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Persistent pulmonary hypertension of the newborn may occur with perinatal asphyxia, either because of direct effects of hypoxia/ischemia on pulmonary arterial function or indirectly because both are associated with meconium aspiration syndrome or perinatal sepsis/pneumonia. Therapies for persistent pulmonary hypertension of the newborn have the potential to affect cerebral function and cerebral perfusion in infants with hypoxic ischemic encephalopathy. Our literature review concludes that hyperventilation should be avoided, bicarbonate therapy is unproven, and hypoxia and hyperoxia should both be avoided. Nitric oxide improves pulmonary artery pressure and systemic perfusion. The effects of inotropic agents on cerebral perfusion or outcomes are uncertain.