Preterm Birth Rates and Racial Disparities during the COVID-19 Pandemic at a Single Institution in the Southeastern United States.

OBJECTIVE: The COVID pandemic has been associated with varied effects on preterm birth (PTB). We sought to compare rates of PTB during the pre- and post vaccination COVID periods with pre-pandemic PTB rates, stratified by race and ethnicity. STUDY DESIGN: Retrospective cohort comparing all deliveries over 20 weeks at a single tertiary center during "early" (March 2020-June 2020) versus "late" COVID (March 2021-June 2021), and "late" COVID versus pre-COVID (March to June 2014-2019). PTBs <37, <34, and <28 weeks were compared and stratified by race/ethnicity. RESULTS: A total of 16,483 deliveries occurred including 2,068 "early" COVID, 2,115 "late" COVID, and 12,300 pre-COVID. The PTB rate during "late" COVID was lower compared to "early" COVID (12.1 vs. 14.6%, p = 0.02). Rate of PTB <34 was also lower during "late" COVID (4.4 vs. 5.7%, p = 0.05). PTB <28 did not differ. When controlling for prior PTB, "late" COVID remained associated with a decreased risk of PTB compared to "early" COVID, adjusted odds ratio (aOR) of 0.82 (95% confidence interval [CI]: 0.68, 0.98). Although there was no difference in PTB among Hispanic individuals when comparing "late" COVID versus pre-COVID, when further subdivided, a small number of Hispanic Puerto Rican individuals had higher odds of PTB < 37 during "late" COVID versus pre-COVID (aOR = 4.29 [95% CI: 1.12, 16.4]). Additionally, White individuals had reduced odds of PTB <37 (aOR = 0.80 [95% CI: 0.65, 0.98]) during "late" COVID versus pre-COVID while the PTB rate was unchanged when comparing "late" COVID versus pre-COVID in all other racial and ethnic groups. CONCLUSION: During 2021, PTB rates decreased from rates observed in 2020 at the height of COVID restrictions. Among White birthing individuals, PTB decreased in 2021 compared to pre-COVID rates. This decrease was not observed in Black and Hispanic birthing individuals. These data highlight the continued racially disparate impact of the COVID-19 pandemic on PTB rates. KEY POINTS: · The COVID-19 pandemic has been associated with varied effects on the preterm birth (PTB) rate.. · PTB rates decreased in "late" COVID compared to "early" COVID.. · When stratified, PTB decreased among white individuals, but not in Black or Hispanic individuals..

The Temporal Relationship Between the Coronavirus Disease 2019 (COVID-19) Pandemic and Preterm Birth.

OBJECTIVE: To evaluate whether preterm birth rates changed in relation to the onset of the coronavirus disease 2019 (COVID-19) pandemic and whether any change depended on socioeconomic status. METHODS: This is an observational cohort study of pregnant individuals with a singleton gestation who delivered in the years 2019 and 2020 at 1 of 16 U.S. hospitals of the Maternal-Fetal Medicine Units Network. The frequency of preterm birth for those who delivered before the onset of the COVID-19 pandemic (ie, in 2019) was compared with that of those who delivered after its onset (ie, in 2020). Interaction analyses were performed for people of different individual- and community-level socioeconomic characteristics (ie, race and ethnicity, insurance status, Social Vulnerability Index (SVI) of a person's residence). RESULTS: During 2019 and 2020, 18,526 individuals met inclusion criteria. The chance of preterm birth before the COVID-19 pandemic was similar to that after the onset of the pandemic (11.7% vs 12.5%, adjusted relative risk 0.94, 95% CI 0.86-1.03). In interaction analyses, race and ethnicity, insurance status, and the SVI did not modify the association between the epoch and the chance of preterm birth before 37 weeks of gestation (all interaction P>.05). CONCLUSION: There was no statistically significant difference in preterm birth rates in relation to the COVID-19 pandemic onset. This lack of association was largely independent of socioeconomic indicators such as race and ethnicity, insurance status, or SVI of the residential community in which an individual lived.

Association Between Giving Birth During the Early Coronavirus Disease 2019 (COVID-19) Pandemic and Serious Maternal Morbidity.

