Background
Evidence is accumulating that coronavirus disease 2019 increases the risk of 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 are unknown.
Objective
This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality.
Study Design
Pregnant patients with a polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 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 as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019–associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 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 mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257–3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7–43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, −0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P <.001).
Conclusion
Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.
Introduction
In the early months of the coronavirus disease 2019 (COVID-19) pandemic, pregnant patients faced uncertain risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection in pregnancy is now known to result in a spectrum of asymptomatic to critical maternal disease. Evidence is accumulating that pregnant patients with SARS-CoV-2 infections are at a higher risk of hospitalization, mechanical ventilation, intensive care unit (ICU) admission, and preterm birth. , In June of 2020, a United States population-based study by the Centers for Disease Control and Prevention (CDC) found that pregnant patients with SARS-CoV-2 infections were at a higher risk of hospitalization, mechanical ventilation, and ICU admission, but mortality rates were similar between pregnant and nonpregnant reproductive-aged women (0.2%). A subsequent CDC study including more cases and restricted to symptomatic cases in pregnancy found an increased risk of mortality among pregnant women vs nonpregnant women with SARS-CoV-2, leading the CDC to revise public health guidance to indicate that pregnant women are at risk of severe COVID-19 disease. However, because pregnancy status was missing or unknown in up to three-quarters of COVID-19 cases reported to the United States CDC, these results may be biased and the extent to which pregnant women experience severe or critical disease with an increased risk of mortality needs further evaluation. ,
Why was this study conducted?
Whether coronavirus disease 2019 (COVID-19) poses a risk for pregnant women to develop severe or critical disease and the impact on maternal mortality and morbidity are poorly understood.
Key findings
In a multicenter retrospective cohort study of facilities covering 61% of annual births in Washington State, there were 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections, 24 COVID-19–associated hospitalizations (10%), and 3 maternal deaths (1.25%). The COVID-19 case-fatality rate in pregnant patients was 13.6-fold higher than similarly aged individuals with COVID-19.
What does this add to what is known?
Our data suggest the impact of COVID-19 on pregnant patients is greater than currently appreciated, with an elevated risk of maternal death.
Additional population-based studies of COVID-19 in pregnancy including fatality rates in pregnancy would help determine the extent to which pregnant patients with COVID-19 are at risk of severe or critical disease similar to the 2009 H1N1 influenza pandemic. Inclusion of all pregnant patients with SARS-CoV-2 including milder and asymptomatic cases managed as outpatients is critical for determining the impact of COVID-19 on pregnancy outcomes and the possibility of severe or critical maternal disease. Furthermore, whether the timing of SARS-CoV-2 infection (eg, trimester of infection, status at time of delivery) is associated with adverse pregnancy outcomes, such as hypertensive disease in pregnancy or preterm birth, has not been thoroughly interrogated. We established the Washington State COVID-19 in Pregnancy Collaborative (WA-CPC) as a multicenter retrospective cohort study to capture COVID-19 cases in pregnancy. The WA-CPC network captures the majority of annual deliveries in the state, gathers clinical data on COVID-19 outcomes in pregnancy, and shares information and strategies to improve patient care. The objective of this study was to describe disease severity and outcomes of COVID-19 in pregnancy across Washington State including pregnancy complications and outcomes, hospitalization, and case fatality.
Methods
Washington State COVID-19 in Pregnancy Collaborative
The WA-CPC includes 35 large hospitals (n=22) and clinic systems providing prenatal care (n=13) in Washington State, encompassing 61% of the approximate 86,000 annual state deliveries ( Supplemental Table ). The majority of the participating hospitals had instituted universal screening for SARS-CoV-2 by nasopharyngeal swab before or at the time of the delivery admission by May 2020 (March, 14%; April, 64%; May, 76%), with the remaining hospitals initiating universal testing for scheduled delivery admissions only.
