Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group.

OBJECTIVE: To examine the effectiveness of respiratory syncytial virus immune globulin administered intravenously (RSV-IGIV) in reducing hospitalization for treatment of RSV in children with congenital heart disease (CHD). METHODS: Children younger than 4 years of age were randomly assigned to a treatment group receiving RSV-IGIV, 750 mg/kg, monthly or to a control group not receiving infusions. Surveillance for respiratory tract infections was carried out and management decisions were made by physicians blinded to treatment group. RESULTS: Hospitalization for treatment of an RSV infection occurred in 32 of 214 (15%) of control children and 21 of 202 (10%) of the children receiving RSV-IGIV, a 31% reduction (P = .16). However, in infants younger than 6 months of age at study entry, 20 of 82 (24%) in the control group and 10 of 96 (10%) in the RSV-IGIV group had RSV hospitalizations (58% reduction, P = .01). The incidence of hospitalization for any respiratory tract symptomatology was lower in the RSV-IGIV group (34 of 202, 17%) than in the control group (57 of 214, 27%; P = .02). There was a significantly higher frequency of unanticipated cyanotic episodes and of poor outcomes after surgery among children with cyanotic CHD in the RSV-IGIV group (22 of 78, 28%) than in the control group (4 of 47, 8.5%; P = .009). CONCLUSION: RSV-IGIV should not be used for prophylaxis of RSV disease in children with cyanotic CHD. RSV-IGIV did not reduce RSV hospitalization in all children with CHD, but it was effective in preventing RSV hospitalization in infants younger than 6 months of age. Further studies in these children are indicated.

Respiratory syncytial virus-enriched globulin for the prevention of acute otitis media in high risk children.

Acute otitis media (AOM) has been associated with respiratory syncytial virus (RSV) infection; AOM develops in up to one third of children with RSV illness. A masked multicenter trial used an immune globulin enriched with RSV-neutralizing antibodies (RSVIG) to prevent RSV infection of the lower respiratory tract in 249 children with either bronchopulmonary dysplasia, congenital heart disease, or prematurity. To determine whether monthly RSVIG therapy might decrease the incidence of AOM, we retrospectively analyzed the records of 109 children in two of the centers. RSVIG was administered during RSV season of a high dose of 750 mg/kg monthly or a low dose of 150 mg/kg monthly; control children received no RSVIG. Children were examined for AOM by masked observers using pneumatic otoscopy. No difference in sex, race, underlying diagnosis, number of persons in the home, exposure to smoking, or atopy was found between groups studied. In recipients of high doses of RSVIG, significantly less AOM developed per season than in control children (mean episodes, 0.15 vs 0.78; p = 0.003), and fewer episodes of RSV-related AOM occurred (0 vs 5; p = 0.047). Low doses of RSVIG did not have a clinically significant impact. High doses of RSVIG appeared to have a significant impact on preventing AOM (both RSV- and non-RSV-related AOM) in these-high risk populations. This finding may have important implications in the development of improved preventive modalities for AOM.

Efficacy and safety of aerosolized ribavirin in young children hospitalized with influenza: a double-blind, multicenter, placebo-controlled trial.

We randomly assigned children hospitalized with influenza who had been ill < or = 48 hours and who had a temperature > or = 37.8 degrees C to receive either ribavirin or placebo. All patients had evaluations performed for fever reduction, use of acetaminophen for temperature > or = 38.3 degrees C, duration and severity of influenza symptoms, and feeding behavior. Sixty-two patients (35 in the placebo group, 27 in the ribavirin group) had a diagnosis of influenza confirmed by laboratory study. The groups did not differ significantly in age, initial signs and symptoms, or in distribution of influenza A or B infections. The time to reduction of temperature < or = 38.3 degrees C for the ribavirin group was 8.9 hours compared with 22.6 hours for the placebo group (p = 0.04). The mean duration of acetaminophen use was 7.4 hours in the ribavirin group and 16.3 hours in the placebo group (p = 0.14). There were no significant differences between the groups in outcome of respiratory rate, pulse rate, cough, or level of consciousness. Convalescent influenza antibody geometric mean titer for the placebo group was 9.8 compared with 3.6 for the ribavirin group (p = 0.04). Ribavirin was more effective than placebo in accelerating normalization of temperature but there were no other significant differences.

