Viral Infections in the Fetus and Neonate

Virus Transmission From Mother to Child

Viruses for which MTCT has well-characterized clinical consequences are listed in Table 93.1 . Whether maternal viral infection is spread to the fetus or neonate is determined by the occurrence of viremia, exposure to virus during labor and delivery, or from virolactia. For many viruses, the prevalence of infection among women of childbearing age and the incidence of new infections during pregnancy contribute to the overall prevalence of fetal or neonatal infection. Transmission of VZV, rubella virus, parvovirus B19, hepatitis E virus, and several agents not listed in Table 93.1 is based on the incidence and timing of maternal infection in relation to pregnancy and delivery. The risk of transmission and the consequences of infection for the fetus or newborn are described elsewhere in this textbook.

MTCT of some viruses not listed in Table 93.1 is known to occur. Studies of hepatitis G virus, a hepatotropic flavivirus that produces chronic infection, show that 60% to 80% of infants born to mothers with viral RNA in their blood are infected. Transiently elevated serum alanine aminotransferase concentrations have been found, but no illness in infants has been associated with perinatal infection. ^, Zika virus, a member of the flavivirus family that is transmitted by the Aedes aegypti mosquito, can be transmitted transplacentally and has been associated with microcephaly and central nervous system damage. Sporadic reports of congenital disease due to enteroviruses or adenovirus and detection of viral nucleic acid by polymerase chain reaction (PCR) testing of amniotic fluid suggest that transplacental transmission of these viruses may be more common than appreciated. ^, While a handful of case reports of vertical transmission with SARS-CoV-2 have been reported, a larger study of 127 pregnant women documented no evidence of viremia or placental infection to suggest vertical transmission, ^{, ,} although more work is needed to determine rare episodes of in utero transmission. Toward that end, the World Health Organization has developed definitions for in-utero, perinatal, and postnatal transmission of SARS-CoV-2 to help standardize the reports in the literature during this fast-moving pandemic.

Infection of the newborn at the time of birth occurs through exposure to virus in the genital tract or perineum; it is the major route of acquisition of HSV, HIV, hepatitis B, and hepatitis C. Labor and delivery prolong the contact between the neonate’s mucosal surfaces and maternal surfaces, secretions, and blood, facilitating the transfer of viruses. The newborn who acquires virus during birth typically becomes viremic or sheds virus in other body fluids within days to a few months postpartum. Intrapartum acquisition of HSV and HIV has well-known clinical consequences. Acquisition of hepatitis B and hepatitis C leads to chronic infection that can progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Intrapartum acquisition of CMV is common, but infection usually is not clinically significant except in a small proportion of very low birth weight premature infants.

MTCT of viruses through human milk is important in the epidemiology of CMV, HTLV-I, and HIV. ^, The nursing infant is exposed to this potential source of infection many times each day for several months. While CMV acquired through breastfeeding is the major route of acquisition, it neither causes acute illness nor is associated with adverse sequelae, with the exception of premature newborns. ^,

HIV and HTLV-I can be transmitted through human milk, with the onset of infection usually beyond the neonatal period. ^, Breast milk also may be the source of hepatitis G virus C and torque teno virus, but neither has been proven to cause disease when transmitted through human milk. ^, Breastfeeding may also be a route of acquisition for rubella virus, HSV, echovirus 18, dengue virus, West Nile virus, Zika virus, and SARS-CoV-2, through the proximity between the infant and a mother actively shedding the virus. ^{, ,} Additionally, viruses that are transmitted through blood can be transmitted during breastfeeding in the setting of bleeding or cracked nipples.

Because of the association of higher infant mortality with formula feeding, the potential transmission of maternal viral infection is rarely a reason to interrupt breastfeeding in developing countries, with the possible exception of HIV infection. In the context of maternal HIV infection, the 2010 World Health Organization guidelines on infant feeding, most recently updated in 2016, recommend that national authorities in each country decide which infant feeding practice should be supported. The previous recommendation that “replacement feeding should not be used unless it is acceptable, feasible, affordable, sustainable, and safe” remains, but stronger support is stated for maternal antiretroviral treatment and continued breastfeeding, especially in countries where avoidance of breastfeeding is associated with increased infant mortality and rates of MTCT of HIV are high. The American Academy of Pediatrics (AAP) Committee on Pediatric AIDS in 2013 recommended complete avoidance of breastfeeding for the US and reaffirmed this policy in 2016 “regardless of maternal viral load and antiretroviral therapy.” The AAP’s 2018 guidance is summarized in Table 93.2 .

Sources of Maternal Infection

The risk of maternal infection is related to the epidemiology of the specific virus and type of exposure. CMV infection is common among young children who shed CMV chronically. Exposure to young children is probably the most important risk factor for maternal CMV infection. Sexual activity is a risk factor for HSV, CMV, HIV, and hepatitis B virus infection. Injecting drug use is a risk factor for HIV, hepatitis B virus, and hepatitis C virus. For viruses that cause acute, self-limited infections with seasonal or periodic epidemics such as parvovirus B19, rubella, and enteroviruses, risk of maternal and congenital infection is related to epidemic activity in the community.

Animal and insect vectors can be the source of maternal viral infections that are spread to the fetus or newborn. Congenital infection due to lymphocytic choriomeningitis virus (LCMV) is likely underdiagnosed in the US. Maternal LCMV infection, especially in the first trimester, can lead to fetal infection with subsequent chorioretinitis, microcephaly or macrocephaly, and intracranial calcifications. Maternal exposure to rodents may be the key epidemiologic clue. ^, West Nile virus is an arthropod-borne pathogen with transplacental and breast milk transmission reported in the US. ^, However, MTCT appears to be rare. Dengue virus, chikungunya virus, and Zika virus are transmitted to humans by A. aegypti mosquitoes and cause similar acute febrile illnesses. Maternal chikungunya virus infection can be transmitted to the fetus and neonate; a transmission rate of almost 50% has been reported with maternal viremia at term.

Although it is unclear whether maternal infection affects the outcome of pregnancy, newborn infection can manifest as sepsis and encephalopathy, often associated with central nervous system sequelae. Dengue virus infection is common in tropical areas, and rates of MTCT range from 12% to 60% when infection occurs during pregnancy. Similar to chikungunya virus infection, maternal dengue viremia at term is associated with neonatal infection that can manifest as sepsis with fever, thrombocytopenia, hepatosplenomegaly, rash, and pleural effusion.

Community-Acquired and Nosocomial Postnatal Infection

Horizontal transmission of viruses to neonates from caregivers or family members occurs primarily through infected droplets or contaminated hands since neonates are more vulnerable than older hosts due to a naïve immune system and since their care requires repeated handling and close contact. Outbreaks of many viruses in newborn nurseries have been described; enterovirus, adenovirus, rotavirus, and RSV are notable because they are common, are difficult to control, and have substantial clinical consequences. Neonates can be infected by the mother, other family members, or hospital personnel. Enterovirus and respiratory virus outbreaks in hospital nurseries usually are associated with community outbreaks. Blood products are another potential source of nosocomial CMV infection, especially in premature infants born to CMV-seronegative mothers. These infections can be prevented by using only CMV-negative blood products or by filtering blood to remove leukocytes. Viruses are the leading cause of illness in infants who come to medical attention with fever before 3 months of age. Enteroviruses and parechoviruses are common causes of sepsis-like illness, rash, and central nervous system infections in newborns. Infections caused by adenovirus, rotavirus, norovirus, astrovirus, influenza, RSV, influenza, and others are common sporadic or seasonal causes of fever, systemic illness, gastrointestinal disease, and respiratory disease in newborns.