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

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.

SARS-CoV-2 and the subsequent development of preeclampsia and preterm birth: evidence of a dose-response relationship supporting causality

“…The fact that 43% (13/30) of the cases of preeclampsia diagnosed after SARS-CoV-2 infection were preterm preeclampsia (<37 weeks) suggests that COVID-19 may be a cause of medically indicated preterm birth, which contributes to the excess preterm birth delivery rate reported previously. 6 This study was designed to examine whether the relationship between SARS-CoV-2 and preeclampsia or preterm birth is causal. Nonetheless, we observed the cases in which preeclampsia preceded infection with SARS-CoV-2.…”

Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters

“…A previous study focused on the incidence of preterm birth in women with SARS-CoV-2 infection and healthy patients, used NP swab testing only at the time of delivery and did not include past infections during pregnancy. Hence, the incidence of medically-induced preterm birth because of COVID-19-related preeclampsia could have been underestimated [ 29 ].…”

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

“…Nonetheless, pregnant women with SARS-CoV-2, particularly in the third trimester, are at increased risk for hospitalization and intensive care 2 , and existing evidence demonstrates that rates of maternal infection increased in the second wave 3 . Although the rates of preterm birth did not seem to be elevated in initial reports, data suggest pregnant women are at a higher risk of subsequent preterm birth, although this effect is mostly due to clinical intervention based on maternal illness rather than the spontaneous onset of preterm labor 4 .…”