What are the most common congenital and connatal infections in pediatrics, including toxoplasmosis, rubella, Cytomegalovirus (CMV), Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV)?

Congenital and Connatal Infections in Pediatrics

Cytomegalovirus (CMV) is the most common congenital infection in the United States, occurring in 0.2-2.2% of live births, followed by the other TORCH infections (toxoplasmosis, rubella, CMV, herpes simplex) and vertically transmitted hepatitis B, hepatitis C, and HIV. 1

Definitions and Transmission Timing

Congenital infections are transmitted transplacentally from mother to fetus during pregnancy, while connatal (perinatal) infections occur during labor, delivery, or the immediate postpartum period through direct contact with maternal blood, genital secretions, or breast milk. 2, 3

Most Common Congenital and Perinatal Infections

Cytomegalovirus (CMV)

CMV is the most common perinatally transmitted infection in the United States. 1

• Transmission rates: 30-40% with primary maternal infection during pregnancy; 0.15-1.0% with recurrent maternal infection 1
• Intrapartum/postpartum transmission: Up to 57% of infants exposed at delivery and 53% of breastfed infants with virus-containing milk become infected, though symptomatic disease is much less common than with congenital acquisition 1
• HIV coinfection: Approximately 90% of HIV-infected pregnant women are CMV-coinfected, with higher cervical shedding rates (52-59% vs 14-35% in HIV-uninfected women) 1
• Long-term sequelae: Hearing loss can develop during the first year of life even when absent at birth, similar to other congenital viral infections 1

Toxoplasmosis

Toxoplasma gondii transmission through blood transfusion is particularly concerning for immunocompromised recipients, including HIV-infected individuals and neonates. 4

• Severe manifestations in HIV-infected patients: Encephalitis, pneumonitis, hepatitis, and cardiomyopathy 4
• Congenital transmission: Risk increases with gestational age when maternal infection occurs during pregnancy 4

Rubella

Congenital rubella syndrome has been eliminated in the Americas through immunization programs. 5

• Long-term consequences: In utero rubella infection is associated with autism presenting in early childhood and adult-onset diabetes 1
• Current status: While eliminated in the Americas, rubella remains an important pathogen globally where vaccination coverage is inadequate 5

Hepatitis B Virus (HBV)

Up to 90% of neonates infected with HBV will become chronic carriers, compared to only 6-10% of infected adults. 6

• Maternal transmission: Mothers who are HBsAg-positive or develop active infection during the third trimester can infect infants at or shortly after birth 6
• Chronic carrier consequences: Increased risk of primary hepatocellular carcinoma; HBV infection may be the single most important factor for development of this malignancy 6
• Prevention efficacy: For infants born to HBsAg-positive and HBeAg-positive mothers, a regimen combining hepatitis B immune globulin (HBIG) at birth with the hepatitis B vaccine series is 85-95% effective in preventing chronic carrier state 7
• Vaccination strategy: The Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) recommend universal infant immunization from birth 6
• Long-term prevention: Neonatal HBV vaccination prevents adult hepatocellular carcinoma, making it the first anti-cancer vaccine 6, 8

Hepatitis C Virus (HCV)

Hepatitis C is transmitted perinatally but cannot currently be prevented by vaccines. 5

• Vertical transmission: Occurs primarily during delivery through exposure to maternal blood 2
• Prevention limitations: No vaccine available; prevention relies on identifying infected mothers and minimizing exposure during delivery 2, 5

Human Immunodeficiency Virus (HIV)

HIV-exposed infants require specific diagnostic algorithms and prophylaxis protocols. 1

Diagnostic Criteria for HIV-Exposed Infants:

Definitive infection:

• Two positive virologic tests on separate specimens at any age, OR
• Age >18 months with either positive virologic test or positive confirmed HIV-antibody test 1

Presumptive exclusion in non-breastfed infants:

• No clinical/laboratory evidence of HIV infection AND
• Two negative virologic tests (both ≥2 weeks of age, one ≥4 weeks of age), OR
• One negative virologic test at ≥8 weeks of age, OR
• One negative HIV antibody test at ≥6 months of age 1

Definitive exclusion in non-breastfed infants:

• No clinical/laboratory evidence of HIV infection AND
• Two negative virologic tests (both ≥1 month of age, one ≥4 months of age), OR
• Two or more negative HIV antibody tests at ≥6 months of age 1

Prophylaxis Requirements:

Pneumocystis pneumonia (PCP) prophylaxis indications:

• All HIV-infected or HIV-indeterminate infants aged 1-12 months
• HIV-infected children aged 1-5 years with CD4 count <500 cells/mm³ or CD4% <15%
• HIV-infected children aged 6-12 years with CD4 count <200 cells/mm³ or CD4% <15% 1

First-line PCP prophylaxis:

• TMP-SMX 150/750 mg/m² body surface area per day (max: 320/1600 mg) orally divided into 2 doses daily, administered 3 times weekly on consecutive days 1

Clinical Implications and Long-Term Consequences

The long-term consequences of congenital infections extend far beyond the neonatal period and include endocrine, immunological and cardiovascular disease, deafness, visual problems, intellectual disability, cerebral palsy, and increased cancer risk. 8, 5

Common Pitfalls:

• Delayed manifestations: Some conditions may be absent or difficult to detect at birth (e.g., CMV-related hearing loss, postnatal microcephaly with Zika) 1
• Asymptomatic neonatal presentation: Congenital HBV infection may go undetected for years despite predisposing to cirrhosis and hepatocellular carcinoma in young adults 8
• Maternal screening failures: Universal screening of pregnant women for HBV is recommended but not always implemented 6

Prevention Strategies:

Vaccination remains the primary prevention method where available (HBV, rubella), while for infections without vaccines (CMV, HCV, toxoplasmosis), prevention relies on maternal screening, appropriate counseling, and post-exposure prophylaxis protocols. 2, 5