Perinatal Infections1

Reproductive wastage, obstetric mishaps, and neonatal morbidities are not uncommon. The usual causes are genetic, familial or environmental factors. Infection as a cause is overlooked generally. ‘What the mind does not know, the eye does not see.’ Hence, suspicion is the prime requirement for diagnosing infections. Perinatal infection is a broad area of perinatal medicine that pertains to the mother, her fetus and the newborn infant.

Perinatal infections with adverse neonatal outcome can be classified as:

The two most common bacteria causing neonatal infection are the group B Streptococcus (GBS) and E. coli which together account for 70 percent of all systemic bacterial infection. The pathogenesis of these infections may relate to the lack of type-specific antibodies to these organisms. A specific polysaccharide, sialic acid, found on the outer capsules of both GBS and E. coli prevents activation of the alternative complement pathway and hence destruction of the bacilli by the host immune system.

From 1941, when Gregg associated rubella with congenital anomalies to 1969, when rubella vaccine was developed, a lot of congenital anomalies were reported. In the prevaccination era 80 percent of women of childbearing age were already infected at least once due to the custom of kitty parties. The clinical features of rubella are maculopapular rash, fever, lymphadenopathy and arthropathy. The risks of rubella infection during pregnancy can be classified according to the weeks of gestation:

Toxoplasma is an obligatory intracellular parasite infecting a wide range of birds and small mammals, whereas the human is not a vector. However, the parasite may be acquired by contamination with cat feces or by the ingestion of uncooked meat following which the organism may be transmitted from the mother to her fetus. In India, 80 to 85 percent of women are infected by the age of 20, compared to approximately 20 percent in the United Kingdom and USA. Although most cases of maternal toxoplasmosis are asymptomatic, when infection is evident the most common presentation is a glandular fever like illness.

Cytomegalovirus (CMV) is the most common cause of congenital infection, complicating 0.4 to 2.4 percent of all births. About 50 to 85 percent of women of childbearing age are seropositive. Primary infection in pregnancy is often acquired from young children or from sexual partners. About 30 to 40 percent of infants born to mothers sustaining their primary CMV infection during pregnancy will have congenital infection, of whom 10 percent are symptomatic. Features suggestive of congenital CMV include growth retardation, hepatosplenomegaly, jaundice, petechiae, microcephaly, hydrocephalus, periventricular calcification and chorioretinitis. However, the most common manifestation of congenital CMV is sensorineural hearing loss that occurs in 15 percent of symptomatic and 5 percent of asymptomatic infants. The diagnosis is best made by culturing the virus from neonatal urine or saliva. Demonstrable seroconversion during pregnancy may be helpful, but paired sera are not usually available. At present, there is no effective antiviral therapy for congenital CMV, although 4there are a number of ongoing multicenter trials regarding the use of gancyclovir. Common long-term complications, even amongst asymptomatic infants include deafness and learning disabilities.

Neonatal herpes simplex virus infections are rare. Infection usually results from the perinatal acquisition of HSV, usually type 2, from the maternal genital tract in about 85 percent of cases. Maternal HSV antibodies are protective, particularly if type specific. Infants at the highest risk are those delivered vaginally to mothers who have acquired primary HSV2 late in pregnancy, as they may still be shedding the virus from the genital tract without having had the opportunity to produce protective antibodies. Neonatal infection usually presents toward the end of the first week of life. Neonatal HSV may be localized to the eye, skin or mouth, or be generalized, or may cause isolated pneumonitis or meningo-encephalitis. Only localized external disease has a good prognosis. Without antiviral treatment, 70 percent of localized external cases of neonatal HSV will become disseminated. Therefore, prompt recognition of neonatal herpes using direct immunofluorescence techniques; electron microscopy or PCR is paramount to improving outcome, as antiviral therapy, particularly with acyclovir, may decrease the likelihood of disseminated disease. Prevention of neonatal HSV infection is controversial. A mother with primary genital HSV in labor should be delivered by cesarean section if the membranes have not been ruptured for more than 24 hours. A mother with recurrent symptomatic genital HSV should, probably, also be delivered by cesarean section because of a higher viral load at the time of delivery. The management of asymptomatic recurrences in labor is less clear. Unless the infant is infected at birth or was delivered vaginally to a mother with primary genital HSV, it is best to culture the infant's nasopharynx and conjunctiva and treat only if cultures are positive.

