morphine and benzoylecgonine

Cocaine use during pregnancy is difficult to ascertain, and maternal reports are likely to be inaccurate. Presently, the dose-response characteristics between maternal cocaine use and fetal exposure and adverse effects are unknown. Clinically, some babies are harmed, whereas others are not adversely affected. Taking advantage of the fact that cocaine and its metabolite benzoylecgonine (BE) accumulate and can be detected months after exposure in maternal and neonatal hair, an analytical test for cocaine and BE was developed by the authors. The aim of this study was to describe the characteristics of maternal and neonatal hair cocaine as biomarkers of fetal exposure. Of nearly 10,000 cases, all mother-child pairs in whom at least one had cocaine and/or BE detected in hair were identified. The relationship between maternal and neonatal levels was studied. When available, these data were also compared with meconium levels of cocaine. Median cocaine concentration was 10-fold higher in hair of the mothers compared with the neonates (3.56 ng/mg vs 0.31 ng/mg of hair). Infants' cocaine in hair was positively correlated with maternal cocaine and BE in hair (r2 = 0.41 and r2 = 0.22, respectively, P < 0.001 for both correlations). Infants' BE was also correlated with maternal cocaine and BE concentrations in hair (r2 = 0.50 and r2 = 0.27, P < 0.001 for both correlations). Thirty-nine (40%) babies had negative cocaine and BE results despite their mothers being positive. Mothers whose infants were cocaine-positive had a median hair cocaine concentration of 7.34 ng/mg, significantly higher than those whose infants were negative (1.25 ng/mg). Maternal cocaine levels below 0.24 ng/mg may serve as a relative threshold for detectable fetal exposure during the third trimester of pregnancy. Fetal hair grows in the last trimester. Hence, a positive neonatal hair indicates maternal use after pregnancy became known, a strong indicator of maternal addiction. Transplacental exposure to cocaine of babies of addicted mothers is highly variable. The dose-response relationship of both cocaine and BE between maternal and neonatal hair suggests that the placenta protects some fetuses but not others. More research is needed to understand the mechanisms leading to placental defense against cocaine.

Topics: Cocaine; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Female; Hair; Humans; Infant; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Pregnancy; Substance Abuse Detection; Time Factors

The objective of this study was to examine the effects of prenatal cocaine and polydrug exposure on language development of preschool children using a prospective longitudinal model, controlling for confounders.. Children who were exposed to cocaine in utero (n = 209) and nonexposed children (n = 189) were followed prospectively at birth and at 1, 2, 4, and 6 years of age and were compared on receptive, expressive, and total language scores across time using random coefficient models, controlling for confounders.. A significant, stable effect of cocaine exposure on language development was observed over time for all language domains, with cocaine exposure related to poorer language performance. Cigarette exposure was related to lower receptive language scores. Environmental influences on language scores were also observed. Both the cocaine-exposed and nonexposed children declined in language performance over time.. Prenatal cocaine exposure has a stable negative effect on language skills during the first 6 years of life. Both cocaine-exposed and nonexposed children showed decreased language growth over time; however, cocaine-exposed children demonstrated linguistic deficits compared with nonexposed peers and did not catch up. Cigarette and environmental influences were also noted.

Topics: Adult; Child; Child, Preschool; Cocaine; Cocaine-Related Disorders; Female; Humans; Infant; Language Development; Language Development Disorders; Longitudinal Studies; Meconium; Pregnancy; Prenatal Exposure Delayed Effects; Smoking

