Persistent Pulmonary Hypertension of the Newborn: Therapeutical Approach

Abstract

Persistent pulmonary hypertension of the newborn (PPHN), is defined as a failure of the pulmonary vasculature to relax at birth and consequently of the normal adaptation to extra uterine life of the fetal heart/lung system, resulting in hypoxemia. This condition, occurs in about 1-2 newborns per 1000 live births and despite significant improvements in treatment it is associated with substantial infant mortality and morbidity. Over the years wider application of inhaled nitric oxide (iNO) therapy and improved ventilation strategies including surfactant, high-frequency oscillatory ventilation has led to a decrease in the need for invasive life-sustaining therapies such as extracorporeal membrane oxygenation (ECMO). Mortality rate varies from 10 to 20 % of affected newborns in developed countries, but it is much higher when PPHN is refractory to the above reported therapies or when they are not available. As a consequence, development of new therapeutic strategies for severe PPHN is crucial. In particular, recent studies seem to show that sildenafil, a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance may be a useful therapeutic adjunct to critically ill neonates with PPHN.

A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn

“…18 Despite the recent advances, the clinical approach to PPHN still represents an important challenge for neonatologists. The care of newborns with PPHN requires meticulous therapeutic and ventilation strategies including, besides the stabilization of the newborn, the use of high frequency ventilation, iNO and ECMO.…”

Ocular findings of oral sildenafil use in term and near-term neonates

“…5 Increasingly, sildenafil is being used as a therapeutic adjunct in critically ill neonates with persistent pulmonary hypertension. [6][7] A provocative case report linked sildenafil use to the development of aggressive ROP in a low-weight patient, born at 26 weeks gestation with a protracted clinical course in the intensive care unit. 8 However, the risk of ocular complication in sildenafiltreated newborns, not otherwise at risk for the development of ROP, remains unknown.…”

NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice

“…of vascular transition from fetal to neonatal circulation, which manifests as hypoxemic respiratory failure (22). Mechanisms that interplay in the pathogenesis of PPHN include endothelial dysfunction, inflammation, mechanical strain, and hypoxia (22).…”

“…Mechanisms that interplay in the pathogenesis of PPHN include endothelial dysfunction, inflammation, mechanical strain, and hypoxia (22).…”