Opioid use disorder (OUD) has become a national crisis, affecting over 2 million Americans. The number ofpregnant women with OUD in the U.S. increased almost 5-fold in the past decade, leading to a similar surge ininfants born with neonatal opioid withdrawal syndrome (NOWS), from 1.5 to 8 per 1,000 hospital births (32,000cases total) between 2004 and 2014. Associated hospital costs have risen by 35%, reaching $532 million in2014 ($462 million of which was financed by Medicaid). Among neonates prenatally exposed to illicit opioids,55-94% develop withdrawal symptoms, including respiratory, gastrointestinal, and feeding problems. Infants withsevere NOWS often require prolonged hospitalization, and 2-11% develop serious complications, such asseizures and weight loss. Severe cases often require pharmacological intervention to mitigate negative long-term impacts on the infant's neurological development. Per national guidelines, infants born to opioid users aremonitored (72-96 hours) in the hospital for signs of NOWS. However, different scales are currently in use tomonitor the severity of symptoms, leading to inconsistencies in diagnosis. Moreover, NOWS can presentanywhere from birth to 7 days after, sometimes leading to costly readmissions after release. Whenpharmacologic measures are needed, these delays can lead to an increased risk of infant morbidity. Therefore,there is an urgent need for an accessible, inexpensive, sensitive, and accurate diagnostic tool to support optimalclinical outcomes of infants with NOWS. To meet this need, FYR Diagnostics, alongside the University ofNew Mexico (UNM) and Texas A&M University (TAMU), will develop a convenient, non-invasivediagnostic assay from umbilical cord samples for early detection of severe NOWS to improveidentification of high- and low-risk infants. The assay will be based on two innovations: a) an miRNAsignature that identifies infants with severe NOWS; and b) a proprietary patent-pending ultrasensitive DNAAmplification Reaction (UDAR) chemistry that uses a simple primer design to rapidly and directly detect individualmiRNAs at low concentrations currently below the limit of detection. In Phase I, FYR will demonstrate thefeasibility of this novel quantitative tool by 1) testing the proprietary UDAR chemistry on predictive miRNAbiomarkers using umbilical cord plasma samples previously used by UNM/TAMU; and 2) comparing the UDAR-based assay to traditional RT-qPCR-based assays for detection of NOWS miRNA biomarkers to validate assayperformance and demonstrate that the UDAR-based assay exhibits equivalent or superior specificity andsensitivity. In Phase II, FYR, UNM, and TAMU will conduct a large-scale clinical study to validate the NOWSearly detection tool. The clinical validation study (N=150) will evaluate the analytical and clinical feasibility of theUDAR-based assay, demonstrating that it exhibits comparable performance and predictive utility of NOWSseverity across the clinical variability of infants born to women with OUD. The project will generate the pivotaldata necessary for FDA approval of a multi-center trial and a basis for commercialization efforts.
Public Health Relevance Statement: Narrative
Opioid use disorder is a national crisis affecting over 2 million Americans, and the incidence of neonatal opioid
withdrawal syndrome (NOWS) due to in utero exposure to opioids has been steadily increasing. Severe NOWS
that requires pharmacological intervention is not straightforward to diagnose, and delays lead to increased risk
of infant morbidity, indicating the need for a sensitive and accurate diagnostic tool. FYR Diagnostics, alongside
the University of New Mexico (UNM) and Texas A&M University (TAMU), will develop a convenient, non-invasive
diagnostic assay that uses umbilical cord samples for early detection of infants at high-risk for severe NOWS, in
order to improve clinical management and outcomes of the growing number of infants prenatally exposed to
opioids.
Project Terms: Affect ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Birth ; Parturition ; Blood ; Blood Reticuloendothelial System ; Chemistry ; Clinical Research ; Clinical Study ; Diagnosis ; Equipment ; Exhibits ; Goals ; Hospitalization ; Hospital Admission ; Hospitals ; Incidence ; Infant ; Insurance ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Medicaid ; Methods ; Neonatal Abstinence Syndrome ; Neonatal Opioid Withdrawal Syndrome ; Neonatal Substance Withdrawal ; Neonatal Withdrawal Syndrome ; newborn abstinence syndrome ; New Mexico ; Noise ; Nucleotides ; Legal patent ; Patents ; Pharmacology ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Pregnant Women ; expectant mother ; expecting mother ; pregnant mothers ; Reverse Transcription ; Risk ; RNA ; Non-Polyadenylated RNA ; RNA Gene Products ; Ribonucleic Acid ; Seizures ; Sensitivity and Specificity ; Specificity ; Technology ; Temperature ; Testing ; Texas ; Time ; Umbilical cord structure ; Umbilical Cord ; Universities ; Body Weight decreased ; Weight Loss ; Weight Reduction ; body weight loss ; wt-loss ; Woman ; Measures ; Withdrawal Symptom ; Medication Management ; Analgesic Management ; Pharmacologic Management ; medication therapy management ; Guidelines ; base ; improved ; Clinical ; Phase ; Neurologic ; Neurological ; Multicenter Trials ; Multi-center trial ; Hospital Costs ; Hospitalization cost ; Evaluation ; Individual ; Opioid ; Opiates ; noninvasive diagnosis ; non-invasive diagnosis ; non-invasive diagnostic ; noninvasive diagnostic ; Collaborations ; Exposure to ; tool ; Diagnostic ; vulnerable infant ; high risk infant ; Hour ; Severities ; Clinic ; Reaction ; respiratory ; gastrointestinal ; meetings ; Clinics or Hospitals ; Clinics and Hospitals ; American ; early detection ; Early Diagnosis ; Performance ; hospital re-admission ; re-admission ; re-hospitalization ; readmission ; rehospitalization ; hospital readmission ; novel ; validation studies ; DNA amplification ; Modality ; infant morbidity ; Sampling ; exposed in utero ; fetal exposure ; in utero exposure ; intra-uterine environmental exposure ; intrauterine environmental exposure ; prenatally exposed ; prenatal exposure ; case control ; Intervention Strategies ; interventional strategy ; Intervention ; Nucleic Acid Amplification Technics ; Nucleic Acid Amplification Techniques ; Micro RNA ; miRNA ; miRNAs ; MicroRNAs ; Address ; Symptoms ; Data ; Detection ; Clinical Management ; Pharmacological Treatment ; Monitor ; Development ; developmental ; Output ; neonate ; cost ; feeding ; design ; designing ; fetal opioid exposure ; fetal opiate exposures ; gestational opiate exposure ; gestational opioid exposure ; prenatal opiate exposure ; prenatal opioid exposure ; prenatally opiate exposed ; Outcome ; prospective ; Coupled ; innovation ; innovate ; innovative ; infant outcome ; commercialization ; high risk ; diagnostic assay ; opioid use disorder ; opiate use disorder ; opioid use ; opiate consumption ; opiate drug use ; opiate intake ; opiate use ; opioid consumption ; opioid drug use ; opioid intake ; microRNA biomarkers ; miRNA biomarkers ; miRNA markers ; microRNA markers ; opioid use in pregnancy ; gestational opioid use ; opiate use in pregnancy ; opioids during pregnancy ; opioids in pregnancy ; opoid use during pregnancy ; prenatal opioid use ; illicit opioid ; illicit opiate ; opioid user ; Opiate user ; Opioid drug user ; PWUO ; people who use opioids ; persons who use opioids ; predictive panel ; rapid test ; rapid assay ; rapid tests ; detection assay ; detection limit ; accurate diagnostics ;
