Objective. To assess whether there is an association between the level of in utero cocaine exposure and findings on neonatal cranial ultrasound, controlling for potentially confounding variables. Study Design. In a prospective longitudinal study, three cocaine exposure groups were defined by maternal report and infant meconium assay: unexposed, heavier cocaine exposure (>75th percentile self-reported days of use or of meconium benzoylecogonine concentration) or lighter cocaine exposure (all others). Neonatal ultrasounds from 241 well, term infants were read by a single radiologist who was masked to the exposure group. Results. Infants with lighter cocaine exposure did not differ from the unexposed infants on any ultrasound findings. After controlling for infant gender, gestational age, and birth weightz scores and for maternal parity, blood pressure in labor, ethnicity, and use of cigarettes, alcohol, and marijuana during pregnancy, the more heavily cocaine-exposed infants were more likely than the unexposed infants to show subependymal hemorrhage in the caudothalamic groove (covariate adjusted odds ratio: 3.88; 95% confidence interval: 1.45, 10.35). Conclusions. This is the first study to demonstrate that ultrasound findings suggestive of vascular injury to the neonatal central nervous system are related to the level of prenatal cocaine exposure. Inconsistency in previous research in identifying an association between prenatal cocaine exposure and neonatal cranial ultrasound findings may reflect failure to consider dose effects.
Objective. To compare plasma catecholamine concentrations between cocaine-exposed and unexposed term newborns and to determine the relationship between plasma catecholamines and newborn behavior. Methods. Forty-six newborn infants participating in a prospective study of the neonatal and long-term effects of prenatal cocaine exposure were studied. Based on maternal self-report, maternal urine screening, and infant meconium analysis, 24 infants were classified as cocaine-exposed and 22 as unexposed. Between 24 and 72 hours postpartum, plasma samples for norepinephrine (NE), epinephrine, dopamine, and dihydroxyphenylalanine analysis were obtained. The Neonatal Behavioral Assessment Scale was administered at 1 to 3 days of age and at 2 weeks of age by examiners masked to the drug exposure status of the newborns. Results. The cocaine-exposed newborns had increased plasma NE concentrations when compared to the unexposed infants (geometric mean, 923 pg/mL vs 667 pg/mL). There were no significant differences in plasma epinephrine, dopamine, or dihydroxyphenylalanine concentrations. Analysis for the effect of potential confounding variables revealed that maternal marijuana use was also associated with increased plasma NE, although birth weight, gender, and maternal use of alcohol or cigarettes were not. Geometric mean plasma NE was 1164 pg/mL in those infants with in utero exposure to both cocaine and marijuana compared to 812 pg/mL in those exposed to only cocaine and 667 pg/mL in those exposed to neither. Among the cocaine-exposed infants, plasma NE concentration correlated with an increased score for the depressed cluster (r = .53) and a decreased score for the orientation cluster (r = −.43) of the Neonatal Behavioral Assessment Scale administered at 1 to 3 days of age. Adjusting for marijuana exposure had no effect on these relationships between plasma NE and the depressed and orientation clusters. Conclusion. Plasma NE is increased in newborns exposed to cocaine and marijuana. Increased plasma NE is associated with selected neurobehavioral disturbances among cocaine exposed infants at 1 to 3 days of life but not at 2 weeks.
Objective. To determine in a representative sample of full-term urban newborns of English-speaking mothers whether an immediate or late dose-response effect could be demonstrated between prenatal cocaine exposure and newborn neurobehavioral performance, controlling for confounding factors. Methods. The Neonatal Behavioral Assessment Scale (NBAS) was administered by masked examiners to a total sample of 251 clinically healthy, full-term infants at 2 days and/or 17 days. Three in utero cocaine exposure groups were defined: heavily exposed (n = 44, >75th percentile self-reported days of use during pregnancy and/or >75th percentile of meconium benzoylecognine concentration); lightly exposed (n = 79, less than both 75th percentiles); and unexposed (n = 101, no positive biological or self-report marker). At the 3-week examination there were 38 heavily exposed, 73 lightly exposed, and 94 unexposed infants. Controlling for infant birth weight, gestational age, infant age at the time of examination, mothers' age, perinatal risk, obstetric medication, and alcohol, marijuana, and cigarette use, a regression analysis evaluated the effects of levels of cocaine exposure on NBAS performance. Results. No neurobehavioral effects of exposure on the newborn NBAS cluster scores or on the qualifier scores were found when confounders were controlled for at 2 to 3 days of age. At 3 weeks, after controlling for covariates, a significant dose effect was observed, with heavily exposed infants showing poorer state regulation and greater excitability. Conclusions. These findings demonstrate specific dose-related effects of cocaine on 3-week neurobehavioral performance, particularly for the regulation of arousal, which was not observed in the first few days of life.
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.
Twenty newborns, 12 with prenatal exposure to cocaine and an unexposed control group of 8, were studied to determine concentrations of circulating catecholamines and their relationship to newborn behavior. Birth weight of the cocaine-exposed neonates was significantly lower than that of the control group. Gestational age, length, and head circumference of the cocaine-exposed neonates were also lower, although the differences did not reach statistical significance. Between 24 and 48 hours of age, circulating concentrations of norepinephrine, dopamine, and the catecholamine precursor dihydroxyphenylalanine were measured and behavior was assessed using the Neonatal Behavioral Assessment Scale. Mean dihydroxyphenylalanine concentrations were increased in the cocaine-exposed newborns (10.3 ng/mL vs 5.9 ng/mL, P = .055), while there was no difference between the groups in mean norepinephrine or dopamine concentrations. There was a significant negative correlation between norepinephrine concentration and orientation cluster score for the cocaine-exposed newborns (rp2 .6979,P .005). Norepinephrine concentration did not correlate with the score for any other behavioral cluster, nor did dopamine or dihydroxyphenylalanine concentration correlate with the score for any cluster. These preliminary data from a pilot study suggest that catecholamine activity is increased in cocaine-exposed newborns and may play a role in neurobehavioral disturbances associated with prenatal exposure to this drug.