Natural history of neonatal herpes simplex virus infections in the acyclovir era.

OBJECTIVE: During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. DESIGN/METHODS: Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. RESULTS: Comparisons between patients treated in the periods between 1981-1988 and 1989-1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of >/=10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. CONCLUSION: Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981-1988 vs 1989-1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.

Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections.

OBJECTIVE: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. PARTICIPANTS: Infants who were

Migrating atelectasis in Werdnig-Hoffmann disease: pulmonary manifestations in two cases of spinal muscular atrophy type 1.

Spinal muscular atrophy (SMA) or Werdnig-Hoffmann disease is the second most common neuromuscular disease, with 25% of cases presenting in infancy. Deletions in the survival motor neuron gene are believed responsible for autosomal-recessive SMA. SMA affects about 1 in 10,000 births. Symptomatic newborns have severe hypotonia, may have respiratory distress, may be unable to feed, and rapidly progress to death early in infancy. This paper describes another early pulmonary manifestation of SMA, i.e., migrating or rotating atelectasis, in 2 patients with infantile SMA. Migrating or rotating atelectasis may suggest the diagnosis of SMA.

Wasted health care dollars. Routine cord blood type and Coombs' testing.

OBJECTIVE: To determine if selective newborn cord blood testing (NCBT) could contain costs without increasing morbidity of hemolytic disease of the newborn (HDN). DESIGN: A national telephone survey confirmed the common practice of routine blood type and Coombs' NCBT. Two 12-month study arms, retrospective and prospective, were conducted. Hemolytic disease of the newborn was studied retrospectively under an unrestricted NCBT policy. Then, HDN was studied after a policy change that restricted NCBT to patients in newborn intensive care units and normal newborns with clinical jaundice or Rh-negative mothers, and/or positive maternal antibody screenings, or unavailable maternal blood testing. PARTICIPANTS: All newborns (N = 8501) at the Metro-Health Medical Center, Cleveland, Ohio, were studied (retrospective arm, all 1989 admissions; prospective arm, all July 1990 to June 1991 admissions). OUTCOME MEASURES: Blood type and Coombs' NCBT, maternal blood type and antibody screening, Hobel risk scores for clinical severity of newborn hospitalization, duration of hospitalizations, and peak serum bilirubin levels. RESULTS: No quantitative or qualitative increases in morbidity from jaundice were detected by retrospective analysis with unrestricted NCBT, or prospectively after selective testing on 4498 newborns. Each study arm resulted in 15 readmissions for jaundice; these included two patients with ABO HDN. Furthermore, selective testing resulted in performance of NCBTs on only 390 infants in the "normal" nursery (24% of the original sample). Estimates projected on 1991 US births (4,111,000) showed that selective NCBT offers potential yearly savings above $30.8 million of patient charges, savings above $11.3 million of hospital costs, and the reassignment of more than 112 personnel full-time equivalents. CONCLUSION: Selective NCBT decreases the use of resources and costs without apparent additional patient morbidity from HDN.

Reducing risk of infection when obtaining hematocrit and bilirubin determinations: beyond universal precautions.

Obtaining hematocrit and bilirubin determinations is associated with infection risks, including human immunodeficiency virus infection. This study describes two simple procedures to decrease the risk of infection to health care providers while obtaining hematocrit and bilirubin determinations. Using readily available, inexpensive items (nonsterile gauze, a standard file, and plastic holder) and some simple techniques, the risk of infection can be decreased without increasing the time required. We believe these procedures are very reasonable and simple solutions to a common nursery problem.

Respiratory syncytial virus-specific immunoglobulins in preterm infants.

Incomplete transfer of maternal antibodies specific to respiratory syncytial virus (RSV) has been suggested as an explanation for the increased risk of RSV infections in preterm infants. Antibodies directed against the two major RSV envelope glycoproteins, F and G, are protective in vitro and in vivo. Our study was conducted to measure IgG, IgG1, IgG2, and IgG3 antibody titers against the RSV F and G glycoproteins in cord sera from infants born at different gestational ages. Titers of neutralizing antibody were measured in a subset of the subjects. The mean (+/- SEM) log2 titers of IgG antibodies directed against the RSV F and G glycoproteins were significantly lower in infants born at < or = 28 weeks of gestation (11.2 and 10.8 for F and G glycoproteins, respectively) than in term infants (12.6 and 12.8 for F and G, respectively) (p < 0.05). Preterm infants born at > or = 29 weeks had titers of antibodies against the F glycoprotein comparable to those of term infants. The highest titers of RSV-specific antibodies were in the IgG1 and IgG2 subclasses. Mean (+/- SEM) neutralizing antibody titers were lower in infants born at < or = 28 weeks (7.7 +/- 0.4) than in term infants (10.2 +/- 0.3) (p < 0.001). We conclude that (1) RSV-specific antibody titers were lower than in term infants only in the most premature infants (< or = 28 weeks) and (2) preterm infants born at > or = 29 or > or = 33 weeks of gestation had RSV-specific titers against F and G glycoproteins, respectively, that were comparable to those of term infants. Preterm infants born at < or = 28 weeks could represent a target population for passive immunoprophylaxis.

Prenatal diagnosis of short rib (polydactyly) syndrome with situs inversus.

We present a case of short rib (polydactyly) syndrome in which the diagnosis was made prenatally by ultrasound examination. The more specific diagnosis of short rib (polydactyly) syndrome type III was made on the basis of findings on radiographs obtained at birth. The sonographic and radiographic features are discussed. The patient had complete situs inversus and hypospadias. The former was reported in one other case of type III and the later has not been previously reported in this entity.

Rapid detection of respiratory syncytial virus by a biotin-enhanced immunoassay: test performance by laboratory technologists and housestaff.

A biotin-enhanced enzyme immunoassay (EIA) for respiratory syncytial virus (RSV) antigen detection (TESTPACK RSV) was prospectively compared with virus isolation in cell culture and immunofluorescence. Of 156 nasopharyngeal swab specimens from infants with respiratory symptoms, 81 (52%) yielded RSV in culture. Compared with culture the sensitivity of the EIA was 95% and specificity was 92%; the specificity increased to 97% with a blocking assay. Compared with immunofluorescence the sensitivity of EIA was 92% and specificity was 93%. In order to assess the performance of TESTPACK RSV as a bedside test, nasopharyngeal swabs from 49 children were tested by EIA at the bedside by housestaff and by immunofluorescence in the laboratory; the sensitivity of the EIA was lower (78%) while specificity remained high (95%). Inclusion of older children may have resulted in diminished sensitivity. The TESTPACK RSV is a simple, rapid test that performs well and is easily adaptable to an office setting. Further evaluation of the test in older children may be required.