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Biomedical subjects

S Stagno

Publications and source records attributed to S Stagno.

At least 19 recordsLinked to original sources

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 approximately 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.

Acute Disease↗

Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

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.

Alanine Transaminase↗

Neuroradiographic findings in the newborn period and long-term outcome in children with symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine whether newborn cranial computed tomographic (CT) scan abnormalities predict an adverse neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection and to examine the association between clinical findings at birth and imaging abnormalities. METHODS: The data from 56 children with symptomatic congenital CMV infection who underwent cranial CT scans as newborns and were enrolled in a long-term follow-up study were analyzed. The incidence of sequelae was compared between the groups of children with normal and abnormal imaging studies. The relationship between CT scan results and other newborn findings was also examined. RESULTS: Abnormal CT scans were noted in 70% of subjects; intracerebral calcification was the most frequent finding. Most of the children with an abnormal newborn CT scan (90%) developed at least one sequela, compared with 29% of those with a normal study. Only 1 child with a normal CT scan had an IQ < 70, in contrast to 59% of those with imaging abnormalities. In addition, almost half of the children with CT abnormalities had an IQ < 50 compared with none of those with a normal CT scan. Newborn CT abnormalities were also associated with an abnormal hearing screen at birth and hearing loss on follow-up. None of the neonatal neurologic findings were predictive of an abnormal CT scan. CONCLUSION: In neonates with symptomatic congenital CMV infection, a cranial CT scan is a good predictor of an adverse neurodevelopmental outcome. In addition, newborn clinical and laboratory findings did not predict neuroradiographic abnormalities in neonates with symptomatic congenital CMV infection.

Brain↗

Postictal psychiatric events during prolonged video-electroencephalographic monitoring studies.

BACKGROUND: Postictal psychiatric events presenting as postictal psychotic events and postictal nonpsychotic events are known to occur following seizure clusters. Accordingly, patients undergoing prolonged video-electroencephalographic (EEG) monitoring studies may be at increased risk of experiencing postictal psychiatric event, as they often have flurries of seizures during these studies. OBJECTIVES: To determine the annual incidence and clinical characteristics of postictal psychotic events and postictal nonpsychotic events in video-EEG monitoring studies in patients with partial seizure disorders and to identify potential pathogenic factors. RESULTS: Thirteen patients met the criteria for a postictal psychiatric event during the 18-month study period, 10 presenting as postictal psychotic events and three as postictal nonpsychotic events. The annual incidence of postictal psychiatric events at our monitoring unit for 1988 was 7.8%, 6.4% presenting as postictal psychotic events and 1.4% as postictal nonpsychotic events. Seven patients had their first-ever postictal psychiatric event during the monitoring study. In 12 of the 13 patients, the postictal psychiatric events mimicked well-defined psychiatric entities of shorter duration (mean, 66.5 hours); they appeared 12 to 72 hours after the last seizure and remitted spontaneously or with the use of low-dose psychotropic medication. No significant differences in EEG, neuroradiologic, psychiatric, medical, or psychosocial data were found between the patients with postictal psychiatric events and a group of 13 age-matched control patients. Follow-up data of comparable duration were available in nine patients with postictal psychiatric events and nine controls. Psychiatric events were reported more frequently by patients with postictal psychiatric events than by control patients (P=.03). In three patients, postictal psychiatric events converted to interictal events. CONCLUSION: These findings suggest that monitoring studies increase the risk for postictal psychiatric events, which neurologists need to be familiar with, as they represent important morbidity associated with these studies.

Adult↗

Working parents: the impact of day care and breast-feeding on cytomegalovirus infections in offspring.

The increase in the popularity of breast feeding and utilization of child care arrangements are having a major effect on the epidemiology of cytomegalovirus infections. The impact is greater for women of upper socioeconomic background who send their toddlers to day-care centers and for day-care workers. If primary cytomegalovirus infections occur during pregnancy it is logical to anticipate more cases of severe congenital infections.

Adolescent↗

Linear single-dose pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.

The pharmacokinetic characteristics of ganciclovir were determined in neonates (age range, 2 to 49 days) after an 1-hour intravenous infusion of a single dose of either 4 mg/kg (n = 14) or 6 mg/kg (n = 13). Twenty-seven newborns with symptomatic cytomegalovirus inclusion disease were enrolled in this open phase I-II pharmacokinetics, safety, and tolerance trial of ganciclovir at one of two doses. Ganciclovir disposition was best described by a one-compartment open model with zero-order input and first-order elimination. The mean elimination half-life (t1/2) for both dose groups was 2.4 hours. The mean apparent volume of distribution (Vd) was 669 +/- 70 ml/kg for the 4 mg/kg group and 749 +/- 59 ml/kg for the 6 mg/kg group. The mean total body clearance (CL) for the 4 mg/kg and 6 mg/kg groups was 189 +/- 28 ml/hr/kg and 213 +/- 21 ml/hr/kg, respectively. No significant differences were observed in Vd or CL between the two groups. The Vd, expressed in milliliters, increased with increasing patient weight (r = 0.689; p = 0.0001). The CL, expressed in milliliters per hour per kilogram, increased with increasing age (r = 0.413; p = 0.032). No significant differences were observed between the two dose groups for the area under the curve normalized for dose (AUC/Dose) or the maximum plasma concentration normalized for dose (Cmax/Dose), indicating that ganciclovir exhibited linear pharmacokinetics in these neonates.

