Pulmonary hypertension (PH) is increased blood pressure in the pulmonary artery, sometimes also called ‘pulmonary artery hypertension’ or ‘pulmonary arterial hypertension’. It occurs in approximately 2 per 1000 term and near-term infants and 80 per 1000 extremely preterm infants. The incidence of neonatal PH appears to be increasing in recent years with increased survival of the most immature infants.
The three components that determine pulmonary artery pressure (PAP) are pulmonary vascular resistance (PVR), pulmonary blood flow (PBF) and pulmonary capillary wedge pressure (PcWP) and are related according to this equation:
PBF is elevated in conditions that result in a left-to-right shunt such as atrial septal defect, ventricular septal defect or patent ductus arteriosus.
PVR is determined primarily by the total cross-sectional area of the pulmonary vascular bed (which depends on the number and diameter of blood vessels) as well as other factors including blood viscosity.
PcWP reflects pulmonary venous pressure and is elevated in conditions resulting in pulmonary venous hypertension, such as left ventricular diastolic dysfunction and pulmonary vein stenosis.
In adults and children over 3 months of age, PH is defined as mean PAP > 20 mmHg and often diagnosed using cardiac catheterisation. PH is classified in this population according to 6th World Symposium on Pulmonary Hypertension.
Although echocardiography is the gold standard for diagnosis of neonatal PH, clinical assessment and physiological monitoring also play key roles. Initial evaluation of all babies with hypoxaemic respiratory failure should include a detailed history and physical examination. Chest radiography, pre- and post-ductal oxygen saturation monitoring and blood gas analysis are also key components of this assessment.
Unlike adult and paediatric pulmonary hypertension, there is no agreed definition or accepted classification system in newborn babies < 3 months of age with PH.
Neonatal PH can be categorised in several different ways:
| Aetiology | |
| Primary | Idiopathic |
| Secondary | Meconium aspiration syndrome |
| Respiratory Distress Syndrome (surfactant-deficient lung disease) | |
| Congenital infection (pneumonia, sepsis) | |
| Congenital Diaphragmatic Hernia (CDH) | |
| Pulmonary hypoplasia | |
| Perinatal asphyxia | |
| Bronchopulmonary dysplasia | |
| Chromosomal anomaly (eg.Trisomy 21) | |
| Alveolar capillary dysplasia | |
| Arteriovenous malformation | |
| Maternal diabetes | |
| Polycythaemia | |
| Pulmonary lymphangiectasia | |
| Structural congenital heart disease |
Various phenotypes are recognised including:
Persistent Pulmonary Hypertension of the Newborn (PPHN)
Early neonatal PH characterised by persistently elevated PVR leading to suprasystemic PAP with ductal and/or atrial right-to-left shunts.
Bronchopulmonary dysplasia-PH (BPD-PH)
Late post-neonatal PH typically seen in extremely preterm infants chronically dependent on respiratory support
PH associated with CDH
Triad of PH, pulmonary hypoplasia and ventricular dysfunction.
PH associated with perinatal asphyxia
PH caused by increased PVR from acute pulmonary vasoconstriction (often exacerbated by ventricular dysfunction).
PH associated with Trisomy 21
PH related to multiple aetiologies including abnormal pulmonary development with high PVR.
PH secondary to left-to-right shunt
Flow-driven PH e.g. in infants with prolonged ductal patency.
Although several gene mutations including TBX4, BMPR2 and ACVRL1 are known to be associated with the development of pulmonary arterial hypertension (PAH) in adults and older children, the role of genetic factors in the pathogenesis of neonatal PH remains unknown.
The only licensed treatment for neonatal PH is inhaled nitric oxide (iNO) and is only approved for use in term and near-term babies > 34 weeks’ gestation.
Other therapies commonly used in neonates with PH include the following drugs: