Newborn Drug Testing - Meconium and Umbilical Cord Tissue

  • Diagnosis
  • Background
  • Lab Tests
  • References
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Indications for Testing

  • Detect prenatal exposure to drugs in meconium or umbilical cord tissue for infants
    • Born to mothers with high risk (eg, history of drug use, prostitution, sexually transmitted infection)
    • Born to mothers with little or no prenatal care
    • Born to mothers with unexplained placental abruption or premature labor
    • Born with unexplained neurological complications
    • Born with unexpected intrauterine growth retardation
    • Who develop drug withdrawal symptoms (eg, neonatal abstinence syndrome [NAS])

Laboratory Testing

  • Meconium and umbilical cord tissue reflect drug exposure over approximately the last trimester of a full-term birth; umbilical cord blood and/or infant urine may be used for testing if meconium and tissue are not available, but these specimens will detect only recent drug exposure
  • Umbilical cord tissue testing
    • For more information, refer to Drug Cut-off Limits for Meconium and Umbilical Cord tissue testing
    • Routine analysis includes qualitative detection by mass spectrometric methods for >30 prescription and illicit drugs (opioids, stimulants, sedative hypnotics); qualitative screen for cannabinoids by immunoassay is also included
  • Meconium drug testing
    • For more information, refer to Drug Cut-off Limits for Meconium and Umbilical Cord tissue testing
    • Routine analysis includes a qualitative screen for nine drug classes; specimens testing positive for one or more drugs are reflexed to confirmatory testing by mass spectrometric methods
    • Directed (confirmation only) tests are available when only one drug class is of clinical interest or when quantity of meconium available for testing is very small (eg, <1 g)
  • Maternal drug testing may detect very recent use; urine is the preferred specimen

Exposure to maternal drug use during gestation may adversely affect neonatal development and may lead to acute adverse events including neonatal abstinence syndrome (NAS) and infant mortality.  Prenatal drug exposure may also contribute to long-term behavioral effects and developmental deficits.

Epidemiology

Pathophysiology

  • Umbilical cord tissue
    • Begins to form during the ~5th week of gestation
    • Passed during birth 
  • Meconium
    • Dark, tarry material passed from infant’s rectum in the first days after birth until milk or formula-based stool appears
    • Begins to form during the 12th–16th week of gestation and is usually passed within first 3 days of birth
      • Passage may be delayed when the baby is exposed to opioids or with premature birth
      • May also be expelled in utero or during birth

Clinical Presentation

  • Stimulants
    • Cocaine
      • Infant
        • Irritability and withdrawal at birth
        • Subarachnoid and intracerebral hemorrhage
        • Small infant head size
        • Reduced birth weight
        • Fetal death
        • Childhood behavioral disorders (eg, attention deficit hyperactivity disorder –ADHD)
      • Mother
        • Premature labor
        • Ruptured uterus, abruptio placentae
        • Adult behavioral disorders (eg, ADHD)
    • Amphetamines (particularly methamphetamine)
      • Infant
        • Effects are similar to cocaine
        • Medical problems in early life
      • Mother
        • Effects are similar to cocaine
        • Complications during pregnancy – reduced fetal growth, stillbirth, congenital anomalies
        • Increased rates of premature birth
  • Cannabinoid (marijuana)
    • Infant
      • Evidence for effects on attentional behavior and on visual analysis/hypothesis testing is not firm
      • No effect on global IQ
  •  Opioids, barbiturates, benzodiazepines
    • Infant and mother – withdrawal symptoms
      • Irritability
      • Tremors
      • Hyperactivity
      • Seizures

Detection

  • Timely detection of in utero drug exposure is critical for effective management of withdrawal syndromes and long-term needs (social and medical) for exposed infants
    • Actual time window for detecting exposure with meconium or umbilical cord tissue is unknown  and is drug-dependent, but is thought to represent approximately the last trimester of a full-term birth
  • Detection of drugs depends on
    • Extent of maternal drug use
    • Drug stability
    • Deposition of drug analytes in meconium and umbilical cord tissue
    • Performance of the analytical method
  • Drugs administered to the mother during labor and delivery may be detected in meconium and umbilical cord
  • Drugs administered to the newborn after birth can be detected in meconium if the meconium is collected after drug administration
  • Concentrations of drugs in meconium are much higher than concentrations of drugs in umbilical cord tissue; cutoff concentrations were established to harmonize positivity rates between the two specimen types for most drugs
  • Umbilical cord tissue testing may be preferable to meconium due to
    • Ease of collection of a larger volume of specimen
    • Relatively fast turnaround time if specimen is sent to the laboratory on the day of birth
    • Reflex/confirmation testing not performed
  • Meconium or umbilical cord tissue are preferred over urine for testing of infants
    • Urine testing indicates drug use over the previous 1–10 days, depending on the drug
    • Meconium may be contaminated by urine; umbilical cord tissue may be contaminated by maternal blood
    • Deposition of drugs in umbilical cord tissue is not well studied, but appears consistent across the length of the cord
    • It is preferred that all meconium voids be collected to maximize the potential for drug detection
    • Umbilical cord tissue can be sent to the laboratory immediately after birth
    • Umbilical cord tissue avoids detection of drugs administered directly to the newborn after birth

