Multimodal Fetal and Placental Imaging and Biomarkers of Clinical Outcomes in Opioid Use Disorder

The goal of this observational study is to learn about the long term effects of prenatal opioid exposure. The main objectives are:

• Long term goal: to improve the safety and efficacy of maternal Opioid Use Disorder (OUD) and eliminate neonatal opioid withdrawal syndrome (NOWS) and poor childhood neurodevelopment.
• To characterize prenatal opioid exposure (POE) related placental and fetal brain structural and functional disruptions using longitudinal placenta-fetal brain magnetic resonance imaging (MRI) and determine proteomic, genomic, and epigenetic signatures of NOWS and poor infant neurodevelopment.

In this study participants will:

• Receive two placental-fetal MRIs, one during second trimester and one in third trimester.
• Answer surveys relating to their medical and social history.
• Have blood drawn during pregnancy and delivery.
• Child development follow up: answer surveys on their child's development milestones and at one year of life they will undergo a development assessment.

Study Overview

• Status: Enrolling by invitation
• Conditions: Substance-Related Disorders; Pregnancy Related; Narcotic-Related Disorders; Opioid Use Disorder; Buprenorphine Dependence; Methadone Dependence
• Intervention / Treatment: Drug: Buprenorphine or Methadone Treatment; Diagnostic test: Fetal and Placental MRI; Behavioral: Child Developmental Assessment; Behavioral: Questionnaires; Other: Blood and Placental Samples

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Any woman of the age of 18 or older that is having a single pregnancy, and currently taking buprenorphine or methadone for opioid use disorder.

Description

Pregnant women with opioid use disorder

Inclusion Criteria:

• Age >18 years
• Currently taking buprenorphine or methadone for OUD and are enrolled in a prenatal opioid maintenance program
• Singleton Pregnancy
• Planned delivery at Indiana University or University of Pittsburgh study sites

Exclusion Criteria:

• Serious maternal medical illness as deemed by study physician investigators that would make it challenging to comply with study procedures
• Known or suspected major fetal/ neonatal congenital abnormalities
• HIV or AIDS

Infants with prenatal opioid exposure:

Inclusion:

1. Prenatal buprenorphine or methadone exposure
2. Born to mother enrolled in Opioid Use Disorder arm of study

Exclusion:

Major congenital anomalies or genetic syndromes affecting neurodevelopment

Control Pregnant Women:

Inclusion:

1. Women >18 Years of age
2. Healthy singleton pregnancy
3. Planned delivery at Indiana University or University of Pittsburgh study sites

Exclusion:

1. Serious maternal medical illness as deemed by study physician investigators that would make it challenging to comply with study procedures
2. HIV or AIDS
3. Known or suspected major fetal congenital abnormalities
4. Any history of opioid misuse before or during pregnancy-per self-report and clinical notes.

Control infants:

Inclusion:

Born to control pregnant mother enrolled in study

Exclusion:

Any major congenital anomalies, genetic abnormalities, neurologic abnormalities, syndromes, or chronic medical conditions affecting neurodevelopment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant Mothers with Opioid Use Disorder; 150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment	Drug: Buprenorphine or Methadone Treatment; Pregnant mothers must be taking Buprenorphine or Methadone; Diagnostic test: Fetal and Placental MRI; Two MRIs : Second Trimester; Third Trimester; Behavioral: Child Developmental Assessment; At 1 year of life child will receive a developmental assessment; Behavioral: Questionnaires; Participants will answer questionnaires on their medical history, pregnancy, substance use, and after birth: their child's development; Other: Blood and Placental Samples; At each MRI visit a blood sample will be collected for substances, DNA, RNA, epigenetics, and placental biomarkers. At delivery: A sample of placenta will be collected for RNA, DNA, and epigenetic analysis.
Pregnant Mothers; 100 pregnant mother who to not have a history of opioid use disorder	Diagnostic test: Fetal and Placental MRI; Two MRIs : Second Trimester; Third Trimester; Behavioral: Child Developmental Assessment; At 1 year of life child will receive a developmental assessment; Behavioral: Questionnaires; Participants will answer questionnaires on their medical history, pregnancy, substance use, and after birth: their child's development; Other: Blood and Placental Samples; At each MRI visit a blood sample will be collected for substances, DNA, RNA, epigenetics, and placental biomarkers. At delivery: A sample of placenta will be collected for RNA, DNA, and epigenetic analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alterations in fetal brain volume	Comparing changes in fetal brain volume using MRI between babies who have had prenatal opioid exposure (POE) and controls	Between 20 weeks gestation and delivery
Differences in placenta signal	Comparing differences in placenta signal using MRI between the POE group and controls	Between 20 weeks gestation and delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placental epigenetic changes related to POE	Compare placental DNA methylation in POE group and control group	Between 20 weeks gestation and delivery
Placental dysfunction biomarkers related to POE	Compare concentrations of blood proteins in POE group vs controls	Between 20 weeks gestation and delivery
Neonatal Opioid Withdrawal Syndrome (NOWS) severity	Measuring NOWs severity in the POE group using eat sleep console scores	After birth through one year of life
Length of Hospital Stay	Measuring NOWs severity in the POE group using length of hospital stay	After birth through one year of life
Ages and Stages Questionnaire Scores during infancy	Comparing neurodevelopment of POE group and controls using the ages and stages questionnaire at multiple time points in baby's first year of life. This questionnaire assesses infants developmental level. Scores can identify whether child is below cutoff and needs professional intervention, close to cutoff and requires more developmental support and learning, or above cutoff and on track.	After birth through one year of life
Neurocognitive and behavioral development assessment (Bayley-4) at one year of age	Comparing neurodevelopment of POE group and controls using the Bayley's 4 assessment at one year of age. This assessment is administered by professionals to identify development delays in children.	After birth through one year of life

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Opioid Use Disorder; Buprenorphine; Subutex; Pregnant with Opioid Use Disorder; Pregnant taking buprenorphine/subutex
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Opioid-Related Disorders; Narcotic-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Respiratory System Agents; Antitussive Agents; Buprenorphine; Methadone
• Other Study ID Numbers: RADY-IIR-19751; R01DA059321 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No