Newborn Drug Screening - Meconium and Umbilical Cord Tissue

Neonatal exposure to some drugs during pregnancy can have harmful effects on 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. 

Timely detection of in utero drug exposure supports the identification and clinical management of affected neonates. Detection of drugs depends on the extent of substance use during pregnancy, drug stability, analyte deposition within a given specimen, and test method performance. 

Although no federal or society guidelines currently exist that provide criteria for newborn drug screening, medical institutions typically test when risk factors such as maternal history of substance use disorder are known.  Universal specimen collection (ie, with testing only as needed) may occur based on institutional, local, or state policy.

When testing is indicated, it typically entails the same methods used in adult drug testing (eg, mass spectrometry [MS], immunoassay). Testing can be performed on a range of specimens, although meconium (the first stool of a newborn) and umbilical cord tissue are preferred for evaluating chronic exposure. For further discussion of the various methods that may be used in drug testing, refer to Demystifying Analytical Approaches for Urine Drug Testing to Evaluate Medication Adherence in Chronic Pain Management. 

Quick Answers for Clinicians

Should a universal or risk-based approach be used in newborn drug screening?

Currently, no federal mandates or society guidelines exist that provide criteria for newborn drug testing. In general, medical care facilities and practitioners use either a universal or risk-based testing approach. Both options have benefits and drawbacks and may be influenced by local contexts (eg, laws, substance use prevalence, etc.).

Universal testing involves screening for neonatal drug exposure following each delivery. This approach is beneficial in that it prevents the use of biased testing protocols and may help to identify cases of neonatal drug exposure that would otherwise go untreated. It may be useful in areas where substance use prevalence is higher compared to the national average.  However, universal testing is more costly  and may expose more patients to legal and social risks. 

Risk-based testing involves screening for neonatal drug exposure in the presence of one or more objective risk factors, which can vary between facilities. In areas where substance use prevalence is low or below average, this approach may help to avoid excessive testing while still identifying affected neonates.  However, critics of a risk-based approach suggest that it enables discriminatory testing, especially in low-income and minority populations. It may also lead to missed treatment opportunities in unidentified cases of neonatal drug exposure. 

An approach that may overcome some of these limitations is to practice universal collection, wherein specimens are collected for every birth. Those specimens associated with risk factors could be tested right away, and those not associated could be stored for a period in which unexpected needs for testing could be exposed.

Regardless of the approach taken, the American College of Obstetricians and Gynecologists endorses informed consent and patient advocacy. 

Should testing for neonatal exposure to gabapentin be considered?

Gabapentin is a widely used drug that, alone or with other drugs, has been linked to neonatal abstinence syndrome (NAS).   Notably, newborns coexposed to gabapentin and opioids during pregnancy have been shown to experience increased NAS severity and duration compared with those exposed only to opioids. When testing is indicated, consider a multidrug assay that includes gabapentin as an analyte.

See ARUP Laboratory Tests for a list of primary drugs detected for each assay. For a detailed discussion of the detection of gabapentin coexposure, see Patterns of Neonatal Co-Exposure to Gabapentin and Commonly Abused Drugs Observed in Umbilical Cord Tissue. 

What is the significance of qualitative versus quantitative newborn drug screen results?

Current data suggest little correlation between meconium or umbilical cord drug concentrations and neonatal exposure or outcomes.   For that reason, qualitative results are thought to be sufficient for determining in utero drug exposure. Exact drug concentrations within a sample may be informative when investigating patterns of drug exposure and unexpected results, the latter of which may be influenced by the established cutoff values for a particular test.

Which factors should be considered when interpreting the results of a newborn drug screen?

Several analytic factors (eg, cutoff values, the list of analytes targeted, etc.) can influence how the results of a newborn drug screen are reported. Interpretation of any newborn drug screen should also involve a complete review of the patient’s history, including prescriptions, drugs administered within a medical setting, home environment, and self-reported substance use.

For more on test interpretation, see Evaluation and Interpretation of Results.

Which specimens are preferred for a newborn drug screen?

Meconium is the traditional specimen for newborn drug testing, although its use may pose preanalytic challenges (eg, delayed or segmented collection). Umbilical cord tissue is easily collected at birth but has been found to contain lower drug concentrations than meconium.   For additional information about these specimens, see Preferred Specimen Types.

Urine, hair, and blood (including umbilical cord blood) tests offer different advantages, disadvantages, and windows of detection in newborn drug screening. The use of various specimen types is intended to complement the investigation of potential newborn drug exposure. For further discussion of these and other specimen types, refer to Detection of Drug-Exposed Newborns. 

How long does it take to perform meconium and umbilical cord testing?

