We retrospectively reviewed the clinical data of preterm children between September 2004 and March 2009 at the Ajou University Hospital. During the periods, 135 patients needed for oxygen >21% for at least 28 days and had the clinical diagnosis of CLD (or bronchopulmonary dysplasia). The inclusion criteria specified that children were born at ≤35 weeks of gestation, were <2 yr of age at the onset of the RSV season, and had received medical therapy (supplemental oxygen, bronchodilator, diuretics, or corticosteroid therapy) within six months prior to the RSV season. Children were excluded if they had any of the following: known renal impairment, hepatic dysfunction, immunodeficiency, neuromuscular impairment, chromosomal anomalies, congenital metabolic diseases, major congenital anomalies, or congenital heart disease with cyanosis or heart failure except for those with a patent ductus arteriosus or a septal defect that was uncomplicated and hemodynamically insignificant.

Among the 135 patients with CLD, seven patients were excluded. They had the clinical diagnosis of tetralogy of Fallot (n=1), tracheoesophageal fistula (n=2), congenital diaphragmatic hernia (n=1), 18 trisomy (n=1), congenital hydrocephalus (n=1) and Goltz syndrome (n=1). We enrolled 128 patients with CLD and reviewed their clinical course. Fifty three patients did not receive palivizumab prophylaxis and 75 received at least one dose of palivizumab.

Personal information was collected including demographics (birth weight, gestational age), neonatal course as well as medical and family history. Injection information included the date, dose, frequency, intervals and the response to the injections over seven days after the injection. Data, specific to hospitalization for respiratory illness, included the type of respiratory infection, hospital stay, isolated microorganisms or viruses, treatment, and dates. The study protocol and procedures were reviewed and approved by the Institutional Review Board of Ajou University Hospital.

Palivizumab (Synagis®, Boehringer Ingelheim Pharma, Biberach an der Riss, Germany) prophylaxis was provided from September to March. Patients received palivizumab (15 mg/kg) by intramuscular injection every 30 days. Palivizumab was supplied as a lyophilized powder in vials that were reconstituted with sterile water for injection and dispensed as a unit dose in a syringe. The final concentration of palivizumab was 100 mg/mL.

The severity of CLD (or bronchopulmonary dysplasia) was classified by the "new" bronchopulmonary dysplasia (BPD) definition criteria (10). Patients hospitalized for respiratory illness were classified into one of four clinical syndromes, according to Denny and Clyde (11).

RSV hospitalization was defined as any hospitalization with a duration of 24 hr or longer in a patient with positive RSV testing. The decision to admit to the hospital was based on the guidelines of the Denver Children's Hospital (Denver, CO, USA) (12). Patients were admitted when they had a poor response to oral medication and/or inhalation therapy, poor oral feeding, apnea, hypoxia, signs of dehydration, and/or signs of sepsis.

Compliance with the injection regimen was determined by comparing the actual number of injections received with the expected number of doses, based on the month the first injection was given.

Nasopharyngeal aspirates were collected on hospital admission by inserting a 5 Fr nasogastric tube into the nasopharynx with negative pressure suction. The aspirates were collected into viral transport medium and delivered to the laboratory. RSV was detected by either the immunofluorescence rapid antigen test with the Respiratory Panel Viral Screening & Identification Kit®(Chemicon, Temecula, CA, USA) or RT-PCR. Virological tests were performed by the clinical laboratory at the Seoul Medical Science Institute.

The characteristics of the patients with and without prophylaxis were compared with the Student's t-test and Fisher's exact test focusing on differences in demographic characteristics, risk factors for RSV infection and RSV associated hospitalization. The severity of BPD in these patients was compared using Pearson chi-square tests. The data were entered into a Microsoft Excel database and SPSS 11.0 was used for the data analysis.

The characteristics of all patients are summarized in Table 1. All patients received oxygen therapy for more than 28 days after birth. A total of 53 patients did not receive palivizumab prophylaxis. Twenty one patients were diagnosed during the 2004 to 2005 RSV season prior to the approval of palivizumab prophylaxis, and 32 patients did not receive palivizumab because their parents declined the injection due to financial problems. Seasonal RSV prophylaxis injections were given to 75 children between September 2005 and March 2009.

There were no significant differences in the neonatal demographics including gestational age, birth weight, gender, and type of delivery. The follow-up duration and initial duration of the hospital stay showed no statistically significant differences. The severity of BPD and co-morbidities included multiple births, congenital heart disease, and patent ductus arteriosus; there were no statistically significant differences among these factors (Table 1).

Seventy one patients received one season of prophylaxis; a second-season of prophylaxis was given to one patient with moderate BPD and three patients with severe BPD. Palivizumab prophylaxis increased during the 2008 to 2009 RSV season (Table 1). Palivizumab injection was started at the neonatology intensive care unit in 63 patients. A total of 284 injection doses were provided. The mean±SD of received injections was 3.4±1.6 (range 1-6). A total of six doses were injected in four patients. All of the expected injections were given to 62 patients. Compliance (Actual No. of injections/No. of recommended injections×100) was 92.2%. None of the patients dropped out; however, the last injection dose was not received in 13 patients. The mean interval between injections was 31.3 days; all doses were given within 35 days after previous injection.

There were no systemic, respiratory or gastrointestinal symptoms noted after the injections. Erythema and swelling at the injection site was noted in three patients, and subsided within three days (Table 2).

Overall, respiratory hospitalizations occurred in 23 patients that did not receive prophylaxis and in 32 patients that received palivizumab prophylaxis. The total number of respiratory hospitalizations, characteristics of lower respiratory tract infections (LRTI), and the length of hospital stay showed no statistically significant differences between patients with or without prophylaxis. Of 55 hospitalized patients, 49 patients were tested for laboratory tests for RSV. The rate of LRTI hospitalizations associated with RSV was 22.6% (12/53) in cases without prophylaxis and 4.0% (3/75) in cases with prophylaxis. Monthly prophylaxis with palivizumab significantly reduced the RSV associated hospitalization. Intubation and intensive care were needed in four patients with RSV, in two patients with a metapneumovirus infection, and in one patient with parainfluenza infection. One of the patients without prophylaxis, with RSV, died while receiving intensive care treatment with mechanical ventilation in January 2005. The length of the RSV hospital stay was not significantly different between the two groups (Table 3). Prior to the hospitalization for RSV, 14 patients were at home and one patient who received prophylaxis was in a rehabilitation facility. RSV hospitalizations occurred throughout the RSV season and in April (Table 4). Of the patients who received RSV prophylaxis, RSV was detected 31 days after previous prophylaxis in two patients, and 32 days after previous prophylaxis in one patient, respectively.