(See also Overview of Perinatal Respiratory Disorders Overview of Perinatal Respiratory Disorders Extensive physiologic changes accompany the birth process (see also Neonatal Pulmonary Function), sometimes unmasking conditions that posed no problem during intrauterine life. For that reason... read more .)
Extensive physiologic changes Perinatal Physiology The transition from life in utero to life outside the womb involves multiple changes in physiology and function. See also Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more accompany the birth process, sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation Neonatal Resuscitation Extensive physiologic changes accompany the birth process, sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation... read more skills must attend each birth. Gestational age Gestational Age Gestational age and growth parameters help identify the risk of neonatal pathology. Gestational age is the primary determinant of organ maturity. Neonatal gestational age is usually defined... read more and growth parameters Growth Parameters in Neonates Growth parameters and gestational age help identify the risk of neonatal pathology. Growth is influenced by genetic and nutritional factors as well as intrauterine conditions. Growth parameters... read more help identify the risk of neonatal pathology.
Persistent pulmonary hypertension of the newborn (PPHN) is a disorder of pulmonary vasculature that affects term or postterm infants Postterm Infants A postterm infant is an infant born at ≥ 42 weeks of gestation. The cause of postmaturity is generally unknown, but previous postterm delivery increases the risk 2- to 3-fold. Postmaturity may... read more .
Etiology of PPHN
In normal fetal circulation Normal Fetal Circulation Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births ( 1). Among birth defects, congenital heart disease is the leading cause of infant mortality... read more , blood entering the right side of the heart has already been oxygenated via the placenta. Because the lungs are not ventilated, only a small amount of blood needs to go through the pulmonary artery. Most blood from the right side of the heart bypasses the lungs through the foramen ovale and ductus arteriosus. Normally, these two structures close shortly after birth. (See also Neonatal Cardiovascular Function Neonatal Cardiovascular Function The transition from life in utero to life outside the womb involves multiple changes in physiology and function. See also Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more .)
In PPHN (previously known as persistent fetal circulation), prenatal stress, postnatal stress, and anatomical differences may result in the persistence of elevated pulmonary vascular resistance after birth. Hypoxemia and acidosis cause the pulmonary arterioles to constrict and the ductus arteriosus to dilate, reversing the usual processes establishing newborn circulation at delivery and resulting in right-to-left shunting through the ductus arteriosus, foramen ovale, or both. This right-to-left shunting bypasses the lungs and causes nonoxygenated or poorly oxygenated blood to be delivered systemically.
The most common causes of persistent pulmonary hypertension of the newborn involve
Perinatal asphyxia or hypoxia
A history of meconium staining of amniotic fluid or meconium in the trachea is common. Hypoxia triggers reversion to or persistence of elevated pulmonary vascular resistance, a normal state in the fetus.
Additional causes include
Premature ductus arteriosus or foramen ovale closure, which increases fetal pulmonary blood flow and may be triggered by maternal nonsteroidal anti-inflammatory drug (NSAID) use (1 Etiology references Persistent pulmonary hypertension of the newborn is the persistence of or reversion to pulmonary arteriolar constriction, causing a severe reduction in pulmonary blood flow and right-to-left... read more )
Pulmonary hypoplasia with associated pulmonary vasculature hypoplasia leading to PPHN (2 Etiology references Persistent pulmonary hypertension of the newborn is the persistence of or reversion to pulmonary arteriolar constriction, causing a severe reduction in pulmonary blood flow and right-to-left... read more )
Congenital diaphragmatic hernia Diaphragmatic Hernia Diaphragmatic hernia is protrusion of abdominal contents into the thorax through a defect in the diaphragm. Lung compression may cause persistent pulmonary hypertension. Diagnosis is by chest... read more , in which one lung is severely hypoplastic, also leading to pulmonary vasculature hypoplasia and PPHN
Neonatal sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more or neonatal pneumonia Neonatal Pneumonia Neonatal pneumonia is lung infection in a neonate. Onset may be within hours of birth and part of a generalized sepsis syndrome or after 7 days and confined to the lungs. Signs may be limited... read more presumably because vasoconstrictive prostaglandins are produced by activation of the cyclooxygenase pathway by bacterial phospholipids, and acidosis due to systemic hypoperfusion caused by the infection also contributes to PPHN in this scenario
1. Van Marter LJ, Hernandez-Diaz S, Werler MM, et al: Nonsteroidal anti-inflammatory drugs in late pregnancy and persistent pulmonary hypertension of the newborn. Pediatrics 131(1):79–87, 2013. doi: 10.1542/peds.2012-0496
2. Chandrasekharan PK, Rawat M, Madappa R, et al: Congenital diaphragmatic hernia—A review. Matern Health Neonatol Perinatol 3:6, 2017. doi: 10.1186/s40748-017-0045-1
Pathophysiology of PPHN
Whatever the cause, elevated resistance in the pulmonary arteries causes abnormal smooth muscle development and hypertrophy in the walls of the small pulmonary arteries and arterioles and right-to-left shunting via the ductus arteriosus or a foramen ovale, resulting in intractable systemic hypoxemia. Both pulmonary and systemic resistances are high, which leads to an increased load on the heart. This load increase may result in right heart dilation, tricuspid insufficiency, and right heart failure.
