The association of inflammatory, autoimmune and coagulation factors with cerebral palsy (CP) was examined at the National Institutes of Health, Bethesda, MD, and the Immunochemistry Laboratory, George Washington University Medical Center, using dried, preserved neonatal blood spot specimens of 31 children enrolled in the California Birth Defects case-controlled study of spastic CP and compared to 65 control children.
Concentrations of interleukins 1, 8, 9, tumor necrosis factor-x, and RANTES were elevated in the neonatal blood specimens of children with CP. CP children with lower Apgar scores and those with known intrauterine exposure to infection immediately prior to birth had especially high values of inflammatory cytokines. Spastic diplegia was associated with higher mean concentrations of inflammatory cytokines and chemokines than hemiplegia. Higher concentrations of antibodies to antiphospholipid, antithrombin III, factor V Leiden mutation, and to proteins C and S were found in the blood analytes of CP children compared to controls. 
COMMENT. In children born at term with low Apgar scores and without known prenatal cerebral pathology, the etiology of a subsequently diagnosed spastic cerebral palsy may be explained by a prenatal or perinatal inflammatory or coagulation abnormality. Elevated cytokine concentrations detected in the neonatal blood of CP children are known to be neurotoxic and can trigger changes in immune, coagulation, and neuroendocrine factors. The role of autoimmune and coagulation disorders in neonatal encephalopathy and seizures and as a cause of CP requires further study. Factor V Leiden mutation has been linked to in utero ischemic infarction and congenital hemiplegic CP (see Ped Neur Briefs Oct 1997;11:75). This continuing NIH study of causes of CP, emphasizing involvement of infectious and coagulation disorders, supports previous conclusions that factors other than birth asphyxia may be more important in etiology (see Progress in Pediatric Neurology III, PNB Publ, 1997;p377). The reliability of dried neonatal blood spot samples for immunoassay of inflammatory cytokines may permit a correlation between prenatal or perinatal infection and the development of childhood neurobehavioral disorders, including ADHD, often associated with subtle neurologic abnormalities.
Criteria for inclusion of cases in CP Registers are discussed in an article from the University of Western Australia . As generally accepted, CP is a motor impairment resulting from brain pathology that is non-progressive and is manifested in early childhood. Exclusion criteria are those motor disorders caused by neurodegenerative diseases, neuromuscular disorders, spinal neural-tube defects, and brain tumors. The MRI and other laboratory investigations have permitted an etiological approach to classification of cases of CP that was formerly regarded as a “waste-basket” diagnosis.