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Clarity in Newborn Toxicology | v.10 i.1

Facing Fentanyl In Utero A growing threat to public health

v.10 i.1 2 Facing Fentanyl In Utero 6 Levels of Detection 10 Confronting FASDs with Advanced Newborn Alcohol Biomarker Testing


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FACING FENTANYL IN UTERO by Kelly Hack, Content Writer

According to the Centers for Disease Control and assessed by identifying the following symptoms: Prevention (CDC), the prevalence of neonatal tremors, jitteriness, irritability, excessive crying and abstinence syndrome (NAS) throughout the diarrhea. These indicators have been determined United States has risen dramatically. From 2000 in the medical field as the standards for identifying 1 to 2012, NAS has increased by 383 percent. In a compromised central nervous system. Prenatal response to an ongoing opioid epidemic, medical professionals This synthetic opioid is extremely addictive and when used while and advocates are invested in pregnant can cause devastating outcomes to the fetus including providing education, resources, neural tube defects, congenital heart defects, gastroschisis, testing and preventative care stillbirth and pre-term delivery.2 in efforts to combat one of the most powerful opioids in the use/abuse of fentanyl can increase an infant’s risk world-Fentanyl. This synthetic opioid for developing NAS. is extremely addictive and when used while pregnant can cause What Makes Fentanyl So Dangerous? devastating outcomes to the fetus including neural tube According to the United States Drug Enforcement defects, congenital heart Administration (DEA), fentanyl is approximately defects, gastroschisis, 100 times more potent than morphine and stillbirth and pre-term 50 times more potent than heroin.2 Its initial delivery.2 development was intended as a licit intravenous anesthetic; however, it has now become a public Newborns are often health threat as pharmaceutical products are diagnosed with NAS subjected to theft, fraudulent prescriptions as a direct result of a and illicit or less regulated distribution and sudden interruption manufacturing. The drug is often abused by of fetal exposure to injecting, snorting/sniffing, oral tablets/pills or prescription and removing the gel on fentanyl patches and then illicit substances that injecting or ingesting. The attraction/popularity were used or abused of fentanyl within drug addicted communities by the mother. derive from the addictive effects the drug produces Diagnosing an infant - relaxation, euphoria, pain relief and sedation. with NAS is often However, abused fentanyl also produces fatal side



effects including: confusion, dizziness, nausea, vomiting, urinary retention, pupillary constriction and respiratory depression.

Fentanyl’s Long-term Effects on Fetus Prenatal substance abuse can lead to long-term, irreversible damage to a developing fetus. In relation to fentanyl, these effects can consist of the following when associated with NAS:4 • Cognitive and motor development deficiencies • Infections • Vision complications • Sudden Infant Death Syndrome (SIDS) • Susceptible to future substance abuse

Fentanyl and Toxicology Confirmation According to the American Academy of Pediatrics, NAS is a clinical diagnosis, however toxicological confirmation is necessary to identify the exact type of substance that the mother was using or abusing and to confirm or rule out the use of other licit or illicit substances during pregnancy.5 Due to the recent increase of cases regarding pregnant women and fentanyl exposure-it is imperative now more than ever to utilize testing that can help detect

the latest drugs of abuse. Fentanyl testing in umbilical cord tissue is a powerful tool to help address this epidemic. Similar to meconium, the umbilical cord belongs to the baby, therefore maternal consent is not needed. The umbilical cord specimen is available immediately for 100 percent of births and requires only 1 collection by 1 collector. The window of detection may be up to approximately 20 weeks, providing a more precise depiction of potential substance use/abuse. Our efficient laboratory turnaround time, produces results within 24 hours for screen negative and an additional 24-48 hrs if further testing is needed. Our methodology and advanced instrumentation provides hospitals an opportunity to address this public health concern with confidence. The validity of newborn toxicology results has never been more imperative. Through our partnership and services, we can customize a flexible comprehensive drug testing program based on your population health needs. Today’s substance abuse landscape is drastically different than it used to be-collaboration is vital to protect and enrich these young lives.

References 1. Morbidity and Mortality Weekly Report (MMWR). (2017, August 17). Retrieved from https://www. cdc.gov/mmwr/volumes/65/wr/mm6531a2.htm 2. Center for Disease Control and Prevention, U. (n.d.). Pregnancy and Opioid Pain Medications. Retrieved from https://www.cdc.gov/drugoverdose/pdf/pregnancy_opioid_pain_factsheet-a.pdf. 3. Department of Education, U. (n.d.). Drugs of Abuse Guide (2017)(pp. 40-41) (United States). 4. Long-Term Outcomes of Infants With Neonatal Abstinence Syndrome. (n.d.). Retrieved from https://www.seattlechildrens.org/healthcare-professionals/education/continuing-medicalnursingeducation/neonatal-nursing-education-briefs/long-term-outcomes-of-infants-with-nas/ 5. Kocherlakota, P. (2014, August 01). Neonatal Abstinence Syndrome. Retrieved from http:// pediatrics.aappublications.org/content/134/2/e547

Kelly Hack, Content Writer for USDTL holds a Master’s of Science in Journalism, along with a versatile professional portfolio including investigative, educational, feature and profile writing. Hack currently strives to capitalize her knowledge-base in efforts to provide readers with information that is accurate, concise and pertinent.


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Level of Detection Understanding Screening and Confirmation Cutoff Levels for Newborn Drug and Alcohol Testing by Michelle Lach, Editor-in-Chief

Drug Classes, Drugs, and Drug Metabolites Preliminary testing (i.e., initial testing, screening), confirmation, and cutoff levels are some of the complexities of drug testing that can often be misunderstood by those outside of the laboratory setting. To shed more light on the topic, we wanted to break down the steps of our testing and explain how they correspond to the results we send out to our clients. To begin, it is important to understand the difference between drug classes, and drugs, including drug metabolites. Drug classes are the overarching groups under which individual drugs with similar pharmacological and some chemical properties are categorized, and thus are the basis of how our drug Fig. 1


testing panels are classified (i.e., amphetamines, cannabinoids, opiates, etc.) (Figure 1). Please note: For the sake of simplicity, we have used only umbilical cord tissue panels and cutoff levels as examples in this article. Different specimen types may have different drugs, drug metabolites, and cutoff levels associated with them. Within a drug class, there are drugs and their metabolites (formed when a drug is metabolized by the body). We test for specific drugs and/or drug metabolites that are deemed most useful to detect in the realm of substance abuse. For example, there are many different substances that fall under the amphetamine drug class, but we only test for amphetamine, MDA, MDEA, Fig. 2

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MDMA, and methamphetamine (Figure 2). The same is true for cannabinoids, there are well over 100 individual compounds that can be categorized under that drug class. However, the main pharmacologically active ingredient of the cannabis plant is tetrahydrocannabinol (THC), so our testing looks only for THC, more specifically in umbilical cord tissue, it is looking for the drug metabolite, Carboxy THC.

Initial Testing and Results Screening is the process of sending all specimens through highly sensitive instrumentation that is quick and effective for determining whether a specimen might contain substances of interest. The screening process cumulatively tests for many compounds that fall within the given drug classes. The drug classes screened are determined by the drug panels selected by the client for testing. If a specimen runs through the screening process and nothing is detected (within the scope of testing), our

Confirmation Testing and Results As an accredited forensic toxicology laboratory, all specimens that do not screen negative require confirmation testing. To perform confirmation testing, another portion from the original specimen is analyzed by a more advanced and specific technique, typically based on mass spectrometry. Due to the screening results, we have an idea of what we need to look for and what drugs to consider for the confirmation process. Confirmation testing takes longer to complete than screening because the instrument is looking for individual drugs and drug metabolites. Confirming positive results can take up to 24-48 additional hours after the screening results have been completed.

