A new study published in The Lancet, reviewed clinical data from Providence St Joseph Health (PSJH) electronic health records for pregnant people (aged 18 years and older and younger than 45 years) who delivered in the USA at the Providence, Swedish, or Kadlec sites in Alaska, California, Montana, Oregon, and Washington between March 5, 2020, and July 4, 2021, in order to understand the effects of maternal SARS-CoV-2 infection on birth outcomes.
Multiple studies have reported increased preterm birth, but not stillbirth, following SARS-CoV-2 infection, with higher rates among symptomatic versus asymptomatic people. Additionally, SARS-CoV-2 infection has been associated with increased rates of pre-eclampsia.
Thus far, studies have been done either with small study populations and greater clinical detail, or with large populations but limited detail (insurance claims or aggregate reporting). It is also well known that minority and low-income communities are disproportionately impacted by COVID-19, and many risk factors associated with poor birth outcomes are elevated in these populations, which could account for some of the disparity in birth outcomes for pregnant people infected with SARS-CoV-2.
Throughout pregnancy, there are crucial periods during which there is a greater impact of in utero shocks on fetal development. Fetuses are most vulnerable to maternal stress during the fifth and sixth month of pregnancy, resulting in higher rates of preterm birth, low birthweight, and small for gestational age (SGA) than exposure during other periods of pregnancy.
Likewise, the effect of maternal influenza infection on birth outcomes depends on the timing of exposure. Influenza exposure during pregnancy is associated with increased infant and neonatal mortality during the first trimester, decreased birthweight during the second trimester, and increased preterm birth and decreased birthweight during the third trimester. Thus, the researchers expected a difference in birth outcomes based on the gestational age at time of maternal SARS-CoV-2 infection.
The impact of maternal SARS-CoV-2 infection remains unclear. In this study, the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs, was evaluated. Models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy were also developed.
The SARS-CoV-2 positive cohort included people who had a positive SARS-CoV-2 PCR-based test during pregnancy, subdivided by trimester of infection. No one in this cohort had been vaccinated for COVID-19 at time of infection. The SARS-CoV-2 negative cohort were people with at least one negative SARS-CoV-2 PCR-based test and no positive tests during pregnancy.
Cohorts were matched on common covariates impacting birth outcomes, and univariate and multivariate analysis were done to investigate risk factors and predict outcomes. The primary outcome was gestational age at delivery with annotation of preterm birth classification.
Between March 5, 2020, and July 4, 2021, 73 666 pregnant people delivered, 18 335 of whom had at least one SARS-CoV-2 test during pregnancy before Feb 14, 2021. PSJH observed 882 people infected with SARS-CoV-2 during their pregnancy and 19 769 people who have never tested positive for SARS-CoV-2 and received at least one negative SARS-CoV-2 test during their pregnancy.
SARS-CoV-2 infection indicated an increased risk of preterm delivery and stillbirth accounted for primarily by first and second trimester SARS-CoV-2 infections. Gestational age at SARS-CoV-2 infection was correlated with gestational age at delivery and had the greatest impact on predicting gestational age at delivery. The people in this study had mild or moderate SARS-CoV-2 infections and acute COVID-19 severity was not correlated with gestational age at delivery.
These results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity.