Elizabeth M. Planalp, PhD. University of Wisconsin. Madison, Wisconsin. Elizabeth S. Moore, PhD ... Kim SY, Shin SH, Kim HS, Jung YH, Kim EK, Choi JH.
THE JOURNAL OF PEDIATRICS • www.jpeds.com Pulmonary arterial hypertension after ibuprofen treatment in the first week of life? To the Editor: We read with great interest the report by Kim et al.1 There is a gap of knowledge on ibuprofen prophylaxis and treatment side-effect profiles in the first week of age in infants born very low birth weight. Although a recent meta-analysis supports the effective use of ibuprofen treatment to augment closure of a patent ductus arteriosus (PDA),2 the study by Kim et al1 suggests that the existence of a high incidence of pulmonary arterial hypertension (PAH) after treatment with ibuprofen. Some aspects of this message may be misleading based on the methodology of the study and the interpretation of the results. The incidence of PAH in infants born very low birth weight in the first week of age varies from 2% to 40%.3,4 In this study, 10 of 144 (6.9%) infants who received ibuprofen developed PAH, but the authors do not report for comparison the incidence of PAH in the infants without a PDA (n = 219), or the incidence of PAH in infants with a PDA who did not receive ibuprofen (n = 74). Using a broad echocardiogram-based definition of PAH, Mourani et al4 demonstrated that evidence of PDA at 7 days of age was associated with early PAH. The mere presence of increased left-to-right flow through the PDA could impact the echocardiographic assessment of PAH and lead to pulmonary vascular remodeling and pulmonary vascular disease, irrespective of the treatment options for a PDA. The small sample size prevents the inclusion of additional perinatal confounders of pulmonary vasculature growth and development, (ie, chorioamnionitis, pre-eclampsia, diabetes mellitus, smoking, asthma, and surfactant replacement therapy). Causality cannot be proven from the retrospective, nonrandomized design, and the results should be
LETTERS TO THE EDITOR
interpreted within the framework of these study limitations. Further randomized prospective studies are needed to isolate the impact of PDA and its treatment options on the risk for PAH in this population. Philip T. Levy Department of Pediatrics Washington University School of Medicine St Louis, Missouri Department of Pediatrics Goryeb Children’s Hospital Morristown, New Jersey Afif EL-Khuffash Department of Neonatology The Rotunda Hospital Department of Pediatrics School of Medicine Royal College of Surgeons in Ireland Dublin, Ireland
References 1. Kim SY, Shin SH, Kim HS, Jung YH, Kim EK, Choi JH. Pulmonary arterial hypertension after ibuprofen treatment for patent ductus arteriosus in very low birth weight infants. J Pediatr 2016;doi:10.1016/ j.jpeds.2016.08.103. 2. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev 2015;(4):CD003481. 3. Steinhorn RH. Advances in neonatal pulmonary hypertension. Neonatology 2016;109:334-44. 4. Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD, et al. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 2015;191:87-95.
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