Neonates represent a unique at-risk population for coronavirus disease 2019 (COVID-19). Their potential exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multiple: in utero, intrapartum and postpartum, from their mothers and family members and from healthcare workers, for those on neonatal units. Understanding the pathogenesis and epidemiology of COVID-19 in this group is essential to define optimal infection prevention and management guidelines.
Mark et al1 have summarized the emerging data on outcomes among pregnant women with COVID-19 and neonates with perinatal COVID exposure, and this provides a welcome addition to the literature. Nevertheless, with more than 106 million reported cases of COVID-19 worldwide, it seems that our understanding of the effect of SARS-CoV-2 on pregnant women, fetuses and infants is far from complete.
The authors reviewed studies published through August 15, 2020, on outcomes among pregnant women with confirmed COVID-19 and neonates with perinatal SARS-CoV-2 exposure. They identified 196 unique studies reporting 1922 pregnant women and 1361 neonates, dominated by reports from the United States. Only 61 neonates (4%) tested positive. Where it occurs, it seems that neonatal COVID-19 is largely postnatally acquired and a self-limited illness with good outcomes. However, we cannot yet be confident with these conclusions. As the authors acknowledge, further, large and prospective case-control and cohort studies are needed to fully understand the risk and impact of COVID-19 on neonates. To that end, national and international COVID-19 registries are a welcome step forward, but these must adopt standardized terminology and reporting for maximal benefit. Such studies should include both symptomatic pregnant women, as well as those who are asymptomatic, as the latter are common, and we know little about them. We do not yet know, for example, the implications of maternal asymptomatic or mild infection for the fetus and newborn infant. Many other important questions remain unanswered, such as the effect of COVID-19 in early pregnancy on miscarriage, intrauterine fetal growth restriction, congenital anomalies, long-term growth and neurodevelopmental outcomes.
A major implication of identifying a burden of disease in the fetus and newborn is its potential for prevention through maternal vaccination. A more pressing rationale for vaccination in pregnancy is the burden of disease that currently exists in pregnant women themselves. We have some insight into this from the review where Caesarean section, premature labor, ICU admission and need for mechanical ventilation appear more common in affected pregnant women.2–5 Given this increased risk, pregnant women should have the option to be vaccinated, just as with their nonpregnant peers. For many of the vaccine technologies now in clinical trials or widespread use under emergency use authorization, either no trials have ever been done in pregnant women or no studies of COVID-19 vaccines have yet commenced in pregnant women. A comprehensive document published by the Pregnancy Research Ethics for Vaccines, Epidemics and New Technologies Working Group in 2019 provided ethical guidance for preparedness, research and response for pregnant women and vaccines against emerging epidemic threats.6 Alas, the call was not taken up with the urgency required, and so we are now left with a range of tentative and variable national recommendations for pregnant women currently living through this pandemic. We welcome the recent announcement of clinical trials in pregnancy and postpartum and hope that clear guidance for vaccination of pregnant and breast-feeding women can emerge rapidly.
1. Mark EG, McAleese S, Golden WC, et al. Coronavirus disease 2019 in pregnancy and outcomes among pregnant women and neonates: A literature review. Pediatr Infect Dis J. 2021; 40:473–478.
2. Allotey J, Stallings E, Bonet M, et al.; for PregCOV-19 Living Systematic Review Consortium. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020; 370:m3320.
3. Ellington S, Strid P, Tong VT, et al. Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-June 7, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69:769–775.
4. Khalil A, von Dadelszen P, Draycott T, et al. Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic. JAMA. 2020; 324:705–706.
5. Zambrano LD, Ellington S, Strid P, et al.; COVID-19 Response Pregnancy and Infant Linked Outcomes Team. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69:1641–1647.
6. Krubiner CB, Faden RR, Karron RA, et al.; PREVENT Working Group. Pregnant women & vaccines against emerging epidemic threats: ethics guidance for preparedness, research, and response. Vaccine. 2021; 39:85–120.