INTRODUCTION — Infections acquired in utero or during the birth process are a significant cause of fetal and neonatal mortality and an important contributor to early and later childhood morbidity. The infected newborn infant may show abnormal growth, developmental anomalies, or multiple clinical and laboratory abnormalities [1]. The TORCH acronym is well recognized in the field of neonatal/perinatal medicine [2]. It includes:
●Toxoplasmosis
●Others (syphilis, Zika virus, varicella-zoster virus)
●Rubella
●Cytomegalovirus (CMV)
●Herpes simplex virus (HSV)
Other well-described causes of in utero infection include enteroviruses, parvovirus B19, and lymphocytic choriomeningitis virus. Thus, broadening the "other" category to include additional pathogens has been proposed [3,4].
An overview of the clinical features of specific TORCH infections and an approach to the infant with suspected intrauterine infection will be provided below. The individual TORCH infections are discussed in more detail separately:
●(See "Toxoplasmosis and pregnancy" and "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)
●(See "Syphilis in pregnancy" and "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis" and "Congenital syphilis: Management and outcome".)
●(See "Varicella-zoster virus infection in pregnancy" and "Varicella-zoster infection in the newborn".)
●(See "Zika virus infection: Evaluation and management of pregnant patients" and "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)
●(See "Rubella in pregnancy" and "Congenital rubella".)
●(See "Cytomegalovirus infection in pregnancy" and "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Congenital cytomegalovirus infection: Management and outcome".)
●(See "Genital herpes simplex virus infection and pregnancy" and "Neonatal herpes simplex virus infection: Clinical features and diagnosis" and "Neonatal herpes simplex virus infection: Management and prevention".)
●(See "Parvovirus B19 infection during pregnancy".)
SCREENING FOR TORCH INFECTIONS
Screening during pregnancy — The practice of screening pregnant women for TORCH infections varies geographically. In the United States, the American College of Obstetricians and Gynecologists (ACOG) recommends that pregnant women be screened for rubella and syphilis at the first prenatal visit. In other countries, pregnant women also may be screened for toxoplasmosis. Prenatal screening recommendations are discussed in greater detail separately. (See "Prenatal care: Initial assessment", section on 'Standard panel'.)
Newborn screening — Asymptomatic infants generally are not screened for congenital infections, with the following exceptions:
●Toxoplasmosis – Some European countries and a few select states in the United States have adopted universal newborn screening for toxoplasmosis [5-7]. This is discussed separately. (See "Congenital toxoplasmosis: Clinical features and diagnosis", section on 'Newborn screening'.)
●Cytomegalovirus (CMV) – Targeted newborn screening for congenital CMV infection (ie, testing infants who fail the newborn hearing screen) is performed in some institutions. Universal screening has been proposed, but the most reliable and cost-effective method for screening has not been established, and this practice has not gained widespread adoption. This is discussed in greater detail separately. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Newborn screening for congenital cytomegalovirus'.)
Although identification of immunoglobulin M (IgM) antibodies in the newborn is suggestive of congenital infection (because IgM antibodies do not cross the placenta), indiscriminate screening for TORCH infections with a battery of "TORCH titers" is costly and has a poor diagnostic yield [8-11]. Our preferred approach involves testing of infants with suspected congenital infections for specific pathogens based upon their clinical presentation [12]. (See 'Approach to the infant with suspected intrauterine infection' below.)
CLINICAL FEATURES OF TORCH INFECTIONS
Congenital toxoplasmosis — Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii. Primary infection during pregnancy can result in congenital disease. (See "Toxoplasmosis and pregnancy".)
Most infants with congenital toxoplasmosis are asymptomatic or without apparent abnormalities at birth. Although subclinical disease is the rule, signs present at birth may include fever, maculopapular rash, hepatosplenomegaly, microcephaly, seizures, jaundice, thrombocytopenia, and, rarely, generalized lymphadenopathy (picture 1). The so-called classic triad of congenital toxoplasmosis consists of chorioretinitis, hydrocephalus, and intracranial calcifications (image 1).
