Cerebrospinal fluid monoamine precursors and metabolites in human neonates following in utero cocaine exposure: a preliminary study.
BACKGROUND
Cocaine acts in the central nervous system by increasing dopamine release and inhibiting the reuptake of dopamine and other monoaminergic neurotransmitters. Prenatal cocaine exposure may cause neurochemical changes in developing monoaminergic neurons and might alter brain structure and function. No data have been published on central nervous system monoamine precursors and metabolites in human neonates exposed prenatally to cocaine.


METHODS
Cerebrospinal fluid (CSF) was obtained from neonates undergoing lumbar puncture to rule out infection. The CSF was analyzed for the neurotransmitter precursors and metabolites tryptophan, tyrosine, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and 5-hydroxyindoleacetic acid. Drug exposure was ascertained by medical record review and urine and meconium assays.


RESULTS
Eleven neonates were cocaine-exposed, based on positive meconium or urine assays for benzoylecgonine; 20 were unexposed, based on both negative history and assay. The exposed and unexposed groups did not differ significantly in gender, perinatal stress, clinical illness, or exposure to other illicit drugs, but did differ in mean gestational age, growth parameters, and exposure to cigarettes. Cocaine-exposed neonates had significantly lower levels of CSF homovanillic acid (mean 148.1 vs 218.5 ng/mL, P = .01). The magnitude of this difference was similar after correcting for each of four potential confounding factors, although no longer statistically significant in all cases (P values ranged from .044 to .17). No significant differences were observed for tyrosine, tryptophan, 5-hydroxyindoleacetic acid, or 3-methoxy-4-hydroxyphenylglycol.


CONCLUSIONS
These preliminary results suggest an association between prenatal cocaine exposure and decreased CSF homovanillic acid, the principal metabolite of dopamine. Prenatal cocaine exposure may result in changes in central dopaminergic systems in the human neonate.
Division of Developmental and Behavioral Pediatrics, Boston City Hospital, MA 02118.
R
R
Needlman
B
B
Zuckerman
G M
GM
Anderson
M
M
Mirochnick
D J
DJ
Cohen
D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001921:Brain / Q000187:drug effects; D016022:Case-Control Studies; D003042:Cocaine / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D007231:Infant, Newborn; D015999:Multivariate Analysis; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid