Analysis of umbilical cord tissue as an indicator of in utero exposure to toxic adulterating substances

Abstract

In utero drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been employed to measure illicit drug exposure, as drugs used by the mother during the third trimester may be retained in the UCT. Focus has also been given to potential adverse health effects among drug users, resulting from exposure to pharmacologically active adulterants and cutting agents in the street drug supply. The in utero effects of these substances have not been well studied in humans, nor has their presence been demonstrated as a means for assessing adverse health effects in the neonate. Here, we describe the application of a novel test method to analyze UCT for the presence of more than 20 common adulterating/cutting substances via LC/Q-TOF. In total, 300 de-identified UCT samples were analyzed-all had previously tested positive for cocaine or opiates. Generally, the positivity rates of individual compounds were similar between the Cocaine and Opiates Subgroups, apart from levamisole, xylazine, dipyrone (metabolites), and promethazine. Many of the adulterants used in the street drug supply do have legitimate medicinal/therapeutic uses, including several of the compounds most frequently detected in this study. Caffeine and lidocaine were the most frequently identified compounds both individually (>70% each) and in combination with each other. Alternatively, levamisole, an adulterant with no legitimate therapeutic use, was present in 12% of cases. Importantly, this data demonstrates that the detection of traditional drugs of abuse may serve as indicators of potential in utero exposure to toxic adulterating substances during gestation. While there is cause for concern with respect to any unintentional drug exposure, illicit drug use during pregnancy, including uncontrolled dosing, poly-adulterant consumption, and the interactions of these drug mixtures, produces a significant public health threat to the neonate which warrants further study.

Keywords: adulterant; dipyrone; levamisole; neonate; phenacetin; umbilical cord; xylazine.

Figure 1

Umbilical cord tissue poly-drug adulterant frequency in Cocaine (black) and Opiates (blue) Subgroups. Individual samples were found to contain anywhere from 0 to 7 adulterating substances.

Figure 2

Comparison of toxic adulterant positivity between the Cocaine (black) and Opiates (blue) Subgroups. Positivity rates were determined as a percentage of the total number of positive cases for each adulterant.

Figure 3

UpSet plot showing adulterant frequency (set size) and poly-drug intersections in umbilical cord tissue from the Cocaine Subgroup. The set size bar graph indicates the total number of positive cases identified for that individual adulterant within the Cocaine Subgroup. Poly-drug combinations, or intersections, are illustrated by the dot diagrams with connecting lines indicating adulterants found in combination with one another. A lone dot indicates a single drug finding. The frequency of each intersection is shown by the histogram at the top of the plot with the frequency number indicated for each combination seen. For example, the Cocaine Subgroup contained 138 lidocaine positive cases, 12 of which were positive for lidocaine-only. The following scope adulterants were not identified in any Cocaine Subgroup samples tested and were not included in the plot: 4-methylaminoantipyrine, xylazine, aminopyrine, 4-aminoantipyrine, procaine, benzocaine, and diltiazem.

Figure 4

UpSet plot showing adulterant frequency (set size) and poly-drug intersections in umbilical cord tissue from the Opiates Subgroup. The set size bar graph indicates the total number of positive cases identified for that individual adulterant within the Opiates Subgroup. Poly-drug combinations, or intersections, are illustrated by the dot diagrams with connecting lines indicating adulterants found in combination with one another. A lone dot indicates a single drug finding. The frequency of each intersection is shown by the histogram at the top of the plot with the frequency number indicated for each combination seen. For example, the Opiates Subgroup contained 92 caffeine positive cases, 28 of which were positive for the combination of caffeine and lidocaine. The following scope adulterants were not identified in any Opiates Subgroup samples tested and were not included in the plot: noxiptiline, benzocaine, and diltiazem.