SERIES: PULMONARY VASCULAR DISEASE
Pulmonary hypertension in the newborn

https://doi.org/10.1016/j.prrv.2005.03.005Get rights and content

Summary

Pulmonary hypertension of the newborn occurs in 1.9 per 1000 live births and affected infants are hypoxaemic because of right-to-left shunts through the ductus arteriosus and foramen ovale. Pulmonary hypertension of the newborn may be primary, or secondary to a variety of conditions including intrapartum asphyxia, infection, pulmonary hypoplasia, congenital heart disease or drug therapy. It may occur in association with a normal number (maladaptation) or a decreased number of arteries (for example with pulmonary hypoplasia). Few strategies used in infants with pulmonary hypertension of the newborn have been subjected to rigorous evaluation. Inhaled nitric oxide has been shown to reduce the need for extracorporeal membrane oxygenation but not mortality, in term or near term born infants. Preliminary evidence suggests that other vasodilators given by the inhaled route may improve oxygenation and new vasodilators have become available; appropriately designed trials with long-term outcomes are required to test such therapies.

Section snippets

INTRODUCTION

Pulmonary hypertension of the newborn (PHN) occurs in 1.9 per 1000 live births, but a wide variation in the incidence (0.43–6.82 per 1000 live births) has been reported between centres.1 Infants with PHN have right-to-left shunting at the level of the ductus arteriosus and the foramen ovale. Persistent pulmonary hypertension of the newborn (PPHN), which persists from fetal life, has been called persistent fetal circulation, but that term is inaccurate as the placenta is missing.

CHANGES IN THE CIRCULATION AT BIRTH

In the fetus, the pulmonary circulation is a high resistance circuit but the systemic circulation includes a low resistance, high flow component, the placenta. Blood is shunted away from the lungs across the ductus arteriosus and only approximately 10% of the right ventricular output enters the pulmonary circulation. After birth, there is no longer a placenta and venous return through the inferior cava to the right side of the heart is reduced and the right atrial pressure falls. The flow

PATHOPHYSIOLOGY

PHN may be primary or secondary to a variety of disorders affecting the cardiac, pulmonary, haematological and metabolic systems; these include severe intrapartum asphyxia, infection, pulmonary hypoplasia, alveolar capillary dysplasia, congenital heart disease, polycythaemia (hyperviscosity resulting in functional obstruction of the pulmonary vascular bed) and drug therapy (for example administration of prostaglandin synthesis inhibitors before delivery). Pulmonary hypertension may occur in

CLINICAL FEATURES

Infants with PPHN present within 12 hours of birth with cyanosis but relatively mild respiratory distress. The second heart sound is loud, because of the high pulmonary artery pressure and there may be a systolic murmur due to tricuspid regurgitation. Infants with secondary PHN will, in addition, have the features of their underlying condition.

DIAGNOSIS

The diagnosis should be considered when the infant's hypoxaemia is out of proportion to the degree of severity of the abnormalities on the chest radiograph. In PPHN, there may be no or only minimal chest radiograph abnormalities, but in secondary PHN there will be the abnormalities associated with the underlying condition. Right-to-left shunting is evidenced by a discrepancy in the pre- and post-ductal saturations; a PaO2 difference of at least 20 mmHg between the pre (right radial) and post

TREATMENT

Infants with PPHN can be extremely ‘brittle’ and can become hypoxaemic following even gentle handling and minimal interventions. As a consequence, chest physiotherapy is contraindicated and suctioning should only be undertaken to ensure patency of the endotracheal tube. Use of sedation and paralysis has been advocated.6 Treatment of babies with PHN is aimed at maximising pulmonary blood flow and minimising pulmonary vascular resistance without compromising cardiac output (Table 1). The size of

MORTALITY AND MORBIDITY

In a recent retrospective review, the mortality rate of infants with PHN in 12 level three neonatal intensive care units was reported to be 11% (range 4–33%).1 The mortality rate, however, varies according to the underlying condition and is as high as 50% in infants with group B streptococcal sepsis; most babies dying from irreversible hypoxia or myocardial failure. Some infants with PHN will have required a high level of respiratory support and develop BPD, others suffer neurological damage as

PRACTICE POINTS

  • Pulmonary hypertension may occur in association with a normal number (maladaptation) or a decreased number of arteries (e.g. in association with pulmonary hypoplasia).

  • The diagnosis should be suspected if the hypoxaemia is out of proportion to the chest radiograph changes.

  • Treatment is directed at reducing the size of the right-to-left shunt by improving the systemic blood pressure and administering pulmonary vasodilators

  • Inhaled nitric oxide in infants born at or near term reduces the need for

RESEARCH DIRECTIONS

  • The efficacy and optimum use of inhaled nitric oxide (iNO) in prematurely born infants.

  • The role of prophylactic iNO in preventing bronchopulmonary dysplasia (BPD).

  • The safety and efficacy of vasodilators, such as prostacyclin or tolazoline, given by inhalation.

  • The optimum combinations of agents to use in pulmonary hypertension of the newborn (PHN) to minimise pulmonary vascular resistance (PVR) without deterioration in oxygenation or a fall in systemic blood pressure.

References (38)

  • M.C. Walsh-Sukys et al.

    Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes

    Pediatrics

    (2000)
  • C.W. Leffler et al.

    The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis

    Pediatr Res

    (1984)
  • D.L. Pearson et al.

    Neonatal pulmonary hypertension–urea–cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function

    N Engl J Med

    (2001)
  • J.B. Gordon et al.

    Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets

    Pediatr Res

    (1999)
  • R.K. Lyrene et al.

    Alkalosis attenuates hypoxic pulmonary vasoconstriction in neonatal lambs

    Pediatr Res

    (1985)
  • M.D. Schreiber et al.

    Increased arterial pH, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs

    Pediatr Res

    (1986)
  • HIFO Study Group. Randomised study of high frequency oscillatory ventilation in infants with severe respiratory...
  • Bhuta T, Clark RH, Henderson-Smart DJ. Rescue high frequency oscillatory ventilation versus conventional ventilation...
  • V. Chan et al.

    High frequency oscillation for preterm infants with severe respiratory failure

    Arch Dis Child

    (1994)
  • Cited by (0)

    View full text