Cerebral palsy in very preterm infants: new epidemiological insights

Abstract

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.

Maternal Infection and Risk of Cerebral Palsy in Term and Preterm Infants

“…However, preterm birth may be associated with CP through other, noninflammatory mechanisms as well. 26,27 In our study, preterm delivery in the absence of infection was associated with an eightfold increase in risk of CP overall when compared to term noninfected infants. The risk of CP was 24-fold greater for the very preterm noninfected infants when compared to term non-infected infants.…”

Gut microbiota, the immune system, and diet influence the neonatal gut–brain axis

“…The stress created by NEC has adverse consequences in the brain via the GBA (55). Microbial toxicants and proinflammatory cytokines released into the systemic circulation from infected and damaged intestine have a causal relationship with the long-term psychomotor and intestinal disabilities seen after NEC (55). The degree of injury to the intestine in NEC correlates with the levels of oxidant stress and other mediators associated with brain injury (56).…”

“…Several mechanisms define the beneficial effects of human milk oligosaccharides in the immature intestinal tract of human preterm infants. NEC is an intestinal disease of preterm infants, which produces intense inflammation (92) and indirect brain injury via the GBA (55,72). The preceding reasons are why we emphasize feeding colostrum right after birth and give freshly expressed mother's milk during the neonatal intensive care unit stay (90,93,94).…”

MR Imaging for Diagnostic Evaluation of Encephalopathy in the Newborn

“…Up to 19% of infants born before 28 weeks of gestation develop cerebral palsy. Approximately 50% of cases of cerebral palsy occur in infants born prematurely (12).…”