Cerebrospinal fluid activin a measurement in asphyxiated full-term newborns predicts hypoxic ischemic encephalopathy.

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 …

[1]  G. Buonocore,et al.  Activin A Plasma Levels at Birth: An Index of Fetal Hypoxia in Preterm Newborn , 2003, Pediatric Research.

[2]  G. Hankins,et al.  Defining the Pathogenesis and Pathophysiology of Neonatal Encephalopathy and Cerebral Palsy , 2003, Obstetrics and gynecology.

[3]  W. Brück,et al.  Increased activin levels in cerebrospinal fluid of rabbits with bacterial meningitis are associated with activation of microglia , 2003, Journal of neurochemistry.

[4]  G. Gibori,et al.  Decidual Activin: Its Role In the Apoptotic Process and Its Regulation by Prolactin1 , 2003, Biology of reproduction.

[5]  Klaus Jung,et al.  Comparison of eight computer programs for receiver-operating characteristic analysis. , 2003, Clinical chemistry.

[6]  B. Romner,et al.  Biochemical serum markers for brain damage: a short review with emphasis on clinical utility in mild head injury. , 2003, Restorative neurology and neuroscience.

[7]  G. Salvesen,et al.  Caspases on the brain , 2002, Journal of neuroscience research.

[8]  S. Werner,et al.  Fibroblast growth factors and neuroprotection. , 2002, Advances in experimental medicine and biology.

[9]  F. Petraglia,et al.  Expression and secretion of activin A: possible physiological and clinical implications. , 2001, European journal of endocrinology.

[10]  M. Hedger,et al.  Evidence for activin A and follistatin involvement in the systemic inflammatory response , 2001, Molecular and Cellular Endocrinology.

[11]  H. Spekreijse,et al.  Predictive value of neonatal neurological tests for developmental outcome of preterm infants. , 2000, The Journal of pediatrics.

[12]  S. Werner,et al.  Induction of activin A is essential for the neuroprotective action of basic fibroblast growth factor in vivo , 2000, Nature Medicine.

[13]  P. Gluckman,et al.  Administration of recombinant human activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid lesion model of Huntington's disease , 1999, Neuroscience.

[14]  P. Gluckman,et al.  Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat 1 Published on the World Wide Web on 8 June 1999. 1 , 1999, Brain Research.

[15]  J. Brown,et al.  An international network for evaluating neuroprotective therapy after severe birth asphyxia. , 1999, Seminars in perinatology.

[16]  R. Romero,et al.  Increased midtrimester amniotic fluid activin A: a risk factor for subsequent fetal death. , 1999, American journal of obstetrics and gynecology.

[17]  K. Nelson,et al.  Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. , 1998, American journal of obstetrics and gynecology.

[18]  M. Dragunow,et al.  Focal brain injury increases activin βA mRNA expression in hippocampal neurons , 1997, Neuroreport.

[19]  N. Nishiyama,et al.  Activin exerts a neurotrophic effect on cultured hippocampal neurons , 1997, Brain Research.

[20]  S. Werner,et al.  Strong induction of activin expression after hippocampal lesion. , 1996, Neuroreport.

[21]  K. Unsicker,et al.  TGF‐beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity. , 1995, The EMBO journal.

[22]  K. Hildén,et al.  The tissue distribution of activin beta A- and beta B-subunit and follistatin messenger ribonucleic acids suggests multiple sites of action for the activin-follistatin system during human development. , 1994, The Journal of clinical endocrinology and metabolism.

[23]  W. Fischer,et al.  Activin is a nerve cell survival molecule , 1990, Nature.

[24]  J. Ellenberg,et al.  Obstetric complications as risk factors for cerebral palsy or seizure disorders. , 1984, JAMA.

[25]  V. Fidler,et al.  Preterm birth, growth retardation and acidemia in relation to neurological abnormality of the newborn. , 1979, Early human development.

[26]  H. Sarnat,et al.  Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. , 1976, Archives of neurology.