Assessment of biological matrices for the detection of in utero cannabis exposure
Marta Concheiro
John Jay College of Criminal Justice, City University of New York, New York, NY, USA
Search for more papers by this authorFrank Martin Gutierrez
John Jay College of Criminal Justice, City University of New York, New York, NY, USA
Search for more papers by this authorAlejandro Ocampo
John Jay College of Criminal Justice, City University of New York, New York, NY, USA
Search for more papers by this authorElena Lendoiro
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorEva González-Colmenero
Sección de Neonatología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
Search for more papers by this authorAna Concheiro-Guisán
Sección de Neonatología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
Search for more papers by this authorPatricia Peñas-Silva
Sección de Ginecología y Obstetricia, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorManuel Macías-Cortiña
Sección de Ginecología y Obstetricia, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorAngelines Cruz-Landeira
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorManuel López-Rivadulla
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorCorresponding Author
Ana de-Castro-Ríos
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Correspondence
Ana de-Castro-Ríos, Toxicology Service, Institute of Forensic Sciences, Faculty of Medicina, Universidade de Santiago de Compostela C/San Francisco s/n, Santiago de Compostela 15782, Spain.
Email: [email protected]
Search for more papers by this authorMarta Concheiro
John Jay College of Criminal Justice, City University of New York, New York, NY, USA
Search for more papers by this authorFrank Martin Gutierrez
John Jay College of Criminal Justice, City University of New York, New York, NY, USA
Search for more papers by this authorAlejandro Ocampo
John Jay College of Criminal Justice, City University of New York, New York, NY, USA
Search for more papers by this authorElena Lendoiro
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorEva González-Colmenero
Sección de Neonatología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
Search for more papers by this authorAna Concheiro-Guisán
Sección de Neonatología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
Search for more papers by this authorPatricia Peñas-Silva
Sección de Ginecología y Obstetricia, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorManuel Macías-Cortiña
Sección de Ginecología y Obstetricia, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorAngelines Cruz-Landeira
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorManuel López-Rivadulla
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Search for more papers by this authorCorresponding Author
Ana de-Castro-Ríos
Sección de Toxicología, Instituto de Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Correspondence
Ana de-Castro-Ríos, Toxicology Service, Institute of Forensic Sciences, Faculty of Medicina, Universidade de Santiago de Compostela C/San Francisco s/n, Santiago de Compostela 15782, Spain.
Email: [email protected]
Search for more papers by this authorFunding information: Plan Nacional Sobre Drogas, Ministerio de Sanidad, Servicios Sociales e Igualdad, Gobierno de España, Grant/Award Number: 2016I005; Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, Grant/Award Number: ED481D-2019/025
Abstract
Cannabis consumption has been increasing worldwide among pregnant women. Due to the negative effects of prenatal cannabis exposure, it is necessary to develop an objective, sensitive, and specific method to determine cannabinoids use during pregnancy. In this study, we compared four different biological samples, maternal hair, meconium, umbilical cord, and placenta, for the detection of in utero cannabis exposure. The biological samples were collected from 627 mother–newborn dyads. All hair and meconium samples were analyzed, and umbilical cord and placenta if hair and/or meconium were positive for cannabinoids. Meconium and hair showed to complement each other, with an agreement between hair and meconium results of 96.7% but only 34.3% if just positive results were considered. Umbilical cord and placenta results showed a better agreement with meconium (91.3% and 92.6%, respectively) than with hair (39.1% and 34.6%, respectively). The predominant metabolites in meconium were 11-nor-carboxy-THC (THCCOOH) and 8,11-dihydroxy-THC (diOHTHC), and in umbilical cord and placenta was THCCOOH-glucuronide. Cannabidiol (CBD) and cannabinol (CBN) were detected in meconium but not in any umbilical cord or placenta. For the first time, prenatal marijuana exposure was analyzed and compared in paired hair, meconium, umbilical cord, and placental samples. Hair and meconium positivity rate was similar, but a more sensitive and specific analytical method for the hair may resolve discrepancies between the matrices. Umbilical cord and placenta may be considered suitable alternative matrices to meconium through the determination of THCCOOH-glucuronide as a biomarker of cannabis exposure.
