On behalf of the Washington State COVID-19 in Pregnancy Collaborative 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 reactioneconfirmed 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 2019eassociated 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, 2.3e5.3);(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, 257e3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7e43.6) 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, À0.3 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 casefatality 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...

Background During the early months of the coronavirus disease of 2019 (COVID-19) pandemic, risks to pregnant women of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were uncertain. Pregnant patients can serve as a model for the success of the clinical and public health response during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of SARS-CoV-2 infections in pregnancy are unknown due to incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early pandemic is poorly understood. Objective(s) To estimate the SARS-CoV-2 infection rate in pregnancy and examine disparities by race/ethnicity and English-language proficiency in Washington State. Study Design Pregnant patients with a polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 1-June 30, 2020 were identified within 35 hospitals/clinic systems capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health (ACH) region and cross-sectionally compared to SARS-CoV-2 infection rates in similarly aged adults in Washington State. Race/ethnicity and language used for medical care among the pregnant patients were compared to recent data from Washington State. Results A total of 240 pregnant patients with SARS-CoV-2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study are: 1) The SARS-CoV-2 infection rate in pregnancy was 13.9/1,000 deliveries (95% confidence interval [CI], 8.3-23.2) compared to 7.3/1,000 (95%CI 7.2-7.4) in 20-39 year old adults in Washington State (Rate Ratio [RR] 1.7, 95%CI 1.3-2.3), 2) the SARS-CoV-2 infection rate reduced to 11.3/1000 (95%CI 6.3-20.3) when excluding 45 cases of SARS-CoV-2 detected through asymptomatic screening (RR 1.3, 95%CI 0.96-1.9), 3) the proportion of SARS-CoV-2 cases in pregnancy among most non-white racial/ethnic groups was 2-4 fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018, and 5) the proportion of SARS-CoV-2 infected pregnant patients receiving medical care in a non-English language was higher than estimates of limited English proficiency in Washington State (30.4% versus 7.6%). Conclusions The SARS-CoV-2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial/ethnic minority groups and patients receiving medical care in a non-English...

Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics.