1221
sha: 8382a014e9ca6756d34562ad86bfca126d3d2453
doc_id: 1022111
cord_uid: 4u3v4vyu

Background Evidence is accumulating that coronavirus disease 2019 (COVID-19) increases the risk for hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection is unknown. Objectives To describe disease severity and outcomes of SARS-CoV-2 infections in pregnancy across Washington State including pregnancy complications and outcomes, hospitalization, and case fatality. Study Design Pregnant patients with a polymerase chain reaction confirmed SARS-CoV-2 infection between March 1 and June 30, 2020 were identified in a multi-center retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case fatality rates in pregnancy were compared to COVID-19 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. Results The principal study findings were: 1) among 240 pregnant patients in Washington State with SARS-CoV-2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for COVID-19, and 1 in 80 died; 2) the COVID-19-associated hospitalization rate was 3.5-fold higher than in similarly-aged adults in Washington State [10.0% vs. 2.8%; rate ratio (RR) 3.5, 95% confidence interval (CI) 2.3-5.3]; 3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes, autoimmune disease, and Class III obesity; 4) three maternal deaths (1.3%) were attributed to COVID-19 for a maternal mortality rate of 1,250/100,000 pregnancies (95%CI 257-3,653); 5) the COVID-19 case fatality in pregnancy was a significant 13.6-fold (95%CI 2.7-43.6) higher in pregnant patients compared to similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95%CI -0.3-2.6); and 6) preterm birth was significantly higher among women with severe/critical COVID-19 at delivery than for women who had recovered from COVID-19 (45.4% severe/critical COVID-19 vs. 5.2% mild COVID-19, p<0.001). Conclusions COVID-19 hospitalization and case fatality rates in pregnant patients were significantly higher compared to similarly aged adults in Washington State. This data indicates that pregnant patients are at risk for severe or critical disease and mortality compared to non-pregnant adults, as well as preterm birth.

Background: Evidence is accumulating that coronavirus disease 2019 increases the risk for hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection is unknown.

Objectives: To describe disease severity and outcomes of SARS-CoV-2 infections in pregnancy across Washington State including pregnancy complications and outcomes, hospitalization, and case fatality.

CoV-2 infection between March 1 and June 30, 2020 were identified in a multi-center retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case fatality rates in pregnancy were compared to fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery.

The principal study findings were: 1) among 240 pregnant patients in Washington State with SARS-CoV-2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for COVID-19, and 1 in 80 died; 2) the COVID-19associated hospitalization rate was 3.5-fold higher than in similarly-aged adults in Washington State [10.0% vs. 2.8%; rate ratio (RR) 3.5, 95% confidence interval (CI) 2.3-5.3]; 3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes, autoimmune disease, and Class III obesity; 4) three maternal deaths (1.3%) were attributed to COVID-19 for a maternal mortality rate of 1,250/100,000 pregnancies (95%CI 257-3,653); 5) the COVID-19 case fatality in pregnancy was a significant 13.6fold (95%CI 2.7-43.6) higher in pregnant patients compared to similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95%CI -0.3-2.6); and 6) preterm birth was significantly higher among women with severe/critical J o u r n a l P r e -p r o o f 7 COVID-19 at delivery than for women who had recovered from severe/critical COVID-19 vs. 5.2% mild COVID-19, p<0.001).

Conclusions: COVID-19 hospitalization and case fatality rates in pregnant patients were significantly higher compared to similarly aged adults in Washington State. This data indicates that pregnant patients are at risk for severe or critical disease and mortality compared to non-pregnant adults, as well as preterm birth. Evidence is accumulating that pregnant patients with SARS-CoV-2 infections are at 6 higher risk for hospitalization, mechanical ventilation, intensive care unit (ICU) 7 admission and preterm birth. (2, (7) (8) (9) (10) (11) In June of 2020, a U.S. population-based study by 8 the Centers for Disease Control (CDC) found that pregnant patients with SARS-CoV-2 9 infections were at higher risk for hospitalization, mechanical ventilation and ICU 10 admission, but mortality rates were similar between pregnant and non-pregnant 11 reproductive age women (0.2%). (8) were abstracted from electronic medical records and each record was reviewed by a 54 second abstractor for quality control.(2) Final disease and delivery outcome data were 55 abstracted between July 7-September 10, 2020 based on site capacity. COVID-19 56 disease severity was defined as: (1) mild (asymptomatic, non-pneumonia, mild 57 pneumonia); (2) severe (dyspnea, respiratory rate of ≥30 breaths/min, percutaneous 58 oxygen saturation of ≥93% on room air at rest, arterial oxygen tension over inspiratory shock, or multiple organ dysfunction or failure).(17, 18) Hospitalized participants were 62 considered "hospitalized due to COVID-19 concern" based on the reason for admission 63 noted by the abstracting team, including respiratory concerns and "other" COVID-19 64 concerns. Patients admitted for concurrent obstetrical (ex: delivery) and COVID-19 65 concerns were considered hospitalized for COVID-19 concern.

66 67 This multi-site medical records review was approved by Institutional Review Boards procedures. Hospitalization and case fatality rates at the state level were estimated 101 between March 1, 2020-September 26, 2020 since outcomes were collected for some 102 study participants through September, and to account for the lag between infection 103 detection and mortality outcomes. Both crude RR and RD were calculated given the 104 small number of events in this study population to ascertain both relative and absolute 105 risk.

