Which is better for confirming in utero opioid exposures; umbilical cord tissue or meconium?

Opioids are a large class of narcotic/analgesic drugs that are frequently used in the management of pain.  Beginning in the mid 1990s, opioid prescription rates began to increase in the U.S., and over time, the increased accessibility of these drugs gave rise to an epidemic of opioid misuse and abuse.  Opioid use during pregnancy is especially concerning, as prenatal exposure to opioids can have very serious health consequences for neonates.   One of the most severe is the development of neonatal abstinence syndrome (NAS), a withdrawal syndrome which can require weeks of treatment in a neonatal intensive care unit.  

While the initial diagnosis of NAS is often made using maternal history and/or clinical symptoms, toxicology testing is routinely used to confirm the diagnosis.  Meconium, which is the stool produced during gestation and passed in the first few days of life, has long been considered the best specimen for drug testing neonates.  Substances that enter the fetal circulation can become concentrated in meconium, which makes it especially sensitive for detection of remote exposures.  However, meconium can be difficult to collect and occasionally it is unavailable.  Umbilical cord tissue, which is always available immediately after birth, has been proposed as an alternative specimen.  Cord tissue offers a number of advantages over meconium, but the literature supporting the use of cord testing to confirm opioid exposures is limited.  

In a retrospective study, we compared the detection of 10 opioids (6-monoacetylmorphine, codeine, EDDP, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and propoxyphene) in 217 paired cord tissue and meconium samples collected from neonates at risk for in utero drug exposure.  Cord tissue was analyzed using liquid chromatography time of flight mass spectrometry, which yielded presumptive positive results.  Meconium was analyzed using a traditional immunoassay screen, and presumptive positive meconium samples were confirmed using gas or liquid chromatography mass spectrometry.  The limits of detection achieved by the cord tissue screen were 4 to 7 times lower than the limits of detection for the meconium screen.  In spite of this, we found that meconium captured more information on exposure to the opioids we studied, and if we define meconium as the gold standard, the cord tissue test was nearly 35% less sensitive for opioid exposure.  

Several factors may be contributing to the discrepancies we observed between the paired samples, including that the cord tissue and meconium tests were performed using different methodologies.  In addition, drug deposition into cord and meconium is thought to occur by different mechanisms and to different extents.  Meconium has been shown to reflect exposures occurring as early as the end of the 2nd trimester; a result of the direct excretion of drugs into meconium.  On the other hand, most drugs do not preferentially accumulate in cord tissue, which leads to a shorter window of detection.

A diagnosis of NAS has serious physical and social consequences for the mother-baby dyad, which is why it is crucial that the test that’s used to confirm an opioid exposure be sensitive and specific.  The body of evidence supporting the use of umbilical cord tissue is so much smaller than that supporting meconium testing, and our study demonstrated that discrepancies between the two occur frequently.  Until more is known about when and how drugs are deposited in cord tissue, meconium may still be the better specimen for confirming prenatal opioid exposures.