Cutoff Levels Cutoff levels, also known as decision points by the Scientific Working Group of Forensic Toxicology (SWGTOX), is “an administratively defined cutoff or concentration that is at or above the method’s limit of

We are frequently asked how a regular umbilical cord drug test can confirm positive for Carboxy THC at, let’s say 0.6 ng/g (60 pg/g), when the screening cutoff is well over that limit at 0.1 ng/g (100 pg/g). The answer is that the screening and confirmation tests are completely different tests, using different instruments, looking at different things.

Negative Certifying Scientists verify the negative results and the negative report is sent out. This is why the negative results generally have a quick turnaround time. If a specimen runs through the screening process and something is detected, it means we need to take a closer look to see what it is, but it does not mean that it has tested positive for any specific drug or drug metabolite yet. It just means the specimen did not test negative when it was tested for the many different compounds. At this point, the specimen must go in to confirmation testing.


detection or limit of quantitation and is used to discriminate between positive and negative results.”1 To use the cannabinoid example, our screening cutoff level for the cannabinoid drug class in umbilical cord tissue is 0.1 ng/g or 100 pg/g. If any of the hundreds of different cannabinoids cumulatively register at or above this cutoff level, the specimen would go into confirmation testing. At this point, our confirmation instrumentation is only looking for one specific drug metabolite, Carboxy THC (the metabolite of THC). Any other cannabinoids that might have contributed to reaching the screening cutoff levels are not tested


Figure 3

for during confirmation since they are not currently considered relevant. Screening and confirmation cutoff levels often cause confusion when it comes to testing results. We are frequently asked how a regular umbilical cord drug test can confirm positive for Carboxy THC at, let’s say 0.6 ng/g (60 pg/g), when the screening cutoff is well over that limit at 0.1 ng/g (100 pg/g). The answer is that the screening and confirmation tests are completely different tests, using different instruments, looking at different things. The screening cutoff levels were reached with multiple cannabinoids being tested that registered above the screening test cutoff level (0.1 ng/g or 100 pg/g). When the specimen went into separate confirmation testing (an entirely different test from start to finish) only Carboxy THC was being


Figure 4

measured, with different cutoff levels (0.05 n/g or 50 pg/g). This means that, of all the cannabinoids that registered in the specimen, there was only 0.6 ng/g (60 pg/g) of Carboxy THC. Figure 3 illustrates a screening test on a specimen for cannabinoids. In this example, there are numerous cannabinoids that are detected in the specimen that could result in a test needing a closer look with confirmation testing. The cumulative level of all cannabinoid compounds detected would contribute to reaching the cutoff level for screening (0.1 ng/g or 100 pg/g). • If the detectable amount of compounds in a specimen falls below the screening cutoff level, the specimen will be reviewed and verified by a Negative Certifying Scientist and reported out as a negative result.

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Figure 4 illustrates the confirmation test for cannabinoids that would follow the screening test from the specimen example in Figure 3 if the detectable amount of compounds in the cannabinoid drug class was equal or greater than the screening cutoff level of 0.1 ng/g (100 pg/g). Since this is a confirmation test for Carboxy THC it will be detecting the specific levels of the Carboxy THC only. • If the levels are equal to or greater than (≥) the Carboxy THC confirmation cutoff level (0.05 n/g or 50 pg/g), the results will be reviewed and verified by a Positive Certifying Scientist and then reported out as a confirmed positive result. • If the levels of Carboxy THC are less than (<) the confirmation cutoff levels, the results will be reviewed and verified by a Negative Certifying Scientist and reported out as a negative result.

Methodologies and Specimens Screening and confirmation techniques, as well as the cutoff levels can vary from one specimen to another, and from one laboratory to another. It is incredibly important to understand the differences between specimen cutoffs levels, and the methodology used (e.g., instrumentation used, specimen screening plus confirmation testing, specimen screening only, etc.) when deciding which laboratory and specimen test to use. Instrumentation between laboratories can vary because laboratories are not required to use any particular instrumentation for testing. Finding a laboratory that uses the highest standards for their testing is imperative, especially when the testing is used as a once in a lifetime test for the most vulnerable patients. The lower the limits of detection or cutoff levels for drugs and drug metabolites, the higher the standard is for the test being performed.


