Prophylactic Indomethacin Revisited

Abstract

Persistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years.^, Surgical ligation of the ductus was first performed in children nearly 80 years ago and proved that prevention of prolonged exposure to left-to-right shunting through the ductus arteriosus improved pulmonary, cardiac, and systemic outcomes. In the 1970s, the discovery that nonsteroidal anti-inflammatory drugs could induce PDA closure^– and are effective in infants born preterm^, provided neonatologists with a pharmacologic alternative to surgery. The clear advantages, however, of having a medical approach have been clouded by conflicting information on the long-term benefits of treatment, disagreement regarding the clinical indicators that warrant treatment for PDA, optimal drug choice, preferred dosing regimens, and indecision regarding the best time to treat a select population of fragile preterm infants.

Keywords: bronchopulmonary dysplasia; ductus arteriosus; indomethacin; prophylaxis.

Figure 1

PDA-associated morbidities. PDA has been associated with numerous pathologic conditions that occur in small preterm infants. Cause-effect relationships have not been proven for most of these outcomes but are inferred from the best available data. AKI, acute kidney injury; NDI, neurodevelopmental impairment; NEC, necrotizing enterocolitis; Pulm Hem, pulmonary hemorrhage; RDS, respiratory distress syndrome; ROP, retinopathy of prematurity; SIP, spontaneous intestinal perforation.

Figure 2

BPD rate in preterm infants with and without contributing pathologic conditions. Hypothetical plot of BPD rates according to gestational age, based on values obtained from national registries in the US and Europe. The idealized incidence of BPD among infants born preterm with pathologic conditions that are associated with worse BPD outcomes contributes to a greater rate of BPD than baseline rates of BPD among infants without those contributors. PDA may be one of the modifiable components in hospitals with high-use prophylaxis. Elimination of PDA and other contributors potentially would reduce the incidence of BPD at a given gestation to match the rate of more mature infants. pHTN, pulmonary hypertension.