Brenna L. Hughes

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

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.

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.

Abstract Background Women with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or “17P”) to placebo has been published, and this trial was stopped early due to a large treatment benefit. Objective This study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. Study Design This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT 01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB &lt; 35 weeks and a neonatal morbidity composite index. The composite included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB &lt; 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%–11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. Results Baseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had &gt;1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and &lt;2% had cervical shortening &lt;25 mm. There were no significant differences in the frequency of PTB &lt; 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71–1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68–1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4–1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB &lt; 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. Conclusion In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.