1. Rubella: [German measles]
Infection can occur at any time during pregnancy but early gestation infection is very destructive. Congenital rubella syndrome presents as cataract, IUGR, retinopathy, microcephaly, meningoencephalitis, congenital heart disease, splenomegaly, thrombocytopenic purpura. With maternal infection in first 12 weeks, the rate of fetal infection is 81%. As the gestational age advances the infection rate drops. Risk for congenital defects is low if fetal infection occurs beyond 20 weeks.
Prenatal diagnosis:
It is mainly done by isolating virus from amniotic fluid and by identification of rubella specific IgM by percutaneous umbilical blood sampling. These tests have limited sensitivity and specificity.
Postnatal diagnosis:
Definitive diagnosis is by virus isolation in pharyngeal washings, CSF, conjunctiva and lens at autopsy. Rubella virus RNA can be detected by PCR in clinical specimens. Detection of rubella specific IgM in neonatal or cord blood is also confirmatory.
Table 1. Interpretation of ELISA for rubella specific antibodies
Rubella IgM / IgG : Negative <0.9 U / ml
Equivocal : 0.91 – 1.1 U / ml
Positive :> 1.1 U / ml
Management
There is no specific therapy for maternal or congenital rubella infection. If primary maternal infection occurs during first trimester of pregnancy termination is advised. Initially, the infant may need general supportive care. Long-term care requires a multidisciplinary approach consisting of occupational and physical therapy, close neurologic and audiologic monitoring and surgical interventions as needed for cardiac malformations and cataracts.
2. Cytomegalovirus
The rate of intrauterine transmission from primary maternal infection is 30-40%. Approximately 18% develop significant disease. In mothers with recurrent infection the fetus and newborn rarely show clinical symptoms. Risk of transmission in relation to gestational age is uncertain although infection during early gestation carries a higher risk of fetal disease. Symptomatic CMV presents either as an acute fulminant infection with multisystem involvement like petechiae, purpura, hepato splenomegaly and jaundice. A second insidious presentation is with microcephaly, IUGR, chorioretinitis, periventricular calcifications, mental retardation, hearing deficits, motor abnormalities, visual disturbances etc.
Prenatal diagnosis:
Amniocentesis and cordocentesis to detect CMV DNA by PCR.
Postnatal diagnosis:
Infant presents with the characteristic symptoms.
Isolation of virus or demonstration of CMV DNA by PCR from urine or saliva at birth or within 1-2 weeks indicates definitive diagnosis. When detected after 2 weeks it might have been perinatally acquired. Cell viral cultures are used for better isolation. The determination of CMV antibody titres has got limited use. (Table 2).
Table 2. Interpretation of CMV antibody titres
CMV IgG / IgM antibodies
Negative : <0.91 U / ml
Equivocal : 0.91 – 1.1 U / ml
Positive :> 1.1 U / ml
Management of CMV
- I.V. Ganciclovir, Valganciclovir x 6 weeks
- Side effects : Neutropenia – Thromobcytophenia
- Hyper Immune CMV Immunoglobulin also tried.
3. Herpes simplex virus
Intrapartum transmission is the most common mode of transmission and is associated with active shedding from cervix and vagina. Intrauterine infection is rare. Diagnosis is by high degree of clinical suspicion. An infant presents with the disease as vesicles on 6th – 9th day over skin, eye and mucocutaneous membranes. One third of affected children present with encephalitis and another one third with disseminated infection with seizures, shock and DIC / hepatitis.
Virus isolation from lesions of or and nasopharynx.
In encephalitis identification of viral DNA in CSF by PCR, increased CSF protein levels and pleocytosis.
HSV – Management
Anti viral therapy
Acyclovir
Dose: 45-60 mg/kg/day Std. Dose is 30 mg/kg/day.
Localized infection:
10-15 mg/kg/day x 8th hour x 14 days.
CNS Disease:
10-15 mg/kg x tds x 21 days.
4. Human immunodeficiency virus
Inutero and intrapartum transmission from infected mother accounts for 90% of pediatric cases. Transmission can occur throughout gestation and HIV has been isolated from cord blood and products of conception as early as 14-20 weeks of gestation.