Infants with subclinical congenital toxoplasmosis who do not receive treatment have an increased risk of long-term sequelae. The most common late finding is chorioretinitis (picture 2), which can result in vision loss. Intellectual disability, deafness, seizures, and spasticity also can be seen in a minority of untreated children.
The diagnosis, management, and prevention of congenital toxoplasmosis are discussed separately. (See "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)
Congenital syphilis — Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted from a pregnant woman to her fetus. Infection can result in stillbirth, hydrops fetalis, or prematurity and associated long-term morbidity. Because of this morbidity, great emphasis has been placed on routine syphilis screening of all pregnant women. (See "Syphilis in pregnancy", section on 'Maternal screening'.)
The incidence of congenital syphilis reflects the rate of syphilis in women of childbearing age. Many congenital cases develop because the mother received no prenatal care, no penicillin treatment, or inadequate treatment before or during pregnancy.
Most neonates with congenital syphilis are asymptomatic at birth. Overt infection can manifest in the fetus, the newborn, or later in childhood. Clinical manifestations after birth are divided arbitrarily into early (≤2 years of age (table 1)) and late (>2 years of age (table 2)).
The diagnosis, management, and prevention of congenital syphilis are discussed separately. (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis" and "Congenital syphilis: Management and outcome".)
Congenital varicella syndrome — Most cases of congenital varicella syndrome occur in infants whose mothers were infected between 8 and 20 weeks gestation. Characteristic findings in neonates may include:
●Cutaneous scars, which may be depressed and pigmented in a dermatomal distribution
●Cataracts, chorioretinitis, microphthalmos, nystagmus
●Hypoplastic limbs
●Cortical atrophy and seizures
The clinical manifestations and diagnosis of congenital varicella syndrome are discussed separately. (See "Varicella-zoster virus infection in pregnancy", section on 'Fetal effects of VZV infection' and "Varicella-zoster virus infection in pregnancy", section on 'Congenital varicella syndrome'.)
Congenital Zika syndrome — Congenital Zika virus infection is associated with severe congenital anomalies; the greatest risk of serious fetal sequelae is with first-trimester infection. The principal clinical features of congenital Zika syndrome (CZS) include (picture 3):
●Microcephaly
●Facial disproportion
●Hypertonia/spasticity and hyperreflexia
●Seizures
●Irritability
●Arthrogryposis
●Ocular abnormalities
●Sensorineural hearing loss
●Neuroradiologic abnormalities (eg, intracranial calcifications, ventriculomegaly (image 2A-B))
The features of CZS have been described in case reports and small case series. However, the full spectrum of the syndrome is still evolving. The clinical manifestations and diagnosis of congenital Zika virus infection are reviewed in greater detail separately. (See "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)
Congenital rubella — Rubella typically causes a mild, self-limited illness; its major impact occurs during pregnancy, when it can have devastating effects on the developing fetus.
Congenital rubella syndrome (CRS) is rare in developed countries with established rubella immunization programs. It is no longer endemic in the United States, although an average of five to six cases are reported to the National Congenital Rubella Registry each year, usually in infants whose mothers emigrated from countries without rubella immunization programs.
Clinical manifestations of CRS include sensorineural deafness, cataracts, cardiac malformations (eg, patent ductus arteriosus, pulmonary artery hypoplasia), and neurologic and endocrinologic sequelae (table 3). Neonatal manifestations may include growth retardation, radiolucent bone disease (not pathognomonic of congenital rubella), hepatosplenomegaly, thrombocytopenia, purpuric skin lesions (classically described as "blueberry muffin" lesions (picture 4) that represent extramedullary hematopoiesis), and hyperbilirubinemia.
The diagnosis, management, and prevention of CRS are discussed separately. (See "Congenital rubella".)
