Enteral Feeding during Indomethacin and Ibuprofen Treatment of a Patent Ductus Arteriosus

Abstract

Objective To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive “trophic” (15 ml/kg/day) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus (PDA). Study design Infants were eligible for the study if they were 231/7 – 306/7 weeks gestation, weighed 401–1250 g at birth, received maximum enteral volumes ≤60 ml/kg/day and were about to be treated with indomethacin or ibuprofen. A standardized “feeding advance regimen” and guidelines for managing feeding intolerance were followed at each site (n=13). Results Infants (n=177; 26.3±1.9 wks (±SD) gestation) were randomized at 6.5±3.9 days to receive “trophic” feeds (“feeding” group, n=81: indomethacin=80%, ibuprofen=20%) or no feeds (“fasting (npo)” group, n=96: indomethacin=75%, ibuprofen=25%) during the drug administration period. Maximum daily enteral volumes prior to study entry were 14±15 ml/kg/day. After drug treatment, infants randomized to the “feeding” arm required fewer days to reach the study’s feeding volume endpoint (120 ml/kg/day). Although the enteral feeding endpoint was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the two groups. There were no differences between the two groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation or other neonatal morbidities. Conclusion Infants required less time to reach the feeding volume endpoint if they were given “trophic” enteral feedings when they received indomethacin or ibuprofen treatments.

Prophylactic Indomethacin and Intestinal Perforation in Extremely Low Birth Weight Infants

“…A study by Clyman et al in 177 premature infants comparing trophic feeds at 15 mL/kg/day versus no feeds during indomethacin or ibuprofen PDA treatment reported that infants fed during treatment required 3 to 4 fewer days to reach 120 mL/kg/day of enteral feeds without evidence of increased feeding intolerance or increased SIP or necrotizing enterocolitis. 11 Our study in contrast to that of Clyman et al examined prophylactic rather than therapeutic indomethacin in relation to early enteral nutrition. We did not examine the interaction of ibuprofen and early enteral feeding concerning SIP.…”

“…[15][16][17] A case-control study 8 and a randomized controlled trial 11 18 provides prospective longitudinal data pertaining to both indomethacin treatment within the first 24 hours after birth for any indication and the occurrence and timing of SIP. The primary hypothesis was that in ELBW infants, concomitant prophylactic intravenous indomethacin within the first 24 hours after birth, and any enteral feeding within the first 3 days after birth would be associated with a $20% increased relative risk of SIP during the first 14 days after birth compared with those who received prophylactic indomethacin but no feeding within the first 3 days after birth.…”

“…A previous NRN publication has shown that 29% of these patients receive prophylactic indomethacin. 11 It was estimated that ∼14% of ELBW infants may have died before receiving any prophylactic indomethacin. This resulted in an expected study population of 16 500 infants who were eligible to receive prophylactic indomethacin and any enteral feeding within the first 3 days after birth.…”

“…A randomized controlled trial 11 and a case-control study 8 have examined the safety and efficacy of indomethacin and concurrent enteral feeding. A study by Clyman et al in 177 premature infants comparing trophic feeds at 15 mL/kg/day versus no feeds during indomethacin or ibuprofen PDA treatment reported that infants fed during treatment required 3 to 4 fewer days to reach 120 mL/kg/day of enteral feeds without evidence of increased feeding intolerance or increased SIP or necrotizing enterocolitis.…”

Prophylactic Indomethacin and Intestinal Perforation in Extremely Low Birth Weight Infants

“…[15][16][17] A case-control study 8 and a randomized controlled trial 11 have shown that enteral feeding concurrent with treatment of a PDA with indomethacin results in fewer days to reach full enteral feeds without evidence of increased feeding intolerance or increased SIP or necrotizing enterocolitis. The question of whether ELBW infants who receive prophylactic indomethacin should concurrently receive enteral nutrition or have their feeds withheld temporarily because of the risk of SIP remains unanswered.…”