OBJECTIVE: We aimed to evaluate whether delivering during the early the coronavirus disease 2019 (COVID-19) pandemic was associated with increased risk of maternal death or serious morbidity from common obstetric complications compared with a historical control period. METHODS: This was a multicenter retrospective cohort study with manual medical-record abstraction performed by centrally trained and certified research personnel at 17 U.S. hospitals. Individuals who gave birth on randomly selected dates in 2019 (before the pandemic) and 2020 (during the pandemic) were compared. Hospital, health care system, and community risk-mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in response to the early COVID-19 pandemic are described. The primary outcome was a composite of maternal death or serious morbidity from common obstetric complications, including hypertensive disorders of pregnancy (eclampsia, end organ dysfunction, or need for acute antihypertensive therapy), postpartum hemorrhage (operative intervention or receipt of 4 or more units blood products), and infections other than SARS-CoV-2 (sepsis, pelvic abscess, prolonged intravenous antibiotics, bacteremia, deep surgical site infection). The major secondary outcome was cesarean birth. RESULTS: Overall, 12,133 patients giving birth during and 9,709 before the pandemic were included. Hospital, health care system, and community SARS-CoV-2 mitigation strategies were employed at all sites for a portion of 2020, with a peak in modifications from March to June 2020. Of patients delivering during the pandemic, 3% had a positive SARS-CoV-2 test result during pregnancy through 42 days postpartum. Giving birth during the pandemic was not associated with a change in the frequency of the primary composite outcome (9.3% vs 8.9%, adjusted relative risk [aRR] 1.02, 95% CI 0.93-1.11) or cesarean birth (32.4% vs 31.3%, aRR 1.02, 95% CI 0.97-1.07). No maternal deaths were observed. CONCLUSION: Despite substantial hospital, health care, and community modifications, giving birth during the early COVID-19 pandemic was not associated with higher rates of serious maternal morbidity from common obstetric complications. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT04519502.

First- or second-trimester SARS-CoV-2 infection and subsequent pregnancy outcomes.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy. OBJECTIVE: This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness. STUDY DESIGN: A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at <20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at <37 weeks of gestation and <34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of <5th or <10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at <37 weeks of gestation. RESULTS: Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at <37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at <37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at <34 weeks of gestation, any major congenital malformation, and size for gestational age of <5th or <10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features. CONCLUSION: There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

Pregnancy-Associated Extracorporeal Membrane Oxygenation in the United States.

OBJECTIVE: The use of extracorporeal membrane oxygenation (ECMO) therapy has increased in the adult population. Studies from the H1N1 influenza pandemic suggest that ECMO deployment in pregnancy is associated with favorable outcomes. With increasing numbers of pregnant women affected by COVID-19 (coronavirus disease 2019) and potentially requiring this life-saving therapy, we sought to compare comorbidities, costs, and outcomes between pregnancy- and nonpregnancy-associated ECMO therapy among reproductive-aged female patients. STUDY DESIGN: We used the 2013 to 2019 National Readmissions Database. Diagnosis and procedural coding were used to identify ECMO deployment, potential indications, comorbid conditions, and pregnancy outcomes. The primary outcome was in-hospital mortality during the patient's initial ECMO stay. Secondary outcomes included length of stay and hospital charges/costs, occurrence of thromboembolic or bleeding complications during ECMO hospitalization, and mortality and readmissions up to 330 days following ECMO stay. Univariate and multivariate regression models were used to model the associations between pregnancy status and outcomes. RESULTS: The sample included 324 pregnancy-associated hospitalizations and 3,805 nonpregnancy-associated hospitalizations, corresponding to national estimates of 665 and 7,653 over the study period, respectively. Pregnancy-associated ECMO had lower incidence of in-hospital death (adjusted odds ratio [aOR]: 0.56, 95% confidence interval [CI]: 0.41-0.75) and bleeding complications (aOR: 0.67, 95% CI: 0.49-0.93). Length of stay was significantly shorter (adjusted rate ratio (aRR): 0.86, 95% CI: 0.77-0.96) and total hospital costs were less (aRR: 0.83, 95% CI: 0.75-0.93). Differences in the incidence of thromboembolic events (aOR: 1.04, 95% CI: 0.78-1.38) were not statistically significant. CONCLUSION: Pregnancy-associated ECMO therapy had lower incidence of in-hospital death, bleeding complications, total inpatient cost, and length of stay when compared with nonpregnancy-associated ECMO therapy without increased thromboembolic complications. Pregnancy-associated ECMO therapy should be offered to eligible patients. KEY POINTS: · Pregnancy-related ECMO use was compared with nonpregnant use.. · Outcomes were equal or favored pregnancy-related deployment.. · These data may be useful when considering ECMO use in pregnancy..

