Vol. 12: Fall, 1995
Teratogen Update
Maternal Infections
TORCH infections generally refer to a group of maternally acquired communicable diseases that include Toxoplasmosis, Other (varicella, Venezuelan equine encephalitis, mumps, coxsackie, parvovirus, HIV), Rubella, Cytomegalovirus and Herpes.
The following list describes many of the features that can be seen in children who are exposed to TORCH infections during pregnancy.
| TORCH Infections - Common Clinical Manifestations |
| General: SGA, prematurity, failure to thrive
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| Vital Signs: hypo/hyperthermia, apnea, tachypnea
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| Skin: petechiae, purpura, pallor, maculopapular rash, jaundice
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| Head: microcephaly, large fontanelle, hydrocephalus
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| Eyes: chorioretinitis, cataracts, glaucoma, microphthalmia
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| Chest: pneumonia
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| Cardiovascular: structural defects causing murmurs, congestive heart failure
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| Abdomen: hepatosplenomegaly
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| CNS: hypo/hypertonia, seizures, microcephaly
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All TORCH infections have been associated with varying degrees of pregnancy loss. The magnitude of the risk is somewhat related to the severity of the maternal illness.
Rubella
First described in 1941, this prototype of congenital infections is characterized by congenital heart defects, cataracts, deafness and mental retardation. Maternal infection in the first eight weeks of pregnancy is associated with an 85% risk for congenital rubella syndrome (CRS). The risk decreases to that of the general population by approximately 20 weeks gestation. Despite an active immunization program, it is estimated that 6"-1"0% of postpubertal women are seronegative. Therefore, cases of CRS continue to occur in the US.
Data collected by the CDC suggests that inadvertent use of rubella vaccination in pregnancy or in the three months prior to pregnancy is not associated with congenital rubella syndrome or any increase in the rate of birth defects. However, theoretical risks dictate that the rubella live-virus vaccine be avoided during pregnancy. It is highly recommended that non-rubella immune new mothers be vaccinated prior to discharge from the hospital.
Cytomegalovirus (CMV)
CMV is a member of the herpes virus family and is ubiquitous in the environment. It is associated with a mononucleosis-like illness that may be indistinguishable from other viral illnesses.
Between 1-4% of non-immune pregnant women have a primary CMV infection during pregnancy. Forty percent of the time, the infection is transmitted to the fetus. The risk for congenital infection appears to be highest when the maternal infection has occurred in the first half of pregnancy. Of those fetuses that are infected, 10"-1"5% have clinically apparent disease at birth, typically including microcephaly, hepatosplenomegaly and chorioretinitis. The mortality in symptomatic newborns is 20-30%. The 85-90% with inapparent disease have a 5"-1"5% chance for long-term sequelae (most commonly hearing loss).
Primary infection does not confer total immunity for future pregnancies. However, poor outcome of infected fetuses is substantially less when the infection occurs in a mother who has previously had a CMV infection. Testing for CMV during pregnancy can be difficult. A single high titer does not differentiate between a primary and non-primary infection. Therefore, either two analyses four weeks apart looking for rising titers, or both IgG and IgM titers can be obtained. IgM is often available only at reference laboratories. Due to the difficulties in testing, routine screening of all pregnant women is not recommended.
Toxoplasmosis
Toxoplasmosis is caused by a parasite which is transmitted by raw or uncooked meat, or through infected cat feces. It is also associated with a mononucleosis-like illness. However, unlike CMV, prior infection does confer immunity.
Transmission rate to the fetus is 15-20% in the first trimester but rises to 60% in the third trimester. However, sequelae are more severe with first trimester infection and are similar to those seen with CMV infections.
Diagnosis in a pregnant woman should be made by either rising antibody titers or an IgM specific for toxoplasmosis.
Although it is controversial, there is some evidence that treatment with antiparasitical medications can ameliorate the effects in the fetus.
Herpes Simplex Virus (HSV)
The greatest concern for fetal embryopathy (growth, learning and ocular abnormalities) is from primary infection in the first half of pregnancy. Although it is very rare, infection of the fetus has also been reported with recurrent maternal infections.
The more common scenario, accounting for 80% of neonates with HSV, is infection in the intrapartum period which can lead to skin lesions, encephalitis, and disseminated disease involving many organ systems (CNS, lung, liver, adrenals, skin, eye and/or mouth). A C-section should be considered if the patient has active genital lesions at the time of delivery. Treatment of the newborn with antiviral medications has been effective.
Varicella
Varicella infection during pregnancy is associated with a less than 10% risk for fetal embryopathy. The effects include microcephaly, growth disturbances, ocular abnormalities and limb defects with cicatricial skin scarring in a dermatomal pattern when the mother is infected in the first half of pregnancy. Shingles (or herpes zoster) may be associated with similar findings but in a much smaller percentage of exposed infants.
Congenitally acquired varicella is associated with overwhelming illness in approximately 25% of babies who are exposed at or near the time of birth. The highest risk is for those infants to develop a rash at 5"-1"0 days of age. VZIG may be given to the at-risk newborn.
Mumps
The data are limited, but suggest an increased rate of pregnancy loss. There is also some evidence for a small risk for endocardial fibroelastosis in the newborn.
Measles (rubeola)
Based on a small amount of data, there does not appear to be an increase in the rate of birth defects in exposed fetuses.
AIDS
HIV infection in the mother is currently not felt to be associated with a fetal embryopathy. However, the perinatal transmission rate is approximately 30%. Recent evidence suggests that use of AZT (zidovudine) during pregnancy dramatically reduces the fetal transmission rate.
Fifth Disease (erythema infectiosum)
Fifth disease is caused by human parvovirus B19. It produces a mild illness in children and adults consisting of a facial rash (slapped cheek appearance), "lacy" body rash, malaise, flu-like symptoms and joint pain (especially in adults). It is spread by respiratory droplets. The incubation period is approximately two weeks. Fifty percent of the adult population is immune by virtue of the fact that they had fifth disease in childhood. However, since this is a mild illness in children, previous infection is generally not documented.
Human parvovirus affects red blood cell precursors, causing anemia. In pregnant women, this can lead to non-immune fetal hydrops. The risk for fetal death from hydrops in an infected woman is 5% or less. In utero transfusions have been successfully used. However, there have also been several case reports of spontaneous resolution of hydrops with a normal fetal outcome. At this time, there does not appear to be a significant risk for birth defects in the fetus.
Pregnant women can be tested for the presence of IgG and IgM, specific for parvovirus, to determine if they have been infected during the pregnancy. However, testing should be limited to those with significant exposure, an unidentified maternal rash-like illness or fetal hydrops.
See References: Maternal Infections
The Genetic Drift Newsletter is not copyrighted. Readers are free to duplicate all or parts of its contents. The Genetic Drift Newsletter is published semiannually by the Mountain States Genetics Network for associates & those interested in Human Genetics. In accordance with accepted publication standards, we request acknowledgement in print of any article reproduced in another publication. The views expressed in the newsletter do not necessarily reflect local, state, or federal policy. For additional information, contact Carol Clericuzio, M.D., Editor, Department of Pediatrics, The University of New Mexico, Albuquerque, NM, 87131
Table Of Contents: Teratogen Update
Introduction
Medications
Substances of Abuse
Maternal Infections
Maternal Disorders
Mutagens
Etiology of Congenital Malformations in Humans: (Table 1)
Known Human Teratogens: (Table 2)
References
Facts About Neural Tube Defects and Folic Acid
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