Perinatal and neonatal considerations in COVID-19

Key points

The incidence of COVID-19 in newborns is low; however, COVID-19 can still cause severe illness and complications.
Evidence related to the COVID-19 pandemic and perinatal and neonatal care continues to evolve, but many unanswered questions remain.
Pregnant and non-pregnant individuals have similar manifestations of COVID-19 symptoms, but pregnant individuals are at increased risk for severe COVID-19–associated illness; risk is reduced with vaccination.
Perinatal transmission of SARS-CoV-2 from mothers to their infants is most likely via environmental exposure to aerosolized droplets of viral particles after birth.
Clinical practices to reduce the transmission have changed throughout the pandemic.
The COVID-19 pandemic has exposed and magnified disparities deeply rooted in structural racism and socioeconomic inequality that must be addressed when caring for mothers and their newborns.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a ribonucleic acid (RNA) respiratory virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. The pandemic’s global health crisis continues to challenge countries and public health organizations worldwide. ^, COVID-19 was first reported and described in Wuhan, Hubei Province, China, in December 2019. ^, Since then, World Health Organization (WHO) data indicate that there have been over 600 million cases globally and over 6 million deaths worldwide. Most deaths have come from the United States (>93 million cases). In adults, including pregnant individuals, symptoms range from asymptomatic through mild influenza-like symptoms to severe respiratory illness, multiple organ failure, and death. ^, ^, Perinatal and postnatal transmission is low, particularly when appropriate precautions are met. Signs of neonatal disease have most commonly ranged from asymptomatic to mildly symptomatic; although relatively rare, the risk of infants acquiring the infection and developing complications is still considerable. Severe COVID-19 in pregnancy has been associated with an increased risk of stillbirth, preterm delivery, fetal growth restriction, and cesarean delivery. ^, The COVID-19 pandemic has additionally exposed and magnified racial and ethnic health disparities deeply rooted in structural racism and socioeconomic inequality that must be addressed when caring for mothers and their newborns. As the rate of infection worldwide continues to change, and scientific evidence continues to evolve, this chapter includes recommendations and important perinatal and neonatal considerations in COVID-19.

SARS-CoV-2 origin

SARS-CoV-2 is an RNA respiratory virus, part of the Coronaviridae family, and is responsible for the COVID-19 pandemic. ^, Coronaviruses have been described since the 1960s and have been responsible for causing other pandemics, including SARS-CoV in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. However, coronavirus is most commonly known for being the agent responsible for the common cold. ^,

SARS-CoV-2 most likely originated through a zoonotic event, meaning that the infection was likely transmitted from animals to humans. In this case, the virus naturally evolved and most likely spread from a bat to humans or through an intermediate reservoir (possibly a pangolin). ^, ^, Given that SARS-CoV-2 has a high rate of genetic mutations, there have been many variants identified in different parts of the world, including Delta and Omicron, which are the predominant variants in the United States.

Viral cell entry

The SARS-CoV-2 virus core has a viral capsid with a receptor-binding domain of the SARS-CoV-2 spike (S) glycoprotein that enables binding to the human cell-surface protein angiotensin-converting enzyme 2 (ACE2) on the host cell and initiates viral entry. The S glycoprotein is cleaved by the host protease transmembrane serine protease 2 (TMPRSS-2), allowing the virus to enter the cell cytoplasm by either endocytosis or fusion. ^, ^, Once inside the cell, the single-stranded viral RNA is replicated into a large polyprotein cleaved by a viral protease into smaller pieces of viral RNA. The viral RNA and proteins are then packed into a nucleocapsid and assembled into a new virion released with new viral copies to infect the host further. ^, Given that ACE2 is mainly expressed in the epithelial surfaces in upper and lower airways (also found in other tissues such as the small intestine, brain, blood vessels, and muscle), SARS-CoV-2 causes mainly respiratory illness. The expression of ACE2 and TMPRSS2 in children’s airway epithelia is lower compared with adults. These findings, in addition to an immature immune system, likely contribute to the decreased rate of infection and transmission in children, as well as to a milder clinical course. ^,

Mode of transmission

Perinatal transmission of SARS-CoV-2 is most commonly via environmental exposure to aerosolized droplets of viral particles after birth and not via the transplacental route. ^, ^, Other possible evaluated routes include vertical transmission via the placenta, contact with infected secretions during delivery, and breast milk. Although there have been a few positive cases of neonates born to individuals with SARS-CoV-2 right after delivery, there is not enough evidence to support vertical transmission. ^, ^, SARS-CoV-2 has not yet been isolated from breast milk, but there are a few case reports of viral RNA detection; the latter does not demonstrate potential for transmission by this route, however. In systematic reviews, the percentage of positive tests among neonates born to positive SARS-CoV-2 individuals (as a proxy for perinatal transmission) range from 1% to 9.1%, with no difference between vaginal and cesarean births. ^, ^, The rates vary depending on the study size, timing of publication before and after implementation of maternal surveillance testing, different waves of the pandemic, and different variant peaks. For this reason, the true incidence of neonatal test positivity is unknown. In a multicenter cohort in Massachusetts, the leading risk factor for neonatal test positivity was “maternal social vulnerability.”

Prenatal and obstetrical considerations

Pregnant and non-pregnant individuals have similar manifestations of COVID-19 symptoms, but pregnant individuals are at increased risk for severe COVID-19–associated illness. Immunologic and physiologic adaptive alterations during pregnancy, including diaphragm elevation and increased heart rate and oxygen consumption, may increase the risk for more severe illness and complications, particularly in respiratory infections. ^, ^, ^, In addition to more severe illness, symptomatic pregnant and recently pregnant people with COVID-19 are at increased risk for hospitalization, admission to the intensive care unit, need for mechanical ventilation, need for extracorporeal membrane oxygenation, and death compared with nonpregnant individuals of reproductive age. ^, ^, Some complications have been associated with the increased predisposition to hypercoagulability and thrombotic changes in the placenta that may predispose to abnormal oxygenation and adverse perinatal outcomes, including stillbirth. For example, there is an increased prevalence of decidual arteriopathy and other features of maternal vascular malperfusion that may compromise perfusion of the maternal and fetal vasculature. ^, Cases of stillbirth have been associated with extensive histological changes with placentitis (marked intervillositis with a mixed inflammatory infiltrate and massive perivillous fibrinoid deposition with trophoblast damage). More studies are needed to clarify the impact of SARS-CoV-2 infection on the physiology of pregnancy, the placenta, and resultant fetal complications.

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