Eligible cases were pregnant patients (≥18 years old) with a polymerase chain reaction (PCR) test–confirmed SARS-CoV-2 infection during any trimester of pregnancy detected between March 1, 2020, and June 30, 2020. Pregnant women were tested for many reasons including exposure to a known SARS-CoV-2 case, symptoms, recent travel, personal requests, and universal screening at labor and delivery. Collaborating sites identified eligible patients using diagnostic codes and site-specific algorithms. Deidentified data were abstracted from electronic medical records, and each record was reviewed by a second abstractor for quality control. Final disease and delivery outcome data were abstracted between July 7, 2020, and September 10, 2020, based on site capacity. COVID-19 disease severity was defined as (1) mild (asymptomatic, nonpneumonia, mild pneumonia), (2) severe (dyspnea, respiratory rate of ≥30 breaths per minute, percutaneous oxygen saturation of ≥93% on room air at rest, arterial oxygen tension over inspiratory oxygen fraction of <300 mm Hg, or lung infiltrates of >50% within 24–48 hours), and (3) critical (severe respiratory distress, respiratory failure requiring mechanical ventilation, shock, or multiple organ dysfunction or failure). , Hospitalized participants were considered “hospitalized owing to COVID-19 concern” based on the reason for admission noted by the abstracting team, including respiratory concerns and “other” COVID-19 concerns. Patients admitted for concurrent obstetrical (eg, delivery) and COVID-19 concerns were considered hospitalized for COVID-19 concern.
This multisite medical records review was approved by institutional review boards (IRBs) at the University of Washington (STUDY# 00009701, approved March 6, 2020) and Swedish Medical Center (STUDY #2020000172, approved March 19, 2020). All other sites entered into reliance agreements with the University of Washington IRB.
Statistical analyses
Demographic and SARS-CoV-2 infection characteristics in pregnancy were summarized by proportions and medians (interquartile range [IQR]) overall and were compared across COVID-19 hospitalization status using chi-squared and Kruskal-Wallis tests. Maternal, delivery, and neonatal outcome characteristics were summarized for patients who had delivered by the time of final chart abstraction. These characteristics were described overall, by trimester of infection, and by the patient’s COVID-19 status at the time of delivery. Pregnant patients were categorized as “COVID-19 recovered” if they were SARS-CoV-2 negative at the time of delivery or their last positive test was >14 days before delivery in alignment with quarantine guidelines during the study period; this categorization was independent of disease severity. Women who were PCR positive for SARS-CoV-2 in the preceding 14 days of delivery or admitted with post–COVID-19 complications at the time of delivery (even in absence of continued PCR positivity) were considered to have “active COVID-19” and further classified by mild or severe or critical disease status. Delivery outcomes were compared among COVID-19 recovered, mild COVID-19, and severe or critical COVID at delivery and by trimester of infection, using the chi-squared and Kruskal-Wallis tests, where appropriate.
Collaborating sites captured the majority of pregnancies in Washington State with the highest coverage in regions most affected by COVID-19 ( Supplemental Table ). We calculated crude rate ratios (RRs) and rate differences (RDs) with Poisson exact 95% confidence interval (CI) to compare COVID-19–associated hospitalization and case-fatality rates in our study population with rates experienced by 20- to 39-year-old adults with SARS-CoV-2 in Washington State using publicly available data from the Washington State Department of Health; this comparison group served as the best publicly available proxy for rates in reproductive-aged women because data were only available by age group or gender, but not both. Notably, nonpregnant adults were tested for SARS-CoV-2 for the same reasons as pregnant people including universal screening before medical procedures. Hospitalization and case-fatality rates at the state level were estimated between March 1, 2020, and September 26, 2020, because outcomes were collected for some study participants through September and to account for the lag between infection detection and mortality outcomes. Both crude RR and RD were calculated given the small number of events in this study population to ascertain both relative and absolute risks.
Results
Severe acute respiratory syndrome coronavirus 2 infections in pregnancy
A total of 240 confirmed cases of SARS-CoV-2 infections in pregnancy were detected by WA-CPC sites including 24 (10.0%) who were hospitalized for a COVID-19 respiratory concern. Demographic and coexisting conditions are presented in Table 1 . Of these, 46 cases were previously published including details on 8 deliveries. The median age was 28 years (IQR, 24–33.5). Nearly half were white (113 of 240) and half reported Hispanic ethnicity (126 of 240). Two-thirds were publicly insured (160 of 240). The most common underlying conditions were prepregnancy obesity (body mass index of ≥30.0, 45.3% [102 of 225]), asthma (8.3%; 20 of 240), type 2 diabetes mellitus (5.4%; 13 of 240), and hypertension (4.6%; 11 of 240). Pregnant patients with SARS-CoV-2 infections who were hospitalized for a COVID-19 concern were slightly older (median, 32 vs 28 years old; P =.04) and more likely than nonhospitalized pregnant patients with SARS-CoV-2 infection to have at least 1 comorbidity or underlying condition (45.8% vs 17.6%; P =.001), such as asthma (20.8% vs 6.9%; P =.02), hypertension (20.8% vs 2.8%; P <.001), type 2 diabetes mellitus (12.5% vs 4.6%; P =.11), autoimmune disease (8.3% vs 0.9%; P <.01), and class III obesity (21.1% vs 6.3%; P =.01) ( Table 1 ).
