We have investigated the association of single nucleotide polymorphisms with cerebral palsy in infants born very prematurely, using archived neonatal blood. Four genetic variants were associated with increased risk of cerebral palsy; the targeted genes have roles in inflammation, coagulation, or vasomotor regulation. A paper describing these results is in press. We are investigating the association of these genetic variants with features observed on neonatal cranial ultrasonography. We are now seeking to corroborate (or refute) and extend the initial findings in an investigation in the Laboratory of Molecular Technology, using additional biologic samples from California plus a large material, cases and controls, from a population-based registry of cerebral palsy in Australia, with the collaboration of Dr. Alastair MacLennan. Genotyping is also proceeding on DNA from buccal smears from the study of pediatric stroke with Dr. John Lynch. Dr. Lynch has a paper on adult stroke in press, and a paper on pediatric and perinatal stroke, from the NINDS Pediatric Stroke Study, is in preparation. In collaboration with Dr. Robert Yolken we are involved in a study of antibodies to selected bacterial and viral agents in archived neonatal blood of children with cerebral palsy or autism, and control children. With Dr. Phillip Nelson (NICHD) we have examined concentrations of total protein and of certain neurotrophins, neuropeptides, and cytokines in neonatal blood of children with Down syndrome or autism, and examining the developmental trajectory of these substances in the blood of very premature infants, term infants, and healthy adults recruited from the Blood Bank of NIH. Blood concentrations of brain derived neurotrophic factor increased with age, while values of interleukin-8 were highest in very premature infants and in term infants with Down syndrome, and CGRP concentrations were higher in control newborns than in healthy adults, suggesting some function of this neuropeptide in infancy. A manuscript describing these findings is in preparation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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Hankins, Gary D V; MacLennan, Alastair H; Speer, Michael E et al. (2006) Obstetric litigation is asphyxiating our maternity services. Obstet Gynecol 107:1382-5
Nelson, Karin B; Leviton, Alan (2006) Hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 354:1643-5; author reply 1643-5
Lynch, John Kylan; Han, Christina J; Nee, Linda E et al. (2005) Prothrombotic factors in children with stroke or porencephaly. Pediatrics 116:447-53
Wu, Yvonne W; Lynch, John K; Nelson, Karin B (2005) Perinatal arterial stroke: understanding mechanisms and outcomes. Semin Neurol 25:424-34
Nelson, Karin B (2005) Neonatal encephalopathy: etiology and outcome. Dev Med Child Neurol 47:292
Nelson, Karin B; Dambrosia, James M; Iovannisci, David M et al. (2005) Genetic polymorphisms and cerebral palsy in very preterm infants. Pediatr Res 57:494-9
Nelson, Karin B; Lynch, John K (2004) Stroke in newborn infants. Lancet Neurol 3:150-8
Grether, Judith K; Nelson, Karin B; Walsh, Eileen et al. (2003) Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants. Arch Pediatr Adolesc Med 157:26-32
Nelson, Karin B (2003) Can we prevent cerebral palsy? N Engl J Med 349:1765-9
Lynch, John Kylan; Hirtz, Deborah G; DeVeber, Gabrielle et al. (2002) Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 109:116-23

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