COVID-19 worsens maternal, fetal outcomes, studies find

Women who gave birth within 28 days of a positive COVID-19 test died at a significantly higher rate than their healthy counterparts, finds a Scottish study yesterday in Nature Medicine. They were also more prone to poor birth outcomes, even if they weren't severely ill, according to a US study in The Lancet Digital Health.

Vaccine uptake low in pregnant women

In the first study, University of Edinburgh and Public Health Scotland researchers analyzed national, population-level data on COVID-19 vaccine uptake and SARS-CoV-2 infections in pregnant women.

From the launch of a COVID-19 vaccination program in Scotland on Dec 8, 2020, to Oct 31, 2021, 18,457 pregnant women received 25,917 doses. Uptake was much lower in this group than among nonpregnant women ages 18 to 44 years, with 32.3% giving birth in October 2021 having received two doses of the Pfizer/BioNTech, Moderna, or AstraZeneca/Oxford vaccine, compared with 77.4% of other women.

There were 4,950 COVID-19 infections among pregnant women. The death rate among women who delivered babies within 28 days of a COVID-19 diagnosis was 22.6 per 1,000 births (95% confidence interval [CI], 12.9 to 38.5), compared with the pandemic background rate of 5.6 per 1,000 births (95% CI, 5.1 to 6.2).

A total of 2,364 babies were born to COVID-infected women. Among them, 2,353 were live births, of which 241 were preterm, for a preterm birth rate of 10.2% (95% CI, 9.1% to 11.6%). The preterm birth rate among babies born within 28 days of maternal COVID-19 diagnosis was 16.6% (95% CI, 13.7% to 19.8%).

Among the 2,364 births, 11 were stillborn, and 8 live-born babies died within 28 days of birth, for a perinatal death rate of 8.0 per 1,000 births after maternal infection at any point in pregnancy (95% CI, 5.0 to 12.8). Ten stillbirths and four neonatal deaths occurred in babies born within 28 days of maternal infection.

Over the study period, the background preterm birth rate was 8.0% (95% CI, 7.8% to 8.1%), and the extended perinatal death rate was 5.6 per 1,000 births (95% CI, 5.1 to 6.2).

Overall, 77.4% (95% CI, 76.2% to 78.6%) of infections, 90.9% (95% CI, 88.7% to 92.7%) of COVID-related hospitalizations, and 98% (95% CI, 92.5% to 99.7%) of women requiring critical care, as well as all newborn deaths, occurred in pregnant women who were unvaccinated at diagnosis.

Of all first-trimester COVID-19 infections, 6.7% (95% CI, 5.5% to 8.1%) led to hospitalization, compared with 10.7% (95% CI, 9.3% to 12.2%) of those in the second trimester and 33.5% (95% CI, 31.2% to 35.9%) of those in the third trimester. No infections in the first trimester led to the need for critical care, compared with 2.0% (95% CI, 1.4% to 2.8%) of those in the second trimester and 4.3% (95% CI, 3.4% to 5.5%) in the third trimester.

"Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron," the study authors wrote. "Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic."

In expert comments from the Science Media Centre, Allyah Abbas-Hanif, MBBS, of Imperial College London, said, "We have seen maternal deaths increasing with each progressive wave of the pandemic, a trend reversed in other high-risk groups by the protection afforded by vaccines."

She called for revisiting the long-term practice of excluding pregnant and breastfeeding women from clinical trials and drug development. "There is now more medication use and disease in pregnancy than ever before, despite this, only one medicine designed for use in pregnancy has been licensed in four decades," Abbas-Hanif said. "Moving forwards, the covid-19 pandemic must catalyse improved research and health equity for pregnant women and their babies."

Risk of preterm delivery, low birth weight, stillbirth

A study led by Institute for Systems Biology researchers in Seattle showed that pregnant women infected with SARS-CoV-2 have higher odds of adverse birth outcomes, including preterm birth, small size for gestational age, low birth weight, and stillbirth.

The team used data from the Providence St. Joseph Health electronic medical records for pregnant women who gave birth at sites in Alaska, California, Montana, Oregon, or Washington from Mar 5, 2020, to Jul 4, 2021. None of the women were vaccinated against COVID-19.

A total of 73,666 pregnant women gave birth, 18,335 of whom had at least one COVID-19 test during pregnancy before Feb 14, 2021. Of the 73,666 women, 882 tested positive for COVID-19 during pregnancy, 85 in the first trimester, 226 in the second trimester, and 571 in the third semester. Overall, 19,769 women never tested positive for COVID-19 and received at least one negative test during pregnancy.

COVID-19 infection conferred an increased risk of preterm delivery and stillbirth, most often in the first and second trimester. Gestational age at diagnosis correlated with and had the most impact on predicting gestational age at delivery. The women all had mild or moderate illness, and disease severity didn't correlate with gestational age at delivery.

Infected women were more likely than their uninfected peers to be Hispanic or another race other than Asian or White and to have Medicaid insurance, lower age, higher body mass index, and lower education level.

"Due to increased risk of maternal–fetal health of SARS-CoV-2 infection, we propose prioritisation of vaccination of pregnant people in areas where vaccine distribution is scarce," the  authors wrote.

In an Institutes for Systems Biology news release, corresponding author Jennifer Hadlock, MD, said that pregnant women could benefit from increased monitoring after COVID-19 diagnosis. "Both maternal and fetal health are at increased risk with COVID-19," she said. "Therefore, this reinforces the importance of protecting pregnant women."

In a commentary in the same journal, Elizabeth Barr, PhD, and Damiya Whitaker, PsyD, both of the National Institutes of Health, and Pamela Stratton, MD, of Scientific Consulting Group in Gaithersburg, Md., said that maternal health and COVID-19 disparities in the United States demand attention.

"[COVID-19] has dramatically illuminated both persistent health inequities and the failure of research, clinical care, and medical education to address the social and structural factors that generate and perpetuate these inequities among those at greatest risk of adverse pregnancy outcome," they wrote.

Barr and colleagues called for a more inclusive body of research and a dialog on the importance of maternal healthcare and infectious disease prevention in women. "Piekos and colleagues' recommendation to closely monitor preganant [sic] people who have had a SARS-CoV-2 infection during the first or second trimester of pregnancy is an essential beginning," they said.

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