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Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
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antiretroviral drugs in Meconium detection for different gestational periods of exposure
The Journal of Pediatrics, 2015Co-Authors: Sarah K Himes, Katherine Tassiopoulos, Ram Yogev, Marilyn A HuestisAbstract:Objectives To determine whether antiretroviral (ARV) medications can be detected in Meconium from second or third trimester, labor and delivery (LD administration of these ARVs occurred between gestational weeks 25-28 in the positive samples. Days without lopinavir or tenofovir before delivery significantly correlated with decreasing concentrations of lopinavir and tenofovir in Meconium. Tenofovir and lamivudine concentrations significantly correlated with increasing gestational age among infants with continuous second and third trimester exposure. Zidovudine given during L&D or for neonatal prophylaxis was detected in 95.1% and 94.6% of Meconium samples, respectively. Conclusions Changes in ARV treatments during pregnancy offered a unique opportunity to investigate ARV detection in Meconium. ARVs in Meconium primarily reflect third trimester ARV exposures, although 6 of 107 second trimester only exposures were detected. Zidovudine administration during L&D was detected in Meconium indicating potential urine contamination or rapid incorporation into Meconium. These data will improve interpretation of Meconium drug test results.
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nicotine and metabolites in Meconium as evidence of maternal cigarette smoking during pregnancy and predictors of neonatal growth deficits
Nicotine & Tobacco Research, 2010Co-Authors: Teresa R Gray, Rina D Eiden, Kenneth E Leonard, Gerard J Connors, Shannon Shisler, Marilyn A HuestisAbstract:Introduction: Many women continue tobacco use during preg- nancy despite known adverse consequences on neonatal growth and development. Testing Meconium, the first neonatal feces, for tobacco biomarkers offers objective evidence of prenatal tobacco exposure. However, relationships between the amount, frequency, and timing of cigarette smoking during gestation and tobacco biomarker Meconium concentrations and neonatal outcomes are unclear. Methods: Eighty-seven pregnant women provided detailed self-reports of daily tobacco consumption throughout pregnancy. Nicotine, cotinine, and trans-3-hydroxycotinine were quanti- fied in neonatal Meconium by liquid chromatography-tandem mass spectrometry. Results: Among nonsmokers, all Meconium specimens were negative, whereas nearly all Meconium specimens were positive if the mother self-reported tobacco use into the third trimester. Tobacco biomarker concentrations were significantly albeit weakly correlated with mean cigarettes per day in the third trimester. Reduced birth weight, gestational age, or head cir- cumference were observed if Meconium contained one or more tobacco biomarkers, but deficits did not correlate with bio - marker concentrations. Conclusion: While previously thought to reflect second and third trimester drug exposure, Meconium appears to reliably identify only third trimester drug use. While a 10 ng/g nicotine, cotinine, or trans-3-hydroxycotinine cutoff in Meconium was previously proposed to differentiate tobacco-exposed from nonexposed or passively exposed neonates, improved maternal self-reporting techniques in this cohort suggest that a lower cutoff, equivalent to the analytic limits of quantification, is more appropriate.
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Meconium Nicotine and Metabolites by Liquid Chromatography–Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures
Clinical Chemistry, 2008Co-Authors: Teresa R Gray, Raquel Magri, Diaa M Shakleya, Marilyn A HuestisAbstract:Background: Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in Meconium is poorly characterized, and correlation of analytes’ concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans -3′-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in Meconium, identify the best biomarkers of in utero tobacco exposure, compare Meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration-outcome relationships. Methods: We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in Meconium from tobacco-exposed and nonexposed neonates by liquid chromatography-tandem mass spectrometry. We compared Meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. Results: Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant Meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine Meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite Meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference. Conclusions: Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in Meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal tobacco exposure.
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correlations of maternal buprenorphine dose buprenorphine and metabolite concentrations in Meconium with neonatal outcomes
Clinical Pharmacology & Therapeutics, 2008Co-Authors: S L Kacinko, Hendree E Jones, Rolley E Johnson, Robin E Choo, Marilyn A HuestisAbstract:For the first time, relationships among maternal buprenorphine dose, Meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in Meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted Meconium concentrations or neonatal outcomes. Total buprenorphine Meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the Meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive Meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the Meconium may predict the onset and frequency of NAS.
