Lecture no.

Congenital and Perinatal Infections

Infections in the newborn infant can be classified as congenital or perinatal. It is important to

make this distinction as the clinical presentations, causative organisms, diagnostic approaches,
treatments and long-term considerations differ for these two groups.
A congenital infection is an infection seen in the newborn infant that was acquired
transplacentally during the first, second, or early third trimester.
In contrast, a perinatal infection is acquired either around the time of delivery or during the
first week of extrauterine life.

Congenital infections
The incidence of congenital infection in the fetus and newborn infant is relatively high at 0.5-
2.5%. The most common causative agents are:
– rubella virus,
– cytomegalovirus (CMV),
– Toxoplasma gondii,
– Treponema pallidum,
– human immunodeficiency virus (HIV).
Despite the diversity of these organisms, many produce similar syndromes in the newborn
infant grouped under the acronym TORCH.
Common manifestations of congenital infections include growth retardation, hepatomegaly,
splenomegaly, jaundice (secondary to direct hyperbilirubinemia), hemolytic anemia, petechiae and
ecchymoses, microcephaly, hydrocephaly, and pneumonitis. However, the majority of affected
infants are entirely asymptomatic.

Rubella syndrome. The incidence of congenital rubella syndrome is 0.5 per 1000 live births.
Infants are usually born small for gestational age.
Common clinical findings include:
– purpura, thrombocytopenia,
– hepatosplenomegaly,
– cardiac defects,
– eye defects (glaucoma and cataracts),
– pneumonia and
– meningoencephalitis.
Diffuse purpuric lesions on the skin resembling a "blueberry muffin", represent cutaneous
extramedullary hematopoietic tissue that may be seen in this and other congenital infections.
Congenital rubella infection can be diagnosed with an elevated anti-rubella IgM titer in the
perinatal period or high anti-rubella IgG titers throughout the first year of life. Virus can also be
isolated from a throat swab, CSF or urine.
Common long term problems seen in infants with congenital rubella include communication
disorders, hearing defects, mental and/or motor retardation, microcephaly, learning deficits, balance
and gait disturbances, and behavioral problems.
Although live attenuated rubella virus vaccine is available to prevent the disease, there is no
specific therapy for congenital rubella.

Congenital cytomegalovirus infection. CMV infection occurs in roughly 1% of all neonates