Universal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Testing for Obstetric Inpatient Units Across the United States.

BACKGROUND: The purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates. METHODS: A cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1-3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis. RESULTS: Data were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0-3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708). CONCLUSIONS: Given the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2-related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates.

Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications.

Importance: It remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity. Objective: To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications. Design, Setting, and Participants: Retrospective cohort study of 14 104 pregnant and postpartum patients delivered between March 1, 2020, and December 31, 2020 (with final follow-up to February 11, 2021), at 17 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Gestational Research Assessments of COVID-19 (GRAVID) Study. All patients with SARS-CoV-2 were included and compared with those without a positive SARS-CoV-2 test result who delivered on randomly selected dates over the same period. Exposures: SARS-CoV-2 infection was based on a positive nucleic acid or antigen test result. Secondary analyses further stratified those with SARS-CoV-2 infection by disease severity. Main Outcomes and Measures: The primary outcome was a composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. The main secondary outcome was cesarean birth. Results: Of the 14 104 included patients (mean age, 29.7 years), 2352 patients had SARS-CoV-2 infection and 11 752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was significantly associated with the primary outcome (13.4% vs 9.2%; difference, 4.2% [95% CI, 2.8%-5.6%]; adjusted relative risk [aRR], 1.41 [95% CI, 1.23-1.61]). All 5 maternal deaths were in the SARS-CoV-2 group. SARS-CoV-2 infection was not significantly associated with cesarean birth (34.7% vs 32.4%; aRR, 1.05 [95% CI, 0.99-1.11]). Compared with those without a positive SARS-CoV-2 test result, moderate or higher COVID-19 severity (n = 586) was significantly associated with the primary outcome (26.1% vs 9.2%; difference, 16.9% [95% CI, 13.3%-20.4%]; aRR, 2.06 [95% CI, 1.73-2.46]) and the major secondary outcome of cesarean birth (45.4% vs 32.4%; difference, 12.8% [95% CI, 8.7%-16.8%]; aRR, 1.17 [95% CI, 1.07-1.28]), but mild or asymptomatic infection (n = 1766) was not significantly associated with the primary outcome (9.2% vs 9.2%; difference, 0% [95% CI, -1.4% to 1.4%]; aRR, 1.11 [95% CI, 0.94-1.32]) or cesarean birth (31.2% vs 32.4%; difference, -1.4% [95% CI, -3.6% to 0.8%]; aRR, 1.00 [95% CI, 0.93-1.07]). Conclusions and Relevance: Among pregnant and postpartum individuals at 17 US hospitals, SARS-CoV-2 infection was associated with an increased risk for a composite outcome of maternal mortality or serious morbidity from obstetric complications.

Symptomatic versus asymptomatic COVID-19: does it impact placental vasculopathy?

This study sought to assess the impact of COVID-19 on placental vasculature in the context of maternal symptomatology - comparing asymptomatic to symptomatic pregnant patients - and disease severity - comparing pregnant patients with mild, moderate, severe, and critical COVID-19 infection. PCR-confirmed COVID-19 positive pregnant patients in a single health system who delivered between 3/2020-5/2021 included. All patients had positive COVID test and delivered during the study period. Primary outcome was incidence of any vascular malperfusion on placental pathology. Secondary outcomes were FVM and MVM on placental pathology. Placental pathology compared between symptomatic (sCOVID) and asymptomatic (aCOVID) patients. Secondary analysis of symptomatic patients, comparing placental pathology between mild disease(mCOVID) and worse disease(moderate, severe, or critical-defined by 2020 NIH guidelines) (dCOVID), also performed. Of 112 patients, 53 (47%) had symptoms. Twenty-seven (24.1%) patients had evidence of vascular malperfusion; 26 (23.2%) had MVM. When comparing aCOVID and sCOVID patients, no difference in rate of vascular malperfusion identified, nor any differences in rates of FVM or MVM. Among sCOVID patients (n = 53), 39 (74%) had mCOVID and 14 (26%) had dCOVID (moderate n = 4, severe n = 9, critical n = 1). Patients with dCOVID had earlier median delivery GA (37.4wks vs 39.2wks, p = .03). No difference in latency from diagnosis to delivery seen between mCOVID and dCOVID groups (4.4 vs 3.0wks, p = .96). Twelve (30.8%) patients had vascular malperfusion on pathology, all had mCOVID (p = .02). Eleven (28.2%) mCOVID patients had MVM; no dCOVID patients had evidence of vascular malperfusion (p = .03). No difference in FVM was found between cohorts. Symptomatic COVID-19 infection did not impact placental vasculature differently than asymptomatic infection, even when stratifying by trimester of infection. Among pregnant patients with symptomatic COVID-19, mild disease was associated with placental vascular changes on the maternal side while severe disease was not. Further studies are needed to understand the implications of these findings.