Symptoms and Signs of PPHN
Symptoms and signs of persistent pulmonary hypertension of the newborn include tachypnea, retractions, and severe cyanosis or desaturation unresponsive to supplemental oxygen.
In infants with a right-to-left shunt via a patent ductus arteriosus Patent Ductus Arteriosus (PDA) Patent ductus arteriosus (PDA) is a persistence of the fetal connection (ductus arteriosus) between the aorta and pulmonary artery after birth. In the absence of other structural heart abnormalities... read more , oxygenation is higher in the right brachial artery than in the descending aorta; thus, cyanosis may be differential (ie, oxygen saturation in the lower extremities is ≥ 5% lower than in the right upper extremity).
Diagnosis of PPHN
Cyanosis unresponsive to oxygen therapy
X-ray to identify underlying disorders
Diagnosis of persistent pulmonary hypertension of the newborn should be suspected in any near-term infant with arterial hypoxemia, cyanosis, or both, especially one with a suggestive history whose oxygen saturation does not improve with administration of 100% oxygen.
Diagnosis is confirmed by echocardiogram, which can confirm the presence of elevated pressures in the pulmonary artery and simultaneously can exclude congenital heart disease.
Blood cultures should be done because prenatal infection is a possible cause of persistent pulmonary hypertension in the newborn.
On x-ray, lung fields may be normal or may show changes due to the underlying disorder (eg, meconium aspiration syndrome Meconium Aspiration Syndrome Intrapartum meconium aspiration can cause inflammatory pneumonitis and mechanical bronchial obstruction, causing a syndrome of respiratory distress. Findings include tachypnea, rales and rhonchi... read more , neonatal pneumonia Diagnosis Neonatal pneumonia is lung infection in a neonate. Onset may be within hours of birth and part of a generalized sepsis syndrome or after 7 days and confined to the lungs. Signs may be limited... read more , congenital diaphragmatic hernia Diagnosis Diaphragmatic hernia is protrusion of abdominal contents into the thorax through a defect in the diaphragm. Lung compression may cause persistent pulmonary hypertension. Diagnosis is by chest... read more ). X-ray abnormalities may be difficult to distinguish from bacterial pneumonia.
Treatment of PPHN
Oxygen to dilate pulmonary vasculature and improve oxygenation
Mechanical ventilation support
Inhaled nitric oxide
ECMO as needed
Correction of metabolic and/or respiratory acidosis
The goal of treatment is to reverse the conditions that caused pulmonary vasoconstriction and treat the underlying conditions.
Treatment with oxygen, which is a potent pulmonary vasodilator, is begun immediately to prevent disease progression. Oxygen is delivered via bag-and-mask or mechanical ventilation Mechanical Ventilation Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more ; mechanical distention of alveoli aids vasodilation. FIO2 should initially be 1 but can be titrated downward to maintain PaO2 between 50 and 90 mm Hg to minimize lung injury once there is evidence of decreased pulmonary vascular resistance. Once PaO2 is stabilized, weaning can be attempted by reducing FIO2 in decrements of 2 to 3%, then reducing ventilator pressures; changes should be gradual, because a large drop in PaO2 can cause recurrent pulmonary artery vasoconstriction. High-frequency oscillatory ventilation expands and ventilates the lungs while minimizing barotrauma and should be considered for infants with underlying lung disease in whom atelectasis and ventilation/perfusion (V/Q) mismatch may exacerbate the hypoxemia of PPHN.
The oxygenation index (mean airway pressure [cm H2O] × fraction of inspired oxygen [FIO2] × 100/PaO2) is used to assess disease severity and determine timing of interventions (in particular for inhaled nitric oxide [oxygenation index 15 to 25] and extracorporeal membrane oxygenation [ECMO—oxygenation index > 35 to 40]).
Inhaled nitric oxide relaxes endothelial smooth muscle, dilating pulmonary arterioles, which increases pulmonary blood flow and rapidly improves oxygenation in as many as half of patients. Initial dose is 20 ppm, titrated downward by effect.
ECMO Extracorporeal Membrane Oxygenation (ECMO) Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more may be used in newborns with severe hypoxic respiratory failure defined by an oxygenation index > 35 to 40 despite maximum respiratory support.
Normal fluid, electrolyte, glucose, and calcium levels must be maintained. Infants should be kept in a neutral thermal environment and treated with antibiotics for possible sepsis until culture results are known. Inotropes and pressors may be required as part of circulatory support.
Prognosis for PPHN
Overall mortality ranges from 10 to 60% and is related to the underlying disorder. About 25% of survivors exhibit developmental delay, hearing deficits, functional disabilities, or a combination. This rate of disability may be no different from that of other infants with severe illness.
Prolonged hypoxia and/or acidosis or disorders that increase pulmonary blood flow cause smooth muscle hypertrophy in small pulmonary arteries, resulting in persistent pulmonary hypertension.
Persistent pulmonary hypertension causes right-to-left shunting via the ductus arteriosus or a foramen ovale, resulting in intractable systemic hypoxemia; right-sided heart failure may develop.
Confirm diagnosis by echocardiography.
Give oxygen to dilate pulmonary vasculature, mechanical ventilation, inhaled nitric oxide, and, for severe cases, extracorporeal membrane oxygenation (ECMO).