Creatinine↗

Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990.

Cytomegalovirus (CMV) is the leading cause of congenital viral infection in the United States. To prevent damaging congenital CMV infections, it is necessary to have accurate population estimates of prevalence and to identify maternal factors associated with an elevated risk of congenital infection in the newborn. From 1980 through 1990, 17,163 offspring of predominantly low-income nonwhite women who delivered at a public hospital and 9892 newborns of predominantly mid- to upper-income white women who delivered at a private hospital were screened for congenital CMV infection. Women < 20 years old (adjusted prevalence odds ratio [POR], 4.8; 95% confidence interval [CI], 2.6-8.9) at the public hospital and all nonwhite women (adjusted POR, 1.6; 95% CI, 1.1-2.2) had an increased risk of delivering an infected newborn. Newborns of adolescent women in both populations had the highest prevalence of clinically apparent infection. Offspring of nonwhite low-income adolescents are at greatest risk for congenital CMV infection and more damaging sequelae.

Adolescent↗

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

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 (18 percent). After a mean follow-up of 4.7 years, one or more sequelae were seen in 25 percent of the primary-infection group and in 8 percent of the recurrent-infection group. Thirteen percent of infants whose mothers had primary infection during pregnancy had mental impairment (IQ less than or equal to 70), as compared with none of those whose mothers had recurrent CMV infections. Sensorineural hearing loss was found in 15 percent of those in the primary-infection group and in only 5 percent of those in the recurrent-infection group. Bilateral hearing loss was identified only among children in the primary-infection group (8 percent). CONCLUSIONS: The presence of maternal antibody to CMV before conception provides substantial protection against damaging congenital CMV infection in the newborn. Primary maternal infection during pregnancy is associated with more severe sequelae of congenital CMV infection.

Antibodies, Viral↗

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.

Cytomegalovirus Infections↗

Evaluation of a microtiter plate fluorescent-antibody assay for rapid detection of human cytomegalovirus infection.

The use of monoclonal antibody (MAb) p63-27, which is reactive with the major immediate-early human cytomegalovirus (HCMV) protein pp72, was explored for the rapid diagnosis of HCMV viruria. The rapid assay detected all but 1 of 19 specimens identified by standard virus isolation methods from 1,676 newborn urine specimens, achieving a sensitivity of 94.5% and a specificity of 100%. The monoclonal antibody recognized 260 randomly obtained clinical isolates of HCMV, indicating the suitability of this reagent for use in screening assays. The sensitivity of the microtiter plate method declined rapidly for specimen from older infants and children with congenital CMV infection and virus-infected children attending a day-care center and was judged to be unacceptable for screening populations in this age group.

Antibodies, Monoclonal↗

Impact of asymptomatic congenital cytomegalovirus infection on size at birth and gestational duration.

Cytomegalovirus (CMV) is the most common viral agent causing congenital infection in humans, affecting 0.2 to 2.4% of all live births. Symptomatic congenital CMV infection has previously been shown to cause low birth weight and prematurity. Whether or not asymptomatic congenital CMV infection, which represents the majority of cases (90 to 95%), affects intrauterine growth or gestational duration is unknown. Using a population of 146 infants with asymptomatic congenital CMV infection and 1419 controls from two socioeconomically diverse populations (biracial low income and white mid- to upper income), determinants of body size (birth weight and crown-heel length) were investigated using multiple regression techniques. We found that congenital infection following the transmission of maternal primary and "unknown" CMV infection resulted in a significant mean birth weight deficit of 163 g (P less than 0.04) for the low income term infants (blacks and whites), but not in the mid- to upper income white infants. Newborns with congenital infection following the transmission of maternal reactivated (recurrent) CMV infection were significantly shorter by a mean of 1 cm (P less than 0.03) than controls, a finding that was consistent regardless of socioeconomic status or race.

Birth Weight↗

Intellectual ability of children after perinatal cytomegalovirus infection.

The intellectual ability of 16 children who had not had congenital cytomegalovirus (CMV) infection, but acquired it before the age of six months, was compared with that of two other groups: one comprising 32 children who had had CMV-excreting mothers but who were not infected themselves: the other comprising 18 healthy controls. Serial audiological, ophthalmological and psychometric examinations were performed. The only statistically significant difference found was that the children with acquired CMV infection had lower mean arithmetic scores. The results suggest that healthy term infants who acquire early CMV infection are not at increased risk of intellectual impairment.

Child↗

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.

Animals↗