| Characteristics | All pregnant patients (N=240) a | Not hospitalized for COVID-19 concern (n=216) | Hospitalized for COVID-19 concern (n=24) | P value |
|---|---|---|---|---|
| Demographics | ||||
| Age (y) | 28 (24–34) | 28 (24–33) | 32 (26–35) | .04 |
| Race | .14 | |||
| American Indian or Alaska Native | 10 (4.2) | 8 (3.7) | 2 (8.3) | |
| Asian | 8 (3.3) | 8 (3.7) | 0 (0) | |
| Native Hawaiian or other Pacific Islander | 8 (3.3) | 5 (2.3) | 3 (12.5) | |
| Black or African American | 20 (8.3) | 19 (8.8) | 1 (4.2) | |
| White | 113 (47.1) | 104 (48.2) | 9 (37.5) | |
| Multiracial | 2 (0.8) | 2 (0.9) | 0 (0) | |
| Other | 28 (11.7) | 26 (12.0) | 2 (8.3) | |
| Unknown | 51 (21.3) | 44 (20.4) | 7 (29.2) | |
| Ethnicity | .29 | |||
| Hispanic or Latino | 126 (52.5) | 117 (54.2) | 9 (37.5) | |
| Not Hispanic or Latino | 108 (45.0) | 94 (43.5) | 14 (58.3) | |
| Unknown | 6 (2.5) | 5 (2.3) | 1 (4.2) | |
| Type of insurance at diagnosis | .11 | |||
| Public | 160 (66.7) | 146 (67.6) | 14 (58.3) | |
| Private | 74 (30.8) | 66 (30.6) | 8 (33.3) | |
| Other | 4 (1.7) | 2 (0.9) | 2 (8.3) | |
| Uninsured | 1 (0.4) | 1 (0.5) | 0 (0) | |
| Unknown | 1 (0.4) | 1 (0.5) | 0 (0) | |
| Pregnancy history b | ||||
| Parity | 1 (1–3) | 1 (1–2) | 1.5 (1–4) | .08 |
| History of preterm birth | 23 (9.6) | 21 (9.8) | 2 (8.3) | .82 |
| Prepregnancy comorbidities or underlying conditions | ||||
| Any comorbidity or underlying condition (excluding obesity) c | 49 (20.4) | 38 (17.6) | 11 (45.8) | .001 |
| Asthma | 20 (8.3) | 15 (6.9) | 5 (20.8) | .02 |
| Type 2 diabetes mellitus | 13 (5.4) | 10 (4.6) | 3 (12.5) | .11 |
| Hypertension | 11 (4.6) | 6 (2.8) | 5 (20.8) | <.001 |
| Cardiovascular disease | 6 (2.5) | 5 (2.3) | 1 (4.2) | .58 |
| Autoimmune disease | 4 (1.7) | 2 (0.9) | 2 (8.3) | <.01 |
| Hypothyroidism | 4 (1.7) | 3 (1.4) | 1 (4.2) | .31 |
| Prepregnancy BMI (kg/m 2 ) d | .02 | |||
| Underweight (<18.5) | 3 (1.3) | 3 (1.5) | 0 (0) | |
| Normal (18.5–24.9) | 57 (25.3) | 55 (26.7) | 2 (10.5) | |
| Overweight (25.0–29.9) | 63 (28.0) | 56 (27.2) | 7 (36.8) | |
| Obese (≥30.0) | 102 (45.3) | 92 (44.7) | 10 (52.6) | |
| Class 3 obesity (BMI of ≥40 kg/m 2 ) d | 17 (7.6) | 13 (6.3) | 4 (21.1) | .02 |
a Summarized as number (percentage) or median (IQR)
b Parity and history of preterm birth missing for 1 participant
c Comorbidities assessed for the data collection tool included diabetes mellitus, asthma, reactive airway disease, hypertension, hypothyroidism, cardiovascular disease, autoimmune disease, HIV, immunosuppressive medication use, cirrhosis, hepatitis A history, hepatitis C antibody, previous or current cancer, tuberculosis, prepregnancy kidney disease, chronic obstructive pulmonary disease, seizure disorder, and cerebrovascular disease
d Data only available for 225 patients. Prepregnancy weight or weight before 12 weeks’ gestational age was used if prepregnancy weight was not available. For 1 patient, their weight at 14 weeks’ gestation was used to calculate prepregnancy BMI.