 

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Drug Detection Panel, Umbilical Cord Tissue, Qualitative 2006621
Method: Qualitative Liquid Chromatography/Tandem Mass Spectrometry/Enzyme-Linked Immunosorbent Assay

Recommended Use 

Detect and document maternal drug use during approximately the last trimester of a full-term birth

Test results are qualitative; quantitative results are not provided

Panel includes detection of the following parent drugs, listed by unique drug or drug class:

  • Opioids: buprenorphine, codeine, fentanyl, heroin (6-acetylmorphine), dihydrocodeine, hydrocodone, hydromorphone, meperidine, methadone, morphine, naloxone, oxycodone, oxymorphone, propoxyphene, tapentadol, tramadol
  • Stimulants: amphetamine, cocaine, methamphetamine, MDMA (Ecstasy), phentermine
  • Sedative-hypnotics: alprazolam, butalbital, clonazepam, diazepam, lorazepam, midazolam, nordazepam, oxazepam, phenobarbital, temazepam, zolpidem
  • Phencyclidine (PCP)
  • Cannabinoids (11-nor-9-carboxy-THC)
  • Several drug metabolites are also included to increase likelihood of detection and increase confidence in results
Limitations 

Negative results do not exclude the possibility that a mother used drugs during pregnancy

Cannot determine date of maternal drug use, what specific drug was taken, or amount taken

Marijuana metabolites (eg, THC) are detected by immunoassay and are not confirmed

Test results are qualitative; quantitative results are not provided

Drugs of Abuse Panel, Meconium - Screen with Reflex to Confirmation/Quantitation 0092516
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Quantitative Gas Chromatography-Mass Spectrometry/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use 

Preferred meconium test to detect and document maternal drug use during approximately the last trimester of a full-term birth

Targeted single-drug class testing is appropriate if only a particular drug class or classes are of clinical interest, or when quantity of meconium available for testing is very small (eg, <1g)

Reflex approach to testing – if specimen screens positive, confirmation/quantitation by GC/MS and/or LC-MS/MS will be added, and quantitative results will be reported

Panel includes detection of the following parent drugs, listed by unique drug or drug class

  • Opioids – buprenorphine, codeine, heroin (6-acetylmorphine), hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone
  • Stimulants – amphetamine, cocaine, methamphetamine, MDMA (Ecstasy)
  • Sedative-hypnotics – alprazolam, butalbital, chlordiazepoxide, clonazepam, diazepam, lorazepam, midazolam, oxazepam, phenobarbital, temazepam
  • Phencyclidine (PCP)
  • Cannabinoids (11-nor-9-carboxy-THC)
  • Several drug metabolites are also included to increase likelihood of detection and increase confidence in results
Limitations 

Negative results do not exclude the possibility that a mother used drugs during pregnancy

Cannot determine date of maternal drug use, what specific drug was taken, or amount taken

May detect drugs administered directly to the newborn if meconium is collected after drug administration

Follow-up 

See the pediatric peer-reviewed literature for infant treatment recommendations

General References

Adrian M, Van Truong M, Osazuwa T. Measuring levels of comorbidity in drug user* emergency patients treated in Ontario hospitals. Subst Use Misuse. 2007; 42(2-3): 199-224. PubMed

Araojo R, McCune S, Feibus K. Substance abuse in pregnant women: making improved detection a good clinical outcome. Clin Pharmacol Ther. 2008; 83(4): 520-2. PubMed

de Castro A, Jones HE, Johnson RE, Gray TR, Shakleya DM, Huestis MA. Methadone, cocaine, opiates, and metabolite disposition in umbilical cord and correlations to maternal methadone dose and neonatal outcomes. Ther Drug Monit. 2011; 33(4): 443-52. PubMed

Gareri J, Klein J, Koren G. Drugs of abuse testing in meconium. Clin Chim Acta. 2006; 366(1-2): 101-11. PubMed

Lozano J, Garcia-Algar O, Vall O, de la Torre R, Scaravelli G, Pichini S. Biological matrices for the evaluation of in utero exposure to drugs of abuse. Ther Drug Monit. 2007; 29(6): 711-34. PubMed

Marcellus L. Is meconium screening appropriate for universal use? Science and ethics say no. Adv Neonatal Care. 2007; 7(4): 207-14. PubMed

Moller M, Gareri J, Koren G. A review of substance abuse monitoring in a social services context: a primer for child protection workers. Can J Clin Pharmacol. 2010; 17(1): e177-93. PubMed

Rayburn WF. Maternal and fetal effects from substance use. Clin Perinatol. 2007; 34(4): 559-71, vi. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Barakauskas VE, Davis R, Krasowski MD, McMillin GA. Unresolved discrepancies between cannabinoid test results for infant urine. Clin Chem. 2012; 58(9): 1364-7. PubMed

Chittamma A, Marin SJ, Williams JA, Clark C, McMillin GA. Detection of in utero marijuana exposure by GC-MS, ultra-sensitive ELISA and LC-TOF-MS using umbilical cord tissue. J Anal Toxicol. 2013; 37(7): 391-4. PubMed

Coles R, Clements TT, Nelson GJ, McMillin GA, Urry FM. Simultaneous analysis of the Delta9-THC metabolites 11-nor-9-carboxy-Delta9-THC and 11-hydroxy-Delta9-THC in meconium by GC-MS. J Anal Toxicol. 2005; 29(6): 522-7. PubMed

Coles R, Kushnir MM, Nelson GJ, McMillin GA, Urry FM. Simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS-MS. J Anal Toxicol. 2007; 31(1): 1-14. PubMed

Marin SJ, Christensen RD, Baer VL, Clark CJ, McMillin GA. Nicotine and metabolites in paired umbilical cord tissue and meconium specimens. Ther Drug Monit. 2011; 33(1): 80-5. PubMed

Marin SJ, Coles R, Merrell M, McMillin GA. Quantitation of benzodiazepines in urine, serum, plasma, and meconium by LC-MS-MS. J Anal Toxicol. 2008; 32(7): 491-8. PubMed

Marin SJ, Coles R, Urry FM, McMillin GA. Confirmation of cannabinoids in meconium using two-dimensional gas chromatography with mass spectrometry detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 858(1-2): 59-64. PubMed

Marin SJ, Keith L, Merrell M, McMillin GA. Comparison of drugs of abuse detection in meconium by EMIT II and ELISA. J Anal Toxicol. 2009; 33(3): 148-54. PubMed

Marin SJ, Keith L, Merrell M, McMillin GA. Evaluation of a new ELISA kit for the detection of benzodiazepines in meconium. J Anal Toxicol. 2009; 33(3): 177-81. PubMed

Marin SJ, McMillin GA. Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS. Methods Mol Biol. 2016; 1383: 59-68. PubMed

Marin SJ, Moore C, McMillin GA. Cross-reactivity of phentermine with an immunoassay designed to detect amphetamine in a meconium specimen. Clin Chem. 2009; 55(3): 589-90. PubMed

Marin SJ, Roberts M, Wood M, McMillin GA. Sensitive UPLC-MS-MS assay for 21 benzodiazepine drugs and metabolites, zolpidem and zopiclone in serum or plasma. J Anal Toxicol. 2012; 36(7): 472-6. PubMed

McMillin GA, Wood KE, Strathmann FG, Krasowski MD. Patterns of drugs and drug metabolites observed in meconium: What do they mean? Ther Drug Monit. 2015; 37(5): 568-80. PubMed

Wood KE, Krasowski MD, Strathmann FG, McMillin GA. Meconium drug testing in multiple births in the USA. J Anal Toxicol. 2014; 38(7): 397-403. PubMed

Wood KE, Sinclair LL, Rysgaard CD, Strathmann FG, McMillin GA, Krasowski MD. Retrospective analysis of the diagnostic yield of newborn drug testing. BMC Pregnancy Childbirth. 2014; 14: 250. PubMed

Medical Reviewers

McMillin, Gwendolyn A., PhD, DABCC (CC, TC), Medical Director of Toxicology and Pharmacogenomics at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

Last Update: October 2017