Congenital and Perinatal Infections

General Approach

Infectious as well as noninfectious processes, such as underlying congenital heart disease, genetic disorders, and inborn errors of metabolism, should be considered in the differential diagnosis of congenital and perinatal infections. Because maternal infection is a prerequisite for infection in the fetus, a thorough history is essential to assess the mother for her symptoms, travel, diet, medication use, occupational exposures, and any sexually transmitted infections (STIs) during pregnancy. Clinical manifestations are varied and overlap for many of the pathogens causing intrauterine infection. Laboratory testing and/or radiologic imaging is often required to confirm the diagnosis. Treatment depends on the specific pathogen and can range from symptomatic management with close follow-up for long-term sequelae to targeted antimicrobial therapy.

Pathogenesis

The route and timing of infection can provide helpful clues as to the potential infectious etiology ( Fig. 131.1 and Table 131.1 ). First-trimester infection may alter embryogenesis and result in malformations of the heart and eyes, as seen in congenital rubella syndrome. Third-trimester infection (e.g., congenital toxoplasmosis) can result in active infection with signs of hepatomegaly, splenomegaly, and generalized lymphadenopathy at birth. Infections that occur late in gestation (e.g., congenital syphilis) may lead to a delay in clinical manifestations until weeks to years after birth.

Intrauterine infection from cytomegalovirus (CMV), Treponema pallidum , Toxoplasma gondii , rubella virus, varicella-zoster virus (VZV), and human parvovirus B19 may cause minimal or no symptoms in the mother but still may be transmitted across the placenta to the fetus. The presence of maternal antibodies to rubella prevents infection, but transmission of CMV can occur despite preexisting antibodies. Regardless of the mother's immune status, the placenta may act as a barrier, and the fetus may or may not be infected. If infection occurs, signs may or may not be noted in the fetus during pregnancy. Infection can result in spontaneous abortion, congenital malformation, intrauterine growth restriction (IUGR), premature birth, stillbirth, acute or delayed disease in the neonate, or asymptomatic persistent infection with sequelae later in life.

Clinical Manifestations

The clinical manifestations of intrauterine infections can range from asymptomatic to severe multiorgan system complications. For some agents (e.g., CMV, T. pallidum ), ongoing injury after birth leads to late sequelae. The specific clinical signs in the newborn period are usually not sufficient to make a definitive diagnosis but are useful to guide more specific laboratory testing. Symptomatic congenital infections often affect the central nervous system (CNS; brain and eyes) and the reticuloendothelial system (RES; bone marrow, liver, and spleen). Table 131.2 presents the clinical manifestations of some specific congenital infections. Congenital Zika virus infection has features that are rarely seen with other congenital infections ( Table 131.3 ). No hematologic or hepatic laboratory abnormalities have been documented in infants with congenital Zika virus infection. Table 131.4 provides late sequelae of some congenital infections.

Diagnosis