Role of antibody and use of respiratory syncytial virus (RSV) immune globulin to prevent severe RSV disease in high-risk children.

Infants with cardiac disease or infants born prematurely with or without bronchopulmonary dysplasia are at increased risk of severe respiratory syncytial virus (RSV) disease. A recently developed RSV immune globulin (RSVIG) was studied in a 3-year multicenter trial to determine safety and efficacy in the prevention of severe RSV disease in children who are at high risk of severe RSV illness. Two hundred forty-nine children were studied; 102 had bronchopulmonary dysplasia, 87 had congenital heart disease, and 60 were born prematurely. RSVIG was given on a monthly basis to 81 children at a high dose of 750 mg/kg (15 ml/kg) and to 79 children at a low dose of 150 mg/kg (3 ml/kg). The 89 children in the control group did not receive RSVIG. There were 64 episodes of RSV infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. High-dose recipients had significantly fewer RSV lower respiratory tract infections, hospitalizations, hospital days, intensive care unit days, and less use of ribavirin compared with control subjects. Only 19 adverse events were reported during the 580 infusions administered (3%). No death was attributed to RSV disease or RSVIG therapy. Treated children did not acquire exaggerated RSV illness in a subsequent year. Thus high-dose RSVIG reduced the incidence and severity of RSV lower respiratory tract infection. It is a safe and effective means of RSV prophylaxis in selected high-risk children.

Early ribavirin treatment of respiratory syncytial viral infection in high-risk children.

A 3-year prospective, blinded, multicenter study was done to assess the efficacy of early ribavirin intervention in mild respiratory syncytial virus illness in children with bronchopulmonary dysplasia or with congenital heart disease. A cohort of 178 children younger than 36 months of age with bronchopulmonary dysplasia or congenital heart disease were followed. Forty-seven infants whose respiratory syncytial virus infection resulted in mild symptoms of less than or equal to 72 hours' duration received ribavirin (n = 20) or water placebo aerosol (n = 27) either in a hospital or at home. Outcome measures included respiratory and analog score, room air oxygen, saturation, and oxygen flow needed to maintain saturation at greater than or equal to 91%. No difference in age, gender, family size, passive smoking, baseline oxygen saturations in room air, or duration of symptoms before treatment was found between groups. After 3 days of therapy, ribavirin produced a greater rate of improvement of analog scores (p = less than or equal to 0.001), lower oxygen requirements (p = 0.01), and higher oxygen saturation (p = 0.01). Respiratory scores and total hospital days did not differ significantly between the groups. Treatment failure occurred in 2 of 20 children (10%) in the ribavirin group versus 5 of 27 children (18%) in the placebo group, a nonsignificant difference. No child required assisted ventilation or had an adverse reaction. We conclude that early ribavirin therapy may help to reduce morbidity from respiratory syncytial virus infection in high-risk young children.

Effect of carbohydrate ingested on outcome in infants with mild gastroenteritis.

Children with mild acute gastroenteritis have not been observed for specific evidence of lactose intolerance yet are frequently fed a nonlactose formula. To determine whether such intervention is justified, 85 infants with mild acute gastroenteritis were followed prospectively. Infants were blindly and randomly assigned to 20 calorie/oz formula containing one of four carbohydrates: lactose, sucrose, polycose, or combined sucrose-polycose. Daily diaries were kept by parents, and patients were reexamined on days 2, 7, and 14 of the study. Evidence for rotavirus was detected in 23 infants, and five had bacterial pathogens. Symptoms resolved in most patients within 7 days, but five infants were subsequently hospitalized. Stool frequency, weight gain, and need for hospitalization did not differ significantly among the groups. Recovery from mild acute gastroenteritis occurred within 2 weeks irrespective of carbohydrate ingested.