Table 2.
Randomized controlled trials comparing dexamethasone vs. placebo.
| Reference (authors, year) | Population (n) | Inclusion criteria | Exclusion criteria | Doses of steroids | Start at | Extubation (days of life) | Duration of therapy by protocol (days) | More than one cycle of steroids | Administration of other steroids |
|---|---|---|---|---|---|---|---|---|---|
| Doyle (31) | Intervention: 29 Control: 26 | GA <28 weeks or BW <1,000 g, ventilator dependent in the I week of life | Congenital defects, chromosomal anomalies | 0.89 mg/kg over 10 days | After 7 days of life | ND | 10 | ND | ND |
| Doyle (32) | Intervention: 35 Control: 35 | GA <28 weeks or BW <1,000 g, ventilator dependent in the I week of life | Congenital defects, chromosomal anomalies | 0.89 mg/kg over 10 days | After 7 days of life | Intervention: 14 Control: 21 | 10 | Treatment with second course intervention: 10 Control: 10 | A small proportion of infants in each group had been exposed to short-course, low-dose corticosteroids before trial entry, for purposes of blood pressure control |
| Yeh (33) | Intervention: 72 Control: 74 | BW <2,000g, severe radiographic respiratory distress syndrome requiring mechanical ventilation within in the first 6 h of life | Absence of prenatal infection, congenital anomalies, and lethal cardiopulmonary status | Two doses/day, days 1 through 7, 0.25 mg/kg/dose; days 8 through 14, 0.12 mg/kg/dose; days 15 through 21, 0.05 mg/kg/dose; and days 22 through 28, 0.02 mg/kg/dose | Within 12 h after birth | ND | 28 | ND | ND |
| Walther (34) | Intervention: 19 Control: 17 | GA ≤32 weeks and RDS required mechanical ventilation | Sepsis or other infection, congenital heart disease, systemic hypertension, unstable clinical status, multiple congenital anomalies | At day 7–14. 14 days-treatment (0.2 mg/kg/day start, max 1.9 mg/kg cumulative) | 7–14 after birth | ND | 14 | ND | ND |
| Romagnoli (35) | Intervention: 15 Control: 15 | Oxygen and ventilator dependent on the 10th day of life and at high risk of chronic lung disease | No consent | 0.5 mg/kg/day for the first 6 days, 0.25 mg/kg/day for the next 6 days, and 0.125 mg/kg/day for the last 2 days of treatment (total dose 4.75 mg/kg) | At 10 days of life | NE | 14 | ND | Five infants in each group received two doses of 0.5 mg/kg dexamethasone to facilitate weaning from mechanical ventilation after the first month of life |
| Romagnoli (36) | Intervention: 25 Control: 25 | BW <1,250 g, GA <32 weeks, ventilator and oxygen-dependent at 72 h of life and at high risk of chronic lung disease | Prenatal infections, congenital malformations, and evidence of sepsis | From the 4th day of life for 7 days: 0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day on day 7 | At 4th days of life | ND | 7 | ND | ND |
| O'Shea (37) | Intervention: 50 Control: 45 | BW <1,501 g, age between 15 and 25 days, <10% decrease in ventilator settings for previous 24 h and FiO2 >0.3, no signs of sepsis and echocardiogram indicating the absence of a patent ductus arteriosus | no consent | 0.25 mg/kg twice a day for 3 days, then 0.15 mg/kg twice a day for 3 days, then a 10% reduction in the dose every 3 days until the dose of 0.1 mg/kg was reached on day 34. After 3 days on this dose, 0.1 mg/kg qod was given until 42 days after entry. | Between 15 and 25 days of life | NE | 42 | ND | ND |
| Kothadia (38) | Intervention: 57 Control: 61 | BW <1,501 g, age between 15 and 25 days, <10% decrease in ventilator settings for previous 24 h and FiO2 >0.3, no clinical signs of sepsis and echocardiogram indicating the absence of a patent ductus arteriosus | Congenital malformation, congenital viral infection, or mother with positive serologic testing for hepatitis B or HIV | 0.25 mg/kg twice a day for 3 days, then 0.15 mg/kg twice a day for 3 days, then a 10% reduction in the dose every 3 days until the dose of 0.1 mg/kg was reached on day 34. After 3 days on this dose, 0.1 mg/kg qod was given until 42 days after entry | Between 15 and 25 days of life | NE | 42 | ND | ND |
| Lin (39) | Intervention: 20 Control: 20 | BW <2,000g, radiography respiratory distress syndrome, ventilated at 6 h of life | Prenatal infection, congenital anomalies, and lethal cardiopulmonary status shortly after birth | Days 1–7: 0.25 mg/kg/dose; days 8–14: 0.12 mg/kg/dose; days 15–21: 0.05 mg/kg/dose; days 22–28: 0.02 mg/kg/dose | First days of life | NE | 28 | ND | ND |
| Yeh (40) | Intervention: 132 Control: 130 | BW <2,000g, severe radiographic respiratory distress syndrome requiring mechanical ventilation within the first 6 h of life | Absence of prenatal infection, congenital anomalies, and lethal cardiopulmonary status | Two doses/day, days 1 through 7, 0.25 mg/kg/dose; days 8 through 14, 0.12 mg/kg/dose; days 15 through 21, 0.05 mg/kg/dose; and days 22 through 28, 0.02 mg/kg/dose | <12 h of life | ND | 28 | ND | Six infants in the dexamethasone group (8%) and seven in the control group (9%) who had severe BPD required glucocorticoid therapy after the completion of the initial study. Because of the relatively short duration of therapy, these were included in the analyses as members of their initially assigned groups |
| Suske (41) | Intervention: 14 Control: 12 | GA <34 weeks with surfactant-treated respiratory distress syndrome | Septicaemia during the I week of life, relevant cardiac anomalies, except for patent ductus arteriosus, or malformations | 0.5 mg/kg IV into two fractions, for 5 days, first doses <2 h after the first surfactant dose | <2 h of life | Intervention: 6 Control: 14 | 5 | ND | ND |
| Brozanski (42) | Intervention: 39 Control: 39 | BW 1,500 g, ventilator support at 7 days of postnatal age | Congenital anomalies, pulmonary hypoplasia, or hemodynamic instability | Beginning at 7 days of postnatal age pulse doses of 0.25 mg/kg/dose for 3 days, repeated every 10 days until the infant reached 36 weeks postmenstrual age, or the infant no longer required ventilator support or supplemental oxygen | After 7 days of life | ND | 3 days, repeated every 10 days until the infant reached 36 weeks postmenstrual age, or the infant no longer required ventilator support or supplemental oxygen | ND | ND |
| Durand (43) | Intervention: 23 Control: 20 | BW of 501–1,500 g, GA 24–32 weeks, ventilator-dependent at 7–14 days of age despite weaning trials, ventilator rate more than 15 cydes/min, Fi02 requirement of 0.30 or more to maintain a pulse oximeter oxygen saturation of 90% or more | Documented sepsis, evidence of systemic hypertension, congenital heart disease, renal failure, grade IV intraventricular hemorrhage, and infants with multiple congenital anomalies | 0.5 mg/kg/day in two divided doses for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.1 mg/kg/day on the seventh day | 7–14 days of life | ND | 7 | Six patients (26%) in the dexamethasone group required a second 7-day course of steroid therapy | After the study period, 13 patients in the control group were subsequently treated with dexamethasone at a later postnatal age if the clinical team felt the infant could benefit from dexamethasone therapy |
| Kari (44) | Intervention: 17 Control: 24 | BW <1,500 g or less, GA >23 weeks, dependence on mechanical ventilation at 10 days of age, no signs of patent ductus arteriosus, sepsis, gastrointestinal bleeding, or major malformation at entry | No consent | 0.5 mg/kg/day in two doses for 7 days | After 10 days of life | NE | 7 | ND | ND |
| Couser (45) | Intervention: 27 Control: 23 | Required mechanical ventilation and had either traumatic or multiple intubations or if the duration of intubation was more than 14 days | Congenital anomalies, who either had previously been treated with dexamethasone for chronic lung disease or who had received pancuronium bromide therapy or other sedation 12 h before extubation | 0.25 mg/kg per dose approximately 4 h before the scheduled extubation and then again, every 8 h for a total of three doses | More than 14 days of life | ND | ND | ND | ND |
| Cummings (46) | Intervention: 25 (42-days 13, 18-days 12) Control: 11 | BW ≤1,250 g, GA ≤30 weeks, dependence on mechanical ventilation or oxygen at 2 weeks of life | Symptomatic patent ductus arteriosus, sepsis or renal failure at entry | 42 days: 0.5 mg/kg/day for the first 3 days, 0.3 mg/kg/day for the next 3 days, then reduced by 10% every 3 days until a dose of 0.1 mg/kg was reached at day 34. After 3 days at this dose, the drug was given on alternate days for 1 week and discontinued 18 days: same initial dose of 0.5, but their dose then decreased more rapidly, dropping by 50% every 3 days until a dose of 0.06 mg/kg was reached at days 10. After 3 days of this dose, the drug was given on alternate days for 1 week and then discontinued. For the remaining 24 days saline placebo | After 2 weeks of life | ND | 42 and 18 | ND | ND |
ND, not declared; GA, gestational age; BW, birth weight.