Table 1 Characteristics of Included Studies
Study | Country | Study Design | Participants | Intervention | Outcomes | Surfactant Administration | ||
|---|---|---|---|---|---|---|---|---|
Inositol | Control | Primary | Secondary | |||||
Hallman 1986 | US | Single-center randomized double blind placebo-controlled trial | Preterm infants (n = 74), BW < 2000 g, with a diagnosis of RDS, requiring mechanical ventilation | IV or po supplemental inositol given daily for ten days | Placebo (5% glucose) | Number of neonatal deaths and infant deaths | Number of infants with BPD, IVH, ROP, NEC, and sepsis | No |
Hallman 1992 | US | Single-center randomized double blind placebo-controlled trial | Preterm infants (n = 233), BW < 2000 g and a PMA of 24.0 to 31.9 weeks at birth, with evidence of RDS, requiring mechanical ventilation. | IV inositol daily for five days, with repeated courses at day 10 and day 20 if necessary (infant continued to require ventilation, required supplemental O2 or did not tolerate enteral feeds) | Placebo (5% glucose) | Number of neonatal deaths and BPD | Number of infant death, ROP, IVH (all grades, grade > 2), NEC, and sepsis | Yesa |
Friedman 1995 | US | Double-center randomized placebo-controlled trial | Preterm infants (n = 48), BW < 1500 g with a diagnosis of RDS, requiring mechanical ventilation | Feed high-inositol formula (2500 μmol/L inositol) eternally. Duration of supplemental inositol was not reported. | Feed low-inositol formula (242 μmol/L inositol) eternally | Number of infants with ROP | Number of deaths, infants with bacteremia, NEC, IVH (> grade 2), BPD, duration of mechanical ventilation | Yes |
Phelps 2013 | US | Multi-center randomized double-blind placebo-controlled PK trial | Preterm infants (n = 76), with 230/7–296/7 weeks gestation age and ≥ 600 g birthweight, had no major congenital anomalies, and had received no human milk or formula feedings since birth. | IV 5% inositol with a single low (60 mg/kg) (n = 25) or high (120 mg/kg) (n = 24) dose over 20 min | Placebo (5% glucose) | Pharmacokinetic data for inositol | Number of adverse events in the first 7 days as well as neonatal morbidities from birth through hospital discharge (or 120 days if sooner) | Yes |
Phelps 2016 | US | Multi-center randomized double-blind phase II clinical trial | Preterm infants (n = 125), with 230/7 to 296/7 weeks GA, weighed at least 400 g, and could receive study drug by 72 h after birth, had no major congenital anomalies, severe oliguria, or a moribund state | IV 10, 40 or 80 mg/kg/day inositol (divided every 12 h) from enrolment on day 1 to 3 to 10 weeks of age, to 34 weeks PMA or to discharge. Once feedings were established the same dose of study drug was given eternally. | Placebo (5% glucose) | Population pharmacokinetics data for inositol | Number of type 1 ROP and other adverse events | Yes |
Phelps 2018 | US | Multi-center randomized double-blind placebo-controlled phase III clinical trial | Extremely preterm infants (n = 638) born before 280/7 weeks of gestation, surviving for at least 12 h, admitted to 1 of the 18 Neonatal Research Network centers before 72 h’ postnatal age, without major congenital anomaly, eye anomaly, or moribund condition | IV 40 mg/kg/day inositol (divided every 12 h) from enrolment on day 1 to 3 to 10 weeks of age. Once feedings were established the same dose of study drug was given eternally. | Placebo (5% glucose) | Number of participants with unfavorable outcome, defined as severe retinopathy of prematurity (ROP) or death prior to reaching acute/final ROP status | Number of any type of ROP, type 2 ROP or greater, all-cause mortality, BPD, IVH and other adverse events | Yes |