with those who are not congenitally infected contracting the infection possibly through breast milk.
Twelve percent of these infants will die and more than 90% of survivors will suffer late complications,
most commonly sensorineural hearing loss. Congenital CMV infection may be the result of a newly
acquired maternal infection or a reactivated old maternal infection. Although less common, newly
acquired maternal infection poses a much higher risk of severe disease and a worse prognosis.
Ninety percent of infected newborns are surprisingly asymptomatic at birth. However, those that
are symptomatic are small for gestational age and often present with petechiae, ecchymoses,
thrombocytopenia, jaundice, direct hyperbilirubinemia, anemia, hepatosplenomegaly, elevated
SGOT, microcephaly, seizures and chorioretinitis. The diagnosis of congenital CMV infection is best
made by isolating the virus in urine culture. Periventricular calcifications can be seen on cranial
ultrasound. Of the affected infants that survive the neonatal period, 1/3 will have hearing loss, one
third will have neuromuscular disorders (seizures or spasticity) and a few will have vision problems
secondary to chorioretinitis. Although there is no specific therapy for congenital CMV infection, trials
examining the effectiveness of ganciclovir, alpha interferon and CMV immune globulin are underway.
Congenital toxoplasmosis. The incidence of congenital toxoplasmosis infection varies with
geographic location and local dietary habits. Maternal toxoplasma infection is usually due to
ingestion of tissue cysts found in raw or undercooked meats or consumption of water or other foods
containing oocysts from infected cats. Congenital infection with Toxoplasmosis gondii occurs during
maternal parasitemia. In the neonate, the primary focus of toxoplasma infection is in the central
nervous system, leaving necrotic, calcified cystic lesions dispersed within the brain. Less commonly,
similar lesions can be found in liver, lungs, myocardium, skeletal muscle, spleen and other tissue.
Approximately 85% of infants with congenital infection have normal examinations and are
asymptomatic. Those infants that exhibit illness at birth frequently present with fever,
hepatosplenomegaly, jaundice, rash and pneumonitis. The classic triad of toxoplasmosis,
chorioretinitis, hydrocephalus and intracranial calcification occurs in only a small proportion of
symptomatic patients. Abnormal laboratory findings include anemia, thrombocytopenia,
eosinophilia, and abnormal CSF studies. Seizures, mental retardation, spasticity, and relapsing
chorioretinitis are common long-term complications of congenital toxoplasmosis, even if not present
at birth. Antenatal ultrasound can suggest the diagnosis of congenital toxoplasma infection when
bilateral, symmetric ventricular dilatation, intracranial calcifications, increased placental thickness,
hepatomegaly and ascites are noted. Postnatal diagnosis is also made by detection of anti-
Toxoplasma IgM antibodies in the infant's serum. Treatment, antenatally and postnatally, consists of
pyrimethamine and sulfadiazine. Spiramycin may also be used, if available. Historically, prognosis in
untreated infants is poor. However, with recent advances in antenatal diagnostic capabilities and
available medical therapies, the frequency of major neurologic sequelae has decreased.
Syphilis is caused by the spirochete Treponema pallidum. Transplacental transmission usually
occurs during the second half of pregnancy. Most infants born to mothers with primary or secondary
syphilis have congenital infection; though only half of those who are infected are symptomatic.
Because congenital syphilis is associated with significant neurodevelopmental morbidity, it is
imperative that both maternal status and infant risk for syphilis be checked in all pregnancies. Early
features of congenital syphilis include hepatosplenomegaly, skin rash, anemia, jaundice, metaphyseal
dystrophy, periostitis and CSF abnormalities including elevated protein and mononuclear pleocytosis.
However, in some cases, the infant is asymptomatic and may not develop any signs or symptoms of
congenital infection for weeks or months. "Snuffles" is obstruction of the nose with initial clear
discharge progressing to purulent or sanguineous discharge. It is seen in infants with congenital
syphilis usually after the newborn period. Detection of IgM-FTA-ABS (fluorescent treponemal
antibody absorption) in the newborn's blood is the most reliable method of diagnosing congenital
syphilis. However, this test is not always positive early on in life, thus repeat testing at 3 to 4 week
intervals is frequently indicated. Treatment for both the pregnant mother and baby is penicillin G.
Despite antibiotic therapy, it is recommended that infants undergo repeat blood and CSF testing
during the first 12-15 months of life until negative or stable low titer levels are achieved. Vision,
hearing and developmental evaluations are also indicated before three years of age in infants with
congenital syphilis.

