Sergio Stagno

The outcome of congenital cytomegalovirus infection in relation to maternal antibody status.

Abstract Background. Intrauterine transmission of cytomegalovirus (CMV) can occur whether a mother has prior immunity or acquires CMV for the first time during pregnancy. The degree of protection afforded an infected infant by the presence of antibody in the mother before conception is uncertain. Methods. We compared the outcomes of CMV-infected infants born to mothers who acquired primary CMV infection during pregnancy (primary-infection group) with those of CMV-infected infants born to mothers with immunity (recurrent-infection group). Screening for viruria identified 197 newborns with congenital CMV infection. Stored serum samples were used to categorize maternal infection as either primary or recurrent. We followed 125 infants from the primary-infection group and 64 from the recurrent-infection group. Serial medical, audiologic, psychometric, and eye examinations were used to identify sequelae of CMV infection. Results. Only infants in the primary-infection group had symptomatic CMV infection at birth...

Congenital Cytomegalovirus Infection: The Relative Importance of Primary and Recurrent Maternal Infection

We studied the incidence of primary and recurrent cytomegalovirus infection in 3712 pregnant women--2698 of middle to high income and 1014 of low income--to determine whether there were differences in the effects on the fetus. In the higher-income group, 1203 women (45 per cent) did not have antibodies to cytomegalovirus and were therefore susceptible to primary infection, as compared with 179 women (18 per cent) of low income. Congenital infection occurred more often (1.6 vs. 0.6 per cent) in infants in the low-income group. In this group it was associated with recurrent maternal infection more often (in 82 per cent) than with primary maternal infection, whereas in the upper-income group, it was associated with primary maternal infection in half the cases. Altogether, there were 32 cases of congenital cytomegalovirus infection - 16 in each group. Whereas primary maternal infection resulted in fetal infection in only half the cases, it was more likely to ge associated with clinically apparent disease than was recurrent infection. When these cases were combined with 28 cases of congenital infection retrospectively identified at other prenatal clinics, five of 33 infected infants born after primary maternal infection had clinically apparent disease, as compared with none of 27 born after recurrent maternal infection. We conclude that congenital cytomegalovirus infection resulting from primary maternal infection is more likely to be serious than that resulting from recurrent infection, and is more likely to occur in upper socioeconomic groups.

Symptomatic congenital cytomegalovirus infection : neonatal morbidity and mortality

Knowledge of the natural history of symptomatic congenital cytomegalovirus (CMV) infection in the newborn is essential in order to anticipate complications and assess the potential benefit from antiviral therapy. To define the disease course we reviewed data on 106 neonates with symptomatic congenital CMV infection diagnosed and managed by the investigators. Petechiae, jaundice and hepatosplenomegaly were each noted in 70% or more patients. Microcephaly was noted in 54 of 102 (53%) at birth. Elevated alanine aminotransferase, conjugated hyperbilirubinemia and thrombocytopenia were seen in 83, 81 and 77%, respectively. Eighty-six percent had at least two of the manifestations highly suggestive of congenital infection. Platelet count fell to its nadir during the second week of life whereas elevated alanine aminotransferase and direct bilirubin persisted past the first month. In spite of the difficulty in assessing central nervous system function in the newborn, evidence of damage was present in the majority. Seventy-two had microcephaly, poor suck, lethargy/hypotonia or seizures. Abnormal computerized tomographic scan was present in 16 of 20 (80%) and decreased hearing in 20 of 39 (56%). Cerebrospinal fluid protein was greater than 120 mg/dl in 24 of 52 (46%) and this elevation was associated with neurologic abnormalities as well as hearing loss. The mean length of hospital stay was 13 and 22.4 days for term and preterm infants, relatively. Thirteen infants (12%) died during the first 6 weeks of life. Disseminated CMV infection with multiorgan involvement was evident in 7 of 9 at postmortem examination. We conclude that neonates with symptomatic congenital CMV infection have a multi-system disease with significant morbidity and mortality.