To assess whether there is an association of level of fetal cocaine exposure to developmental precursors of speech-language skills at 1 year of age, after controlling for confounding factors.. In a prospective, longitudinal, quasi-experimental, matched cohort design, 3 cocaine exposure groups were defined by maternal self-report and infant meconium assay: nonexposure (n = 131), heavier exposure (n = 66), >the 75th percentile for maternal self-report and >the 70th percentile of benzoylecgonine concentration, and all others as lighter exposure (n = 68). At 1 year of age, the Preschool Language Scale-3 was administered by examiners unaware of infant drug status.. Independent of confounding drug, medical, and environmental factors, more heavily exposed infants had lower auditory comprehension scores than nonexposed infants and lower total language scores than lighter and nonexposed infants. More heavily exposed infants were also more likely to be classified as mildly delayed by total language score than nonexposed infants. There were positive linear relationships between the concentration of benzoylecgonine in meconium and all outcomes and between maternal report of severity of prenatal cocaine use with poorer auditory comprehension indicating a relationship between amount of exposure and poorer outcomes.. This study documents significant behavioral teratogenic effects of fetal cocaine exposure on attentional abilities underlying auditory comprehension skills considered to be precursors of receptive language. Pediatricians are in a unique position to monitor early development of cocaine-exposed infants and make timely referrals for intervention.

Topics: Analysis of Variance; Cocaine; Cocaine-Related Disorders; Female; Humans; Infant; Infant, Newborn; Language Development Disorders; Language Tests; Longitudinal Studies; Male; Meconium; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Regression Analysis; Statistics, Nonparametric

Recently, meta-hydroxybenzoylecgonine (m-OH BE) was identified by gas chromatography-mass spectroscopy during quantitative analysis for cocaine. Identification of m-OH BE in addition to the routinely identified benzoylecgonine by gas chromatography-mass spectroscopy confirmatory assays may increase detection of cocaine-exposed infants and decrease false negative results. However, it is not known whether m-OH BE is derived directly from benzoylecgonine or from hydroxylated cocaine, or whether this metabolite is produced in the fetus or transferred across the placenta from the maternal circulation. We quantitated the recovery of cocaine, benzoylecgonine, and m-OH BE from amniotic fluid, fetal meconium, fetal intestine, and maternal urine for up to 4 days after single dose administration of either cocaine or benzoylecgonine to pregnant time-bred guinea pigs. m-OH BE was recovered from meconium after maternal injections of cocaine and benzoylecgonine. There was no significant detection of m-OH BE from amniotic fluid or intestine and minimal recovery from maternal urine after either cocaine or benzoylecgonine administration. Detection of m-OH BE in meconium increased the identification of in utero exposed guinea pigs, and the greatest yield of m-OH BE from meconium occurred later than that observed for cocaine or benzoylecgonine.

Topics: Amniotic Fluid; Animals; Cocaine; Female; Fetus; Gas Chromatography-Mass Spectrometry; Guinea Pigs; Intestinal Mucosa; Intestines; Maternal-Fetal Exchange; Meconium; Metabolic Clearance Rate; Pregnancy; Tissue Distribution

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.. 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.. 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 weight z 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).. 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.

Topics: Cocaine; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Echoencephalography; Female; Fetus; Humans; Infant, Newborn; Intracranial Hemorrhages; Longitudinal Studies; Meconium; Odds Ratio; Pregnancy; Pregnancy Complications; Prospective Studies; Risk Factors

Topics: Amniotic Fluid; Case-Control Studies; Cocaine; Female; Gastric Juice; Humans; Infant, Newborn; Meconium; Neonatal Screening; Pregnancy; Pregnancy Complications; Substance Abuse Detection; Substance-Related Disorders; Urinalysis

Among 95 term infants with benzoylecgonine, the cocaine metabolite, detectable in their meconium, there was an inverse relation between the concentration of benzoylecgonine and birth weight, length, and head circumference. Multiple regression analysis confirmed these relations after controlling for gestational age and maternal use of marijuana, cigarettes, and alcohol. These data suggest a dose-response relation between the magnitude of prenatal cocaine exposure and impaired fetal growth.

