Newborn

Toxicology
Screening
MARTIN J MCCAFFREY, MD, CAPT USN (RET)
DIRECTOR OF THE PERINATAL QUALITY COLLABORATIVE OF NORTH CAROLINA (PQCNC)
PROFESSOR OF PEDIATRICS
DEPARTMENT OF PEDIATRICS
DIVISION OF NEONATAL PERINATAL MEDICINE
UNC CHAPEL HILL SCHOOL OF MEDICINE
MJMCCAFF@EMAIL.UNC.EDU
 Overview

u Review specimens used for assessment of

infant drug exposure
u Testing limitations
u Sensitivity
u Invasiveness
u Window for detection
u Challenges related to specimen collection
 Newborn Drug
Testing Protocol

Wabuyele, SL. Detection of Drug-Exposed Newborns. Therapeutic Drug Monitoring. 2018;40(2):166–185

 Newborn Urine Screening
u Traditional specimen sent for screening
u Timing is a severe limitation
u First void is often missed
u Testing later voids is less sensitive because they are not as reflective of drug exposure in
utero.
u Only recent maternal drug use (days before delivery) is likely to be detected with urine.
u Many drugs rapidly metabolized
u Variable collection methods
u A wide range of collection procedures in place for neonate urine collection at one
institution.
u Collection bag, cotton balls, gauze
u Exposure to soaps causing false positives
u Benefit for very acute exposures (hours)

Cotton SW. Drug testing in the neonate. Clinics in Laboratory Medicine. 2012;32(3):449-466
 Newborn Urine Screening
u Exposure to collection fibers potentially causing false negatives

u Some soaps are associated with false positives for THC

u Analytical challenges in testing newborn urine for drugs
u Composition of newborn urine and distribution of drug analytes may be different than
adult urine.
u Reagent manufacturers have formulated and packaged their kits on the basis of
standard workplace drug testing thresholds.
u Some of these thresholds are too high for clinical testing, the consequence of which
has been underestimation of drug exposure

1. Cotton SW. Drug testing in the neonate. Clinics in Laboratory Medicine (2012), 32; (3):449-466
2. https://www.alliance2020.com/wp-content/uploads/Drug-Testing-Cutoff-Levels.pdf
 Newborn Urine Screening

u Urine drug screening almost exclusively uses immunoassay-based

platforms that target cocaine, amphetamines, cannabinoids,
opiates, or phencyclidine.
u Clinical laboratories confirm presumptive positive results using MS
coupled with LC or GC that imparts increased sensitivity and
specificity for quantitating a specific set of compounds.
u Given the medical and legal implications it is recommended that all
toxicology screening results for drugs of abuse be confirmed.
u Confirmatory testing uses a more sensitive and specific method such
as GC/MS or LC tandem MS.

Cotton SW. Drug testing in the neonate. Clinics in Laboratory Medicine. 2012;32(3):449-466
 Urine Drug Screening

u Immunoassay-based screening is prone to both false-positive and false-negative

results due to variable cross-reactivity with different drugs within a given class
and variable cutoffs.
u Some labs skip the immunoassay step and go directly to a mass spectrometric
method for targeted testing of specific drug analytes.
u Sensitivity of a urine drug-of-abuse test depends on the threshold (cutoff)
chosen.
u There are no recommended thresholds for testing of clinical samples, usually
urine, for drugs of abuse. Most clinical laboratories have adopted for maternal
and infant urine testing programs the thresholds used in workplace drug testing
(54).
u Reagent manufacturers have formulated kits on the basis of standard
workplace drug testing thresholds
u Some thresholds have been shown to be too high for clinical testing in newborn
specimens, the consequence of which has been underestimation of drug exposure