Diagnosis:
Positive IgG in a child less than 18 months indicates maternal infection but cannot diagnose fetal infection
Virus co-culture, p 24 antigen detection, HIV specific IgM have low sensitivity in 1st week of life.
Early diagnosis of HIV DNA is by PCR assay, positive predictive value in neonates is 56% and older infants is 83%.
False positive PCR : Contamination with maternal blood
Child exposed to HIV should be tested at 1, 2, 4 months by viral culture and PCR.
If negative at 4 months there is a> 95% assurance that infant is not infected.
Exposed infant is considered negative of there are
- no physical finding of infection
- virological tests are –ve
- immunological tests – CD4 counts are normal
- >12 months of age and two or more HIV antibody tests are negative.
Management
The major part of the management of HIV infection is antiretroviral therapy. This should be offered to all symptomatic patients regardless of CD4+ cell count. But the goal of antiretroviral therapy is to suppress the HIV viral load to non-detectable and to maintain or reconstitute CD4+ cell numbers to greater than 25%. Generally, these agents are of three classes:
- Nucleoside or nucleotide analogue Reverse Transcriptase Inhibitors (NRTIs: e.g., zidovudine / AZT).
- Non-nucleoside analogue Reverse Transcriptase Inhibitors (NNRTIs: e.g., nevirapine). They are generally more potent than the NRTIs, but resistance can develop rapidly if the viral load is not controlled.
- Protease Inhibitors (PIs) prevent processing of viral proteins. These agents are quite potent.
5. Varicella zoster virus
Congenital varicella syndrome following maternal infection in first trimester is 2%.
Prenatal diagnosis:
By sonographic abnormalities like hypoplastic extremities, clubfoot, flexed limbs, ventriculomegaly, porencephalic cyst, polyhydramnios, ascites, hydrops and calcification of lungs and myocardium.
VZV specific IgM in fetal blood is nonspecific
VZV DNA detection by PCR in amniotic fluid is specific
At birth: Virus isolation from vesicular fluid on culture. Demonstration of four fold rise in VZV antibody titre by fluorescent antibody to membranes antigen.
Treatment:
Therapy with acyclovir is generally recommended. Acyclovir is used for the treatment of neonatal varicella.
There is no established immunotherapy for the treatment of V-Z virus infections, but varicella-zoster immune globulin (VZIG) may be of prophylactic value. When administered within 72 hours of exposure, VZIG is effective in preventing or attenuating V-Z virus infection. The dose for newborns is 125 units intramuscularly.
6. Parvovirus
Overall rate of transmission from an infected mother to fetus is 33%. Risk of fetal loss is 10%. It has been firmly linked to non-immune fetal hydrops by affecting the hematopoietic cell lines. If acute or recent parvovirus B 19 infection is confirmed in pregnant woman by positive B19 specific IgM assay, serial ultrasonogram should be done for fetal hydrops or meconium peritonitis.
Prenatal diagnosis:
Fetal blood and amniotic fluid for parvovirus IgM specific antibody.
PCR to detect B 19 DNA. 100% results when fetal blood is subjected to insitu hybridization.
Postnatal diagnosis :
Serum IgM rises in 3 days and falls by 2–3 months. Serum IgG appears a few days after IgM disappears and lasts for years.
7. Hepatitis Viruses
- Hepatitis C
There is high transmission rate in mothers with high viral loads. Coinfection with HIV increases transmission.
- Hepatitis B
Intrauterine transmission is rare. Detection is by HBsAg specific IgG in serum.
Management at birth
The following precautions should be taken if the mother is HBsAg positive: Avoid contact of maternal blood and amniotic fluid with skin or mucus membranes; gentle resuscitation and suction of the baby to avoid nasopharyngeal trauma; and thorough cleaning and bath after initial stabilization. These babies should receive HBIG 0.5 ml at birth (efficacy declines markedly if delayed beyond 2 days) along with the first dose of HB vaccine. Breast-feeding should continue.