Topics: Birth Weight; Cocaine; Embryonic and Fetal Development; Female; Humans; Infant, Newborn; Linear Models; Meconium; Pregnancy; Prenatal Exposure Delayed Effects

When blood or urine is unavailable, postmortem meconium or stool from infants or stillbirths can be used to detect drugs-of-abuse, thus providing datum in assessing drug-abuse exposure. Two case reports illustrate how drugs-of-abuse findings in post-mortem specimens were used to substantiate exposure prior to death or a history of maternal drug abuse. The first, a congenital hydrocephalus, born to a non-drug abusing mother, expired at the age of 41 days, had opiates in the stool by screening method, enzyme multiplied immunoassay technique, confirmed by gas chromatographic/mass spectrometric (GC/MS) analysis. Investigation revealed that morphine had been administered for three days prior to death. The second was a stillbirth infant born to a drug abuser. Almost equal amounts of benzoylecgonine were found in different bowel segments, a finding consistent with admitted cocaine use throughout pregnancy.

Topics: Adult; Cocaine; Feces; Female; Fetal Death; Humans; Hydrocephalus; Infant; Infant, Newborn; Male; Meconium; Morphine; Pregnancy; Substance-Related Disorders

Our objective was to investigate the methodologic detection of cocaine abuse during pregnancy by determining the viability of meconium analysis for cocaine and its metabolites using chromatographic procedures as an alternative to urine testing using enzyme multiplied immunoassay technique. Our design was as follows: meconium and urine were taken from 106 very low birthweight premature babies. Meconium analysis for cocaine and its metabolites using extraction and chromatographic analysis was compared with the criterion standard immunoassay testing for urine. The work was carried out at The University of Chicago Hospital, Department of Pediatrics and the University of Illinois at Chicago, Department of Pharmacodynamics. Our patients were very low birthweight, premature babies (mean birthweight 1109 g; mean gestational age 29.1 weeks). Gender was evenly divided between male and female. The outcome measures were as follows: two active metabolites, norcocaine and cocaethylene, were detected in the meconium, but not in the urine, of some of the neonates. Determination of cocaine exposure in the newborn influenced assignment of babies in research studies as well as psychosocial evaluation and subsequent treatment of the neonate. Our results were: of the 106 meconium samples analyzed, 21 (19.8%) were positive for cocaine (n = 19, 0.24-0.78 mg/kg), norcocaine (n = 7, 0.10-0.56 mg/kg), cocaethylene (n = 1, 0.12 mg/kg) or combinations thereof. Benzoylecgonine was not detected in any of the samples. Of the urine samples analyzed by immunoassay, only 8 (7.5%) were positive for cocaine metabolites. We conclude that meconium is a better sample than urine for determining cocaine exposure in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chromatography, High Pressure Liquid; Cocaine; Dopamine Uptake Inhibitors; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Infant, Premature; Male; Meconium; Pregnancy; Pregnancy Complications; Prospective Studies; Substance Abuse Detection; Urine

We report a case of lack of fetal exposure to cocaine and benzoylecgonine as evidenced by meconium and hair analysis, but exposure to nicotine and its metabolite cotinine, after extensive maternal use of cocaine and nicotine. These data suggest that the mode of maternal use of cocaine and individual differences in placental handling of the drug may protect some fetuses, and highlight the need to address interpatient variability.

Topics: Adult; Cocaine; Cotinine; Female; Hair; Humans; Infant, Newborn; Meconium; Mothers; Narcotics; Nicotine; Placenta; Pregnancy; Smoking; Substance Abuse, Intravenous

Cocaethylene, a metabolite of cocaine and ethanol, exhibits cardiac and neurobehavioral effects. In order to determine the prevalence of this compound in meconium specimens, samples which gave a positive result for benzoylecgonine using fluorescence polarization immunoassay were analyzed by gas chromatography/mass spectrometry for cocaine, cocaethylene and benzoylecgonine. Deuterated cocaine, cocaethylene and benzoylecgonine were used as internal standards. Gas chromatography/mass spectrometry cutoff concentrations of 5.0 ng/g were utilized for all analytes. Of the 361 specimens which consecutively confirmed positive for cocaine or benzoylecgonine, 114 (31.6%) tested positive for cocaethylene. Further, cocaethylene accumulates in greater concentrations in meconium than urine, and is a useful analyte for identifying fetal alcohol exposure.