Perinatal infections
Perinatally acquired infections are those that are acquired either around the time of delivery
or during the first week of extrauterine life. Common pathogens include bacteria, such as group B
streptococci, E. Coli, and Listeria, herpes simplex virus, hepatitis viruses and human
immunodeficiency virus. Infants with perinatally acquired viral infections are often normal at birth,
developing illness later in life.
A few pathogens like cytomegalovirus (CMV) can cause both congenital and perinatally
acquired infection in the newborn with striking contrasts in presentation. The infants with congenital
infections can present with growth restriction, anemia, thrombocytopenia, extramedullary
hematopoiesis, and intracranial calcifications, all indicative of a chronic process; namely, congenital
CMV infection that was transmitted transplacentally during the first or second trimester of
pregnancy. Perinatally, CMV can be transmitted through breast milk or vaginal secretions.
Premature infants however, are particularly susceptible to transmission through transfusion of blood
products. The resulting syndrome is characterized by shock, pneumonitis and lymphocytosis. The role
of ganciclovir in perinatally acquired CMV infection is unclear.
The majority of neonatal herpes simplex virus (HSV) infection is acquired from the maternal
genital tract with an incidence of approximately 1 case per 3500 live births. However, infection may
also be acquired after birth from mother or other persons with non-genital tract lesions (e.g., oral
herpes, herpetic whitlow) following close contact with the infant or handling. Primary maternal
infection is associated with a 50% risk of perinatal/neonatal infection, while a risk of <5% is seen with
recurrent maternal infection. Of note, active HSV lesions are present at the time of delivery in only
1/3 of mothers of affected infants. Several defects in cellular immune function contribute to
neonatal susceptibility to HSV. Perinatally acquired HSV infection results in massive coagulation
necrosis of the liver, lungs, adrenal glands and brain. Most infants are asymptomatic at birth,
developing illness during first 1 to 2 weeks of life. Clinical illness can be characterized as being
localized or disseminated. Disseminated illness can be further described as those with and those
without central nervous system involvement. Systemic symptoms of disseminated HSV infection
usually present towards the end of the first week of life, including poor feeding, lethargy, fever,
irritability, and seizures with rapid progression to hypotension, disseminated intravascular
coagulation, apnea and shock. Skin vesicles are present in less than half of patients. With antiviral
therapy, 15-20% of patients die and 40-55% of survivors suffer long-term neurologic impairment.
Localized disease may involve the central nervous system alone, the central nervous system and skin,
eyes, and oral mucosa or only the skin, eyes and oral mucosa. Except in cases of isolated viral
encephalitis, HSV is readily recovered in culture from scrapings of skin vesicles, blood, cerebrospinal
fluid, conjunctivae, respiratory secretions, and urine. Once neonatal HSV infection is suspected,
antiviral therapy should be started immediately. Parenteral acyclovir is the treatment of choice for
herpes neonatorum. Treatment duration varies depending on whether the infection involves the
CNS and/or is disseminated. Despite antiviral therapy, overall outcome for survivors is poor. More
than half of infants who survive disseminated disease will develop microcephaly, spasticity, paralysis,
seizures, deafness, or blindness. Those with skin involvement may be subject to recurrent vesicular
outbreaks for several years. Of note, HSV can also be transmitted in utero during the first or second
trimesters of pregnancy (congenital infection). Those fetuses that are not stillborn or spontaneously
aborted demonstrate a syndrome similar to other congenital viral infections like CMV. Treatment is
supportive as acyclovir has no proven benefit for these infants.
Hepatitis. The most important of the hepatitis viruses for the general pediatrician is Hepatitis
B. The virus is found primarily in the liver parenchyma, but can be found in circulating blood from a
few days to many years. Regardless of maternal acute or chronic infection, the virus rarely crosses
the placenta, thus perinatal/neonatal infection is most likely acquired from infected maternal blood
encountered during the delivery process. Overall, there is 60-70% chance of transmission during
delivery if mother has an acute infection at that time. Mothers may also be carriers which still has a
risk of transmission to the newborn. By 2 to 6 months of age, liver enzymes are often elevated and
infants are antigen seropositive. Occasionally, infection may present with jaundice, fever,
hepatomegaly and anorexia, followed by complete recovery or chronic active disease.
Approximately 95% of perinatally acquired HBV infection can be prevented by early active and
passive immunoprophylaxis of infants born to HBsAg positive mothers. Infants born to HBsAg
positive mothers should receive the initial dose of hepatitis B vaccine and hepatitis B immune
globulin (HBIG) within 12 hours of birth (given at separate injection sites). Infants born to
unscreened mothers should receive their first hepatitis B vaccine within 12 hours of birth while
awaiting maternal blood test results. If the mother should be found to be HBsAg positive, HBIG
should be given within the first week of life. All infants should complete the hepatitis B
immunization series by 6 months of age. Infants born to HBsAg positive mothers should be tested
for anti-HBsAg antibodies and HBsAg 1 to 3 months after the third dose of vaccine is given to
determine those who may be chronically infected and those who may require additional doses of the
vaccine. Breastfeeding by an HBsAg positive mother has not been shown to cause hepatitis B
infection in infants.
Once seen exclusively in children who had received blood products, pediatric human
immunodeficiency virus (HIV) infection is now overwhelmingly the result of perinatal transmission.
There are three distinct modes of transmission of human immunodeficiency virus (HIV) from mother
to fetus. Congenital HIV infection results from the transplacental transmission of virus during early
pregnancy. Intrapartum transmission may occur following exposure of the infant to mother's blood
or as a result of maternal-fetal transfusion during the delivery. Perinatal infection with HIV can occur
either during the birthing process or shortly after birth through breastfeeding. Risk factors associated
with perinatal HIV transmission include maternal viral load (plasma and genital tract), primary
infection of late stage HIV, low CD4 count, STDs/other co-infections, pre-term delivery, increasing
duration of rupture of membranes, placental disruption, invasive fetal monitoring (eg. scalp probes),
vaginal delivery and lack of AZT prophylaxis. The transmission rate from mother to infant is
approximately 20-30%. However, recent studies have shown that for select HIV-infected women,
zidovudine (AZT) may decrease transmission to 8% of their infants. Maternal treatment with AZT in
combination with elective cesarean section delivery prior to rupture of membranes and the onset of
labor has shown further reduction of the transmission rate to 2%. Infants with congenital infection
present in a similar fashion to other congenital infections and may also exhibit craniofacial
abnormalities. Infants with perinatally acquired infection are usually asymptomatic at birth. To
maximize the opportunity to prevent perinatal transmission of HIV infection, maternal HIV status
should be determined during the first trimester of pregnancy. Anti-retroviral therapy should be
started in those found to be HIV positive. During labor and delivery, AZT, 2mg/kg should be
administered IV during the first hour, then 1mg/kg per hour until delivery. The infant should then be
started on AZT syrup, 8-12 hours after birth, 2mg/kg QID until 6 weeks of age when the infant's HIV
status can be determined. Detection of HIV antibody by ELISA or Western blot in the newborn is
complicated by transplacental passage of maternal IgG and should not be performed before 18
months of age. Detection of HIV DNA by PCR is the preferred test for diagnosis of HIV infection in
infants. Testing should be performed at birth, then at 1-2 months of age, and a third time between 3
and 6 months of age. Any time an infant tests positive, a second repeat specimen should be obtained
immediately to confirm the diagnosis of HIV infection. Viral culture for HIV can also be done;
however, issues of cost, regional availability and delay in reporting results make it less useful than
HIV DNA by PCR. Umbilical cord blood should not be used for testing. An infant with at least 2
negative HIV virology tests from separate specimens, 1 of which was performed at 1 month of age
and 1 of which was performed after 4 months of age can be considered "not infected with HIV".
Finally, because transmission of HIV through breastmilk has been reported, counseling to discourage
breastfeeding should be provided to all mothers who are HIV positive.