The amount of time it takes to obtain meconium and umbilical cord test results may be influenced by many factors, including the timing of sample collection, the proximity of the laboratory performing the test, the method used for testing, and the possible need for reflex or confirmatory testing. Additionally, because meconium and umbilical cord tissue are solid specimens, processing them for testing requires more time and effort compared with the time and effort to process a liquid specimen used in rapid testing.

The expected time to obtain results should be weighed against other considerations (eg, test performance, included analytes, etc.) to determine the appropriate testing. When results are needed more promptly, single-step testing by a mass spectrometric method may be helpful. Because umbilical cord tissue can be collected immediately at birth, its use may also enable more rapid results.  

How sensitive are meconium and umbilical cord tissue drug tests?

The clinical sensitivity of newborn drug testing is not well characterized. Results will only reflect the drugs an individual test is designed to detect, and findings may not match preanalytic expectations (ie, drugs may not always be detected, even when admissions of drug use are made).

In terms of analytic sensitivity, factors that may influence analyte detection in meconium and umbilical cord tissue testing include frequency and timing of drug use during pregnancy, sample quality, specimen processing, and test-specific cutoff concentrations for each drug. Analytic sensitivity also relates heavily to test method and cutoff concentrations. Notably, mass spectrometry (MS) is a highly sensitive and specific test method, and its use for confirmatory or primary testing minimizes the possibility of false results.

Is chain of custody needed for meconium and umbilical cord samples?

Because umbilical cord tissue and meconium drug screens are usually performed to support clinical and social management decisions rather than to facilitate law enforcement or criminal actions, chain of custody may not be required when testing. Consult local authorities and laws for more information.

When chain of custody may be a concern, consider testing that includes step-by-step specimen tracking. If chain of custody is not available or results seem otherwise questionable, comparing test results with patient history to identify expected substances (eg, prescriptions) alongside target analytes can reinforce the credibility of the test results. 

Indications for Testing

Screening practices for neonatal drug exposure vary by facility and occur on a universal basis or in the presence of predefined objective risk factors. Universal specimen collection (ie, with later testing as needed) may also occur.

As part of a risk-based approach, testing should be considered if there is a patient history of high-risk behavior (eg, a documented history of substance use, misuse, or abuse), minimal or no prenatal care, or unexplained obstetric events (eg, placental abruption or premature labor). 

Additionally, testing should be considered in infants with unexplained neurologic complications, unexpected intrauterine growth restriction, or drug withdrawal symptoms (eg, NAS). 

Laboratory Testing

Laboratory testing for neonatal drug exposure can be performed using the same methods that apply to adult drug testing (eg, MS, immunoassay). MS, which has a high level of sensitivity and specificity, is widely used for initial testing but can also be used to confirm a previous test result. Immunoassays may also be used for initial testing, but due to a potential for cross-reactivity, these tests may require confirmation when results are positive or unanticipated.

For further discussion of the various methods that may be used in drug testing, see Demystifying Analytical Approaches for Urine Drug Testing to Evaluate Medication Adherence in Chronic Pain Management. 

Preferred Specimen Types

The most common specimen types used in newborn drug testing are meconium and umbilical cord tissue. Although meconium is traditionally preferred and has been used in a clinical setting for over two decades, umbilical cord tissue has been acknowledged as an effective sample type in recent years.

Both meconium and umbilical cord tissue are appropriate to detect drug use in the third trimester of a full-term pregnancy, although key aspects of these differ, as shown in the Meconium-Umbilical Cord Tissue Specimen Comparison table below. Because of the various preanalytic factors uniquely associated with each specimen type, testing multiple sample types may produce discrepant results. 

Other specimen types, such as hair and blood (including umbilical cord blood), are used less often in newborn drug screening. Urine may be used but it offers a shorter window of detection. For further discussion of these sample types, refer to Detection of Drug-Exposed Newborns. 

Meconium-Umbilical Cord Tissue Specimen Comparison
Meconium Umbilical Cord Tissue

Nonlinear accumulation starting as early as 12 wks of pregnancy

Nonlinear growth throughout pregnancy

Collection often within 48 hrs of birth but may occur over several days

Collection at time of birth

Collection requires a coordinated effort, and a sufficient sample may not be available

Collection requires minimal effort, and a sample is available with each pregnancy

Concentrations of drug analytes are higher in meconium

Concentrations of drug analytes are lower in umbilical cord tissue

May contain drugs administered to the parent during delivery

May contain drugs administered to the parent during delivery

May contain drugs administered to the newborn after delivery Unaffected by drugs administered to the newborn after delivery
Some concordance of results among twins and triplets Better concordance of results among twins and triplets

