The widespread use of cocaine by women of child-bearing age has resulted in a number of reports of adverse fetal and neonatal outcomes associated with in utero cocaine exposure. Specific causality is difficult to ascertain because of multiple confounding variables associated with substance abuse. In an effort to better define the effects of cocaine exposure, it is necessary to adequately document drug exposure and adjust for associated covariates. In this proposal, the syndromes produced by cocaine intoxication and withdrawal will be defined by measuring cord blood concentrations of cocaine and its metabolites (benzylecgonine, anhydroecgoninemethyl-ester and coca-ethylene). It is our hypothesis that there are clinical parameters available that can distinguish between intoxication and withdrawal. Using a detailed neurological and adaptive capacity examination that has been tested and defined previously, the correlation between signs on the examination and blood levels of cocaine and/or its metabolites will be made. Using the data obtained from patients with positive assays for coca-ethylene, which is a metabolite of cocaine in the presence of alcohol, we will attempt to separate effects of cocaine from fetal alcohol exposure. Recent reports of stroke and other central nervous system lesions suggest that cocaine may exert a teratogenic effect on the brain. Impaired cerebral blood flow, excitotoxic injury and impaired neuronal development have been implicated as possible mechanisms of injury. At one month of life, cocaine-exposed neonates will be reexamined to determine which signs persist beyond intoxication and withdrawal and may represent an embryopathic effect. In addition, the incidence of delayed visual maturation will be determined and will be analyzed to see if its occurrence can be used as a marker for cocaine effects on the developing nervous system. The identification of these neonates who are cocaine exposed will allow the development of a cohort for longitudinal studies on the incidence and types of neurological complications seen. The ability to define these syndromes and recognize complications will enable us to understand better the mechanisms of ischemic injury to the developing central nervous system. The identification of clinical signs and symptoms in the neonatal period in cocaine-exposed babies will help determine which infants are at risk for developmental disabilities. With this information, clinical recommendations regarding followup care and assessment can be made more accurately.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory Grants (P20)
Project #
5P20NS032553-03
Application #
3738757
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kim, Young S; Honkaniemi, Jari; Sharp, Frank R et al. (2004) Expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in the brain during experimental group B streptococcal meningitis. Brain Res Mol Brain Res 128:95-102
Hajnal, Beatrice Latal; Ferriero, Donna M; Partridge, J Colin et al. (2004) Is exposure to cocaine or cigarette smoke during pregnancy associated with infant visual abnormalities? Dev Med Child Neurol 46:520-5
Loeffler, J M; Ringer, R; Hablutzel, M et al. (2001) The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis. J Infect Dis 183:247-252
Dempsey, D A; Hajnal, B L; Partridge, J C et al. (2000) Tone abnormalities are associated with maternal cigarette smoking during pregnancy in in utero cocaine-exposed infants. Pediatrics 106:79-85
Leib, S L; Leppert, D; Clements, J et al. (2000) Matrix metalloproteinases contribute to brain damage in experimental pneumococcal meningitis. Infect Immun 68:615-20
Auer, M; Pfister, L A; Leppert, D et al. (2000) Effects of clinically used antioxidants in experimental pneumococcal meningitis. J Infect Dis 182:347-50
Vexler, Z; Berrios, M; Ursell, P C et al. (1999) Toxicity of fructose-1,6-bisphosphate in developing normoxic rats. Pharmacol Toxicol 84:115-21
Bergeron, M; Evans, S M; Sharp, F R et al. (1999) Detection of hypoxic cells with the 2-nitroimidazole, EF5, correlates with early redox changes in rat brain after perinatal hypoxia-ischemia. Neuroscience 89:1357-66
Dugan, L L; Kim, J S; Zhang, Y et al. (1999) Differential effects of cAMP in neurons and astrocytes. Role of B-raf. J Biol Chem 274:25842-8
Hajnal, B L; Sahebkar-Moghaddam, F; Barnwell, A J et al. (1999) Early prediction of neurologic outcome after perinatal depression. Pediatr Neurol 21:788-93

Showing the most recent 10 out of 32 publications