Superior mesenteric artery blood flow velocities following medical treatment of a patent ductus arteriosus.

We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.

Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus.

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/d) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus. STUDY DESIGN: Infants were eligible for the study if they were 23(1/7)-30(6/7) weeks' gestation, weighed 401-1250 g at birth, received maximum enteral volumes ≤60 mL/kg/d, 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 weeks' mean ± 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 [nil per os]" group, n = 96: indomethacin 75%, ibuprofen 25%) during the drug administration period. Maximum daily enteral volumes before study entry were 14 ± 15 mL/kg/d. After drug treatment, infants randomized to the "feeding" arm required fewer days to reach the study's feeding volume end point (120 mL/kg/d). Although the enteral feeding end point was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the 2 groups. There were no differences between the 2 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 end point if they were given "trophic" enteral feedings when they received indomethacin or ibuprofen treatments.

Increased indomethacin dosing for persistent patent ductus arteriosus in preterm infants: a multicenter, randomized, controlled trial.

OBJECTIVE: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. STUDY DESIGN: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. RESULTS: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). CONCLUSION: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.

Risk factors for persistent ductus arteriosus patency during indomethacin treatment.

OBJECTIVE: To test the hypothesis that patent ductus arteriosus that fail to close with prostaglandin inhibition may be regulated by mechanisms that act independently of prostaglandin production. STUDY DESIGN: We examined a cohort of 446 infants who were treated with indomethacin (within 15 hours of birth) to inhibit prostaglandin production. We used multiple logistic regression modeling to determine which perinatal/neonatal variables were most closely associated with the persistence of ductus patency in the presence of diminished prostaglandin production. RESULTS: We identified 4 variables (immature gestational age, lack of exposure to antenatal betamethasone, severity of respiratory distress, and Caucasian race) that were significantly and independently associated with the degree of ductus patency. CONCLUSION: Gestational age, antenatal glucocorticoid exposure, respiratory distress, and race are independent risk factors that appear to affect ductus closure even when indomethacin has been used to inhibit prostaglandin production. Future studies of these risk factors may identify new potential targets for patent ductus arteriosus treatment.