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/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.
Subject(s)
Ductus Arteriosus, Patent/therapy , Enteral Nutrition , Ibuprofen/therapeutic use , Indomethacin/therapeutic use , Combined Modality Therapy , Ductus Arteriosus, Patent/drug therapy , Female , Humans , Infant, Newborn , Male , Prospective Studies , Time FactorsABSTRACT
Three independent risk factors (immature gestation, absence of antenatal glucocorticoid exposure, and presence of the rs2817399(A) allele of the gene TFAP2B) are associated with patent ductus arteriosus (PDAs) that fail to close during prostaglandin inhibition. We hypothesized that these three factors may affect a common set of genes that increase the risk of persistent PDA after birth. We studied baboon ductus from term, preterm, and glucocorticoid-treated preterm fetuses and found that both immature gestation and absence of antenatal glucocorticoid exposure decreased RNA expression of calcium- and potassium-channel genes involved in oxygen-induced constriction, and phosphodiesterase genes (that modulate cAMP/cGMP signaling). Ductus obtained from second trimester human pregnancies were genotyped for TFAP2B polymorphisms. When present, the rs2817399(A) allele also was associated with decreased expression of calcium- and potassium-channel genes. In contrast, alleles of two other TFAP2B polymorphisms, rs2817419(G) and rs2635727(T), which are not related to the incidence of PDA after birth, had no effect on RNA expression. In conclusion, three calcium- and potassium-channel genes (CACNA1G/ alpha1G, CACNB 2/CaL-beta2, and KCNA2/ Kv1.2) were similarly affected by each of the PDA risk factors. We speculate that these channels may play a significant role in closing the preterm ductus during prostaglandin inhibition and may be potential targets for future pharmacologic manipulations.
Subject(s)
Ductus Arteriosus, Patent/etiology , Ductus Arteriosus/embryology , Gene Expression Regulation, Developmental , Animals , Calcium Channels, L-Type/genetics , Calcium Channels, T-Type/genetics , Drug Administration Schedule , Ductus Arteriosus, Patent/genetics , Ductus Arteriosus, Patent/prevention & control , Female , Gene Expression Regulation, Developmental/drug effects , Genetic Predisposition to Disease , Gestational Age , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Kv1.2 Potassium Channel/genetics , Linear Models , Logistic Models , Papio , Polymorphism, Single Nucleotide , Pregnancy , RNA, Messenger/analysis , Risk Assessment , Risk FactorsABSTRACT
OBJECTIVE: To examine whether a more conservative approach to treating patent ductus arteriosus (PDA) is associated with an increase or decrease in morbidity compared with an approach involving early PDA ligation. STUDY DESIGN: In January 2005, we changed our approach to infants born at ageSubject(s)
Ductus Arteriosus, Patent/drug therapy
, Ductus Arteriosus, Patent/surgery
, Indomethacin/therapeutic use
, Female
, Humans
, Infant, Newborn
, Ligation
, Male
, Prospective Studies
, Time Factors
, Treatment Failure
ABSTRACT
We hypothesized that there is a significant relationship between a neonatologist's belief that feedings must be stopped in the presence of a patent ductus arteriosus (PDA) and his or her willingness to ligate a PDA. We administered the same survey questionnaire to two separate populations of neonatologists to assess their beliefs regarding PDA treatment practices. Although >90% of U.S. and non-U.S. neonatologists reported that they would ligate a PDA when infants with birth weights <900 g required mechanical ventilation (and indomethacin was contraindicated or had failed to close the PDA), U.S. neonatologists reported that they were significantly more likely to ligate a PDA when less respiratory support was required. U.S. neonatologists were also more likely to stop feedings when a PDA was present. The reported likelihood that a neonatologist would ligate a PDA in infants who did not require mechanical ventilation was significantly increased if the neonatologist believed that feedings had to be stopped because of the PDA. After controlling for the belief that "feedings must be stopped in the presence of a PDA," the significant difference between U.S. and non-U.S. neonatologists, in their reported desire to ligate infants who did not require mechanical ventilation, was no longer present.