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quantification of nicotine cotinine trans 3 hydroxycotinine nornicotine and norcotinine in human Meconium by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2008Co-Authors: Teresa R Gray, Diaa M Shakleya, Marilyn A HuestisAbstract:Abstract There are no analytical methods that simultaneously quantify nicotine, cotinine, trans -3′-hydroxycotinine, nornicotine and norcotinine in human Meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose–Meconium concentration relationships exist, and whether nicotine Meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in Meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5–500 ng/g. Method applicability was evaluated with Meconium collected from an in utero tobacco exposed infant.
Teresa R Gray - One of the best experts on this subject based on the ideXlab platform.
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nicotine and metabolites in Meconium as evidence of maternal cigarette smoking during pregnancy and predictors of neonatal growth deficits
Nicotine & Tobacco Research, 2010Co-Authors: Teresa R Gray, Rina D Eiden, Kenneth E Leonard, Gerard J Connors, Shannon Shisler, Marilyn A HuestisAbstract:Introduction: Many women continue tobacco use during preg- nancy despite known adverse consequences on neonatal growth and development. Testing Meconium, the first neonatal feces, for tobacco biomarkers offers objective evidence of prenatal tobacco exposure. However, relationships between the amount, frequency, and timing of cigarette smoking during gestation and tobacco biomarker Meconium concentrations and neonatal outcomes are unclear. Methods: Eighty-seven pregnant women provided detailed self-reports of daily tobacco consumption throughout pregnancy. Nicotine, cotinine, and trans-3-hydroxycotinine were quanti- fied in neonatal Meconium by liquid chromatography-tandem mass spectrometry. Results: Among nonsmokers, all Meconium specimens were negative, whereas nearly all Meconium specimens were positive if the mother self-reported tobacco use into the third trimester. Tobacco biomarker concentrations were significantly albeit weakly correlated with mean cigarettes per day in the third trimester. Reduced birth weight, gestational age, or head cir- cumference were observed if Meconium contained one or more tobacco biomarkers, but deficits did not correlate with bio - marker concentrations. Conclusion: While previously thought to reflect second and third trimester drug exposure, Meconium appears to reliably identify only third trimester drug use. While a 10 ng/g nicotine, cotinine, or trans-3-hydroxycotinine cutoff in Meconium was previously proposed to differentiate tobacco-exposed from nonexposed or passively exposed neonates, improved maternal self-reporting techniques in this cohort suggest that a lower cutoff, equivalent to the analytic limits of quantification, is more appropriate.
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identification of prenatal amphetamines exposure by maternal interview and Meconium toxicology in the infant development environment and lifestyle ideal study
Therapeutic Drug Monitoring, 2009Co-Authors: Teresa R Gray, Linda L Lagasse, Lynne M Smith, Chris Derauf, Penny Grant, Rizwan Shah, Amelia M Arria, Sheri Della Grotta, Arthur Strauss, William HaningAbstract:The Infant Development Environment and Lifestyle study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or Meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration, and magnitude of maternal MAMP exposure affect qualitative and quantitative Meconium results. Interviews regarding maternal drug use were collected shortly after birth; Meconium specimens were screened for amphetamines, cannabis, and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry. The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) Meconium results were confirmed by gas chromatography mass spectrometry. Tobacco exposure was equally detected by immunoassay cotinine screening and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use or frequency or route of MAMP use. Maternal self-report was more sensitive than Meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence Meconium toxicology results. Most women stopped MAMP and cannabis use before the third trimester. In the first trimester, Meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in Meconium. Low confirmation rates in Meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers.
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Meconium Nicotine and Metabolites by Liquid Chromatography–Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures
Clinical Chemistry, 2008Co-Authors: Teresa R Gray, Raquel Magri, Diaa M Shakleya, Marilyn A HuestisAbstract:Background: Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in Meconium is poorly characterized, and correlation of analytes’ concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans -3′-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in Meconium, identify the best biomarkers of in utero tobacco exposure, compare Meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration-outcome relationships. Methods: We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in Meconium from tobacco-exposed and nonexposed neonates by liquid chromatography-tandem mass spectrometry. We compared Meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. Results: Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant Meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine Meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite Meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference. Conclusions: Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in Meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal tobacco exposure.