Congenital cytomegalovirus — Congenital cytomegalovirus (CMV) infection is the leading cause of nonhereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities, including cerebral palsy, intellectual disability, vision impairment, and seizures.
CMV infection is common worldwide. Despite its listing as the fourth infection in the TORCH designation, CMV has emerged as the most common congenital viral infection. Maternal CMV infection during pregnancy most often results from close contact with young children, particularly children attending daycare centers.
At birth, most infants with congenital CMV are asymptomatic, but approximately 10 percent have symptoms. Clinical manifestations include petechiae (picture 5), jaundice at birth, hepatosplenomegaly, thrombocytopenia, small size for gestational age, microcephaly, intracranial calcifications (image 3A-B), sensorineural hearing loss, chorioretinitis, and seizures.
Sensorineural hearing loss is the most common sequela of congenital CMV and is detected at birth in approximately one-third of infants with symptomatic disease. Many infants with congenital CMV infection are identified solely on the basis of a failed newborn hearing screen. Delayed-onset hearing loss also occurs, although the risk is lower if antiviral treatment is provided in infancy.
The diagnosis, management, and prevention of congenital CMV are discussed separately. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Congenital cytomegalovirus infection: Management and outcome" and "Cytomegalovirus infection in pregnancy", section on 'Strategies for prevention of maternal and/or fetal infection'.)
Herpes simplex virus — Genital herpes simplex virus (HSV) infection during pregnancy poses a significant risk to the developing fetus and newborn.
●Perinatally acquired infection – Most cases of neonatal HSV infection are perinatally acquired. HSV is transmitted to an infant during birth, primarily through an infected maternal genital tract. The risk of transmission is greater with primary HSV infection acquired during pregnancy compared with reactivation of previous infection. Among mothers with primary infection, acquisition near the time of labor is the major risk factor for transmission to the neonate. (See "Genital herpes simplex virus infection and pregnancy".)
Most newborns with perinatally acquired HSV appear normal at birth, although many are born prematurely. HSV infection in newborns usually develops in one of three patterns, which occur with roughly equal frequency (table 4):
•Localized to the skin, eyes, and mouth
•Localized central nervous system (CNS) disease
•Disseminated disease involving multiple organs
The initial manifestations of CNS disease frequently are nonspecific and include temperature instability, respiratory distress, poor feeding, and lethargy; they may progress quite rapidly to hypotension, jaundice, disseminated intravascular coagulation, apnea, and shock. Vesicular skin lesions (picture 6A-C) may or may not be present and develop late in some patients; the absence of skin lesions complicates recognition of the infection. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis".)
●Congenital (in utero) infection – Intrauterine HSV infection is rare and usually results from maternal viremia associated with primary HSV infection during pregnancy. Live-born infants with congenital HSV infection may exhibit a characteristic triad of skin vesicles, ulcerations, or scarring (picture 7); eye damage; and severe CNS manifestations, including microcephaly or hydranencephaly. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Intrauterine HSV'.)
The diagnosis, management, and prevention of neonatal HSV infections are discussed separately. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Evaluation and diagnosis' and "Neonatal herpes simplex virus infection: Management and prevention".)
APPROACH TO THE INFANT WITH SUSPECTED INTRAUTERINE INFECTION
Overview — A high index of suspicion for congenital infection and awareness of the prominent features of the most common congenital infections can help to facilitate early diagnosis and tailor appropriate diagnostic evaluation (table 5). For many of the infections discussed in the previous sections, timely diagnosis is crucial to ensure that appropriate therapy is initiated. It also allows for family counseling regarding the prognosis, so that an appropriate care plan can be put in place.
