Congenital & Perinatal Infections: From Fetal Infection To Management

General Principles

Infections may be mild/asymptomatic in pregnant females but can have disastrous results in fetuses/neonates. No role of routine TORCH serology testing since IgG antibodies in the mother may show past infections and can be passively transferred. A pathogen-specific fetal IgM indicates infection but has variable sensitivity and specificity (higher specificity, moderate sensitivity). A negative fetal IgM does not rule out congenital infection. Paired IgG titres in mother and baby are useful in congenital syphilis.

Congenital CMV (Cytomegalovirus)

Agent: Cytomegalovirus (CMV)- A dsDNA, an enveloped virus that belongs to the Herpes family. Highly-species specific and affected cells appear large, with abundant cytoplasm and both intranuclear and cytoplasmic inclusions. CMV is a virus that is present in all body secretions and is highly transmissible.

Epidemiology of Congenital CMV

Maternal infection with CMV during pregnancy

1. Primary: First time infection during pregnancy

• Rare
• The fetal infection rate is almost 30% (Cloherty: 30-40%).

2. Secondary: Reactivation or reinfection during pregnancy.

• Common especially in Asia, Africa, and India.
• The fetal infection rate is almost 1-2%
• Congenital CMV is more common in HIV-exposed infants, and co-infection produces rapid progression of HIV infection.

Also read: Pediatric Neonatology High Yield One Liners

Clinical Picture in Congenital CMV

90% of patients are asymptomatic and 10% of patients are symptomatic(<5%-severe multiorgan dysfunction). The most common symptoms are petechiae and Purpura rash (57-79%). Other symptoms:

• Hepatosplenomegaly
• Jaundice (increased conjugated bilirubin level in about 50% of patients)
• Pneumonitis 
• Prematurity and Microcephaly (1/3rd )
• IUGR
• Chorioretinitis (20% of patients)
• Blueberry muffin spots

Diagnosis of Congenital CMV

1. Serology: Detection of IgM and IgG antibodies (obsolete)
2. CMV-PCR test
3. Isolation of the virus
4. Blood for PP65 antigen assay: To check for efficacy of therapy.
5. Supportive tests: CBC test, liver function test in children, USG/MRI/CT, CSF studies, etc.

Treatment

• No drugs are indicated in asymptomatic congenital CMV
• Symptomatic patients (CNS, hepatitis, pneumonitis, thrombocytopenia)
  • IV ganciclovir is the DOC given for 6 weeks.
  • Side effect: Bone marrow suppression, mostly Neutropenia (Patients may require subcutaneous injections of GM- CSF)
  • Alternative: Oral Valganciclovir X 6 months
  • Valganciclovir produces milder Neutropenia

Also read: NEET SS Pediatric Neonatology Important Topics

Congenital Rubella

• Agent: Rubella
  • Single stranded RNA virus, and
  • Members of the Togavirus family.
  • Also called German Measles virus or 3-day measles virus.
  • It is human specific
• It produces a mild febrile illness with a rash in unimmunized pregnant females.
• Highest transmission occurs if the mother is infected in the first trimester and highest risk of fetal infection is also in the 1st trimester (90% risk of birth defects if <11 weeks, 33% at 11-12 weeks, 11% at 13-14 weeks and 24% at 15-16 weeks)
• Spares the fetus if the maternal infection occurs beyond 16 weeks.

Diagnosis of Congenital Rubella

• Evidence of maternal infection in pregnancy–Clinical picture in unimmunized female +/- 4-fold rise in IgG titers
• Evidence of fetal/neonatal infection
  • Rubella-specific IgM in cord blood or neonatal blood—highest detection rate if test is done within 3 months.
  • Persistence of IgG titers in the neonate > 6 months: less sensitive.
  • Rubella isolation is not widely available

Treatment of Congenital Rubella

• No therapy available
• Only supportive treatment can be given.
• In case an unimmunized pregnant woman who gets a confirmed Rubella infection in the 1st trimester: -Consider MTP

Also read: Intraventricular Hemorrhage In Neonates

Congenital Toxoplasmosis 

Causative agent: Toxoplasma gondii. An obligate intracellular protozoan parasite. Cats are the definitive host and man is an intermediate host. Most cases of congenital infection occur via transplacental spread. Mother gets primary infection in pregnancy via infected cysts.