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quantification of nicotine cotinine trans 3 hydroxycotinine nornicotine and norcotinine in human Meconium by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2008Co-Authors: Teresa R Gray, Diaa M Shakleya, Marilyn A HuestisAbstract:Abstract There are no analytical methods that simultaneously quantify nicotine, cotinine, trans -3′-hydroxycotinine, nornicotine and norcotinine in human Meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose–Meconium concentration relationships exist, and whether nicotine Meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in Meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5–500 ng/g. Method applicability was evaluated with Meconium collected from an in utero tobacco exposed infant.
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Quantification of nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and norcotinine in human Meconium by liquid chromatography/tandem mass spectrometry.
Journal of Chromatography B, 2008Co-Authors: Teresa R Gray, Diaa M Shakleya, Marilyn A HuestisAbstract:Abstract There are no analytical methods that simultaneously quantify nicotine, cotinine, trans -3′-hydroxycotinine, nornicotine and norcotinine in human Meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose–Meconium concentration relationships exist, and whether nicotine Meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in Meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5–500 ng/g. Method applicability was evaluated with Meconium collected from an in utero tobacco exposed infant.
Jacob M Puliyel - One of the best experts on this subject based on the ideXlab platform.
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Lactate: creatinine ratio in babies with thin Meconium staining of amniotic fluid
BMC Pediatrics, 2006Co-Authors: Rishi Kant Ojha, Saroj K Singh, Sanjay Batra, V Sreenivas, Jacob M PuliyelAbstract:Background ACOG states Meconium stained amniotic fluid (MSAF) as one of the historical indicators of perinatal asphyxia. Thick Meconium along with other indicators is used to identify babies with severe intrapartum asphyxia. Lactate creatinine ratio (L: C ratio) of 0.64 or higher in first passed urine of babies suffering severe intrapartum asphyxia has been shown to predict Hypoxic Ischaemic Encephalopathy (HIE). Literature review shows that Meconium is passed in distress and thin Meconium results from mixing and dilution over time, which may be hours to days. Thin Meconium may thus be used as an indicator of antepartum asphyxia. We tested L: C ratios in a group of babies born through thin and thick Meconium, and for comparison, in a group of babies without Meconium at birth. Methods 86 consecutive newborns, 36 to 42 weeks of gestation, with Meconium staining of liquor, were recruited for the study. 52 voided urine within 6 hours of birth; of these 27 had thick Meconium and 25 had thin Meconium at birth. 42 others, who did not have Meconium or any other signs of asphyxia at birth provided controls. Lactate and creatinine levels in urine were tested by standard enzymatic methods in the three groups. Results Lactate values are highest in the thin MSAF group followed by the thick MSAF and controls. Creatinine was lowest in the thin MSAF, followed by thick MSAF and controls. Normal babies had an average L: C ratio of 0.13 (± 0.09). L: C ratio was more among thin MSAF babies (4.3 ± 11.94) than thick MSAF babies (0.35 ± 0.35). Median L: C ratio was also higher in the thin MSAF group. Variation in the values of these parameters is observed to be high in the thin MSAF group as compared to other groups. L: C ratio was above the cutoff of 0.64 of Huang et al in 40% of those with thin Meconium. 2 of these developed signs of HIE with convulsions (HIE Sarnat and Sarnat Stage II) during hospital stay. One had L: C Ratio of 93 and the other of 58.6. A smaller proportion (20%) of those with thick Meconium had levels above the cutoff and 2 developed HIE and convulsions with L: C ratio of 1.25 and 1.1 respectively. Conclusion In evolving a cutoff of L: C ratios that would be highly sensitive and specific (0.64), Huang et al studied it in a series of babies with severe intrapartum asphyxia. Our study shows that the specificity may not be as good if babies born through thin Meconium are also included. L: C ratios are much higher in babies with thin Meconium. It may be that Meconium alone is not a good indicator of asphyxia and the risk of HIE. However, if the presence of Meconium implies asphyxia then perhaps a higher cut-off than 0.64 is needed. L: C ratios should be tested in a larger sample that includes babies with thin Meconium, before L: C ratios can be applied universally.
