What is the approach to diagnosing and treating congenital infections?

Approach to Congenital Infections: A Comprehensive Framework

Introduction to Congenital Infections

Congenital infections require systematic screening, prompt diagnosis, and timely treatment to minimize morbidity, mortality, and optimize quality of life for affected infants. These infections, acquired in utero, can cause significant long-term sequelae even when asymptomatic at birth, making early identification crucial 1.

Major Congenital Infections (TORCH+Z)

Toxoplasmosis

• Causative agent: Toxoplasma gondii
• Transmission: Maternal acquisition during pregnancy (foodborne, cat feces exposure)
• Screening approach:
  • Serologic testing for IgG/IgM antibodies during pregnancy
  • Amniocentesis with PCR for suspected cases
• Treatment:
  • Maternal infection: Spiramycin (1g PO TID) for infections before 18 weeks gestation without confirmed fetal infection 1
  • Confirmed fetal infection or maternal infection ≥18 weeks: Pyrimethamine (loading 100mg/day for 2 days, then 50mg/day) + sulfadiazine (loading 75mg/kg, then 100mg/kg/day divided BID) + folinic acid (10-20mg/day) 1
  • Neonatal treatment continues for 12 months

Cytomegalovirus (CMV)

• Causative agent: Human cytomegalovirus
• Transmission: Maternal primary or reactivated infection
• Screening approach:
  • Maternal serologic testing (IgG, IgM, avidity)
  • Amniotic fluid PCR for suspected cases
  • Neonatal urine or saliva PCR within first 3 weeks of life 2
• Treatment:
  • Symptomatic infants: Valganciclovir 16mg/kg PO BID for 6 months 3, 4
  • Not FDA-approved for congenital CMV but commonly used based on clinical evidence 5

Rubella

• Causative agent: Rubella virus
• Transmission: Maternal infection during pregnancy
• Screening approach:
  • Universal maternal serologic screening prenatally
  • Fetal diagnosis via amniotic fluid PCR
• Prevention: MMR vaccination before pregnancy
• Treatment: Supportive care (no specific antiviral therapy)

Herpes Simplex Virus

• Causative agent: HSV-1, HSV-2
• Transmission: Usually during delivery, rarely transplacental
• Screening approach:
  • Clinical history of maternal genital herpes
  • Viral culture/PCR from lesions
• Treatment:
  • Acyclovir 60mg/kg/day IV divided q8h for 14-21 days for disseminated/CNS disease
  • Suppressive therapy for mothers with active lesions near delivery

Zika Virus

• Causative agent: Zika virus
• Transmission: Maternal infection via mosquito bite, sexual transmission
• Screening approach:
  • Travel history to endemic areas
  • Maternal serology and PCR
  • Fetal ultrasound for abnormalities
• Treatment:
  • No specific antiviral therapy
  • Comprehensive developmental follow-up for affected infants 1

Diagnostic Approach

Maternal Screening

1. Risk assessment:

   • Travel history
   • Exposure to potential sources (cats, raw meat, etc.)
   • Flu-like illness during pregnancy
   • Previous infections/immunity status

2. Serologic testing:

   • First trimester baseline serology for TORCH infections
   • Serial testing for seroconversion in high-risk cases
   • IgM and IgG with avidity testing for timing of infection 6, 2

3. Fetal assessment:

   • Detailed ultrasound for abnormalities
   • Amniocentesis with PCR testing for suspected infections
   • Fetal blood sampling (less commonly used now) 6

Neonatal Diagnosis

1. Clinical evaluation:

   • Physical examination for classic findings:
     • Microcephaly, intracranial calcifications
     • Hepatosplenomegaly
     • Petechial rash
     • Chorioretinitis
     • Jaundice

2. Laboratory testing:

   • First 3 weeks critical: Allows distinction between congenital and postnatal acquisition 2
   • Specific testing by pathogen:
     • Toxoplasmosis: Serum IgM, IgA, PCR
     • CMV: Urine/saliva PCR, dried blood spot PCR
     • Rubella: Serum IgM
     • HSV: Surface and CSF PCR, cultures
     • Zika: Serum PCR, neuroimaging

3. Additional assessments:

   • Neuroimaging (ultrasound, CT, MRI)
   • Ophthalmologic examination
   • Hearing evaluation
   • CSF analysis when indicated

Treatment Principles

General Approach

1. Timing is critical: Earlier treatment generally leads to better outcomes 1, 7
2. Symptomatic vs. asymptomatic: Treatment decisions often depend on presence of symptoms
3. Duration: Often prolonged (6-12 months) to prevent relapse and progression

Monitoring and Follow-up

1. Regular assessments:

   • Growth parameters
   • Neurodevelopmental evaluations
   • Vision and hearing assessments
   • Organ function tests based on affected systems

2. Long-term surveillance:

   • Continue monitoring until at least school age
   • Some sequelae may manifest later in childhood 1, 4
   • Hearing loss may be progressive or late-onset, particularly with CMV 3

Prevention Strategies

Primary Prevention

1. Maternal education:

   • Food safety (thoroughly cook meat, wash fruits/vegetables)
   • Avoid cat litter during pregnancy
   • Hand hygiene
   • Mosquito bite prevention in Zika-endemic areas
   • Safe sexual practices

2. Vaccination:

   • Pre-pregnancy MMR vaccination
   • No available vaccines for other TORCH pathogens

Secondary Prevention

1. Maternal screening:

   • Universal or targeted based on risk factors
   • Early intervention when infection detected

2. Antepartum treatment:

   • Reduces vertical transmission rates
   • Improves outcomes when fetal infection occurs 1, 7

Special Considerations

Asymptomatic Congenital Infections

• May develop sequelae later in life
• Need for long-term follow-up even without symptoms at birth
• Particularly important for CMV and toxoplasmosis 3, 4

Emerging Pathogens

• Zika virus demonstrates how new pathogens can emerge as causes of congenital infections
• Surveillance systems needed to identify new threats 1

Common Pitfalls to Avoid

1. Missing the diagnostic window: Testing for congenital CMV must occur within first 3 weeks of life
2. Inadequate follow-up: Many sequelae develop over time, requiring long-term monitoring
3. Overlooking asymptomatic infections: Can still cause significant long-term morbidity
4. Delayed treatment initiation: Earlier treatment leads to better outcomes
5. Focusing only on classic manifestations: Presentations can be subtle or atypical

Conclusion

The approach to congenital infections requires vigilance throughout pregnancy, prompt diagnosis, and appropriate treatment to minimize long-term sequelae. A systematic approach to screening, diagnosis, and management is essential for improving outcomes in affected infants.