Supporting Information
| Filename | Description |
|---|---|
| dta3034-sup-0001-Table_S1.docxWord 2007 document , 19.7 KB |
Supplemental Table 1. Linearity range and parameters for cannabidiol (CBD), cannabinol (CBN), Δ-9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 8-β-11-dihydroxy-THC (diOHTHC), 11-nor-9-carboxy-THC (THCCOOH), THC-glucuronide, and THCCOOH-glucuronide in placenta (n = 4). Supplemental Table 2. Precision and accuracy for cannabidiol (CBD), cannabinol (CBN), Δ-9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 8-β-11-dihydroxy-THC (diOHTHC), 11-nor-9-carboxy-THC (THCCOOH), THC-glucuronide, and THCCOOH-glucuronide in placenta at low and high QC (n = 12). Low QC and high QC were 1.5 ng/g and 15 ng/g for THC-glucuronide; 1.5 ng/g and 60 ng/g for THCCOOH-glucuronide; 15 ng/g and 60 ng/g for THCCOOH, CBD, CBN, and THC. OHTHC and diOHTHC had only a high QC, at 60 ng/g. NA: not available. Supplemental Table 3. Matrix Effect, Extraction Efficiency, and Process Efficiency for cannabidiol (CBD), cannabinol (CBN), Δ-9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OHTHC), 8-β-11-dihydroxy-THC (diOHTHC), 11-nor-9-carboxy-THC (THCCOOH), THC-glucuronide, and THCCOOH-glucuronide at 15 ng/g and 60 ng/g in placenta (n = 10). NA: not available. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1
European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2020. https://doi.org/10.2810/123451. Accessed February 11, 2021.
- 2
Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: results from the 2019 National Survey on Drug Use and Health. HHS Publication No. PEP20-07-01-001, NSDUH Series H-55. 2019. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHNationalFindingsReport2018/NSDUHNationalFindingsReport2018.pdf. Accessed February 11, 2021.
- 3Volkow ND, Han B, Compton WM, McCance-Katz EF. Self-reported medical and nonmedical cannabis use among pregnant women in the United States. JAMA. 2019; 322(2): 167-169. https://doi.org/10.1001/jama.2019.7982
- 4Blasco-Alonso M, González-Mesa E, Gálvez Montes M, et al. Exposure to tobacco, alcohol and drugs of abuse during pregnancy. A study of prevalence among pregnant women in Malaga (Spain). Adicciones. 2015; 27(2): 99-108.
- 5van Gelder MM, Reefhuis J, Caton AR, Werler MM, Druschel CM, Roeleveld N. National birth defects prevention study. Characteristics of pregnant illicit drug users and associations between cannabis use and perinatal outcome in a population-based study. Drug Alcohol Depend. 2010; 109(1–3): 243-247. https://doi.org/10.1016/j.drugalcdep.2010.01.007
- 6Corsi DJ, Hsu H, Weiss D, Fell DB, Walker M. Trends and correlates of cannabis use in pregnancy: a population-based study in Ontario, Canada from 2012 to 2017. Can J Public Health. 2019; 110(1): 76-84. https://doi.org/10.17269/s41997-018-0148-0
- 7Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. Birth outcomes associated with cannabis use before and during pregnancy. Pediatr Res. 2012; 71(12): 215-219. https://doi.org/10.1038/pr.2011.25
- 8Day NL, Goldschmidt L, Day R, Larkby C, Richardson GA. Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults. Psychol Med. 2015; 45(8): 1779-1787. https://doi.org/10.1017/S0033291714002906
- 9Goldschmidt L, Richardson GA, Willford J, Day NL. Prenatal marijuana exposure and intelligence test performance at age 6. J am Acad Child Adolesc Psychiatry. 2008; 47(3): 254-263. https://doi.org/10.1097/CHI.0b013e318160b3f0
- 10Goldschmidt L, Richardson GA, Larkby C, Day NL. Early marijuana initiation: the link between prenatal marijuana exposure, early childhood behavior. And Negative Adult Roles Neurotoxicol Teratol. 2016; 58: 40-45. https://doi.org/10.1016/j.ntt.2016.05.011
- 11Carlier J, Huestis MA, Zaami S, Pichini S, Busardò FP. Monitoring perinatal exposure to cannabis and synthetic cannabinoids. Ther Drug Monit. 2020; 42(2): 194-204. https://doi.org/10.1097/FTD.0000000000000667
- 12González-Colmenero E, Concheiro-Guisán A, Lorenzo-Martínez M, et al. Drug testing in biological samples vs. maternal surveys for the detection of substance use during whole pregnancy. J Addict Dis. 2020; 1-8. https://doi.org/10.1080/10550887.2020.1831137 Online ahead of print