Congenital cytomegalovirus infection. Occurrence in an immune population.

The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception.

Symptomatic Congenital Cytomegalovirus Infection in Infants Born to Mothers With Preexisting Immunity to Cytomegalovirus

Objectives. To determine the frequency of symptomatic congenital cytomegalovirus (CMV) infection in the offspring of women with a recurrent maternal CMV infection and to characterize the demographic and newborn findings. Methods. Study subjects consisted of infants with symptomatic congenital CMV infection identified by a newborn virologic screening program at the University of Alabama Hospital between 1991 and 1997 and were enrolled in a long-term follow-up study. Maternal infections were categorized by an analysis of archival serum specimens collected before pregnancy and at the time of delivery. Demographic data and clinical findings at birth were collected from maternal and newborn hospital records and from parents at the time of initial evaluation. Results. Of the 47 infants with symptomatic congenital CMV infection identified during the study period, 8 were born to mothers with a confirmed nonprimary or recurrent CMV infection. The type of maternal infection could be ascertained in only ∼43% (20/47) of the children with symptomatic congenital CMV infection born at the University of Alabama Hospital during the study period. There were no significant differences in demographic characteristics of the recurrent infection group and the infants who were born to mothers with either primary CMV infection during pregnancy or unclassified maternal infection. Similarly, the range of severity of clinical abnormalities during the newborn period did not differ in the two groups of children. Furthermore, there were no significant differences in the incidence of sequelae at long-term follow-up in the two groups of children. Conclusions. Symptomatic congenital CMV infection can occur after a nonprimary or recurrent maternal infection. However, the exact incidence of symptomatic congenital CMV infection among children born to women with preexisting immunity remains to be defined.

Maternal Cytomegalovirus Excretion and Perinatal Infection

Abstract A prospective study of pregnant women revealed cytomegalovirus excretion from urine or cervix in 12 per cent. Increasing rate of infection with advancing gestation, stable antibody titers ...

Ganciclovir Treatment of Symptomatic Congenital Cytomegalovirus Infection: Results of a Phase II Study

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.

Intrauterine herpes simplex virus infections

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus.

ASSOCIATION OF UREAPLASMA UREALYTICUM INFECTION OF THE LOWER RESPIRATORY TRACT WITH CHRONIC LUNG DISEASE AND DEATH IN VERY-LOW-BIRTH-WEIGHT INFANTS

Endotracheal aspirates from 200 infants who weighted less than or equal to 2500 g and who had evidence of respiratory disease were cultured within 24 h of birth for mycoplasmas, chlamydiae, viruses, and bacteria to evaluate the relation between lower respiratory tract infection and development of chronic lung disease and/or death. Ureaplasma urealyticum, an organism not visible on gram stain, not recovered on routine bacteriological media, and not susceptible to antibiotics commonly used to treat neonatal infections, was the single most common organism isolated. 14% of isolates were from infants born by caesarean section with intact membranes, which indicated that infection had occurred in utero. The findings probably represented true infection of the lower respiratory tract because the organism was recovered in pure culture in numbers greater than 10(3) from 85% of the infants, and also from the blood in 26% of infants. Those infants less than or equal to 1000 g with Ureaplasma urealyticum infection of the lower respiratory tract were twice more likely to have chronic lung disease or to die than were infants of similar birth-weight but who were uninfected, or infants greater than 1000 g. Very-low-birth-weight infants infected with ureaplasmas did not differ from those uninfected, either in demographic features or in potential risk factors for chronic lung disease.

Herpesvirus infections of pregnancy. Part I: Cytomegalovirus and Epstein-Barr virus infections.

CYTOMEGALOVIRUS and herpes simplex, varicella–zoster, and Epstein–Barr viruses, members of the herpesvirus family, are ubiquitous agents that infect almost all human beings at some point during the...