Congenital syphilis is the oldest recognized congenital infection. Syphilis is common among young women, particularly those abusing drugs or with poor antenatal care. The majority of infants are infected in utero by transplacental passage of Treponema pallidum from an infected mother to her fetus, although the newborn can also be infected by contact with an active genital lesion at the time of delivery. The highest risk to the fetus is in the setting of untreated primary syphilis or in the early stages of secondary syphilis. Early recognition and treatment of the mother will prevent 98 percent of cases of neonatal infection. Penicillin is the antibiotic of choice, with treatment failures being as high as 30 percent with erythromycin. The clinical signs and symptoms of congenital syphilis are often nonspecific and similar to those with other intrauterine infections such as CMV and toxoplasmosis. The diagnosis of congenital syphilis relies on serologic testing, although this may be difficult if the mother is diagnosed for the first time close to delivery. Infants should be presumed to have congenital syphilis if they are born to women with untreated syphilis or if there is evidence of reinfection at the time of delivery, if the infant has clinical disease or evidence of neurosyphilis, if the infant's serum nontreponemal titer is four or more times greater than it's mother's, if an infant has specific antitreponemal IgM antibody titers or is at risk of active disease but where the mother has not been 5fully evaluated. If in doubt, it is best to treat the infant with either aqueous crystalline penicillin or procaine penicillin for 10 to 14 days. Treated infants should be followed for at least 12 months, with repeated serological testing.

Hepatitis B is usually acquired following contact with blood or genital secretions. Perinatal transmission occurs primarily as a result of the infant's exposure to infected blood and genital secretions during delivery. Antenatal transmission is quite uncommon. An infant is at risk of infection if the mother is HBsAg positive. The risks increase dramatically if the mother has her primary infection in the third trimester or is HBeAg positive. A combination of passive and active immunization is 85 to 95 percent effective in preventing neonatal hepatitis B infection.

Hepatitis C is almost always transmitted via the parenteral route with sexual transmission now thought to be rare. Vertical transmission is also thought to occur infrequently although vertical transmission may be more frequent if the mother is HIV positive. Because of limited information regarding seroprevalence, conflicting information regarding vertical transmission and the absence of treatment for hepatitis C infection, universal prenatal screening is not recommended. The safer mode of delivery of the fetus is uncertain. Because passive immunoprophylaxis using immunoglobulin appears to reduce the incidence of post-transfusion hepatitis in patients receiving blood transfusions infected with HCV, the use of immunoglobulin to prevent vertical transmission of hepatitis C from the mother to her infant may be beneficial; but at this stage, it should be considered experimental.

The incidence of HIV in India is rising. It is about 0.2 to 0.3 percent at Nowrosjee Wadia Maternity Hospital, Parel (Mumbai). Risk factors for women include IV drug use and unprotected heterosexual intercourse. There is an appreciable risk of perinatal transmission of the virus to the infants. A recent 6study from the United States involving women with asymptomatic HIV demonstrated a significant reduction from 30 to 8 percent in the incidence of HIV in their offspring following the use of perinatal AZT to the fetus and infant. Therefore, mothers known to be HIV positive should receive AZT. Because the virus is secreted into breast milk, in first world countries, such as Australia, the risks to the infant of viral transmission are greater than the disadvantages of formula feeding; and, therefore, in this select group of infants, breastfeeding is contraindicated. However, the converse applies in the third world countries. Pediatric referral and follow-up of infants born to HIV positive mothers is mandatory.

Interestingly, varicella is probably the most common infection that parents, staff and fellow medical practitioners are worried about. Fortunately, approximately 95 percent of women of childbearing age are seropositive and as such cannot transmit the virus to their fetus or infant, except in the setting of herpes zoster, which is rare during pregnancy. Although, only about one-half of seropositive mothers are aware of a past history of varicella, rapid testing for seropositivity is now available in large centers, enabling clarification of a mother's serological status. If a potentially susceptible mother presents following exposure to varicella, and is found to be seronegative, she should be given ZIG within 4 to 6 days as primary varicella during pregnancy is associated with an increased risk to the mother of pneumonitis and even death. If the mother develops varicella during pregnancy, she should receive acyclovir, preferably within 24 hours of the onset of the lesions as this may diminish the severity of her disease.

Listeria monocytogenes is a small, motile gram-positive rod, which grows slowly in the laboratory. It is a facultative intracellular parasite, which can only be transmitted to humans through domestic animals or contaminated food. Early onset infection may occur following either transplacental or vaginal acquisition. Intrauterine infection may lead to abortion or fetal death in utero. Listeria will infect approximately 1.5 per 10,000 infants with the mortality rate being high with early onset neonatal infection. These infants usually have disseminated disease with hepatosplenomegaly and a granulomatous “salmon” colored rash.