- 13Concheiro M, Huestis MA. Drug exposure during pregnancy: analytical methods and toxicological findings. Bioanalysis. 2018; 10(8): 587-606. https://doi.org/10.4155/bio-2017-0260
- 14Concheiro M, Lendoiro E, de Castro A, et al. Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy. Drug Test Anal. 2017; 9(6): 898-904. https://doi.org/10.4155/bio-2017-0260
- 15Montgomery D, Plate C, Alder SC, Jones M, Jones J, Christensen RD. Testing for fetal exposure to illicit drugs using umbilical cord tissue vs meconium. J Perinatol. 2006; 26(1): 11-14. https://doi.org/10.1038/sj.jp.7211416
- 16Palmer KL, Wood KE, Krasowski MD. Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: a retrospective study at an academic medical center. Clin Biochem. 2017; 50(6): 255-261. https://doi.org/10.1016/j.clinbiochem.2016.11.026
- 17Jensen TL, Wu F, McMillin GA. Detection of in utero exposure to cannabis in paired umbilical cord tissue and meconium by liquid chromatography-tandem mass spectrometry. Clin Mass Spectrom. 2019; 14: 115-123. https://doi.org/10.1016/j.clinms.2019.01.002
- 18Colby JM, Adams BC, Morad A, Presley LD, Patrick SW. Umbilical cord tissue and meconium may not be equivalent for confirming in utero substance exposure. J Pediatr. 2019; 205: 277-280. https://doi.org/10.1016/j.jpeds.2018.09.046
- 19Joya X, Pujadas M, Falcón M, et al. Gas chromatography-mass spectrometry assay for the simultaneous quantification of drugs of abuse in human placenta at 12th week of gestation. Forensic Sci Int. 2010; 196(1–3): 38-42. https://doi.org/10.1016/j.forsciint.2009.12.044
- 20Falcon M, Pichini S, Joya J, et al. Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: comparison with testing in placental and fetal remains. Forensic Sci Int. 2012; 218(1–3): 92-96. https://doi.org/10.1016/j.forsciint.2011.10.022
- 21Lendoiro E, Quintela O, de Castro A, Cruz A, López-Rivadulla M, Concheiro M. Target screening and confirmation of 35 licit and illicit drugs and metabolites in hair by LC-MSMS. Forensic Sci Int. 2012; 217(1–3): 207-215. https://doi.org/10.1016/j.forsciint.2011.11.006
- 22Prego-Meleiro P, Lendoiro E, Concheiro M, Cruz A, López-Rivadulla M, de Castro A. Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of cannabinoids and phase I and II metabolites in meconium. J Chromatogr a. 2017; 1497: 118-126. https://doi.org/10.1016/j.chroma.2017.03.066
- 23Kim J, de Castro A, Lendoiro E, Cruz-Landeira A, López-Rivadulla M, Concheiro M. Detection of in utero cannabis exposure by umbilical cord analysis. Drug Test Anal. 2017; 10(4): 636-643. https://doi.org/10.1002/dta.2307
- 24Lendoiro E, Gonzalez-Colmenero E, Concheiro-Guisan A, et al. Maternal hair analysis for the detection of illicit drugs, medicines. And Alcohol Exposure during Pregnancy Ther Drug Monit. 2013; 35(3): 296-304. https://doi.org/10.1097/FTD.0b013e318288453f
- 25Williamson S, Jackson L, Skeoch C, Azzim G, Anderson R. Determination of the prevalence of drug misuse by meconium analysis. Arch Dis Child Fetal Neonatal Ed. 2006; 91(4): F291-F292. https://doi.org/10.1136/adc.2005.078642
- 26Ostrea EM Jr, Knapp DK, Tannenbaum L, et al. Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J Pediatr. 2001; 138(3): 344-348. https://doi.org/10.1067/mpd.2001.111429
- 27Friguls B, Joya X, Garcia-Serra J, et al. Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island. Addiction. 2012; 107(8): 1471-1479. https://doi.org/10.1111/j.1360-0443.2012.03828.x
- 28Cortés L, Almeida L, Sabra S, et al. Maternal hair and neonatal meconium to assess gestational consumption and prenatal exposure to drugs of abuse and psychoactive drugs. Curr Pharm Biotechnol. 2018; 19(2): 136-143. https://doi.org/10.2174/1389201019666180405163612
- 29Joya X, Marchei E, Salat-Batlle J, et al. Drugs of abuse in maternal hair and paired neonatal meconium: an objective assessment of foetal exposure to gestational consumption. Drug Test Anal. 2016; 8(8): 864-868. https://doi.org/10.1002/dta.1921
- 30Joya X, Gomez-Culebras M, Callejón A, et al. Cocaine use during pregnancy assessed by hair analysis in a Canary Islands cohort. BMC Pregnancy Childbirth. 2012; 12: 2. https://doi.org/10.1186/1471-2393-12-2
- 31Lozano J, García-Algar O, Marchei E, et al. Prevalence of gestational exposure to cannabis in a Mediterranean city by meconium analysis. Acta Paediatr. 2007; 96(12): 1734-1737. https://doi.org/10.1111/j.1651-2227.2007.00535.x
- 32Lamy S, Hennart B, Houivet E, et al. Perinatal network of upper-Normandy. Assessment of tobacco, alcohol and cannabinoid metabolites in 645 meconium samples of newborns compared to maternal self-reports. J Psychiatr Res. 2017; 90: 86-93. https://doi.org/10.1016/j.jpsychires.2017.02.012
- 33Bar-Oz B, Klein J, Karaskov T, Koren G. Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse. Arch Dis Child Fetal Neonatal Ed. 2003; 88(2): F98-F100. https://doi.org/10.1136/fn.88.2.f98
- 34Cooper GAA, Kronstrand R, Kintz P. Society of hair testing guidelines for drug testing in hair. Forensic Sci Int. 2012; 218(1–3): 20-24. https://doi.org/10.1016/j.forsciint.2011.10.024
- 35Gray TR, Barnes AJ, Huestis MA. Effect of hydrolysis on identifying prenatal cannabis exposure. Anal Bioanal Chem. 2010; 397(6): 2335-2347. https://doi.org/10.1007/s00216-010-3772-y
- 36Elsohly MA, Feng S. Delta-9-THC metabolites in meconium: identification of 11-OH-delta-9-THC, 8b,11-diOH-delta-9-THC, and 11-nor-delta-9- THC-9-COOH as major metabolites of delta-9-THC. J Anal Toxicol. 1998; 22(4): 329-335. https://doi.org/10.1093/jat/22.4.329
- 37Feng S, Elsohly MA, Salamone S, Salem MY. Simultaneous analysis of delta9-THC and its major metabolites in urine, plasma, and meconium by GC-MS using an immunoaffinity extraction procedure. J Anal Toxicol. 2000; 24(6): 395-402. https://doi.org/10.1093/jat/24.6.395
- 38Marchei E, Pellegrini M, Pacifici R, et al. Quantification of Delta9-tetrahydrocannabinol and its major metabolites in meconium by gas chromatographic-mass spectrometric assay: assay validation and preliminary results of the “meconium project”. Ther Drug Monit. 2006; 28(5): 700-706. https://doi.org/10.1097/01.ftd.0000245380.95186.13
- 39Tynon M, Porto M, Logan BK. Simplified analysis of 11-hydroxy-delta-9-tetrahydrocannabinol and 11-carboxy-delta-9-tetrahydrocannabinol in human meconium: method development and validation. J Anal Toxicol. 2015; 39(1): 35-40. https://doi.org/10.1093/jat/bku107
- 40Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007; 4(8): 1770-1804. https://doi.org/10.1002/cbdv.200790152
- 41Wu F, Scroggin TL, Metz TD, McMillin GA. Development of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of four cannabinoids in umbilical cord tissue. J Anal Toxicol. 2018; 42(1): 42-48. https://doi.org/10.1093/jat/bkx078
- 42Concheiro M, Jones HE, Johnson RE, Choo R, Shakleya D, Huestis MA. Maternal buprenorphine dose, placenta buprenorphine and metabolite concentrations and neonatal outcomes. Ther Drug Monit. 2010; 32(2): 206-215. https://doi.org/10.1097/FTD.0b013e3181d0bd68
- 43Concheiro M, Jones HE, Johnson RE, Choo R, Shakleya D, Huestis MA. Umbilical cord monitoring of in utero drug exposure to buprenorphine and correlation with maternal dose and neonatal outcomes. J Anal Toxicol. 2010; 34(8): 498-505. https://doi.org/10.1093/jat/34.8.498
- 44Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet. 2004; 43(8): 487-514. https://doi.org/10.2165/00003088-200443080-00001
- 45Skopp G, Pötsch L, Mauden M. Stability of cannabinoids in hair samples exposed to sunlight. Clin Chem. 2000; 46(11): 1846-1848.
- 46Scheidweiler KB, Schwope DM, Karschner EL, Desrosiers NA, Gorelick DA, Huestis MA. In vitro stability of free and glucuronidated cannabinoids in blood and plasma following controlled smoked cannabis. Clin Chem. 2013; 59(7): 1108-1117. https://doi.org/10.1373/clinchem.2012.201467
- 47Scheidweiler KB, Himes SK, Desrosiers NA, Huestis MA. In vitro stability of free and glucuronidated cannabinoids in blood and plasma collected in plastic gray-top sodium fluoride tubes following controlled smoked cannabis. Forensic Toxicol. 2016; 34(1): 179-185.
