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Ibubrofen in the Treatment of Patent Ductus Arteriosus in Preterm Infants: What We Know, What We Still Do Not Know.
MedLine Citation:
PMID:  22385060     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The patency of the ductus arteriosus has ever been considered as a pathological situation in preterm infants and one likely cause of mortality and morbidity, including broncho-pulmonary dysplasia, necrotizing enterocolitis, intraventricular haemorrhage, retinopathy of prematurity. The incidence of patent ductus arteriosus is inversely proportional to gestational age and infants with the lowest gestational ages are the most exposed to the complications of prematurity. So, associations between patent ductus arteriosus and the other morbidities may be not causative and patent ductus arteriosus could be more a sign of immaturity and severity of disease than the cause of these problems. Non-steroidal anti-inflammatory agents, such as indomethacin or ibuprofen, have been shown to be effective in closing or preventing patent ductus arteriosus, with differences in side effects. However nearly all randomized controlled trials have been designed with the closure of the ductus arteriosus, not mortality or morbidity, as the main endpoint. Thus, evidence is still lacking on the eventual benefits for the patient of pharmacological or surgical intervention on PDA. Moreover, both ibuprofen and indomethacin efficacy seems markedly reduced in extremely low gestational age infants, who are the most likely to benefit from such intervention. The explanation of the reduced pharmacodymanic effect in such population is unclear; so far, studies using increased dosing of ibuprofen have failed to show a clear benefit. Prophylaxis with indomethacin or ibuprofen has failed to show sustained benefits on neurodevelopment at 2 years of age in low gestational age infants. New curative trials may aim at investigating the effects of early curative administration of ibuprofen, which has reduced side effects compared to indomethacin, on immature kidney function, on mortality and morbidity in very low gestational age infants, ideally with a combined endpoint such as survival in the absence of severe neurodevelopmental alteration at 2 years age. Despite an understandable reluctance given the historical background of systematic, therapeutic closure of ductus arteriosus in preterm infants, there are no definite ethical obstacles to a placebo-controlled design.
Authors:
Isabelle Mercanti; Isabelle Ligi; Farid Boubred; Isabelle Grandvuillemin; Christophe Buffat; Laurance Fayol; Véronique Millet; Umberto Simeoni
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-27
Journal Detail:
Title:  Current pharmaceutical design     Volume:  -     ISSN:  1873-4286     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-3-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Div Neonatology, La Conception Hospital, AP-HM, 147 Boulevard Baille, 13385 Marseille, France. umberto.simeoni@ap-hm.fr.
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