Approximately half of the SARS-CoV-2 cases were detected in the third trimester (56.3%; 135 of 240), with 27.9% (67 of 240) in the second trimester and 15.8% (38 of 240) in the first trimester ( Table 2 ). At the time of the first positive COVID-19 test, 77.1% of pregnant patients (185 of 240) were symptomatic (or reported resolved COVID-19 symptoms) with the remaining being asymptomatic (22.9%; 55 of 240). Mild COVID-19 disease occurred in 90.8% (158 of 240, including 55 asymptomatic cases), with severe and critical disease occurring in 7.5% (18 of 240) and 1.7% (4 of 240), respectively. Notably, 3 maternal deaths owing to COVID-19 complications occurred (1.3%; 3 of 240).
| Characteristic | All pregnant patients N=240 a | Hospitalization status | Trimester of SARS-CoV-2 infection | |||||
|---|---|---|---|---|---|---|---|---|
| Not hospitalized for COVID-19 concern (n=216) | Hospitalized for COVID-19 concern (n=24) b | P value | First (n=38) | Second (n=67) | Third (n=135) | P value | ||
| Trimester of infection c | <.001 | |||||||
| First | 38 (15.8) | 37 (17.1) | 1 (4.2) | |||||
| Second | 67 (27.9) | 62 (28.7) | 5 (20.8) | |||||
| Third | 135 (56.3) | 117 (54.2) | 18 (75.0) | |||||
| Symptomatic at first COVID-19 positive test c | .02 | <.001 | ||||||
| Asymptomatic | 55 (22.9) | 54 (25.0) | 1 d (4.2) | 3 (7.9) | 3 (4.5) | 49 (36.3) | ||
| Symptomatic | 185 (77.1) | 162 (75.0) | 23 (95.8) | 35 (92.1) | 64 (95.5) | 86 (63.7) | ||
| Disease severity | <.001 | .28 | ||||||
| Mild | 218 (90.8) | 213 (98.6) | 5 (20.8) | 37 (97.4) | 62 (92.5) | 119 (88.2) | ||
| Severe | 18 (7.5) | 3 e (1.4) | 15 (62.5) | 0 (0) | 4 (6.0) | 14 (10.4) | ||
| Critical | 4 (1.7) | 0 (0) | 4 (16.7) | 1 (2.6) | 1 (1.5) | 2 (1.5) | ||
| Outcomes | ||||||||
| Hospitalized for COVID-19 concern | 24 (10.0) | 1 (2.6) | 5 (7.5) | 18 (13.3) | .11 | |||
| Admitted to ICU | 8 (3.3) | 0 (0.0) | 8 (33.3) | 0 (0) | 1 (1.5) | 7 (5.2) | .74 | |
| Maternal death | 3 (1.3) | 0 (0.0) | 3 (12.5) | <.001 | 1 (2.6) | 1 (1.5) | 1 (0.7) | .64 |
| Final pregnancy outcome f | 158 (65.8) | 135 (62.5) | 23 (95.8) | .001 | 3 (7.9) | 27 (40.3) | 128 (94.8) | <.001 |
| COVID-19 at final outcome g | 90 (57.0) | 78 (57.8) | 12 (52.1) | .62 | 2 (66.7) | 2 (7.4) | 86 (67.2) | <.001 |
| Recovered from COVID-19 at final outcome | 68 (43.0) | 57 (42.2) | 11 (47.8) | .62 | 1 (33.3) | 25 (92.6) | 42 (32.8) | <.001 |
a Summarized as number (percentage) or median (interquartile range)
b One patient was hospitalized and admitted to ICU twice several months apart
c At the time of the first positive SARS-CoV-2 test
d This patient was tested owing to a known exposure to COVID-19 and became symptomatic before hospitalization
e All 3 patients had dyspnea but were not ultimately hospitalized
f Includes 1 maternal death and 2 spontaneous abortions in pregnant patients with first-trimester SARS-CoV-2 infections
g Includes pregnant patients with mild or severe or critical COVID-19 at the time of final pregnancy outcome.
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