We studied the outcomes at school age in children who had participated in a double-blind, placebo-controlled trial of early postnatal dexamethasone therapy (initiated within 12 hours after birth) for the prevention of chronic lung disease of prematurity.

Objectives. To study the outcome at 2-year corrected age of infants who participated in a double-blind controlled trial of early (<12 hours) dexamethasone therapy for the prevention of chronic lung disease (CLD). Methods and Materials. A total of 133 children (70 in the control group, 63 in the dexamethasone-treated group) who survived the initial study period and lived to 2 years of age were studied. All infants had birth weights of 500 to 1999 g and had severe respiratory distress syndrome requiring mechanical ventilation within 6 hours after birth. For infants in the treatment group, dexamethasone was started at a mean age of 8.1 hours and given 0.25 mg/kg every 12 hours for 1 week and then tapered off gradually over a 3-week period. The following variables were evaluated: interim medical history, socioeconomic background, physical growth, neurologic examinations, mental and psychomotor development index score (MDI and PDI), pulmonary function, electroencephalogram, and auditory and visual evoked potential. Results. Infants in the control group tended to have a higher incidence of upper respiratory infection and rehospitalization than did the dexamethasone-treated group because of respiratory problems. Although there was no difference between the groups in somatic growth in girls, the dexamethasone-treated boys had significantly lower body weight and shorter height than the control boys (10.7 ± 3.0 vs 11.9 ± 2.0 kg; 84.9 ± 5.7 vs 87.5 ± 4.8 cm). The dexamethasone-treated group had a significantly higher incidence of neuromotor dysfunction (25/63 vs 12/70) than did the control group. The dexa-methasone-treated infants also had a lower PDI score (79 ± 26) than did the control group (87 ± 23), but the difference was not statistically significant. Both groups were comparable in MDI, incidence of vision impairment, and auditory and visual evoked potential. Significant handicap, defined as severe neurologic defect and/or intellectual defect (MDI and/or PDI ≤ 69), was seen in 22 children (31.4%) in the control group and 26 (41.2%) in the dexamethasone-treated group. Conclusions. Although early postnatal dexamethasone therapy for 4 weeks significantly reduces the incidence of CLD, this therapeutic regimen cannot be recommended at present because of its adverse effects on neuromotor function and somatic growth in male infants, detected at 2 years of age. A longer follow-up is needed. If early dexamethasone therapy is to be used for the prevention of CLD, the therapeutic regimen should be modified. The proper route of administration, the critical time to initiate the therapy, and the dosage and duration of therapy remain to be defined further.

Rationale: Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. Objectives: To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. Methods: A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O₂ at less than 30% or was extubated. Measurements and Main Results: The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44–0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8–7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3–5 and 7–8 days. Conclusions: In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).

A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences

A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences