Needlman R, Zuckerman B, Anderson G M, Mirochnick M, Cohen D J
Division of Developmental and Behavioral Pediatrics, Boston City Hospital, MA 02118.
Pediatrics. 1993 Jul;92(1):55-60.
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.
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.
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.
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.
可卡因通过增加多巴胺释放并抑制多巴胺及其他单胺能神经递质的再摄取，作用于中枢神经系统。产前接触可卡因可能导致发育中的单胺能神经元发生神经化学变化，并可能改变脑结构和功能。关于产前接触可卡因的人类新生儿中枢神经系统单胺前体和代谢物，尚无数据发表。
从接受腰椎穿刺以排除感染的新生儿获取脑脊液（CSF）。分析脑脊液中的神经递质前体和代谢物色氨酸、酪氨酸、3-甲氧基-4-羟基苯乙二醇、高香草酸和5-羟基吲哚乙酸。通过病历审查以及尿液和胎粪检测确定药物暴露情况。
根据胎粪或尿液中苯甲酰爱康宁检测呈阳性，确定11名新生儿接触过可卡因；根据病史和检测均为阴性，确定20名新生儿未接触过可卡因。暴露组和未暴露组在性别、围产期应激、临床疾病或接触其他非法药物方面无显著差异，但在平均胎龄、生长参数和接触香烟方面存在差异。接触可卡因的新生儿脑脊液中高香草酸水平显著较低（平均148.1对218.5 ng/mL，P = 0.01）。在校正四个潜在混杂因素中的每一个因素后，这种差异的幅度相似，尽管在所有情况下不再具有统计学显著性（P值范围为0.044至0.17）。酪氨酸、色氨酸、5-羟基吲哚乙酸或3-甲氧基-4-羟基苯乙二醇未观察到显著差异。
这些初步结果表明产前接触可卡因与脑脊液中多巴胺的主要代谢物高香草酸水平降低之间存在关联。产前接触可卡因可能导致人类新生儿中枢多巴胺能系统发生变化。