Two hundred and forty confirmed cases of SARS-CoV-2 infections in pregnancy were 111 detected by WA-CPC sites including 24 (10.0%) who were hospitalized for a COVID-19 112 respiratory concern. Demographic and co-existing conditions are reported in Table 1 . Of 113 these, forty-six cases were previously published including details on 8 deliveries.(2) 114 Median age was 28 years old (IQR 24-33.5). Nearly half were White (113/240) and half 115 reported Hispanic ethnicity (126/240). Two-thirds were publicly insured (160/240). The hospitalized for a COVID-19 concern were slightly older (median 32 years old vs 28, 120 p=0.04) and more likely than non-hospitalized pregnant patients with SARS-CoV-2 121 infection to have at least one comorbidity or underlying condition (45.8% vs 17.6%, 122 p=0.001), such as asthma (20.8% vs 6.9%, p=0.02), hypertension (20.8% vs 2.8%, 123 p<0.001), type 2 diabetes (12.5% vs 4.6%, p=0.11), autoimmune disease (8.3% vs 124 0.9%, p<0.01), and Class III obesity (21.1% vs 6.3%, p=0.01; Table 1 ).

Approximately half of the SARS-CoV-2 cases were detected in the third trimester (Table 4 ).

Most pregnant patients hospitalized for COVID-19 had severe or critical disease 145 (79.2%, 19/24), but 20.8% (5/24) admitted for a COVID-19 concern were ultimately 146 considered to have mild disease by the disease severity criteria (Table 2) 

There were three deaths among 240 pregnant patients with a SARS-CoV-2 infection for 165 a maternal mortality rate of 1,250/100,000 pregnancies (95%CI 258-3,653) (Table 4) . 166 Overall, the SARS-CoV-2 case fatality rate among included pregnant patients was a 167 significant 13.6-fold higher in pregnant patients than the 91.7/100,000 rate in similarly 168 aged 20-39 year olds in Washington State (RR 13.6, 95%CI 2.7-43.6); equating to an 169 absolute rate difference of 1.2% (95%CI -0.26-2.57; Table 4 ). The three deaths in 170 pregnant patients constitute 9.4% (3/32) of the total deaths in this age group in 171 Washington State assuming all three deaths were included in the state's surveillance 172 data. were similar by COVID-19 status at delivery (Table 6) . There were three sets of twins for a total of 156 live-born neonates. Neonates born to 217 mothers with severe or critical COVID-19 at the time of delivery were more likely to be 218 low birthweight (<2500 g) and more likely to be admitted to the NICU for fetal indications 219 than those born to women with mild COVID-19 or recovered from COVID-19 at the time 220 of delivery (Table 6 ). Of the 144 neonates with SARS-CoV-2 test results available, one-221 third were tested at least once (31.3%, 45/144) and none tested positive ( Table 5 ). The Finally, it will be important to follow neonates for many years to determine the long-term We would like to thank the pregnant patients contributing data to this manuscript, as 371 well as our partners across Washington State that enabled this investigation. We also 372 recognize the differences between sex and gender, noting that the term "women" is not 373 inclusive for biologically born female individuals that identify as non-binary or 374 transgender. We thank Jane Edelson, who provided assistance with project J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Abbreviations: HELLP, hemolysis, elevated liver enzymes, and a low platelet count; NICU, neonatal intensive care unit; PPROM, preterm premature rupture of membranes.

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i Presented as n(%) and median(IQR)

ii One patient was re-admitted several months after a severe COVID infection due to a COVID-associated complication and was considered to have "Active COVID-19" in this analysis although she had negative polymerase chain reaction testing at the time. iii N=155, excluding two spontaneous abortions. iv COVID-19 was the singular indication or a contributing indication for delivery

v Data collection tools included new onset gestational hypertension, preeclampsia, eclampsia, chronic hypertension with superimposed preeclampsia, and HELLP

viii Testing data missing for 12 neonates, for a total of 57 neonates born to pregnant patients considered COVID-19 recovered at delivery, 78 neonates born to pregnant patients with mild COVID-19 at delivery, and 9 neonates born to pregnant patients with severe COVID-19 at delivery. ix NICU admission occurred for a neonatal health indication. Does not include NICU admission solely for COVID-19 precautions. N=155, data missing for one neonate

Abbreviations: g, grams; HELLP, hemolysis, elevated liver enzymes, and a low platelet count; NICU, neonatal intensive care unit; PPROM, preterm premature rupture of membranes.i Presented as n(%) and median(IQR). ii Excludes three cases of SARS-CoV-2 infection during the first trimester. Two cases ended in spontaneous abortion and one led to a maternal death. iii COVID-19 was either the singular indication or a contributory indication for delivery. iv A new onset hypertensive disorder of pregnancy or postpartum included any of the following diagnoses: new onset gestational hypertension, preeclampsia, eclampsia, chronic hypertension with superimposed preeclampsia, and HELLP. v Live births only (N=156). There were 3 twin gestations. vi Birthweight is missing for 1 neonate (N=155). vii Testing data missing for 12 neonates, for a total of 24 neonates born to pregnant patients with second trimester SARS-COV-2 infections and 120 neonates born to pregnant patients with third trimester SARS-COV-2 infections. viii NICU admission occurred for a neonatal health indication. Does not include NICU admission solely for COVID-19 precautions. N=155, data missing for one neonate.