Topics: Cocaine; Cross Reactions; Fluorescence Polarization Immunoassay; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Meconium

In mothers who had no prenatal care and in their newborns, the presence of cocaine and benzoylecgonine (BE) was determined in urine, hair, and meconium. Samples of urine and hair were obtained from pregnant women who entered the hospital for delivery. Cocaine usage was assessed by a urinary enzyme-multiplied immunoassay technique (EMIT) and by gas chromatography-mass spectrometry (GC-MS). GC-MS was used to detect the presence of cocaine and BE in maternal urine and hair and in meconium and hair obtained from their newborns. In this study of 40 women, the EMIT assay for urinary BE identified 17 (42.5%) of the women as having used cocaine. Of these 17 women, all of their newborns were exposed to cocaine during gestation, based on the analysis of neonatal hair and meconium for cocaine or BE. From the maternal samples that were assayed for cocaine and BE by GC-MS, it appears that hair analysis identified the most cocaine users (70%) of the 40 women who participated in the study. When GC-MS was used to analyze the various samples from mothers and their newborns, 80% of the neonates showed exposure to cocaine. This study shows that women with no prenatal care who have a positive urinary drug screen by EMIT for BE have exposed their newborns to cocaine. The data from pregnant women with a negative drug screen for BE show that 52.2% of their newborns had prior fetal exposure to cocaine.

Topics: Cocaine; Enzyme Multiplied Immunoassay Technique; Female; Gas Chromatography-Mass Spectrometry; Hair; Humans; Infant, Newborn; Maternal-Fetal Exchange; Meconium; Pregnancy; Pregnancy Complications; Substance Abuse Detection

Cocaine and metabolites can be found in the amniotic fluid after maternal use, presumably as a result of fetal urination. The fetus may be repeatedly exposed to the effects of these drugs through contact with amniotic fluid that contains these substances. The purpose of this study was to determine whether the naive fetal lamb generates detectable fetal blood levels of cocaine and metabolites when cocaine is placed directly into the amniotic fluid and, if so, whether fetal swallowing accounts for these findings.. Six pregnant ewes with singleton fetuses of 120 to 125 days' gestation were chronically catheterized for daily sampling of cocaine and metabolite levels in maternal venous plasma, fetal venous plasma, and amniotic fluid over a 7-day period. Esophageal ligation was performed in three additional animals similarly instrumented to evaluate the role of fetal swallowing in the distribution of amniotic fluid cocaine and its metabolites. In each case, at the time of surgery, an Alzet osmotic pump delivering cocaine at 0.5 mg/kg estimated fetal weight per hour into the amniotic fluid was secured to the fetal back. Cocaine and metabolites (benzoylecgonine, ecgonine methyl ester, and norcocaine) were measured daily in material and fetal plasma, amniotic fluid, and meconium by solid-phase extraction and derivatization and quantified by high-performance gas chromatographic techniques.. The concentrations of ecgonine methyl ester were highest in the amniotic fluid followed by cocaine and benzoylecgonine. In the normal and esophagus-ligated groups, cocaine, benzoylecgonine, and norcocaine were found in fetal plasma in concentrations of approximately 3% that of amniotic fluid. Ecgonine methyl ester was not detected in fetal plasma from either group. Meconium samples from sheep with and without esophageal ligation demonstrated high levels of norcocaine.. We conclude that cocaine and metabolites in amniotic fluid enter the fetal circulation to produce detectable plasma levels through routes other than swallowing. Moreover, the results of meconium analyses in the two groups of fetuses suggest that fetal swallowing is not the primary mechanism by which cocaine and metabolites enter the intestine.

Topics: Absorption; Amniotic Fluid; Animals; Cocaine; Deglutition; Female; Fetal Blood; Fetus; Meconium; Pregnancy; Sheep

A large scale drug screening study was done to determine the prevalence of drug use in a large metropolitan, obstetric population. Meconium and first voided urine, as well as maternal urine were collected from 423 consecutive deliveries. Urine samples and methanolic extracts of meconium were initially screened by Enzyme Multiplied Immunoassay Technique (EMIT) and then confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Analysis of cocaine metabolite as benzoylecogonine, cannabinoid as carboxy-THC, codeine, morphine and methadone were included in the study. The positive rate for benzoylecgonine was virtually identical for meconium, maternal urine and neonatal urine (12%). Analysis of meconium was found to be more reliable than analysis of maternal or neonatal urine for the detection of benzoylecgonine. Meconium did not appear to offer an advantage over maternal or neonatal urine for detection of cannabinoid, codeine, morphine, or methadone.

Topics: Adult; Cocaine; Dronabinol; Female; Gas Chromatography-Mass Spectrometry; Humans; Illicit Drugs; Immunoassay; Infant, Newborn; Meconium; Methadone; Narcotics; New York City; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prevalence; Reproducibility of Results; Substance Abuse Detection; Substance-Related Disorders

Meconium has been reported to be a more suitable specimen than maternal or neonatal urine for detecting fetal exposure to cocaine. In a study comparing various immunoassays with gas chromatography/mass spectrometry (GC/MS), several unexplained discrepancies among the assays were noted. Using methanol extracts of meconium samples, an immunoreactive spot that was more polar than benzoylecgonine was detected by thin-layer chromatography (TLC). An extract of this spot analyzed by GC/MS yielded a fragmentation pattern indicative of an aryl hydroxylated benzoylecgonine. Standards of m-hydroxybenzoylecgonine, o-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine were synthesized; it was determined that m-hydroxybenzoylecgonine had the same retention time and ion ratios as the TLC immunoreactive spot. Furthermore, m-hydroxybenzoylecgonine proved to be immunoreactive. Ten meconium samples immunoreactive for benzoylecgonine were analyzed by GC/MS. Results before and after hydrolysis with beta-glucuronidase (type IX) showed free m-hydroxybenzoylecgonine comprising 59 to 94% of the total m-hydroxybenzoylecgonine and showed total m-hydroxybenzoylecgonine values ranging from 0.2 to 6.3 times as high as benzoylecgonine. Therefore, m-hydroxybenzoylecgonine appears to be a quantitatively important cocaine metabolite in meconium, which is responsible for a significant portion of the discrepancy between benzoylecgonine concentrations in meconium extracts as measured by immunoassay and GC/MS.

Topics: Artifacts; Cocaine; Humans; Immunoassay; Meconium

A selective solid-phase extraction technique has been applied to the analysis of cocaine and selected cocaine metabolites in meconium, whole blood, and plasma. This technique uses a mixed-mode Bond Elut Certify column that utilizes the characteristics of hydrophobic and polar interactions and ion exchange chromatography. Following extraction, cocaine, ecgonine methyl ester, benzoylecgonine, and cocaethylene were identified and quantitated using GC/MS. Linear quantitative response curves have been generated for the metabolites over a concentration range of 0-1000 ng/g for meconium and 0-1000 ng/mL for whole blood and plasma. The overall extraction efficiencies, depending on the metabolite, were between 58.1 and 99.7% for meconium, 95.6 and 124.0% for blood, and 86.9 and 128.9% for plasma. Linear regression analyses of the standard curve for the four analytes exhibited correlation coefficients ranging from 0.850 to 0.946 for meconium, 0.939 to 0.993 for whole blood, and 0.981 to 0.996 for plasma. Because of its capability to detect cocaethylene in meconium, blood, and plasma, the procedure can be used to determine if drug exposure occurred during the latter stages of gestation and if it involved only cocaine or a combination of cocaine and ethanol.

