Cerebrospinal Fluid Activin A Measurement in Asphyxiated Full-Term Newborns Predicts Hypoxic Ischemic Encephalopathy

Abstract

Hypoxic ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in full-term newborns, and neurologic handicaps develop in ∼25–28% of these infants (1)(2). The postasphyxia period is crucial because brain damage may be at a subclinical stage or its symptoms may be hidden by the effects of sedation, and radiologic assessment may still be unrevealing (3)(4). Because activin A is a growth factor produced in the central nervous system (CNS) (5)(6), mainly after brain injury to modulate neuronal survival against toxicity (7)(8)(9)(10)(11)(12)(13)(14), in the present study we investigated whether its concentrations in cerebrospinal fluid (CSF) collected from asphyxiated full-term newborns were higher in those developing HIE and whether this measurement could be useful for the early detection of postasphyxia HIE. We conducted a longitudinal cohort study, recruiting any infants consecutively admitted (April 1998 through June 2002) to our Neonatal Intensive Care Units (NICUs), who underwent a lumbar puncture in the first 24-h from birth for clinical indications. We expected approximately one third of asphyxiated infants to exhibit moderate/severe HIE; we therefore planned to enroll 30 infants in the asphyxiated group (full-term infants with a gestational age >36 weeks), with at least 8 of them in the HIE subgroup, which would assure a statistical power of 90% to detect differences ≥10% between group means with a significance level of 95%. Considering that <40% of the infants submitted to lumbar puncture in our NICUs have a history of perinatal asphyxia, we expected that ∼40–50 nonasphyxiated infants could be enrolled to the control group contemporarily with the 30 infants of the asphyxiated group. The Local Ethics Committees approved the study protocol, and parents of the infants examined gave informed consent. All …