MSACL 2024 Abstract

Concordance of Newborn and Maternal Drug Screen Results by Immunoassay and Mass Spectrometry Hannah M. Brown (1), Stephen Roper (1), Dennis Dietzen (1), Bridgit O. Crews (1) (1) Washington University in St. Louis School of Medicine, St. Louis, MO Hannah Brown, PhD (Presenter) Washington University School of Medicine in St. Louis >> POSTER (PDF)

Presenter Bio: Hannah Brown earned her Bachelor of Arts degree in Chemistry and Political Science from St. Olaf College and her Ph.D. in Chemistry from Purdue University under the mentorship of Dr. R. Graham Cooks. Her graduate research focused on the analysis of brain tumor biopsies using intraoperative mass spectrometry (MS)-based platforms for improved glioma diagnostics based on molecular features. She is currently a clinical fellow in Clinical Chemistry at Washington University in St. Louis School of Medicine where she is continuing to find meaningful ways of applying mass spectrometry to clinically relevant challenges.

INTRODUCTION
The interplay between maternal health and neonatal outcomes informs current guidelines that recommend universal screening for substance use disorders in obstetric patients. As part of this screening process, maternal and neonatal drug testing is frequently performed to detect in utero drug exposure. While maternal urine drug testing exhibits high sensitivity and specificity, neonatal urine drug testing faces preanalytical and analytical challenges due to difficult sample collection protocols, low drug concentrations, and drug metabolites differing from those targeted by immunoassay (IA) or mass spectrometry (MS)-based methods. Consequently, meconium is often the preferred specimen type to detect neonatal drug exposure due to a longer window of detection compared to urine. Most laboratories do not have the ability to analyze meconium and, therefore, send out meconium testing to specialized reference laboratories, which can delay results for several days or more. In response highly sensitive MS-based methods for rapid, in-house neonatal urine drug testing have been developed, although the concordance of these methods with gold-standard meconium testing is not well documented.

OBJECTIVE
The primary objective of this study was to evaluate concordance of drug screening results of paired newborn urine and meconium samples with maternal urine samples using IA and liquid chromatography mass spectrometry (LC-MS/MS) methods, aiming to investigate maternal-fetal drug transfer.

METHODS
The number of positive drug screen results for newborns born at Barnes Jewish Medical Center with paired urine and meconium samples from January 2021 to October 2022 were tabulated retrospectively for the de-identified dataset (n=1,424). Of the 1,424 newborns, 831 newborns had mothers with drug screens performed within three days of birth (+/- 3 days). Urine drug testing was performed on freshly collected urine by in-house LC-MS/MS methods. All paired meconium samples were sent to an outside reference laboratory where they were screened by IA and confirmed with MS. The menu of available meconium testing performed in our patient population allowed for a paired urine-meconium comparison for the following drugs: amphetamines, cocaine, cannabinoids, opiates, and cannabinoids. The cutoffs for the MS urine screening method (in ng/mL) were: amphetamines 5, cocaine 1, opiates 25-250 (depending on specific compound), cannabinoids 20 (as 11-nor-9-Carboxy-Δ9-tetrahydrocannabinol glucuronide). The cutoffs for meconium screening (in ng/g) were: amphetamines 100, cocaine 100, opiates 100, cannabinoids 20.

RESULTS
Of the 1,424 newborns, 120 screened positive for amphetamines, 65 screened positive for cocaine, and 2 screened positive for PCP in urine and/or meconium. Positivity rates were equivalent for amphetamines (7.4%), cocaine (3.9%), and PCP (0.1%). McNemar’s test p-values indicate there is no significant difference between urine and meconium for the detection of amphetamines and cocaine (p < 0.001). There was insufficient data to analyze concordance for PCP due to low positivity rate. For opiates, 57 newborns screened positive. The drug class with the highest positivity rate is cannabinoids, with 866 newborns screening positive. There was a significant difference in positivity rate (percent positive agreement (PPA)) for opiates and cannabinoids (20% and 2.5%, respectively). A cohort of 831 newborns with mothers having a urine drug screens performed within three days of birth were identified. Positivity rates were higher in maternal urine for all drug classes except cannabinoids (69.4% positivity rate in maternal urine; 96.9% positivity rate in meconium). Notably, in the case of amphetamines, cocaine, and opiates, an additional 7, 24, and 32 instances of in utero drug exposure were identified in maternal urine alone, accounting for 9%, 34%, and 42% of all positive screens, respectively. Specifically in the case of cannabinoid positivity, 99.8% of all newborns with in utero cannabinoid exposure screened positive in meconium and/or maternal urine.

CONCLUSION
In this retrospective analysis including paired data from meconium and urine collected from 1,424 neonates, we observed that a sensitive and rapid LC-MS/MS method for neonatal urine tests detected equivalent numbers of neonates exposed to cocaine and/or amphetamines in utero compared to common meconium drug testing methods. Further, given the poor analytical performance of screening for cannabinoids in urine, meconium only testing may be appropriate for this drug class, in combination with maternal urine drug testing. Higher positivity rates in maternal urine highlight the importance of incorporating maternal drug screening results into the interpretation of newborn urine drug screens, as it provides a comprehensive understanding of fetal exposure, especially in instances in which meconium is unavailable. This study highlights the potential value of sensitive and rapid LC-MS/MS methods for neonatal urine drug testing.