More sensitive in detecting cannabis

More sensitive in detecting heroin and cocaine

Sources: Wabuyele, 2018 ; McMillin, 2015 ; Pandya, 2022 ; Wu, 2018 ; Wood, 2014 ; Nelson, 2021 

Evaluation and Interpretation of Results

Studies have shown that drugs administered during labor and delivery may be detected in meconium or umbilical cord tissue. Additionally, drugs administered to the newborn after birth may be detected in meconium if the specimen is collected after drug administration. Test results may also reflect exposure to prescribed drugs and should therefore be interpreted within the context of a complete patient history. When results are in question, verifying the presence of unexpected analytes alongside expected analytes can reinforce reliability.  

Results may be reported as either quantitative or qualitative. Current data suggest little correlation between meconium or umbilical cord drug concentrations and neonatal exposure or outcomes.   Accordingly, qualitative results are thought to be sufficient for identifying in utero drug exposure. Reviewing drug concentrations alongside cutoff values may be helpful when assessing an unanticipated result.

Each laboratory currently establishes its own cutoff values for meconium and umbilical cord testing. The targeted analytes can also vary between tests, and results will only reflect the drugs an individual test is designed to detect. Therefore, a negative result does not exclude the possibility of substance use during pregnancy. Obtaining maternal patient history and performing maternal urine testing may also help to identify a possible infant drug exposure; findings should be considered alongside other laboratory results and the infant’s clinical presentation to diagnose a drug exposure.

Finally, opiates and benzodiazepines have complicated metabolic pathways that can lead to errors in result interpretation. For example, morphine is both a parent drug and a metabolite and can reflect the use of legal substances (eg, a codeine prescription) and illegal substances (eg, heroin). When results are ambiguous, analyte proportions can sometimes be useful to correctly identify a substance.  See Benzodiazepine Metabolic Pathway and Opioid Metabolic Pathway for visual representations of the metabolic patterns for these drug classes.

For further information on test result interpretation organized by drug class, refer to ARUP Consult’s Drug Testing topic.

ARUP Laboratory Tests

Meconium Testing

Use to detect and document maternal drug use during approximately the last trimester of a full-term pregnancy

For additional test information, including a complete list of drug cutoff concentrations, refer to the Drug Detection Panel Testing, Meconium and Umbilical Cord Tissue Test Fact Sheet

Primary drugs detected include:

  • Barbiturates: butalbital, phenobarbital
  • Benzodiazepines: alprazolam, clonazepam, diazepam, lorazepam, midazolam, nordiazepam, oxazepam, temazepam, zolpidem
  • Opioids: buprenorphine, codeine, fentanyl, heroin metabolite (6-acetylmorphine), hydrocodone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, tramadol
  • Stimulants: amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine (MDMA-Ecstasy), methylphenidate, phentermine
  • Other drugs: gabapentin, phencyclidine (PCP)

Use to detect in utero exposure to cannabis (marijuana) in neonates consistent with maternal use during approximately the last trimester of a full-term pregnancy

Detects cannabinoid (THC)

Umbilical Cord Tissue Testing

Use to detect and document maternal drug use during approximately the last trimester of a full-term pregnancy

For additional test information, including a complete list of drug cutoff concentrations, refer to the Drug Detection Panel Testing, Meconium and Umbilical Cord Tissue Test Fact Sheet

Primary drugs detected include:

  • Barbiturates: butalbital, phenobarbital
  • Benzodiazepines: alprazolam, clonazepam, diazepam, lorazepam, midazolam, nordiazepam, oxazepam, temazepam, zolpidem
  • Opioids: buprenorphine, codeine, fentanyl, heroin metabolite (6-acetylmorphine), hydrocodone, meperidine, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, tramadol
  • Stimulants: amphetamine, cocaine, methamphetamine, methylenedioxymethamphetamine (MDMA-Ecstasy), phentermine
  • Other drugs: gabapentin, phencyclidine (PCP)

Use to detect in utero exposure to cannabis (marijuana) in neonates consistent with maternal use during approximately the last trimester of a full-term pregnancy

Detects cannabinoid (THC)

Use to detect and document maternal use of ethanol during approximately the last trimester of a full-term pregnancy

For additional test information, refer to the Ethyl Glucuronide, Umbilical Cord Tissue, Qualitative Test Fact Sheet

References

Medical Experts

Contributor
Contributor

McMillin

Gwendolyn A. McMillin, PhD
Professor of Pathology (Clinical), University of Utah
Scientific Director, Mass Spectrometry Platform; Medical Director, Clinical Toxicology and Pharmacogenomics, ARUP Laboratories