Umbilical Cord Tissue: A Better Way to Test for Prenatal Drug Exposure?

Maureen A. O'Reilly, DNP, NNP-BC

Disclosures

June 05, 2018

Clinicians are searching for quicker and easier collection methods and more accurate toxicology testing for infants affected by intrauterine substance exposure. Umbilical cord testing offers some striking advantages over the "gold standard" of meconium testing, making the switch to cord testing increasingly attractive.

Pregnancy and Drugs of Abuse

Women in their reproductive years are at high risk for substance use disorder.[1] Unfortunately, many women continue unhealthy and addictive substance use behaviors throughout their pregnancies.[2] In a 2012 national survey,[2] 5.9% of pregnant women admitted to illicit drug use, 8.5% drank alcohol, and 15.9% smoked cigarettes.[2] The opioid crisis and increased substance use in pregnancy have triggered a national debate,[3] politicizing both detection and treatment for women and their infants. This mix of politics, money, science, and social opinion pressures healthcare clinicians to constantly re-examine how they detect and treat substance use in pregnancy.

The Impact on Newborns

As many as 400,000-440,000 newborns (10%-11% of all births) are exposed to tobacco, alcohol, or illicit drugs each year.[4] In-utero substance exposure is associated with birth defects, premature delivery, fetal alcohol spectrum disorders, and developmental, behavioral, and cognitive problems in affected children.[5,6]

Neonatal abstinence syndrome is a disorder of central and autonomic nervous and gastrointestinal systems that occurs when intrauterine substance exposure causes the newborn to experience withdrawal after birth.[7] Rapid, accurate newborn toxicology testing is crucial in identifying affected newborns, allowing timely initiation of treatment.

Toxicology Testing Matrices

Meconium toxicology has long been the "gold standard" in detecting newborn exposure to drugs of abuse.[8,9] Meconium samples can be difficult to collect. Fetal stressors during labor or delivery can induce meconium passage,[6] or it can be delayed up to a week, depending on gestational age.[9,10] Alternatively, meconium may be passed but not collected because drug use is neither suspected nor reported until after the sample is no longer available, or a parent may discard a diaper with meconium to avoid illicit drug detection.[10]

Other sample matrices for newborn testing have drawbacks. Cutting a hair sample from a newborn is protested by parents for cosmetic reasons and frequently results in inadequate sample size.[6] Fingernails are small and inadequate for sampling in newborns.[6] Vernix caseosa can be used to detect maternal drug use after 24 weeks of gestation; however, the volume is often inadequate for testing.[6] The window of drug detection in urine is narrow.[9] Newborns often void at the time of birth and may not void again for hours. Furthermore, urine samples can be difficult to obtain in the newborn.[11]

A New Method: Umbilical Cord Toxicology

Dianne Montgomery, a neonatal nurse practitioner, was debating the pros and cons of various tissues and waste products for drug detection in newborns, while also trying to address nursing complaints about sample collection difficulties. She approached the United States Drug Testing Laboratory in 2001 to suggest the umbilical cord as an alternative tissue for infant toxicology.[11] Cord toxicology testing first became available commercially in 2012 and is now offered by several US laboratories.[12]

Drugs Detectable by Cord Sampling

Umbilical cord toxicology can identify amphetamines, cocaine, opioids, barbiturates, and cannabinoids,[8,12] along with their metabolites. For example, cannabinoid testing includes carboxy-THC, and the opiate category includes 6-monoacetylmorphine, meconin (a marker of heroin use), codeine, hydrocodone, hydromorphone, and morphine.[12]Methadone and buprenorphine—drugs commonly used to treat opiate addiction—also are detectable in cord tissue,[12] as are alcohol (as phosphatidylethanol)[13] and cotinine (a nicotine metabolite).[14,15] One laboratory offering cord testing states that cord specimens are preferred over meconium for detection of fentanyl, meperidine, propoxyphene, tramadol, tapentadol, phentermine, and zolpidem.[16] Experts caution, however, that "concentrations of drug(s) and drug metabolites(s) may not reliably predict timing of drug use, extent of drug use, or frequency of drug exposures."[17]

Characteristics of Umbilical Cord Toxicology Testing

  • A single person collects a single sample, obviating chain-of-custody issues prevalent with other sample types.