Kwong TC. Detection of intrauterine illicit drug exposure by newborn drug testing. Clinical Chemistry. 1997;43 (1):235–242
 Meconium Drug Screening

u Meconium, the dark green viscous first stool of a newborn

u Disposition of drug in meconium is not well understood.
u Proposed mechanism is that the baby excretes drug into bile and amniotic
fluid
u Drug accumulates in meconium either by direct deposition from bile or
through swallowing of amniotic fluid
u Meconium appears to form early in the second trimester (12 weeks)
u Presence of drugs in meconium has been proposed to be indicative of
in utero drug exposure possibly months before birth
u Presumed to be a longer historical measure than is possible with urine
u But…the production of meconium is nonlinear, with more than two
thirds of meconium forming during the last 8 weeks of gestation, so
third-trimester exposures are more readily detected.
 Meconium Drug Screening

u Studies suggest that meconium testing is more sensitive than urine

testing.
u Meconium passes in 99% of cases….by 48 hours
u Part of the improved detection rate relates to the method of
analysis—urine by enzyme immunoassay (EIA) or fluorescence
polarization immunoassay (FPIA) vs meconium by RIA or GC-MS, or
the thresholds used (300 vs 80 µg/L for benzoylecgonine) rather than
the type of specimen (urine vs meconium).
u When more sensitive urine analytical methods and lower cutoffs
were used, infant urine and meconium analyses yielded equivalent
results for identifying newborns who have been exposed to cocaine
in utero.
1. Concheiro M et al. Bioanalysis for cocaine, opiates, methadone, & amphetamines exposure detection during pregnancy. Drug Test Anal.
2017;9:898–904.
2. Callahan CM et al. Measurement of gestational cocaine exposure: sensitivity of infants’ hair, meconium, and urine. J Pediatr 1992;120:763-768
 Umbilical Cord Drug Screening

u Umbilical cord is universally available

u There is sufficient amount immediately after birth
u Logistical advantages over meconium
u Passed in utero or delayed up to 3 days before the specimen is
available
u May require multiple collections
u Easily and noninvasively collected in a single step for rapid testing.
u Umbilical cord tissue avoids the detection of drugs administered to
the newborn after birth.
u Similar to meconium, non linear drug deposition in accumulating
Wharton’s jelly

de Castro A et al. Methadone, cocaine, opiates, and metabolite disposition in umbilical cord and correlations to maternal methadone
dose and neonatal outcomes. Ther Drug Monit. 2011;33:443–452.
 Umbilical Cord Drug Screening

u Umbilical cord specimens can be collected and stored for later

analysis even when the risk factors for in utero exposure occur days
after meconium has been discarded.
u Segmental analysis of umbilical cord shows consistent drug
concentrations throughout the specimen.
u In babies born to women in buprenorphine treatment, meconium
has been shown to be more sensitive than cord tissue or placenta
for detection of buprenorphine and its metabolites, as well as more
sensitive for identifying relapse with cocaine or opiates.

de Castro A et al. Methadone, cocaine, opiates, and metabolite disposition in umbilical cord and correlations to maternal methadone
dose and neonatal outcomes. Ther Drug Monit. 2011;33:443–452.
Which Specimen to Test????

https://arupconsult.com/content/about-us
 Windows for Newborn Drug
Detection

Wabuyele, SL. Detection of Drug-Exposed Newborns. Therapeutic Drug Monitoring. 2018;40(2):166–185

 Chain of Custody

u The chain of custody form typically includes the time, date, and
condition of the specimen when it was received
u Identifies all personnel who had access to the specimen throughout
the testing processes as well as the laboratory tests performed
including the confirmation of results, and the time and date of the
tests on completion.
u An accurate chain of custody procedure authenticates the
specimen donor and insures that processes were followed to
maximize the biological specimen integrity and validity of the
laboratory test results
 Toxicology Takeaways

u Drug screening in the newborn population comes with unique

challenges.
u Assessment of in utero drug exposure to cocaine, amphetamines,
opiates, marijuana, and ethanol may allow better intervention and
management of withdrawal symptoms for the neonate.
u A range of maternal and neonatal specimens are available, but each
comes with a unique set of limitations regarding sensitivity, availability,
invasiveness, and window of detection.
u Preanalytical issues such as specimen collection and sample extraction
can influence test accuracy
u The potential biological specimens have varying windows of detection
u Critical to discuss with laboratories methods, flow diagram for
confirmatory testing, best test for specific substances and chain of
custody.

Drug Testing in the Neonate. SW Cotton. Clinics in Laboratory Medicine. 2012;32(3):449-466

Thank You!!!