MicroRNA Biomarkers for Neonatal Opioid Withdrawal Syndrome

Understanding the microRNA Response to Opioid Withdrawal and Their Uses as Potential Biomarkers for Neonatal Abstinence Syndrome

Infants with neonatal abstinence syndrome (NAS) experience prolonged hospital stays and poor neurodevelopmental outcomes, in-part because of the lack of accurate, individualized, biologic assessments available to manage this increasingly common medical condition. The proposed study will define the molecular mechanisms that regulate the response to opioid withdrawal in the developing brain by focusing on three candidate microRNAs (let-7a, miR-146a, miR-192) that have been shown to respond to opioid exposure in animal models and adults, and are impacted in both my preliminary study of infants with NAS, and my human neural progenitor cell (NPC) design of opioid withdrawal. By determining the mechanism through which microRNAs impact NPC differentiation in opioid withdrawal, and determining whether exosomal salivary microRNA levels predict treatment dose and neurodevelopmental outcomes in infants with NAS, this study will enhance our knowledge of NAS-related biology and identify potential biomarkers that could improve medical care for this important medical condition.

Study Overview

• Status: Recruiting
• Conditions: Neonatal Abstinence Syndrome; Neonatal Opioid Withdrawal Syndrome
• Intervention / Treatment: Genetic: Buccal swab saliva for further genetic testing

• Study Type: Observational
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rhea E Sullivan, B.S.; Phone Number: 321585 717-531-0003; Email: rsullivan2@pennstatehealth.psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Infants enrolled into the study were exposed to opiates in-utero for at least one month of gestation. All infants enrolled meet the eligibility criteria listed above.

Description

Inclusion Criteria:

• Newborns ≥35weeks gestation with chronic in-utero opioid exposure (>1month of gestation exposure). Maternal exposure will be determined by evaluating the medical records for maternal medication use, maternal urine toxicology and neonatal meconium toxicology results per standard clinical care
• Neonates born at Penn State Hershey Medical Center or transferred at <48 hours after birth
• Mothers with chronic in-utero opioid use during pregnancy ( ≥1month of gestation)

Exclusion Criteria:

• <35 week gestation
• Infant required mechanical ventilation or non-invasive mechanical support
• Infant exposure to magnesium sulfate
• Opioid-exposed neonates who are actively receiving dextrose infusion for persistent neonatal hypoglycemia at the time of enrollment (<48hours after birth).
• Infant with major congenital anomalies
• Parent or guardian unable to provide consent
• Mothers and neonates without history of opioid exposure/dependence

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infants exposed to in utero opiates; Infants that meet IRB-approved inclusion/exclusion criteria.	Genetic: Buccal swab saliva for further genetic testing; Genetic testing. Whole saliva RNA will be isolated for downstream microRNA quantification.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental outcome scores	Measured by Ages and Stages Questionnaire-3, score scale 0-60	6 months of age
Maximum concentration of morphine required for withdrawal symptom control	Measured in mg/kg/ml	Measured during the course of hospital stay
Salivary microRNA level let-7a	Relative fluorescence (Cq) measured by qPCR using established housekeeping gene	Buccal swab collected within 96 hrs of life and at discharge
Salivary level of microRNA-146a	Relative fluorescence (Cq) measured by qPCR using established housekeeping gene	Buccal swab collected within 96 hrs of life and at discharge
Salivary level of microRNA-192	Relative fluorescence (Cq) measured by qPCR using established housekeeping gene	Buccal swab collected within 96 hrs of life and at discharge
Salivary level of microRNA-149-3p	Relative fluorescence (Cq) measured by qPCR using established housekeeping gene	Buccal swab collected within 96 hrs of life and at discharge

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Steven D. Hicks, MD, PhD, Associate Professor of Pediatrics

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): April 10, 2027

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: microRNA; infant; neurodevelopmental; exosomes; saliva
• Additional Relevant MeSH Terms: Mental Disorders; Infant, Newborn, Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neonatal Abstinence Syndrome
• Other Study ID Numbers: 13565; F30DA057094 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No