Our preferred approach to testing infants suspected of having a congenital infection is to test only for select pathogens based upon specific clinical findings (table 5) [3,4]. We discourage the practice of indiscriminate screening of infants who have findings compatible with congenital infection with a battery of "TORCH titers" because such an approach is costly and has a poor diagnostic yield [8-13]. In addition, the number of pathogens responsible for in utero and perinatal infections continues to expand such that the approach of indiscriminate testing has become challenging. The optimal approach remains uncertain, and practice varies considerably [14].
Clinical suspicion — In some cases, intrauterine infection may be suspected on the basis of laboratory results obtained during pregnancy (eg, positive syphilis serology with increasing titers). In the absence of suggestive maternal laboratory results, intrauterine infection may be suspected in newborns with certain clinical manifestations or combinations of clinical manifestations including (but not limited to):
●Hydrops fetalis
●Microcephaly
●Seizures
●Cataract
●Hearing loss
●Congenital heart disease
●Hepatosplenomegaly
●Jaundice
●Rash
●Thrombocytopenia
These findings are not restricted to TORCH infections, and some of the features above may occur in other infections (eg, human parvovirus, Chagas disease) and in conditions other than intrauterine infection (eg, inborn errors of metabolism, Rh incompatibility, etc). Thus, the entire clinical constellation, including maternal history and exposures, must be taken into account when deciding to evaluate an infant for congenital infection.
Initial evaluation — The evaluation of a newborn with clinical findings compatible with intrauterine infection may include [15-17]:
●Review of maternal history (evidence of rubella immunity, syphilis serology, history of herpes simplex virus [HSV], exposure to cats, etc)
●Assessment of physical stigmata consistent with various intrauterine infections (table 5)
●Complete blood count and platelet count
●Liver function tests (particularly important in HSV infection)
●Radiographs of long bones
●Ophthalmologic evaluation
●Audiologic evaluation
●Neuroimaging
●Lumbar puncture
Specific evaluation — The results of the initial evaluation may help to determine whether evaluation for a specific pathogen (or pathogens) is warranted. Findings that are more prominent in particular infections, and may prompt evaluation for a specific pathogen, are listed in the table (table 5).
The diagnostic evaluation for specific infections is discussed separately:
●Congenital toxoplasmosis (see "Congenital toxoplasmosis: Clinical features and diagnosis", section on 'Evaluation')
●Congenital syphilis (see "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis")
●Congenital rubella (see "Congenital rubella", section on 'Evaluation')
●Congenital cytomegalovirus (CMV) (see "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Diagnostic approach')
●Congenital HSV (see "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Evaluation and diagnosis')
●Congenital varicella (see "Varicella-zoster infection in the newborn", section on 'Diagnosis')
●Congenital enterovirus infection (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Laboratory diagnosis')
●Congenital Zika virus infection (see "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate", section on 'Evaluation')
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: TORCH infections".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Avoiding infections in pregnancy (The Basics)")
●Beyond the Basics topic (see "Patient education: Avoiding infections in pregnancy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●TORCH infections – The TORCH acronym (which stands for toxoplasmosis, other [syphilis, varicella, Zika virus], rubella, cytomegalovirus, and herpes simplex virus) is well recognized in the field of neonatal and perinatal medicine. These intrauterine and perinatal infections contribute to fetal and infant mortality, and they are important causes of childhood morbidity. Infected newborns may show abnormal growth and development in conjunction with multiple clinical and laboratory abnormalities (table 5) (see 'Overview' above):
•Congenital toxoplasmosis – The classic triad of congenital toxoplasmosis consists of chorioretinitis (picture 2), hydrocephalus, and intracranial calcifications (image 1); signs present at birth may include fever, maculopapular rash, hepatosplenomegaly, microcephaly, seizures, jaundice, thrombocytopenia, and, rarely, generalized lymphadenopathy (picture 1). However, most infants with congenital toxoplasmosis are asymptomatic or without apparent abnormalities at birth. (See "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)
•Congenital syphilis – Most neonates with congenital syphilis are asymptomatic at birth. Clinical manifestations after birth are divided arbitrarily into early (≤2 years of age (table 1)) and late (>2 years of age (table 2)). (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis" and "Congenital syphilis: Management and outcome".)
