Persistent Pulmonary Hypertension of the Newborn

Persistent pulmonary hypertension of the newborn is a failure of the normal fall in pulmonary vascular resistance after birth, so that high pressure in the lung circulation keeps blood shunting away from the lungs through fetal channels. The result is severe, often labile hypoxemia in a term or near-term infant whose circulation has not made the transition to postnatal life.

Definition

Persistent pulmonary hypertension of the newborn is a syndrome of sustained elevation of pulmonary vascular resistance after birth, with right-to-left shunting across the foramen ovale and/or ductus arteriosus and profound hypoxemia, in the absence of cyanotic congenital heart disease.

Scope

The entry covers the physiology of the failed pulmonary vascular transition, the right-to-left shunting through the foramen ovale and ductus arteriosus that defines the disorder, and its frequent association with conditions such as meconium aspiration. It includes the broad evidence base for inhaled nitric oxide as a pulmonary vasodilator. It is a reference description of disease physiology, not a treatment protocol.

Core questions

• Why does pulmonary vascular resistance normally fall at birth, and what happens when it does not?
• How does right-to-left shunting through fetal channels produce hypoxemia?
• Which neonatal conditions predispose to persistent pulmonary hypertension?
• How does inhaled nitric oxide act on the pulmonary circulation, and what does the trial evidence show?

Key concepts

• Fetal-to-neonatal circulatory transition
• Pulmonary vascular resistance
• Right-to-left shunting (foramen ovale and ductus arteriosus)
• Hypoxic pulmonary vasoconstriction
• Nitric oxide and pulmonary vasodilation
• Maladaptation, maldevelopment, and underdevelopment of the pulmonary vasculature

Mechanisms

Before birth the lung's vascular bed is constricted and most blood bypasses the lungs through the foramen ovale and ductus arteriosus. Normally, with the first breaths, oxygenation and mechanical expansion cause pulmonary vascular resistance to fall and pulmonary blood flow to rise. In persistent pulmonary hypertension this fall fails to occur or reverses, from maladaptation of a structurally normal vasculature, abnormal muscularization (maldevelopment), or a reduced vascular bed (underdevelopment). High pulmonary pressures sustain right-to-left shunting across the fetal channels, so deoxygenated blood reaches the systemic circulation and severe hypoxemia results. Nitric oxide, a key endogenous pulmonary vasodilator, became the rationale for inhaled nitric oxide therapy (Roberts et al., 1992; NINOS, 1997).

Clinical relevance

The disorder is a cause of life-threatening hypoxemia in term and near-term infants and is described here for reference. The entry explains the underlying physiology and evidence and is not guidance for managing any individual infant.

Epidemiology

Persistent pulmonary hypertension occurs mainly in term and near-term infants and is commonly associated with meconium aspiration syndrome, sepsis, pneumonia, perinatal asphyxia, and conditions such as congenital diaphragmatic hernia that limit lung and vascular development.

Evidence & guidelines

Randomized trials established inhaled nitric oxide as a selective pulmonary vasodilator that improves oxygenation and reduces the need for extracorporeal support in term and near-term infants with hypoxic respiratory failure (NINOS, 1997), building on early reports of its pulmonary-selective effect (Roberts et al., 1992). This evidence is summarized for orientation only and is not clinical direction.

History

The condition was historically called persistent fetal circulation, reflecting the idea of a circulation that had not transitioned to postnatal patterns. The discovery of nitric oxide as an endothelium-derived vasodilator led, in the early 1990s, to reports of inhaled nitric oxide selectively lowering pulmonary pressures (Roberts et al., 1992), and randomized trials later confirmed its benefit in hypoxic term infants (NINOS, 1997).

Key figures

• Jesse Roberts
• Warren Zapol
• Robin Steinhorn

Seminal works

• roberts-1992
• ninos-1997

Frequently asked questions

What is persistent pulmonary hypertension of the newborn?

It is a condition in which the high pulmonary blood pressure of fetal life fails to fall normally after birth, so blood continues to shunt away from the lungs through fetal channels, causing severe low oxygen levels in a term or near-term infant.

How is it related to meconium aspiration?

Meconium aspiration and other lung disorders can raise pulmonary vascular resistance and trigger or worsen persistent pulmonary hypertension, which is why the two conditions often occur together in term and post-term infants.