The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis.

BACKGROUND: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. METHODS: We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. MAIN OUTCOME MEASURES: Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. RESULTS: Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32-3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11-2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43-8.94, p <  0.001) was also observed in positive mothers. CONCLUSION: This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.

Cervical Pessary Compared With Vaginal Progesterone for Preventing Early Preterm Birth: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of a cervical pessary and vaginal progesterone to prevent spontaneous preterm births in pregnant women with cervical lengths 25 mm or less as measured by transvaginal ultrasonography. METHODS: This was a multicenter, open-label, randomized, noninferiority trial. Women with singleton pregnancies and a short cervix (25 mm or less) measured transvaginally at the second-trimester ultrasonogram were invited to participate. They were computer-randomized (one to one) into cervical pessary placement or treatment with vaginal progesterone (200 mg/24 hours). The primary outcome was spontaneous preterm delivery before 34 weeks of gestation. The noninferiority margin was set at 4% with a 0.025 one-sided α level and a statistical power of 80%. That is, if the 95% CI upper bound exceeded 4%, the pessary could not be deemed noninferior. A sample size of 254 women was required to show noninferiority of the pessary to progesterone. RESULTS: The trial was conducted from August 2012 to April 2016 with the participation of 27 Spanish hospitals. A total of 254 patients were enrolled and 246 included in the intention-to-treat analysis. Demographic and baseline characteristics were similar across groups. The rate of spontaneous delivery before 34 weeks of gestation was 14% (n=18/127) in the pessary group and 14% (n=17/119) in the progesterone group with a risk difference of -0.11% (95% CI -8.85% to 8.62%; P=.99), that is, noninferiority was not shown for the pessary. The incidence of increased vaginal discharge (87% vs 71%, P=.002) and discomfort (27% vs 3%, P<.001) was significantly higher in the pessary group. CONCLUSION: A cervical pessary was not noninferior to vaginal progesterone for preventing spontaneous birth before 34 weeks of gestation in pregnant women with short cervixes. CLINICAL TRIAL REGISTRATION: EU Clinical Trials Register, 2012-000241-13; ClinicalTrials.gov, NCT01643980.