The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis
Authors:   Spanish Obstetric Emergency Group, Martinez-Perez Oscar , Prats Rodriguez Pilar , Muner Hernandez Marta , Encinas Pardilla Maria Begoña , Perez Perez Noelia , Vila Hernandez Maria Rosa , Villalba Yarza Ana , Nieto Velasco Olga , Del Barrio Fernandez Pablo Guillermo , Forcen Acebal Laura , Orizales Lago Carmen Maria , Martinez Varea Alicia , Muñoz Abellana Begoña , Suarez Arana Maria , Fuentes Ricoy Laura , Martinez Diago Clara , Janeiro Freire Maria Jesus , Alférez Alvarez-Mallo Macarena , Casanova Pedraz Cristina , Alomar Mateu Onofre , Lesmes Heredia Cristina , Wizner de Alva Juan Carlos , Bernardo Vega Rut , Macia Badia Montserrat , Alvarez Colomo Cristina , Sanchez Muñoz Antonio , Pratcorona Alicart Laia , Alonso Saiz Ruben , Lopez Rodriguez Monica , del Carmen Barbancho Lopez Maria , Meca Casbas Marta Ruth , Vaquerizo Ruiz Oscar , Moran Antolin Eva , Nuñez Valera Maria Jose , Fernandez Fernandez Camino , Tubau Navarra Albert , Cano Garcia Alejandra Maria , Baena Luque Carmen , Soldevilla Perez Susana , Gastaca Abasolo Irene , Adanez Garcia Jose , Teulon Gonzalez Maria , Puertas Prieto Alberto , Ostos Serna Rosa , del Pilar Guadix Martin Maria , Catalina Coello Monica , Ferriols Perez Elena , Caño Aguilar Africa , De la Cruz Conty Maria Luisa , Sainz Bueno Jose Antonio 
Published: April 2021

Abstract
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.