Topics: Cocaine; Female; Gas Chromatography-Mass Spectrometry; Humans; Infant, Newborn; Meconium; Pregnancy; Prenatal Exposure Delayed Effects; Time Factors

A method for simultaneous extraction of cocaine and metabolites benzoylnorecgonine, benzoylecgonine and norcocaine from meconium was developed. The procedure uses solid-phase extraction columns with both cation-exchange and hydrophobic properties after vortex-mixing meconium with methanol. Chromatography utilizes reversed-phase high-performance liquid chromatography with a C18 column and phosphate buffer-acetonitrile as mobile phase. The method is specific and sensitive to 50 ng/g meconium for all compounds. Standard curves are linear from 0.05 to 5.0 micrograms/g (r2 > or = 0.989). Intra-assay coefficients of variation were < or = 6.9%. Meconium from infants exposed to cocaine in utero contained varying combinations of the four drugs.

Topics: Chromatography, High Pressure Liquid; Cocaine; Female; Humans; Infant, Newborn; Meconium; Pregnancy; Substance-Related Disorders

We determined the prevalence of prenatal cocaine use in a racially mixed sample of urban and suburban mothers and correlated its use with maternal demographics and newborn measurements.. Meconium from 621 consecutive newborns delivered at two university-affiliated urban hospitals were assayed for benzoylecgonine. Maternal and infant characteristics were linked anonymously with the results. Statistical analysis included t test, Fisher's exact test, Duncan's multiple range analysis, and analysis of covariance, with a value of p < 0.05 considered significant.. We found that 3.4% of meconium samples had benzoylecgonine levels exceeding 0.1 micrograms/ml. Its presence was statistically correlated with maternal and neonatal characteristics. A nurse's opinion of cocaine use was correct 22% of the time.. Prenatal cocaine use was statistically associated with multiparity, multigravidity, late-onset and clinic-based prenatal care, public assistance, nonwhite race, and low academic achievement. A nurse's opinion was a poor predictor of maternal cocaine use. Cocaine-exposed infants were significantly smaller, and this correlated best with nonwhite background.

Topics: Birth Weight; Cocaine; Female; Humans; Infant, Newborn; Meconium; Nurses; Pregnancy; Pregnancy Complications; Prenatal Care; Prevalence; Sensitivity and Specificity; Substance Abuse Detection; Substance-Related Disorders; Suburban Population; Urban Population

This study endeavored to determine the incidence of intrauterine cocaine exposure in a socioeconomically mixed suburban setting. It also assessed the effectiveness of an anonymous questionnaire in eliciting information on maternal use of illicit drugs during pregnancy. Meconium was collected from 500 consecutively born infants and analyzed for the presence of cocaine and its metabolites. An anonymous two-page questionnaire also was distributed to all postpartum mothers. Of the infants' mothers, (73.2%) were covered by some form of insurance (private), whereas 26.8% either had no insurance or were covered by Medicaid (clinic). Fifty-nine (11.8%) babies tested positive for cocaine. The meconium of 6.3% of the babies whose mothers had private insurance tested positive, while the meconium of 26.9% of the babies whose mothers had Medicaid or no insurance tested positive. 316 (63.2%) of the mothers returned a questionnaire. 73% had private insurance and 27% were covered by Medicaid (clinic). Only five mothers with no insurance or covered by Medicaid admitted using cocaine. It appears that neonatal exposure to cocaine may be an even greater problem than previously imagined, particularly in the private population. In addition, anonymous maternal self-reporting forms probably will not be helpful in identifying infants at risk for illicit exposure to drugs.

Topics: Cocaine; Female; Fetus; Humans; Maternal-Fetal Exchange; Meconium; Pregnancy; Pregnancy Complications; Socioeconomic Factors; Substance-Related Disorders; Suburban Population; Surveys and Questionnaires