We are often asked how a newborn’s umbilical cord specimen could be negative when a mother’s urine specimen tested positive. The answer is that individual specimen results have no bearing on the validity of the results of other collected specimen tests. Each matrix is different and has its own advantages, disadvantages, and limits of interpretation. For example, a single dose of methamphetamine 12 hours prior to collection is highly likely to produce a positive urine result, however less likely to generate a positive result for a specimen type with a longer detection window such as umbilical cord tissue, meconium, or hair. The window of detection for urine is about 1-3 days (recent use), where the window of detection for the long-term specimens mentioned (habitual use) are up to approximately 3 months for hair, and up to approximately 20 weeks for meconium and umbilical cord tissue. We hope that having a better understanding of the significance of these elements and their functions within the drug testing realm can help broaden the overall knowledge of how different specimen tests, drug panels, and cutoff levels can be utilized to get the best results possible. References: 1. Scientific Working Group for Forensic Toxicology (SWGTOX). Standard Practices for Method Validation in Forensic Toxicology Journal of Analytical Toxicology 2013;37:453.

Michelle Lach, Editor-in-Chief of Substance/NeoTox and Marketing Manager at USDTL, has over 10 years of experience working in the drug and alcohol abuse and testing industry helping bring a better understanding of advanced drug testing services to the public, so the right tests and the best results can be utilized.


Confronting FASDs with Advanced Newborn Alcohol Biomarker Testing by Kelly Hack, Content Writer According to a recent study reported by the Center for Disease Control and Prevention (CDC), 1 in 10 pregnant women reported alcohol use (at least one drink of any alcoholic beverage in the past 30 days) and 1 in 33 reported binge drinking (consuming four or more drinks on an occasion at least one time in the past 30 days.)1 When pregnant women drink, alcohol enters the bloodstream and reaches the developing fetus by crossing the placenta. Since a fetus metabolizes alcohol at a slower rate than an adult, this causes higher blood alcohol concentrations in the developing baby. Women who drink during pregnancy, are subjecting their child to be at risk of fetal alcohol syndrome disorders (FASDs).2 FASDs are a group of conditions that can occur in a person whose mother drank alcohol during pregnancy. Healthcare professionals, educators and advocates are advising women that there is no safe amount of alcohol during pregnancy or when trying to get pregnant.3 In a 2010-2016 study funded by the National Institute on Alcohol Abuse and Alcoholism (NIH), first-grade children in 4 US communities were evaluated for FASDs utilizing the following assessment tools: growth, dysmorphology, neurodevelopment and prenatal alcohol exposure. The weighted prevalence estimates for fetal alcohol syndrome (FAS) ranged from 0 to 7.8 per 1000 children, partial fetal alcohol syndrome ranged from 8.4 to 59.1 per 1000 children and alcoholrelated neurodevelopmental disorder ranged from 9.7 to 50.4 per 1000 children.4 Fetal alcohol exposure is common in the United States today. Results from the above-mentioned study stress the importance of educating woman


of reproductive age about the long-term and irreversible damage that can occur when a woman participates in any alcohol-related drinking while pregnant.

FASD Signs and Symptoms-Defined by CDC The effects of FASDs can range from mild to severe and can manifest in different forms including: physical abnormalities, social/behavioral and intellectual disabilities. A person affected by an FASD diagnosis may exhibit the following: • Abnormal facial features: smooth ridge between nose and upper lip • Small head circumference • Decreased body weight • Hyperactive behavior • Learning/speech delays • Heart, kidney or bone complications • Vision or hearing difficulties

Types of FASDs-Defined by CDC Fetal Alcohol Syndrome (FAS) • Abnormal facial features, growth problems and central nervous system complications. Alcohol-related Neurodevelopmental Disorder (ARND) • Intellectual disabilities and difficulty with behavior and learning. Alcohol-related Birth Defects (ARBD) • Complications with heart, kidneys, bones and hearing.