  • Cord sampling is truly universal because all newborns have umbilical cords.

  • Cord samples are preserved by refrigeration[18,19]; therefore, questions about maternal drug use that arise postnatally can be addressed by sending a sample for testing up to 21 days later, depending on laboratory parameters.[18,19]

  • Available immediately after birth, cord testing can reduce the wait time for results, potentially shortening lengths of stay for newborns under observation for the symptoms of neonatal abstinence syndrome.[6,20]

  • Clinicians can opt for universal cord sampling (testing all newborns) or risk-based screening, using maternal history. Universal collection is recommended by the American College of Obstetricians and Gynecologists to reduce bias because risk-based screening can unfairly target low-income women.[21]

  • Cord testing has a long window of detection compared with urine samples[9] and also avoids detection of drugs administered to the newborn after birth,[6] which can affect meconium drug levels.

  • Cord collection is pain-free for newborns, whereas the use of adhesive collection devices for urine, especially when repeatedly applied or used on premature infants, can injure the infant's skin.[9]

Which Is Best? Umbilical Cord or Meconium

Comparisons of cord sampling results against the "gold standard" of meconium are generally positive. Early ELISA-based testing confirmed that amphetamines, opiates, cocaine, and cannabinoids could be detected in cord samples.[10] Colby[8] concluded that meconium provided a greater sensitivity for some classes of drugs (eg, opiates) and made an argument for its generally greater sensitivity of detection, although agreement between cord and meconium was 100% for barbiturates. A retrospective review of 2072 records of infants who underwent newborn drug testing found that "umbilical cord tissue toxicology testing yielded a similar detection rate compared to meconium testing."[22]

How to Obtain Umbilical Cord Samples

Immediately following birth, the clinician cuts a section of the cord measuring approximately 6-8 inches (15-20 cm). After "stripping" the cord sample to remove excess blood, the cord sample is rinsed in sterile water or normal saline, patted dry, and placed in a capped container labeled with the infant's data. Sealed with tamper-resistant tape and logged for chain-of-custody verification, the sample is refrigerated until testing.[18,19] If selected for testing, the chain of custody continues by first logging the sample to the laboratory and then to a shipping service because cord testing is currently available only in independent off-site laboratories (Figure).

Figure. Steps in the process of preparing an umbilical cord sample for toxicology testing. Step 1: Cut a 6- to 8-inch segment of umbilical cord. Step 2: "Milk" or "strip" cord to expel blood. Step 3: Rinse and place in sterile container. Step 4: Seal container with tamper-resistant tape and label with infant's data.

Who Owns the Umbilical Cord?

Testing the newborn for illicit drug exposure raises such issues as informed consent and ownership of the sample. Although the placenta is considered a feto-maternal organ,[13] the umbilical cord is usually designated as "fetal." The umbilical cord is considered a discarded tissue[6] and, like meconium, belongs to the baby.[14] However, this is a simplified view. Individual states may have drug testing regulations in place delineating ownership of fluids, cells, and tissues. The American Academy of Pediatrics considers umbilical cord sampling to be a viable testing method because it reflects in utero exposures comparable to meconium.[20] General consent to treatment, obtained when pregnant women are admitted for delivery, may be interpreted as including tissue testing necessary to the well-being of the infant without further informing the parent.[23] However, depending on individual state regulations, it may be necessary to obtain specific maternal consent to perform cord drug toxicology. Clarifying local and state regulations with respect to tissue usage is a necessary step in switching to umbilical cord toxicology testing.

Further complicating the consent issue is the "minor" status of the infant whose treatment is subject to the surrogate consent of the parent/guardian. Some states require a newborn sample for drug testing as evidence of child abuse, rather than relying on maternal testing or admission of use.[9] Alabama, South Carolina, and Tennessee moved to criminalize illicit drug use during pregnancy.[9] Attempting to conceal drug use during pregnancy due to fear of arrest, prosecution, and loss of child custody can motivate parents to refuse infant toxicology testing, delaying appropriate treatment of the newborn.

Toxicology testing methods offer varying levels of accuracy and ease of use. Although meconium testing remains the gold standard, umbilical cord testing offers the clinician a choice of both acceptable accuracy in results and greater simplicity in sampling.

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