Cerebral palsy in very preterm infants: new epidemiological insights

The focus of this review is on new insights from recent epidemiological research on cerebral palsy in preterm infants. These include: 1) a better understanding of issues related to diagnosis and classification; 2) new information about the brain abnormalities underlying cerebral palsy in preterm infants; and 3) a better understanding of biological mechanisms that may underlie previously described epidemiological associations. Ongoing efforts to improve the diagnosis and classification of cerebral palsy have been enhanced by findings from serial examinations of cohorts of very preterm infants. Cranial ultrasonography through the anterior fontanelle of very preterm infants has provided information about grossly evident brain damage, found in about one-half of preterm infants who develop cerebral palsy. Insights into the pathophysiologic basis for certain epidemiologic associations have come from studies of experimental brain damage in animals and clinical studies of neurologic disorders in adults. Much of the current epidemiological research into the causes of cerebral palsy in preterm infants has focused on two potential mechanisms of brain damage. One mechanism involves insufficient cerebral perfusion; the other, cytokine-mediated damage, potentially triggered by events such as maternal infection (e.g., intrauterine or periodontal infection), neonatal infection (e.g., sepsis and necrotizing enterocolitis), and neonatal oxygen- or ventilator-induced lung injury. In addition to the preterm infant's increased exposure to such damaging factors, the high frequency of cerebral palsy in these infants might be due, in part, to insufficient levels of developmentally regulated protective substances, such as thyroid hormone and glucocorticoids. Models of causation currently are being investigated using recently developed methods for quantifying, with small quantities of blood, biomolecules that are suspected to either promote or protect against brain damage in the neonate. Clinical investigations now under way can be expected to identify strategies to be tested in clinical trials that could lower the risk of cerebral palsy in very preterm infants.