•Congenital varicella – Characteristic features of congenital varicella infection include cutaneous scars, cataracts, chorioretinitis, microphthalmos, nystagmus, hypoplastic limbs, cortical atrophy, and seizures. (See "Varicella-zoster virus infection in pregnancy", section on 'Fetal effects of VZV infection' and "Varicella-zoster virus infection in pregnancy", section on 'Congenital varicella syndrome'.)
•Congenital Zika syndrome (CZS) – Congenital Zika virus infection is associated with severe congenital anomalies; the greatest risk of serious fetal sequelae is with first-trimester infection. The principal clinical features of CZS include (picture 3) microcephaly, facial disproportion, hypertonia/spasticity, hyperreflexia, seizures, irritability, arthrogryposis, ocular abnormalities, sensorineural hearing loss, and neuroradiologic abnormalities (eg, intracranial calcifications, ventriculomegaly (image 2A-B)). (See "Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate".)
•Congenital rubella syndrome (CRS) – Clinical manifestations of CRS include sensorineural deafness, cataracts, cardiac malformations (eg, patent ductus arteriosus, pulmonary artery hypoplasia), and neurologic and endocrinologic sequelae. Neonatal manifestations may include growth retardation, radiolucent bone disease (not pathognomonic of congenital rubella), hepatosplenomegaly, thrombocytopenia, purpuric skin lesions (classically described as "blueberry muffin" lesions that represent extramedullary hematopoiesis), and hyperbilirubinemia. (See "Congenital rubella".)
•Congenital cytomegalovirus (CMV) – Most infants with congenital CMV infection are asymptomatic at birth. Among symptomatic infants, clinical manifestations include petechiae, jaundice, hepatosplenomegaly, chorioretinitis, and neurologic involvement (eg, microcephaly, motor disability, sensorineural hearing loss, cerebral calcifications (image 4), lethargy, seizures). Both asymptomatic and symptomatic infants with congenital CMV are at risk of developing late complications including hearing loss, vision impairment, intellectual disability, and delay in psychomotor development. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Congenital cytomegalovirus infection: Management and outcome".)
•Neonatal herpes simplex virus (HSV) – Most cases of neonatal HSV infection are perinatally acquired. Affected newborns typically appear normal at birth, although many are born prematurely. Neonatal HSV infection usually develops in one of three patterns: localized to the skin, eyes, and mouth; localized central nervous system (CNS) disease; and disseminated disease (table 4). The initial manifestations of CNS disease frequently are nonspecific and include temperature instability, respiratory distress, poor feeding, and lethargy; they may progress quite rapidly to hypotension, jaundice, disseminated intravascular coagulation, apnea, and shock. Vesicular skin lesions may or may not be present. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis" and "Neonatal herpes simplex virus infection: Management and prevention".)
•Others – Other well-described causes of in utero infection include enteroviruses, varicella-zoster virus, parvovirus B19, and lymphocytic choriomeningitis virus. Thus, broadening the "other" category to include additional pathogens has been proposed.
●Diagnostic approach – Timely diagnosis of congenital and perinatally acquired infections is crucial to the initiation of appropriate therapy. Intrauterine infection may be suspected based upon maternal laboratory results and/or clinical findings or combinations of clinical findings in the fetus or newborn (eg, hydrops fetalis, microcephaly, seizures, cataract, hearing loss, congenital heart disease, hepatosplenomegaly, jaundice, and/or rash (table 5)).
Our preferred approach to testing infants with suspected congenital infection is to test only for select pathogens based upon specific clinical findings. We discourage the practice of indiscriminate screening with a battery of "TORCH titers" because such an approach is costly and has a poor diagnostic yield. (See 'Approach to the infant with suspected intrauterine infection' above.)
