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Abstract

We wish to thank Mimouni and Hammerman for their insightful comments on our article,1Sung S.I. Chang Y.S. Chun J.Y. Yoon S.A. Yoo H.S. Ahn S.Y. et al.Mandatory closure versus nonintervention for patent ductus arteriosus in very preterm infants.J Pediatr. 2016; 177: 66-71.e1Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar giving us the opportunity to explain in further detail about conservative management of hemodynamically significant patent ductus arteriosus (PDA) in infants born extremely preterm. In this study, to avoid unnecessary treatment exposure, initial evaluation of the PDA and treatment decisions were deferred until the end of the first postnatal week, as spontaneous closure might occur. Because of lack of a standardized method to diagnose a hemodynamically significant PDA, the diagnosis was made only in intubated and ventilated infants with clinical symptoms/signs including respiratory deterioration, cardiac murmur, hyperactive precordium, hypotension, and widened pulse pressure, plus echocardiographic findings of dominant left-to-right flow through a PDA size ≥2 mm. Despite limitations that include its retrospective nature, we believe the real significance of this study resides in the observation that spontaneous closure of hemodynamically significant PDA mostly occurred with conservative treatment alone and that conservative treatment was associated with significantly less bronchopulmonary dysplasia (BPD) compared with mandatory closure, even in infants born preterm near the limit of viability. Dani et al2Dani C. Bertini G. Corsini I. Elia S. Vangi V. Pratesi S. et al.The fate of ductus arteriosus in infants at 23-27 weeks of gestation: from spontaneous closure to ibuprofen resistance.Acta Paediatr. 2008; 97: 1176-1180Crossref PubMed Scopus (44) Google Scholar reported that infants at 23-25 weeks' gestation were at greater risk of developing PDA refractory to ibuprofen, and Jhaveri et al3Jhaveri N. Moon-Grady A. Clyman R.I. Early surgical ligation versus a conservative approach for management of patent ductus arteriosus that fails to close after indomethacin treatment.J Pediatr. 2010; 157 (7 e1): 381-387Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar reported that 81% of infants at 24-25 weeks' GA who did not respond to indomethacin treatment ultimately underwent surgical ligation. Because 64% of the “mandatory closure group” initially was treated with indomethacin in this study, our high rate of indomethacin failure and resultant high surgical ligation rate might be attributable to the younger gestation. Alternatively, the detrimental effects of surgical ligation might outweigh the benefits of PDA closure and thus directly contribute to development of BPD, even though the intention was its prevention. Currently, we are conducting a prospective double-blind randomized controlled trial comparing the efficacy of “exclusive pharmacologic treatment with oral ibuprofen” vs “placebo” (NCT0212819). In conclusion, delayed but spontaneous closure of a hemodynamically significant PDA in infants born extremely preterm at 23-26 weeks' gestational age frequently occurred with conservative treatment and was associated with significantly less BPD compared with mandatory closure. A prospective randomized study is needed to determine the potential benefits and risks of conservative treatment for hemodynamically significant PDA in infants born extremely preterm. Mandatory closure versus nonintervention for patent ductus arteriosus in very preterm infantsThe Journal of PediatricsVol. 182PreviewWe read with great interest the report by Sung et al.1 Regrettably, questions as basic as defining hemodynamic significance, need to treat, and how to treat, remain controversial. We were hopeful that Sung et al would shed light on some of these issues; however, we are concerned that several deficiencies in their methodology serve to further confuse rather than to clarify these dilemmas. Full-Text PDF