Respiratory distress syndrome and inositol supplementation in preterm infants. Inositol supplementation in premature infants with respiratory distress syndrome.
We report a randomised double blind trial of myo-inositol (inositol) supplementation for 10 days in 74 preterm infants with a birth weight less than 2000 g (mean gestational age 29.5 weeks and mean birth weight 1266 g). All infants required artificial ventilation for treatment of respiratory distress syndrome. Inositol (120-160 mg/kg/day) was administered by the ingastric or intravenous route. The 37 infants who received inositol supplementation required less mechanical ventilation during days 4-10, had less failures of indomethacin to close ductus arteriosus, and had less deaths or bronchopulmonary dysplasia, or both, than the infants treated with placebo. There were no detectable adverse effects. These preliminary results suggest that inositol is an important nutrient in immature preterm infants. Inositol influences cellular function and organ maturation. Feeding premature infants inositol-rich breast milk increases their serum inositol concentrations. Whether inositol supplementation benefits infants receiving fluids for parenteral nutrition, which are inositol-free, is not known.
                We carried out a placebo-controlled, randomized, double-blind trial to determine the effects of administering inositol (80 mg per kilogram of body weight per day) during the first five days of life to 221 infants with respiratory distress syndrome who were receiving parenteral nutrition (gestational age, 24 to 32 weeks; birth weight, less than 2000 g). All the infants were treated with mechanical ventilation and some with surfactant as well. The primary end point was survival at 28 days without bronchopulmonary dysplasia.
                The 114 patients given inositol had significantly lower mean requirements for inspiratory oxygen (P less than 0.01) and mean airway pressure (P less than 0.05) from the 12th through the 144th hour of life than did the 107 infants given placebo. Eighty-one infants given inositol and 51 given placebo survived without bronchopulmonary dysplasia (71 vs. 55 percent; P = 0.005). In the 65 infants given surfactant, however, inositol had no effect on the degree of respiratory failure. Thirteen infants given inositol and 21 given placebo had retinopathy of prematurity (13 vs. 26 percent; P = 0.022); none of the infants given inositol had stage 4 disease, whereas 7 of those given placebo did (0 vs. 9 percent; P = 0.012). Among the infants given placebo, those who had poor outcomes (death, bronchopulmonary dysplasia, or stage 4 retinopathy of prematurity) had lower serum inositol concentrations during days 2 through 7 than those who had good outcomes (P less than 0.01).
                The administration of inositol to premature infants with respiratory distress syndrome who are receiving parenteral nutrition during the first week of life is associated with increased survival without bronchopulmonary dysplasia and with a decreased incidence of retinopathy of prematurity.
Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multicenter randomized controlled trial of appropriate size is justified to confirm these findings.