Persistent Pulmonary Hypertension in the Newborn

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of failed circulatory adaptation at birth due to delay or impairment in the normal fall in pulmonary vascular resistance (PVR) that occurs following birth. The fetus is in a state of physiological pulmonary hypertension. In utero, the fetus receives oxygenated blood from the placenta through the umbilical vein. At birth, following initiation of respiration, there is a sudden precipitous fall in the PVR and an increase of systemic vascular resistance (SVR) due to the removal of the placenta from circulation. There is dramatic increase in pulmonary blood flow with a decrease in, and later reversal of shunts at the foramen ovale and ductus arteriosus. The failure of this normal physiological pulmonary transition leads to the syndrome of PPHN. PPHN presents with varying degrees of hypoxemic respiratory failure. Survival of infants with PPHN has significantly improved with the use of gentle ventilation, surfactant and inhaled nitric oxide (iNO). PPHN is associated with significant mortality and morbidity among survivors. Newer agents that target different enzymatic pathways in the vascular smooth muscle are in different stages of development and testing. Further research using these agents is likely to further reduce morbidity and mortality associated with PPHN.

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies

“…High pulmonary vascular resistance (or hypertension in the pulmonary artery) is a natural phenomenon during the fetal period. At birth, after the initiation of respiration (increasing alveolar oxygen tension and ventilation), a sudden precipitous fall in the pulmonary vascular resistance and an increase in systemic vascular resistance appears because of the removal of the placenta from circulation (23). PPHN occurs when an abnormal persistence of high pulmonary vascular resistance at birth disrupts the normal transition.…”

Impact of inhaled nitric oxide stewardship programme in a neonatal intensive care unit

“…1 PPHN is a serious neonatal emergency that can result in hypoxaemic respiratory failure (HRF) and death. 2 It is characterised by increased PVR, intrapulmonary shunting with resultant ventilation-perfusion (V/Q) mismatch, right-to-left extrapulmonary shunting through the ductus arteriosus and foramen ovale, progressively leading to arterial hypoxaemia. 3 PPHN can be one of three types: (i) primary or idiopathic due to remodelled pulmonary vasculature but normal parenchyma; (ii) abnormal pulmonary vasoconstriction following perinatal asphyxia or parenchymal lung disease such as hyaline membrane disease, pneumonia, meconium aspiration; or (iii) hypoplastic vasculature as seen in pulmonary hypoplasia associated with congenital diaphragmatic hernia.…”

“…3 PPHN can be one of three types: (i) primary or idiopathic due to remodelled pulmonary vasculature but normal parenchyma; (ii) abnormal pulmonary vasoconstriction following perinatal asphyxia or parenchymal lung disease such as hyaline membrane disease, pneumonia, meconium aspiration; or (iii) hypoplastic vasculature as seen in pulmonary hypoplasia associated with congenital diaphragmatic hernia. 1,2,4 Treatment of PPHN relies on supportive treatment such as oxygen administration, in addition to effective lung recruitment using CPAP or ventilation. In severe cases, selective dilation of the pulmonary vasculature may be necessary.…”

“…Conditions that interfere with the normal post‐natal decline in PVR/SVR ratio can cause the fetal circulation to persist and could result in persistent pulmonary hypertension of newborn (PPHN) . PPHN is a serious neonatal emergency that can result in hypoxaemic respiratory failure (HRF) and death . It is characterised by increased PVR, intrapulmonary shunting with resultant ventilation‐perfusion (V/Q) mismatch, right‐to‐left extrapulmonary shunting through the ductus arteriosus and foramen ovale, progressively leading to arterial hypoxaemia .…”

Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing

“…Under global alveolar hypoxia, HPV can also cause an increase in pulmonary vascular pressure. This occurs naturally in the hypoxic lungs of the unborn fetus, and inappropriate continuation of HPV after birth causes persistent pulmonary hypertension (PH) of the newborn, which is associated with significant mortality and morbidity (3). HPV also contributes to the development of PH caused by chronic hypoxiainduced pulmonary vascular remodeling, which can eventually lead to right heart failure (4).…”