Connected by the cord—comparison of drug positivity rates and concentrations in a large cohort of paired umbilical cord and meconium specimens
Authors: Pandya Vrajesh , Wilker Chase , McMillin Gwendolyn 
Published: October 2021

Abstract
Substance abuse during pregnancy has significant short- and long-term health, social, and legal implications. Hence, prompt determination of a neonate’s drug exposure status can aid the healthcare team in making treatment choices. Umbilical cord tissue (UC) and meconium are two commonly used specimens to detect fetal drug exposure. However, the current evidence on the sensitivity of one specimen over the other is both limited and conflicting. By utilizing a large cohort (n=4036) of paired UC and meconium samples originating from 13 states, we retrospectively investigated the qualitative and quantitative drug positivity rates for 31 analytes from 5 drug classes (i.e. cannabis, opioids, stimulants, barbiturates, and benzodiazepines). Semi-quantitative drug detection in UC samples was conducted by LC-MS-based assays, whereas an immunoassay screen preceded quantitative LC-MS analysis for meconium specimens. Data were analyzed using R-programming, Microsoft Excel, and GraphPad Prism packages. The overall drug positivity rate for UC was 56.57% compared to 52.38% in meconium. Opioids were the top drug class detected in UC at 35.53% compared to 20.64% in meconium. The detection rates for individual opioid analytes were also higher in UC (0.97-15.49%) relative to meconium (0.0 to 9.09%). Notably, 6-acetylmorphine (heroin metabolite) was only detected in UC (0.97%). In contrast, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC) was more frequently detected in meconium at 34.99% compared to 19.89% in UC. In the stimulant drug class, the overall amphetamine positivity rate was 7.73% in UC while 8.57% in the meconium specimens. Conversely, the cocaine positivity rate in the UC was 3.84% and 2.23% in meconium samples. In the barbiturate drug class, the positivity rate for butalbital was twice as high in UC (1.91%) relative to meconium (0.99%). Phenobarbital positivity rate was comparable in both matrices (~0.15%). The positivity rates for 6 common benzodiazepine drugs ranged from 0.40-0.94% in UC compared to 0.01-0.35% in meconium. Interestingly, a multidrug combination analysis revealed that THC−opioids was the most common two-drug combination detected in both matrices at a rate of 7.22% in UC compared to 5.39% in meconium. Subsequent examination of analyte concentrations between the two matrices revealed higher concentrations in meconium. THC was 48.13 times more concentrated in meconium relative to UC. Amphetamines and cocaine were 6.45-15.01 times more concentrated in meconium relative to UC. For the opioids, the overall concentrations were 21.61-1845.01 times higher in meconium specimens relative to UC. For barbiturates, butalbital had comparable concentrations in the two matrices whereas phenobarbital was 33.10 times more concentrated in the meconium. Lastly, benzodiazepines were overall 6.21-38.75 times more concentrated in meconium than UC. In conclusion, this study shows that despite most drugs being more concentrated in meconium, drug positivity rates were higher with UC for all analytes except THC and amphetamines, suggesting higher detection potential of the UC specimen.