In a recent study published in JAMA Pediatrics, an international team of researchers from Argentina, Brazil, Egypt, France, Ghana, India, Indonesia, Italy, Japan, Mexico, Nigeria, North Macedonia, Pakistan, Russia, Spain, Switzerland, the US and led by investigators from the University of Oxford (UK) studied 2,130 pregnant women age 18 and older and their newborns at 43 different institutions in 18 different countries from March to October 2020, as part of the observational INTERCOVID Multinational Cohort Study. For each woman who tested positive for COVID-19 before delivery, two unmatched, uninfected women of similar gestational age (±2 weeks) were enrolled.
The 706 COVID-19 patients were at much higher risk than their 1,424 uninfected counterparts for preeclampsia/eclampsia (eclampsia is a serious condition where high blood pressure results in seizures during pregnancy), pregnancy-related high blood pressure, infections requiring antibiotics, intensive care unit (ICU) admission, referral to a higher level of care, preterm delivery, medically indicated preterm delivery, severe neonatal illness, and severe perinatal illness and death.
Women with COVID-19 diagnosis, already at high risk of preeclampsia and COVID-19 because of preexisting overweight, diabetes, hypertension, and cardiac and chronic respiratory diseases, had almost 4 times greater risk of developing preeclampsia/eclampsia, which could reflect the known association with these comorbidities and/or the acute kidney damage that can occur in patients with COVID-19.
Compared with uninfected women, those who tested positive for COVID-19 had a lower rate of spontaneous labor but higher rates of cesarean birth and preterm delivery and fetal distress (signs before and during childbirth indicating that the fetus is not well). The most common indications for preterm delivery among women with a COVID-19 diagnosis were preeclampsia/eclampsia (24.7%), small fetus for gestational age (15.5%), and fetal distress (13.2%).
Of the COVID-19 patients, 13% of their 416 newborns tested were also positive for coronavirus. Exclusive breastfeeding and newborn test positivity were not linked.
Cesarean birth was linked to an increased risk of newborn infection, while breastfeeding was not. Mean maternal age was 30.2 years, and 48.6% of infected women were overweight early in pregnancy, compared with 40.2% of uninfected women.
Of the women with a coronavirus diagnosis, 1.6% died (maternal death ratio, 159 per 10,000 births); four of them died of severe preeclampsia, three of respiratory failure requiring mechanical ventilation, and one of a pulmonary embolism. Five women had worsening respiratory failure before delivery, two of whom underwent cesarean delivery and later died, and two developed cough, shortness of breath, and fever within 7 days after a normal delivery and died. Among the uninfected women, one died due to preexisting liver cancer and cirrhosis.
Women infected with SARS-CoV-2 stayed in the ICU for, on average, 3.73 days longer than uninfected women. Increased risk of serious maternal complications in COVID-19 patients was tied to fever and shortness of breath, as were complications in newborns. But the 44.0% of infected women with no symptoms were at higher risk for only maternal illness and preeclampsia.
This multinational cohort study showed that COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications.