Indications for Testing

• Suspected or known maternal drug abuse; obstetrical complications associated with drug abuse (eg, fetal distress)

Laboratory Testing

• Meconium drug testing
  • For more information, refer to Drug Analytes Detected in Meconium and Umbilical Cord
  • Routine analysis includes a qualitative screen for nine drug classes; specimens testing positive for one or more drugs are reflexed to confirmatory testing
  • 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, <1g)
• Umbilical cord tissue testing – may also confirm drug abuse in mother
• Maternal drug testing may detect very recent use; urine is the preferred specimen

Differential Diagnosis

• Metabolic disorder
• In utero exposure to other toxicants
  • Alcohol
  • Nicotine
  • Heavy metals
    • Lead
    • Arsenic
  • Prescription drugs

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

Epidemiology

• Prevalence – approximately 30% of the drug-abuse population is female, and most are of childbearing age

Pathophysiology

• Meconium (dark, tarry material passed from the neonate’s rectum in the first days after birth until milk or formula-based stool appears) is the best specimen for assessing in utero exposure of the neonate to maternal drug use
  • Meconium 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
  • Meconium is preferred over urine for testing of neonates
    • Urine testing indicates drug use only over the last 1–10 days, depending on the drug
    • Meconium documents drug use over an extended period of time, covering at least the last trimester of pregnancy
    • Meconium is easier to obtain than urine (combining all meconium voids can be helpful if sample size is small)
  • Umbilical cord tissue is the preferred specimen for assessing in utero exposure of the neonate to maternal drug use when meconium is not available
    • Deposition of drugs in umbilical cord tissue is not well studied, but window of detection appears similar to meconium

Clinical Presentation

• Stimulants
  • Cocaine
    • Infant
      • Irritability and withdrawal at birth
      • Subarachnoid and intracerebral hemorrhage
      • Small neonatal 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
    • Negative effect on attentional behavior and on visual analysis/hypothesis testing
    • No effect on global IQ
• Opiates, barbiturates, benzodiazepines
  • Infant and mother – withdrawal symptoms
    • Irritability
    • Tremors
    • Hyperactivity
    • Seizures

Tests generally appear in the order most useful for common clinical situations

General

• 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) :520-522.PubMed
• Gareri J, Klein J, Koren G. Drugs of abuse testing in meconium. Clin Chim Acta. 2006; 366 (1-2) :101-111.PubMed
• Koren G, Hutson J, Gareri J. Novel methods for the detection of drug and alcohol exposure during pregnancy: implications for maternal and child health. Clin Pharmacol Ther. 2008; 83 (4) :631-634.PubMed
• Marcellus L. Is meconium screening appropriate for universal use? Science and ethics say no. Adv Neonatal Care. 2007; 7 (4) :207-214.PubMed
• Montgomery 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.PubMed
• Montgomery DP, Plate CA, Jones M, Jones J, Rios R, Lambert DK, Schumtz N, Wiedmeier SE, Burnett J, Ail S, Brandel D, Maichuck G, Durham CA, Henry E, Christensen RD. Using umbilical cord tissue to detect fetal exposure to illicit drugs: a multicentered study in Utah and New Jersey. J Perinatol. 2008; 28 (11) :750-753.PubMed
• Ostrea EM Jr. Understanding drug testing in the neonate and the role of meconium analysis. J Perinat Neonatal Nurs. 2001; 14 (4) :61-82.PubMed
• Rayburn WF. Maternal and fetal effects from substance use. Clin Perinatol. 2007; 34 (4) :559-71, vi.PubMed
• Walsh MC, Fanaroff JM. Meconium stained fluid: approach to the mother and the baby. Clin Perinatol. 2007; 34 (4) :653-65, viii.PubMed

ARUP Institute for Clinical and Experimental Pathology®

• 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) :522-527.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) :80-85.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) :491-498.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) :148-154.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) :177-181.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) :589-590.PubMed

Developmental Delay (DD) or Intellectual Disability (ID) Testing
Drug Testing
Opioids