In this review, we discuss current concepts in the pathogenesis and management of pulmonary hypertension affecting infants and children, with special focus on left-to-right shunting, bronchopulmonary dysplasia, and primary pulmonary hypertension.

In patients of these ages, functional aspects, such as an imbalance between vasoconstricting and vasodilating mechanisms, and morphological alterations of the vessel wall, contribute to the pulmonary hypertension. In the past decades, strategies have emerged for treatment that are targeted at the pathophysiological basis. Thus, in patients with left-to-right shunting and pulmonary hypertension after intra-cardiac repair, treatment with nitric oxide has been introduced effectively, while treatment with prostanoids, such as iloprost, is under investigation. In patients with pulmonary hypertension and bronchopulmonary dysplasia, therapeutic strategies focus on the underlying chronic lung disease and use of vasodilators. The pathogenesis of primary pulmonary hypertension in children remains as yet unclear, although treatment with prostanoids has proven effectively to improve the long-term prognosis.

Primary pulmonary hypertension (PPH) is defined clinically by sustained elevation of pulmonary arterial pressure without a demonstrable cause, and is a progressive, often-fatal disease. PPH can be associated with ingestion of appetite suppressants, human immunodeficiency virus infection and certain autoimmune diseases. Familial PPH is known to account for 6% of all cases. Mutations in the gene encoding the bone morphogenetic protein (BMP) type II receptor have been identified in 72% of affected families and 26% of apparently sporadic cases. BMPs are members of the transforming growth factor β superfamily and affect intracellular signalling via Smads and mitogen-activated protein kinases. Evidence supports a ‘two-hit’ hypothesis in which PPH is triggered by accumulation of genetic and environmental insults in a susceptible individual. Elucidation of the precise molecular and cellular mechanisms underlying PPH will provide a powerful basis for the development of novel therapeutic strategies in the treatment of this devastating condition.