Real Time Data

Umbilical cord testing has seen increasing use over the last decade for the detection of in utero drug exposure. New data from a three month survey of umbilical cord drug testing results sheds light on the deposition of substances of abuse and their metabolites in umbilical cord tissue.

by Irene Shu, Ph.D., DABCC and Joseph Jones, M.S., NRCC-TC

Neonatal abstinence syndrome (NAS) is a growing concern in the United States. The number of newborns exhibiting NAS withdrawal symptoms increased 10-fold from 1995 to 2009.1 From 2004-2013, Neonatal Intensive Care Unit (NICU) admissions due to NAS increased 285%.2 As well, the length of stay in the NICU for NAS related treatment increased from 13 to 19 days.2 According to the 2012 National Survey on Drug Use and Health, at least 5.9% of pregnant women use illicit drugs while pregnant and 8.5% of pregnant women drink during pregnancy, including 2.7% who report risky drinking behavior.3 Additionally, one in six pregnant women smoke during pregnancy.4 Withdrawal symptoms in newborns may result from any of these substances.

Toxicological testing of newborn samples helps to identify precise causes of withdrawal in neonates. Umbilical cord tissue is a highly advantageous specimen to test for in utero alcohol or substance exposure. In contrast to urine, umbilical cord provides a longer detection window, and is much easier to collect than both urine and meconium. Umbilical cord testing has seen increasing use since 2007, however, data on the deposition of drugs and metabolites in umbilical cord as a result of in utero drug exposure is limited.

 USDTL undertook a systematic analysis of umbilical cord samples submitted to our lab for 13-panel drug analysis from July through November of 2014 (5 months). The 13-panel test identifies the following drugs and their metabolites: amphetamines (AMP), cocaine (COC). opiates (OPI), cannabinoids (THC), phencyclidine (PCP), barbiturates (BARB), benzodiazepines (BZP), methadone (MTD), propoxyphene (PPX), oxycodone (OXY), meperidine (MEP), tramadol (TRAM), and buprenorphine (BUP).

All umbilical cord samples were screened by an enzyme linked immuno-sorbent assay (ELISA) method. Presumptive positive samples were then confirmed by either liquid chromatography-tandem mass spectrometry (LC-MS/MS: AMP, COC, OPI, BARB, BZP, MTD, PPX, OXY, TRAM, BUP) or gas chromatography-mass spectrometry (GC-MS: THC, PCP, MEP) methods to identify and quantify drugs and metabolites. 

During the 5-month period, 6,578 umbilical cord samples were received for 13-panel drug testing, 3,256 (49.5%) of which were screened negative. Cannabinoids and opioids were the most commonly seen drug types in positive umbilical cord samples. The five most prevalent drug classes that the specimens confirmed positive for were cannabinoids (15.0%), opiates (13.1%), buprenorphine (11.6%), oxycodone (4.9%), and methadone (3.5%). (Figure 1, page 6)

Single drug class use was the most common result among drug positive specimens, although multiple drug class use was still significant. Of the total tested specimens for 13-panel drugs, 33.9% (2,334/6,578) tested positive for a single drug class, 8.6% (589/6,578) tested positive for two drug classes, and 2.7% (186/6,578) tested positive for three or more drug classes. Multiple drug class use for the five most commonly seen drug classes is shown in figure 1 (page 6). Note that although overall prevalence of AMP and COC positive results is 2.3-2.4% among the 13-panel tested samples, the prevalence increases to 6.9% among the opioid (opiates, buprenorphine, oxycodone, or methadone) positive samples. The concomitant presence of opioids and stimulants may delay the onset of withdrawal symptoms which complicates the patient care strategy.

Maternal heroin use was indicated in 97 samples positive for morphine that also have quantifiable 6-MAM and/or meconin. 6-MAM is a heroin metabolite, and meconin is a metabolite of the illicit heroin contaminant, noscapine. The latter heroin marker allowed us to identify 9 heroin exposed newborns in the absence of 6-MAM results, which constitutes 9.3% (9/97) of the cases.)

There were only 70 samples that tested positive for both hydrocodone and hydromorphone. Almost all of the confirmed buprenorphine positive samples had norbuprenorphine as the predominant analyte, and 47.9% of those did not have the parent drug above quantitation limit. On the other hand, oxycodone was the predominant analyte for that drug class over its metabolite oxymorphone. Methadone was present at higher concentrations than its metabolite EDDP, however, unlike hydrocodone, buprenorphine and oxycodone, both the parent drug and metabolite were almost equally occurring.

Whether the parent drug or its metabolite is the predominant form in umbilical cord varied between drugs, and no consistent pattern among drug classes was discernible. It is unknown whether the observed drug/metabolite ratios are associated with maternal versus fetal pharmacokinetic profiles. That type of research is difficult to conduct due to obvious ethical reasons.  Beyond that, however, these data demonstrate that umbilical cord is a suitable, and in several ways advantageous, alternative to urine and meconium testing for in utero drug exposure.

References

1. Hudak, M.L. and Tan, R.C. (2012). Neonatal Drug Withdrawal. Pediatrics, 101(6), 1079-1088.

2. Tolia, V.N., Patrick, S.W., Bennett, M.M., Murthy, K., Sousa, J., Smith, P.B., and Clark, R.H. (2015). Increasing Incidence of the Neonatal Abstinence Syndrome in U.S. Neonatal ICUs. The New England Journal of Medicine,  372, 2118-2126.

3. Results from the 2012 National Survey on Drug Use and Health: Volume 1. Summary of National Findings (Office of Applied Studies, NSDUH Series H-46, HHS Publication No (SMA) 13-4795). Rockville, MD: Substance Abuse and Mental Health Services Administration, 2010. 

4. Tobacco Use and Pregnancy. Centers for Disease Control and Prevention. Retrieved from http://www.cdc.gov/reproductivehealth/tobaccousepregnancy/