Clinical Presentation of Congenital Infections in Infants
Congenital infections present with a constellation of overlapping clinical features that can be categorized into symptomatic (10%) and asymptomatic (90%) presentations at birth, with the classic triad of jaundice, petechiae, and hepatosplenomegaly being most frequently observed in symptomatic infants. 1
Key Clinical Features by System
Neurological Manifestations
- Microcephaly is a cardinal feature that may be present at birth or develop postnatally, with some infants showing normal head circumference initially but developing postnatal microcephaly within the first year 2
- Hydrocephalus and intracranial calcifications are prominent CNS findings 2
- Seizures, reduced alertness, and focal neurologic deficits (including hemiparesis and apnea) occur frequently 2
- Chorioretinitis and other ocular abnormalities can occur even in infants without microcephaly or other brain anomalies 2
- Sensorineural hearing loss may be absent at birth but develop during the first year of life 2
Dermatologic and Hematologic Findings
- Maculopapular rash and petechiae are among the most common presenting signs 2, 1
- Hematologic abnormalities including anemia, thrombocytopenia, and neutropenia 2
- Jaundice as part of the classic symptomatic triad 1
Systemic Manifestations
- Hepatosplenomegaly is consistently reported across congenital infections 2, 1
- Generalized lymphadenopathy (particularly cervical) 2
- Failure to thrive and feeding difficulties are common early presentations 2
Infection-Specific Presentations
Congenital Toxoplasmosis
The presentation ranges from asymptomatic to severe generalized disease with the aforementioned triad plus substantial CNS involvement 2. Approximately 20-30% of infected infants will not be identified in the neonatal period even with IgA or IgM assays 2.
Congenital Cytomegalovirus (CMV)
Approximately 90% of congenitally infected infants are asymptomatic at birth 1. When symptomatic, the classic triad of jaundice, petechiae, and hepatosplenomegaly predominates 1. Critical to recognize: hearing loss can develop during the first year even when absent at birth 2.
Congenital Syphilis
Kidney involvement may be the only presentation, ranging from mild proteinuria to nephrotic syndrome 2. More commonly presents with anemia, jaundice, hepatosplenomegaly, cutaneous lesions, and neurological symptoms 2.
Congenital Zika Syndrome
Microcephaly at birth is not a necessary feature—infants may have normal head size initially with subsequent deceleration of head growth leading to postnatal microcephaly 2. Eye findings can occur without microcephaly or brain anomalies 2.
Immune Dysregulation Presentations
Omenn Syndrome-Like Features
In infants with congenital athymia (which can result from certain congenital infections), immune dysregulation manifests as:
- Erythroderma, diarrhea, hepatosplenomegaly, lymphadenopathy 2
- Elevated IgE and eosinophilia 2
- Hematologic cytopenias (autoimmune manifestations) 2
Infectious Complications
Early Opportunistic Infections
Infants typically present within the first few months of life with:
- Pneumocystis jirovecii pneumonia or CMV pneumonitis 2
- Persistent respiratory tract infections (RSV, parainfluenza, adenovirus) 2
- Persistent candidiasis 2
- Chronic diarrhea from adenovirus, norovirus, or rotavirus 2
- Septic emboli resulting in osteomyelitis, meningitis, or pneumonia 2
Critical Diagnostic Considerations
Nonspecific Presentations
The clinical manifestations in neonates are variable and nonspecific, often indistinguishable from septicemia or congestive heart failure 2. This necessitates high clinical suspicion based on combinations of features rather than single findings 3.
Timing-Dependent Features
- Infections during organogenesis cause congenital malformations 4
- Late pregnancy infections cause morbidity without structural defects 4
- Some manifestations emerge postnatally, including hearing loss, developmental delay, and postnatal microcephaly 2
High-Risk Clinical Scenarios Warranting Evaluation
Suspect congenital infection in newborns with:
- Hydrops fetalis 3
- Microcephaly with seizures 3
- Cataract or hearing loss 3
- Congenital heart disease with hepatosplenomegaly 3
- Jaundice with rash 3
Common Pitfalls
Classic findings like Osler nodes, Roth spots, Janeway lesions, and splinter hemorrhages are NOT described in neonates with congenital infections 2, unlike older children. Additionally, arthritis is rarely seen in neonates despite being common in older children 2.
The key to diagnosis is recognizing that most congenital infections share overlapping clinical features, but specific combinations and timing of manifestations can help distinguish between pathogens 5, 3. A systematic approach evaluating neurologic, ophthalmologic, auditory, and systemic findings is essential for timely diagnosis 2.