Humans are the only natural hosts for enteroviruses. These viruses have a worldwide distribution and tend to produce seasonal outbreaks during summer and fall in the temperate climates; in the tropics, this seasonal pattern may be absent. Sporadic infections can occur at any time. A geographic and year-to-year variation exists among the serotypes producing infections. For isolates reported to the Centers for Disease Control and Prevention in infants younger than 2 months, echoviruses cause 51% of all nonpolio enteroviral diseases, group Bcoxsackieviruses cause 45%, and group A coxsackieviruses cause 4%. Viral isolates in the neonatal period parallel isolates circulating in the community at that time and vary from year to year. Male infants are more often affected than female infants, with a male-to-female ratio of 1.4:1.0. The usual incubation period is 3 to 6 days after contact, except for acute hemorrhagic conjunctivitis (1 to 3 days).

Perinatal infections can be acquired by transplacental transmission (during maternal viremia and from the infected placenta), but this seems to occur rarely. Most often, infants are infected at the time of delivery or from human-to-human contact (maternal and nonmaternal sources) after birth. Spread is by the fecal-oral route and possibly by the oral-oral (respiratory) route. Enteroviruses may survive on environmental surfaces. Outbreaks or echoviruses and coxsackieviruses in special care and standard nurseries have occurred; the source of
infection was either an infected baby or the nursing personnel. The incidence of congenital infection is rare. Some studies reported an increased risk of abortion after maternal infection with an enterovirus, whereas other studies did not. During the peak season of enterovirus activity, the incidence of infection in the first month of life can be as high as 13%. Most of these infections probably are acquired after birth. An increased risk of infection has been associated with lower socioeconomic status, lack of breast-feeding, and absence of passively transferred maternal antibodies. One study reported a possible association between coxsackievirus B infections and severe congenital anatomic defects of the central nervous system.

Enteroviruses, which are small RNA viruses, are a subgroup of the picornaviruses. Sixty-four enteroviruses are recognized and are divided into different classes: polioviruses (serotypes 1 to 3), coxsackievirus group A (serotypes 1 to 24), coxsackievirus group B (serotypes 1 to 6), echoviruses (serotypes 1 to 34), and enteroviruses (68 to 71). Enteroviruses were originally classified according to their different effects in tissue cultures and animals; however, some strains possess in vitro characteristics belonging to more than one class. Newer strains have been assigned only an enterovirus number. More recently, classification of enteroviruses has been based on their genomic characteristics. These viruses have been divided into polioviruses (PV), human enterovirus A (HEV-A), human enterovirus B (HEV-B), human enterovirus C (HEV-C) and human enterovirus D (HEV-D). Echoviruses 22 and 23 have been reclassified in a new genus called Parechovirus.

After initial replication of the virus in the gastrointestinal or respiratory tract, the infection spreads to the lymphoid tissue. From there, a primary viremia occurs with dissemination to other lymphoreticular tissues such as liver, spleen, and bone marrow. In congenital infection, this viremia corresponds to the initiation of the infection. The virus can multiply in these secondary sites, with production of a secondary viremia and appearance of clinical signs and symptoms; the central nervous system, heart, and striated muscle can be seeded during this phase of the illness. With mounting antibody response, the viremia ceases.

Enteroviruses can produce inflammation and tissue necrosis in different organs, depending on the strain involved and the inoculum of the virus. There seems to be an age-related difference in the severity of illness, with very young neonates more severely affected than older infants and children, especially if vertical transmission from the mother to the fetus occurs before or at the time of delivery. Neonates with fatal enterovirus infections have an onset of disease at birth or within a few days of life.

The spectrum of infection is wide, ranging from asymptomatic colonization to fulminant disease with myocarditis and death. The percentage of neonates asymptomatically infected is variable according to study, strain involved, presence of transplacentally acquired specific antibody, and time of the year. Many children with enterovirus infections are asymptomatic; some heavily infected children manifest only mild clinical symptoms. However, severe disease seems to be more common in neonates than in older children. In one study of enterovirus infection in children younger than 2 months, Morens reported that 74% of patients had severe disease.

Some infants present only with fever and irritability. The temperature can be as high as 39°C, and the fever lasts an average of 3 days (maximum, 8 days). The most severe manifestation is a sepsis-like illness manifested by fever, lethargy, irritability, abdominal distention, decreased feedings, rash, and hypotonia; this clinical presentation may mimic bacterial sepsis. Disseminated intravascular coagulation, hypotension, hepatitis, and jaundice also may be present.

Viral myocarditis in the newborn period is most often caused by coxsackievirus B infections. The onset is acute with fever, anorexia, listlessness, tachycardia, tachypnea, and cyanosis. Cardiac arrhythmias have been reported, and heart failure can occur. In many instances, a biphasic pattern of fever and symptoms exists. The mortality is elevated for these children, and recovery, if they survive, is slow. Many infants have concomitant involvement of the central nervous system and liver.