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19).

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race-ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2-11%) incidence of venous thromboembolism among those with severe-critical illness compared with 0.2% in mild-moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe-critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30-1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18-2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42-5.14) compared with asymptomatic patients. Mild-moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. CONCLUSION: Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe-critical COVID-19, but not those with mild-moderate COVID-19, were at increased risk of perinatal complications.

Coronavirus disease 2019 vaccines in pregnancy.

As of December 1, 2020, nearly 64 million people have been infected with the severe acute respiratory syndrome coronavirus 2 worldwide with nearly 1.5 million global deaths. The impact of this virus has continued to overwhelm hospital infrastructure and demanded remodeling of healthcare systems. With rising concerns for a third, and possibly the largest, wave of individuals infected with the virus, national leaders are continuing to seek avenues by which we can further limit disease transmission and prevent infection with the use of vaccination. To our knowledge, no clinical trial evaluating vaccines to prevent coronavirus disease 2019 has included pregnant women. In December 2020, it was anticipated that the Food and Drug Administration will approve at least 1 or 2 mRNA-based coronavirus disease 2019 vaccine under the Emergency Use Authorization based on phase 3 clinical trial efficacy data. Both Pfizer and Moderna have manufactured mRNA-based vaccines with 95% and 94.1% efficacy against the severe acute respiratory syndrome coronavirus 2. AstraZeneca has manufactured a vaccine using a viral vector demonstrating early efficacy as well, and this next-generation platform has previously been utilized with the Ebola vaccine and safely administered during pregnancy with an acceptable safety profile. Approval of these vaccines will have a tremendous impact on the ongoing pandemic, yet there remains a lack of data for use of coronavirus disease 2019 vaccine in pregnant women. In this article, we seek to discuss the available data regarding treatment and prevention of coronavirus disease 2019 in pregnancy and address the growing questions regarding how best to approach vaccine access and administration in the pregnant population.

Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials.

OBJECTIVE: To characterize hydroxychloroquine (HCQ) exposure in patients with rheumatic disease receiving longterm HCQ compared to target concentrations with reported antiviral activity against the coronavirus disease 2019 caused by SARS-CoV-2 (COVID-19). METHODS: We evaluated total HCQ concentrations in serum and plasma from published literature values, frozen serum samples from a pediatric systemic lupus erythematosus trial, and simulated concentrations using a published pharmacokinetic model during pregnancy. For each source, we compared observed or predicted HCQ concentrations to target concentrations with reported antiviral activity against SARS-CoV-2. RESULTS: The average total serum/plasma HCQ concentrations were below the lowest SARS-CoV-2 target of 0.48 mg/l in all studies. Assuming the highest antiviral target exposure (total plasma concentration of 4.1 mg/l), all studies had about one-tenth the necessary concentration for in vitro viral inhibition. Pharmacokinetic model simulations confirmed that pregnant adults receiving common dosing for rheumatic diseases did not achieve target exposures; however, the models predict that a dosage of 600 mg once a day during pregnancy would obtain the lowest median target exposure for most patients after the first dose. CONCLUSION: We found that the average patient receiving treatment with HCQ for rheumatic diseases, including children and non-pregnant/pregnant adults, are unlikely to achieve total serum or plasma concentrations shown to inhibit SARS-CoV-2 in vitro. Nevertheless, patients receiving HCQ long term may have tissue concentrations far exceeding that of serum/plasma. Because the therapeutic window for HCQ in the setting of SARS-CoV-2 is unknown, well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for HCQ.