Jennifer Colby (Presenter)
Bio: Jen is an assistant professor in the department of Pathology, Microbiology, and Immunology and the medical director of Toxicology and Esoteric Chemistry at Vanderbilt University Medical Center. She earned her BS in molecular and cellular biology from Vanderbilt University and her PhD in molecular toxicology from the University of California, Berkeley. Jen completed her postdoctoral fellowship in clinical chemistry and toxicology at the University of California, San Francisco. Her research focuses on developing mass spectrometry based diagnostics, particularly for use in toxicology and therapeutic drug monitoring. When not in the lab Jen runs, competes in dressage, and enjoys exploring Tennessee with her husband and their Bouvier des Flandres, Devi.
Authorship: Jennifer Colby
Vanderbilt University, Department of Pathology, Microbiology and Immunology
Exposure to drugs in utero has negative health consequences for neonates, and through the involvement of social services, may carry legal ramifications for parents. Drug exposure is confirmed using mass spectrometry based tests of specimens from the neonate, typically meconium or cord tissue. In this study, paired cord tissue and meconium samples were collected from neonates who were diagnosed with a drug withdrawal syndrome. A comparison of drug detection in cord tissue and meconium showed fair concordance, and that in spite of more sensitive analytical methods, fewer drugs were detected in cord tissue than in meconium.
Prenatal exposure to pharmaceuticals, both illicit and prescribed, has many health consequences for neonates (1). One of the most severe is the development of neonatal abstinence syndrome (NAS), a withdrawal disorder that can require weeks of treatment in a neonatal intensive care unit (2). The cost of treatment and the long-term health effects of NAS make the increasing incidence a public health threat (3). While drug-exposed neonates are often identified based on clinical presentation and/or maternal history, exposure is confirmed via toxicology testing on specimens collected from the neonate (4). Confirmation that a neonate was exposed to drugs in utero warrants a referral to social services, and may have bearing on custodial decisions, so a sensitive and specific test is of critical importance (5). Meconium, the stool produced during gestation, has long been considered the gold standard for neonatal drug testing, largely because it has a very long window of detection (4). However, practical considerations make it a challenging specimen. Umbilical cord tissue has several operational advantages compared to meconium, and some evidence suggests that it may be used as an alternative specimen (6-11). The goal of this study was to compare the detection of drugs in paired meconium and umbilical cord tissue samples collected from a cohort of 133 subjects diagnosed with NAS.
Subjects whose providers ordered both umbilical cord and meconium toxicology testing during the study period of 10/1/13-12/31/15 and whose charts were available for review were included in this IRB-approved study. A subject was considered to have a diagnosis of NAS if the ICD9 code 779.5 was associated with his/her stay. All cord tissue and meconium testing was performed by a national reference laboratory using a combination of immunoassay and chromatography-mass spectrometry techniques (including GC-MS, LC-MS/MS, and LC-TOF). With one exception (cannabinoids), the cord tissue analytical methods had significantly lower limits of detection than the meconium methods. Drugs that were only available in either the cord or the meconium panel were excluded from the analysis. Toxicology results were gathered from the laboratory information system and clinical information was collected by chart review.
Paired umbilical cord tissue and meconium results were available for 133 neonates who had a diagnosis of NAS. Samples from 11 subjects (8%) were concordant negative for all drugs; 5 of these 11 subjects had NAS symptoms serious enough to merit pharmacological treatment with morphine. The remaining 122 subjects tested positive for drugs in at least one specimen; one drug class was detected in 62 subjects (47%), two classes were detected in 37 subjects (28%), three classes were detected in 18 subjects (14%). The remaining 5 subjects (4%) tested positive for 4 or 5 drug classes. Amongst all subjects, the most commonly observed drugs were buprenorphine (31%), opiates (27%), and cannabinoids (18%). Just under half (48%) of the 65 subjects who tested positive for buprenorphine were negative for all other drugs, which may indicate that these subjects were born to women who entered buprenorphine treatment before or early in their pregnancies. Defining meconium as the gold standard, the sensitivity of cord tissue ranged from 36-87%, depending on drug class. While agreement between the two matrices was >70% for all drug classes, calculations of Cohen’s kappa indicated only fair to moderate agreement (0.2-0.6).
Taken together, these results indicate that subjects with serious NAS may have negative drug tests regardless of the specimen selected, but that negative results are more likely to occur when cord tissue is tested. In spite of a relatively high screening cut-off, in this study, meconium was the more sensitive specimen. Further, in this cohort, social services decisions were often made before the meconium results were available, which could be problematic if the cord tissue and meconium results were discrepant. Given the importance of the custodial decision, a faster turnaround of meconium results would be beneficial. In addition, improving the analytical sensitivity of the meconium method may provide additional evidence of exposure, increasing the overall yield of testing.
Conclusions & Discussion
Sensitive detection of remote exposures is important for identification of drug-exposed neonates, and neonatal toxicology results are often used to support custodial decisions made by social services. This study demonstrates that within a population of neonates who had a diagnosis of NAS, cord tissue and meconium had substantially different performance. This may be due to a variety of factors, including the timing of exposure and the mechanism of drug deposition into each matrix. These results may be used to guide selection of the most appropriate test to confirm in utero drug exposure.
References & Acknowledgements:
Brad Adams, Stephen Patrick, Anna Morad, and Lauren Presley were instrumental in the conception and design of this study. Brad Adams also retrieved data from the laboratory information system.
1. Patrick SW, Dudley J, Martin PR, Harrell FE, Warren MD, Hartmann KE, et al Prescription Opioid Epidemic and Infant Outcomes. Pediatrics. 2015;135(5):842.
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8. de Castro A, Jones HE, Johnson RE, Gray TR, Shakleya DM, Huestis MA. Methadone, Cocaine, Opiates, and Metabolite Disposition in Umbilical Cord and Correlations to Maternal Methadone Dose and Neonatal Outcomes. Therapeutic Drug Monitoring. 2011;33(4):443.
9. 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. Journal of Perinatology. 2005;26(1):11.
10. Colby JM. Comparison of umbilical cord tissue and meconium for the confirmation of in utero drug exposure. Clinical Biochemistry. 2017;50(13):784.
11. Labardee RM, Swatzweider JR, Gebhardt KE, Pardi JA, Daset AC, Dixon BR, Cotton SW. Method performance and clinical workflow outcomes associated with meconium and umbilical cord toxicology testing. Clinical Biochemistry. 2017;epub.
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