Low-dose indomethacin therapy and extension of intraventricular hemorrhage: A multicenter randomized trial

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

“…Reduced rates of IVH and IVH>grade 2 with indomethacin prophylaxis were apparent (Figures 4a and b) even before publication of trials adequately powered to independently detect them, 100,106,112 and so are not attributable to just one or two trials with anomalous results. The relationships between IVH, PDA, treatments, and outcomes remain ambiguous, however.…”

“…A reduction in cerebral palsy in one small (27 subjects) trial of indomethacin prophylaxis 95 was not confirmed in two larger studies. 100,106 No trial showed beneficial impacts on pulmonary hemorrhage, 96,99,102,103,106 severe pulmonary hemorrhage, 110 PVL, 83,84,86 -89,95,96,100,101,103,107 any ROP 62,64,72 -74,76,84,85,89,90,95,96,105,106 or ROPXstage 2 84 or stage 3, 89,96,111 Bailey mental developmental index 79,96,106 or psychomotor developmental index, 79,96 mean Wechsler Preschool and Primary Scale of Intelligence, revised scores, 112 severe developmental delay, 96,100,106 or neurosensory impairment or neurosensory impairment or death. 96,103,106 In summary, individual randomized-controlled trials provide scant evidence of benefit from prophylaxis or treatment of PDA in preterm infants.…”

“…Ment et al 91,98 found that prophylactic indomethacin was associated with the reduction in both IVH and PDA, but these effects were independent, and PDA closure did not affect progression of IVH to parenchymal involvement. 101 Their large multicenter trial showed both ductal closure and reduced IVH>grade 2, 100 but long-term follow-up revealed few The number of trials (N) and subjects (n) included for each outcome are listed on the right side of each panel (N/n). BPD, bronchopulmonary dysplasia; CLD, chronic lung disease; NEC, necrotizing enterocolitis; SIP, spontaneous intestinal perforation; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; ROP, retinopathy of prematurity; MDI, Mental Development Index; PDI, Psychomotor Development Index; CP, cerebral palsy.…”

Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis

“…9,10 Over the study period, we did not use dexamethasone to prevent chronic lung disease in infants during the first 7 days of life. 16 At the discretion of the attending neonatologist, infants older than 7 days could be treated with dexamethasone to facilitate weaning from mechanical ventilation, but by 1996 this practice was reserved only for those infants with severe chronic lung disease.…”

“…8 Postnatally, indomethacin has been used to effect closure of a patent ductus arteriosus (PDA) 7 or to prevent severe intraventricular hemorrhage in very low birth weight infants. 9,10 Before 1996, postnatal indomethacin administration at our center was used only to treat PDA, 7 but subsequently its use increased following reports that administration of indomethacin to very low birth weight infants within 6 to 12 h after birth was associated with a reduced rate of severe intraventricular hemorrhage. 9,10 With increased frequency and early use of indomethacin several reports linking indomethacin exposure to IIP 6,[11][12][13] and/or to NEC 6,14 emerged.…”