Diaa M Shakleya - One of the best experts on this subject based on the ideXlab platform.
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Meconium Nicotine and Metabolites by Liquid Chromatography–Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures
Clinical Chemistry, 2008Co-Authors: Teresa R Gray, Raquel Magri, Diaa M Shakleya, Marilyn A HuestisAbstract:Background: Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in Meconium is poorly characterized, and correlation of analytes’ concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans -3′-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in Meconium, identify the best biomarkers of in utero tobacco exposure, compare Meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration-outcome relationships. Methods: We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in Meconium from tobacco-exposed and nonexposed neonates by liquid chromatography-tandem mass spectrometry. We compared Meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. Results: Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant Meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine Meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite Meconium results and neonatal outcomes, although presence of a nicotine biomarker predicted decreased head circumference. Conclusions: Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in Meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal tobacco exposure.
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quantification of nicotine cotinine trans 3 hydroxycotinine nornicotine and norcotinine in human Meconium by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2008Co-Authors: Teresa R Gray, Diaa M Shakleya, Marilyn A HuestisAbstract:Abstract There are no analytical methods that simultaneously quantify nicotine, cotinine, trans -3′-hydroxycotinine, nornicotine and norcotinine in human Meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose–Meconium concentration relationships exist, and whether nicotine Meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in Meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5–500 ng/g. Method applicability was evaluated with Meconium collected from an in utero tobacco exposed infant.
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Quantification of nicotine, cotinine, trans-3'-hydroxycotinine, nornicotine and norcotinine in human Meconium by liquid chromatography/tandem mass spectrometry.
Journal of Chromatography B, 2008Co-Authors: Teresa R Gray, Diaa M Shakleya, Marilyn A HuestisAbstract:Abstract There are no analytical methods that simultaneously quantify nicotine, cotinine, trans -3′-hydroxycotinine, nornicotine and norcotinine in human Meconium. Such a method could improve identification of in utero tobacco exposure, determine if maternal dose–Meconium concentration relationships exist, and whether nicotine Meconium concentrations predict neonatal outcomes. The first liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry method for simultaneous quantification of these analytes in Meconium was developed and validated. Specimen preparation included homogenization, enzyme hydrolysis and solid phase extraction. The linear range was 1.25 or 5–500 ng/g. Method applicability was evaluated with Meconium collected from an in utero tobacco exposed infant.
Robert D Christensen - One of the best experts on this subject based on the ideXlab platform.
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testing for fetal exposure to illicit drugs using umbilical cord tissue vs Meconium
Journal of Perinatology, 2006Co-Authors: D P Montgomery, C Plate, Stephen C Alder, Mary Jones, J Jones, Robert D ChristensenAbstract:We assessed the agreement of testing for fetal exposure to illicit drugs contrasting paired specimens of Meconium vs umbilical cord tissue. We obtained paired samples of Meconium and umbilical cord tissue from 118 pregnancies with high suspicion of illicit drug use by the mothers. Each specimen was tested for amphetamines, opiates, cocaine, cannabinoids, and phencyclidine using drug class-specific immunoassays. The agreement of drug screening results between cord and Meconium was above 90% for all drugs tested. Meconium identified 21 cases as positive for amphetamines. The paired cord identified 20 of these, and in addition identified three other positives that the Meconium labeled as negative. Gas chromatography–mass spectrometry confirmed these three cord samples as methamphetamine positive. Meconium identified 97 samples that were negative for amphetamines, while the cord identified 94 of these as negative but three as positive. Agreement of cord with Meconium for amphetamines was 96.6%. The concordance for opiates was 94.9%, for cocaine was 99.2%, and for cannabinoids was 90.7%. Umbilical cord tissue performs as well as Meconium in assessing fetal drug exposure to amphetamines, opiates, cocaine, and cannabinoids. Results of studies using the cord may have a more rapid return to the clinician, because waiting for Meconium to be passed sometimes requires several days. Moreover, in some cases the Meconium is passed in utero making collection impossible, whereas cord should always be available for drug testing.
