Persistent pulmonary hypertension of the newborn

The most common cause of pulmonary hypertension in newborns is persistent pulmonary hypertension of the newborn (PPHN). It occurs in term or late preterms infants, where the fetal shunts persist after birth and fail to close. It falls under group 1.5 of the Dana Point classification system of pulmonary hypertension (2008).

Epidemiology

The incidence of PPHN is approximately 1.9 per 1000 live births . It most often occurs in infants born between 34 to 37 weeks of gestation (i.e. late preterm).

Risk factors predisposing infants to this condition include :

• male gender
• delivery by Cesarean section
• large for gestational age (birth weight above 90th percentile)
• certain maternal factors
  • black or Asian race
  • high prepregnancy BMI
  • diabetes
  • asthma
  • advanced age

Clinical presentation

Prenatal signs of intrauterine or perinatal asphyxia, such as fetal heart rate abnormalities and meconium-stained amniotic fluid, may be associated with future development of PPHN. In the delivery room, they often have low Apgar scores and require ventilatory support .

Neonates usually present with signs of respiratory distress and labile hypoxemia at the time of birth or gradually in the following days, depending on the etiology. These signs include :

• cyanosis
• grunting
• flaring of the nostrils
• intercostal retractions
• tachypnea
• tachycardia
• shock

Upon auscultation, an accentuated single second heart sound may be heard and may be accompanied by a systolic murmur consistent with tricuspid insufficiency. If the persistent shunt is primarily ductal, then pulse oximetry assessment may show a difference >5% between the preductal and postductal vessels. This gradient would also be present for arterial blood gas measurements, yielding a PaO2 difference greater than 20 mmHg , and that arterial partial pressure of oxygen would usually fall below 100 mmHg .

Echocardiography, the gold standard for diagnosis, confirms the presence of pulmonary hypertension and the underlying ductal or foramen ovale shunt .

Pathology

After delivery, the neonate's circulatory system undergoes many critical changes, transitioning from fetal circulation, where the pulmonary and systemic circuits run in parallel, to postnatal circulation in series . These changes are primarily mediated by a decrease in pulmonary vascular resistance (PVR) and an increase in systemic vascular resistance (SVR). The decrease in PVR can be attributed to aeration and oxygenation of the lungs, leading to increased vasodilation of pulmonary capillaries directly by mechanical shear forces and indirectly through local endothelial mediators such as prostaglandins and nitric oxide . The increase in SVR is primarily due to the removal of the placenta, as well as due to the rise in catecholamines and drop in external temperature after delivery . All of these changes lead to a tipping point where the PVR drops below the SVR, which will reverse the flow through the ductus arteriosus and the oxygenated blood will close the fetal physiological shunts .

However, in PPHN one or several of these shunts fail to close after birth, leading to persistently elevated pulmonary blood pressures. This can be secondary to :

• meconium aspiration syndrome
• respiratory distress syndrome (RDS)
• infection, e.g. pneumonia or sepsis
• lung hypoplasia
  • oligohydramnios
  • congenital diaphragmatic hernia (CDH)
  • polycythemia with hyperviscosity
• maldevelopment of the pulmonary vasculature (idiopathic)

Radiographic features

Plain radiograph

Radiographic findings may disclose the etiology for the PPHN, as discussed above.

Chest radiographs may appear normal, however certain signs of pulmonary hypertension may be present, such as :

• cardiomegaly
• decreased pulmonary blood flow
• prominent right ventricular contour

Echocardiography

Echocargiography is the gold standard to confirm the diagnosis of PPHN. It also the best modality to monitor treatment efficacy. Important measurements include :

• presence of ductal and/or foramen ovale shunt, with right to left direction of flow
• flattening or left deviation of the interventricular septum
• right atrial enlargement
• tricuspid insufficiency
• systemic or near systemic right ventricle pressure estimations from Doppler study of tricuspid regurgitation velocity in conjunction with systemic blood pressure measurements
• right ventricle dysfunction (suggests severe pulmonary hypertension) 

Treatment and prognosis

The treatment of PPHN includes management of any underlying disease, as well as supportive care to stabilize the patient's cardiorespiratory function. This is achieved with ventilatory support with oxygen to vasodilate the pulmonary vasculature, or administration of fluid and inotropes to elevate systemic blood pressure and reduce right to left shunting .

If the PPHN is secondary to parenchymal lung disease, such as meconium aspiration syndrome, respiratory distress syndrome, or pneumonia, early administration of surfactant is associated with decreased mortality or the need for extracorporeal membrane oxygenation .

In more severe cases of hypoxemia, inhaled nitric oxide has been shown to be beneficial in rapidly vasodilating pulmonary vessels and decreases by 40% the need for extracorporeal membrane oxygenation, which is reserved as a last resort for refractory cases .

The estimated mortality rate of PPHN is 10%, and survivors are at increased risk of developmental delay or neurological deficits .

Differential diagnosis

General imaging differential considerations include :

• cyanotic congenital heart disease (CHD), which would be found during echocardiography
• primary isolated parenchymal lung disease, such as:
  • neonatal pneumonia
  • transient tachypnea of the newborn (TTN)
  • respiratory distress syndrome (RDS)
• sepsis