Search

The single-stranded DNA parvoviruses occur in humans and many species of animals. In general, they are species-specific and capable of producing disease at any stage of life. Parvoviruses have a requirement to replicate in cells in a permissive S-phase of DNA mitosis. The infections may be cytolytic to select cell groups resulting in specific developmental defects or may produce more generalized effects such as anemia, pancytopenia, or hemorrhage. The fetus is at particular risk for damage because of the vast number of cells in active mitosis. The teratogenic effects may be severe, often resulting in fetal death. Infections in childhood and adulthood are more frequently mild to subclinical. Some of the teratogenic effects recognized in animal species have been identified in humans. With increased knowledge of parvovirus effects in animals, more pathogenic effects may be related to human parvoviral disease. The need for vaccination, currently used annually in many domestic animal species, continues to be evaluated for humans.

A matched case-control methodology was used to assess the risk for a wide range of abnormalities in children associated with serological evidence for 'TORCH' infections in the mothers. Specimens were selected from the large bank of sera from the approximately 54,000 pregnant women who participated in the Collaborative Perinatal Project. There was no clear association between any of the antigens studied and any specific damage to the child. These 'negative' findings are consistent with the absence of frequent significant effects due to these agents in the second and third trimesters of pregnancy.

A review of the events which lead up to the recognition of six infectious agents as teratogens showed that in most cases the associations were made through studies of the pathology of the disease or in association with epidemics which affected large numbers of pregnant women. Epidemiological studies of various populations were then conducted to obtain more complete information about the frequency of infection; the syndrome produced in the child; the effect of time of maternal infection; the method of transmission of infection; and approaches to diagnosis, treatment, and prevention of the disease. Investigation of other possible teratogens should emphasize examination of the pathology of the disease and the analysis of pregnancy outcomes of large numbers of women who experience a given infection.

Human parvovirus B19 (B19) infection during pregnancy has been associated with fetal deaths. We conducted several studies to develop data needed to make recommendations for preventing fetal death associated with infection. In the first study, after an outbreak of B19 infection, specimens of cord blood from 47 infants with congenital anomalies, 10 with suspected intrauterine infection, and gestational age-matched controls were tested for IgG and IgM antibodies to B19. None had evidence of recent infection. Next, 192 women with unknown exposure to B19 who had stillbirths or spontaneous abortions were studied. Two patients and two controls had evidence of recent B19 infection. In a second case-control study of women who had stillbirths after outbreaks of erythema infectiosum in area schools, none of the 20 patients or 26 controls were IgM positive at the time of delivery. The rate of infection, as demonstrated by IgM positivity, among 267 pregnant control subjects was approximately 1%. These studies suggest that among pregnant women unselected for exposure to B19, neither infection nor stillbirths are common.

There are a large number of infectious agents which damage or kill the developing fetus or child. In this report I have summarized the changing status of information available for just six of these diseases. For rubella there has been excellent success with the development of a vaccine for prevention of this disease. Unfortunately the vaccine is only used extensively in a few countries. Herpes simplex has become a particular problem because of the rapid increase in the frequency of genital herpes infections, the spontaneous recurrences of the lesions, and the difficulty in prevention or treating congenital infections. Cytomegalovirus infections are now known to occur in 1% of newborns, and some damage is produced in about 10% of these children. We have no methods for preventing or treating this infection. Varicella at term is also an important risk to the child but this can now be controlled by the use of VZIG. Varicella earlier in pregnancy may be teratogenic. Venezuelan equine encephalitis virus can cause severe brain damage to the fetus, and one of the vaccines for this infection was shown to be teratogenic in monkeys. Lastly, congenital toxoplasmosis has been known for many years to cause fetal damage and death. Further studies of serological detection of infection and treatment are needed. A number of other viral, bacterial, and parasitic diseases must also be considered as part of the total group of these preventable causes of physical and mental damage to the fetus and newborn.