Prevention and 18-Month Outcomes of Serious Pulmonary Hemorrhage in Extremely Low Birth Weight Infants: Results From the Trial of Indomethacin Prophylaxis in Preterms

Abstract

Extremely low birth weight infants with serious pulmonary hemorrhage have an increased risk for poor long-term outcome. Prophylactic indomethacin reduces the rate of early serious pulmonary hemorrhage, mainly through its action on patent ductus arteriosus. Prophylactic indomethacin is less effective in preventing serious pulmonary hemorrhages that occur after the first week of life.

Indomethacin Prophylaxis for Preterm Infants: The Impact of 2 Multicentered Randomized Controlled Trials on Clinical Practice

“…Its secondary goal was to evaluate "the effects of indomethacin on the incidence of PDA, pulmonary hemorrhage, chronic lung disease, necrotizing enterocolitis, intracranial abnormalities, and retinopathy of prematurity". While confirming the previously reported (17) beneficial effects of prophylactic indomethacin on the incidence of PDA, PDA ligation, ICH (grades 3 and 4), and pulmonary hemorrhage (16,18), the trial failed to find a decrease in the incidence of death or neurodevelopmental abnormalities. Although not specifically stated, the trial's conclusion implied that the use of prophylactic indomethacin should be discouraged.…”

“…Several previously reported beneficial effects of indomethacin prophylaxis (8,17) were again observed in the TIPP-trial: reduced incidences of surgical PDA closure, early serious pulmonary hemorrhage, and severe ICH (16,18). These benefits were achieved without an increase in the incidence of other neonatal morbidities (e.g., necrotizing enterocolitis, gastrointestinal perforation, retinopathy, chronic lung disease, or cerebral white matter injury).…”

“…Indomethacin prophylaxis has merits with regards to its effects on such neonatal morbidities as PDA, PDA ligation, pulmonary hemorrhage and severe ICH (16)(17)(18). We questioned whether the negative conclusion of the TIPP-trial (regarding survival and neurodevelopmental outcome) may have been based on an anticipated effect size that was unrealistic for the population that was studied.…”

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

“…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.…”

How useful are B-type natriuretic peptide measurements for monitoring changes in patent ductus arteriosus shunt magnitude?

“…In preterm infants, a PDA alters mesenteric blood flow, impairs pulmonary mechanics, increases the risk of pulmonary hemorrhage and prolongs the need for mechanical ventilation. [1][2][3][4][5][6][7][8][9][10] The echocardiogram has been used as a gold standard for determining the presence of a PDA and for evaluating temporal changes in the magnitude of a PDA left-to-right shunt. Unfortunately, frequent echocardiographic studies can destabilize an infant, may not be readily available in all institutions and increase hospital costs.…”