Diagnosis of Congenital Toxoplasmosis

• History of acute proven toxoplasma infection in mother.
• Positive IgM in serum of neonate – IgM ISAGA is sensitive.
• Toxoplasma PCR positivity in CSF or tissue is diagnostic.
• IgA or IgM ELISA, Sabin Feldman Dye test are the other 2 ways to show toxoplasmosis.
• Persistence of IgG beyond 12 months also indicates underlying Congenital Toxoplasmosis

Treatment and Prevention

• Treat in both symptomatic and asymptomatic cases.
• Combination of Sulfadiazine and Pyrimethamine is given for 1 year. + Folinic acid (Calcium leucovorin) should be given for 1 year.
• Side effects include Bone marrow suppression, especially neutropenia.
• If during the treatment the absolute neutrophil count becomes < 500 then the therapy should be stopped for about 1 week and then restart
• Weekly CBC needs to be done if daily pyrimethamine is given.
• Sulfadiazine may cause haemolysis in G6PD deficient patients.
• Prednisolone can be used for short duration if the CSF protein is found to be ³ 1 g/dl or active chorioretinitis near the macula.
• VP shunt can be done if the patient is having hydrocephalus.

Also read: Neonatal Hypocalcemia

Congenital Parvovirus B19 

• Agent: Human Parvovirus B19, non-enveloped, single-stranded DNA (ssDNA) virus.
• Receptor for virus P blood group antigen-Found on red blood cells, erythroblasts, megakaryocytes, placenta, fetal liver and heart cells.
• Rare people with P antigen absence are resistant to infection.
• Risk of fetal transmission after primary maternal infection: 30%.
• 1st trimester infections- 3-6% fetal loss, within 6 weeks of infection.
• A common cause of non-immune fetal hydrops

Diagnosis 

• Maternal history
• Cordocentesis: Polymerase Chain Reaction (PCR) sequencing for Parvovirus B19 DNA. Not always necessary for diagnosis
• Ultrasound: Features of Fetal hydrops

Treatment

• No specific antiviral treatment for parvovirus B19 infection.
• Intrauterine PRBC (packed red blood cells) transfusion via umbilical vein: If the fetus's Hb < 8 g/dL.

Congenital Zika Virus 

• Agent: Zika virus
• Enveloped single-stranded RNA (ssRNA) virus, of the Flaviviridae family.
• Transmission: Human to human through the bite of an infected Aedes aegypti mosquito.
• Primary maternal Infection in the first trimester, can cause fetal infection with a 10% risk of birth defects.
• Symptomatic Zika virus in mothers have a higher risk of defects.

Diagnosis 

• A definite diagnosis can be made by RT-PCR for ZIKV-RNA in infant serum, urine or CSF,  collected within the 1st 2 days of birth.
• IgM ELISA ZIKV: Positive test implies probable infection
• RT-PCR positive indicates definite infection
• Neuroimaging: All suspected infants should undergo neuroimaging.

Also read: Fetal Assessment: Key Evaluations & Prenatal Diagnosis

Treatment

• Management is primarily supportive.
• No vaccine available, aim at vector control

Congenital Varicella

• Agent: Varicella-Zoster virus (VZV)
  • Double-stranded DNA virus of the Herpesviridae family.
• Teratogenic Syndrome: Congenital varicella syndrome
  • If maternal infection occurs between 7-20 weeks of gestational age

Diagnosis 

• Diagnosis of congenital varicella syndrome is primarily clinical, based on:
  • History of rash in the mother
  • Clinical features in the baby
• DNA-PCR on fetal blood or amniotic fluid is sometimes performed

Treatment

Management is primarily supportive

Also read: Food Allergy in children

Hope you found this blog helpful for your E-learning for NEET SS Pediatrics. For more informative and interesting posts like these, keep reading PrepLadder’s blogs. 

Download the PrepLadder app and get online coaching with world-class video lectures, QBank, Mock Tests and more!