Questions
1. What physical findings suggest that an infant has a congenital infection (TORCH)?
2. How does a congenital infection differ from an infection that is acquired perinatally?
3. What are the most common causes for congenital infection?
4. True/False: A term infant with a normal physical exam and no risk factors for infection
may have congenital infection.
5. Periventricular calcifications in the brain are seen with which congenital infection? Diffuse
calcifications?
6. True/False: An infant born to a woman with recurrent herpes infection is at higher risk for
developing herpes neonatorum than one born to a woman with primary herpes infection at the time
of delivery?
7. Administration of what agents can prevent 95% of perinatally acquired hepatitis B
infections?
8. True/False: Breastfeeding should be encouraged in all mothers who are HIV positive, but
do not have AIDS.
Answers to questions
1. Small for gestational age, microcephaly, jaundice, pale skin, petechiae, blueberry muffin
spots, hepatomegaly, and splenomegaly
2. A congenital infection is an infection seen in the newborn infant that was acquired
transplacentally during the first, second, or early third trimester. A perinatal infection is acquired
either around the time of delivery or during the 1st week of extrauterine life.
3. Rubella virus, cytomegalovirus (CMV) Toxoplasma gondii, Treponema pallidum, human
immunodeficiency virus (HIV)
4. True
5. Periventricular calcifications are seen in congenital CMV while diffuse calcifications in the
brain are seen in congenital toxoplasmosis.
6. False
7. Hepatitis B vaccine and hepatitis B immune globulin.
8. False