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According to the American Academy of Pediatrics, a recent study was conducted among a population of foster and adopted youth, investigating cases of FAS/FASD that were either misdiagnosed or not diagnosed at all.5 The following statistics were reported: • FASD misdiagnosis rate of 6.4 percent. • FASD missed diagnosis rate of 80.1 percent

FAEE - Meconium - 18 Hours After Birth • The direct alcohol biomarker Fatty Acid Ethyl Esters (FAEEs) can be tested in meconium that is collected within 18 hours after birth. The window of detection for FAEE may be up to approximately 20 weeks prior to birth. PEth (Dried Blood Spot) - Before Discharge

Maternal drinking habits often go underreported due to the stigma attached to the behavior during pregnancy. Despite the risks and potential damaging outcomes that can occur, many pregnant women unfortunately still engage in risky drinking activities. Therefore, in efforts to address this disorder with the most vulnerable of patients; mother and baby, USDTL is using highly advanced scientific methods such as alcohol biomarker testing to help achieve the most accurate detection of potential ethanol consumption. As an exclusive laboratory for testing newborn alcohol biomarkers, we offer options that can be collected during multiple phases of the infant’s hospital stay to ensure you never miss an opportunity for detection. Through our comprehensive testing programs, we provide diverse advanced specimen testing in meconium, umbilical cord tissue and dried blood spot (DBS). We are the only laboratory that offers direct alcohol biomarkers (metabolites of ethanol) for newborns in all three of these specimen types.

Alcohol Biomarker Types EtG - Umbilical Cord Tissue - Collected at Birth • The direct alcohol biomarker Ethyl Glucuronide (EtG) can be tested in umbilical cord tissue collected at time of birth. The window of detection for EtG in umbilical cord tissue may be up to approximately 20 weeks prior to birth.


• The direct alcohol biomarker Phosphatidylethanol (PEth) can be tested in dried blood spots (via heel stick) any time after birth. The window of detection for PEth in blood may be up to approximately 2-4 weeks prior to collection. Monitoring alcohol use during pregnancy and at birth is imperative for identifying and addressing at risk mothers and babies. There is no cure for FASD, but research shows that early intervention services can improve a child’s development and we are invested in offering testing that supports this cause. References: 1. Data & Statistics | FASD | NCBDDD | CDC. (n.d.). Retrieved from https://www.cdc.gov/ncbddd/fasd/data. html 2. Fetal alcohol syndrome. (2018, January 10). Retrieved from https://www.mayoclinic.org/diseases-conditions/ fetal-alcohol-syndrome/symptoms-causes/syc20352901 3. Basics about FASDs | CDC. (n.d.). Retrieved from https:// www.cdc.gov/ncbddd/fasd/facts.html 4. Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities – 2018-02-06. (n.d.). Retrieved from https:// hsjcc.on.ca/prevalence-of-fetal-alcohol-spectrum-disordersin-4-uscommunities-2018-02-06/ 5. Chasnoff, I., Wells, A., & King, L. (2015). Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure. Pediatrics,264-270.

Kelly Hack, Content Writer for USDTL holds a Master’s of Science in Journalism, along with a versatile professional portfolio including investigative, educational, feature and profile writing. Hack strives to capitalize her knowledge-base in efforts to provide readers with information that is accurate, concise and pertinent.


NeoTox volume 10 issue 1


Content Writer

Managing & Design Editor

Michelle Lach, MSIMC

Kelly Hack, MS

Travis Hoying

Science Advisory Board

Douglas Lewis, D.Sc. Joseph Jones, Ph.D., NRCC-TC Adam Negrusz, Ph.D., F-ABFT

NeoTox is a news magazine of science, data, and news about newborn toxicology and substance exposure issues. It is our mission to distill the technical world of toxicology, drug testing, and addiction science into plain words. If you have suggestions for topics you would like to know more about or are interested in contributing to our publication, let us know.

To receive electronic copies of NeoTox, please join our mailing list on our website, www.USDTL.com.


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