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

• Conditions: Substance-Related Disorders; Pregnancy Related; Methadone Dependence; Buprenorphine Dependence; Opioid Use Disorder; Narcotic-Related Disorders
• Interventions: Drug: Buprenorphine or Methadone Treatment; Diagnostic Test: Fetal and Placental MRI; Behavioral: Child Developmental Assessment; Behavioral: Questionnaires; Other: Blood and Placental Samples

• Registration Number: NCT06415994
• Lead Sponsor: Indiana University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-13
• Study First Submitted: 2024-03-04
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-14
• Last Update Submitted: 2024-05-14
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16
• Primary Completion: 2028-12-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 250

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Pregnant Mothers with Opioid Use Disorder	Questionnaires	150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment
Pregnant Mothers with Opioid Use Disorder	Fetal and Placental MRI	150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment
Pregnant Mothers with Opioid Use Disorder	Blood and Placental Samples	150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment
Pregnant Mothers	Fetal and Placental MRI	100 pregnant mother who to not have a history of opioid use disorder
Pregnant Mothers	Child Developmental Assessment	100 pregnant mother who to not have a history of opioid use disorder
Pregnant Mothers with Opioid Use Disorder	Buprenorphine or Methadone Treatment	150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment
Pregnant Mothers with Opioid Use Disorder	Child Developmental Assessment	150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment
Pregnant Mothers	Questionnaires	100 pregnant mother who to not have a history of opioid use disorder
Pregnant Mothers	Blood and Placental Samples	100 pregnant mother who to not have a history of opioid use disorder

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Placental dysfunction biomarkers related to POE	Between 20 weeks gestation and delivery	Compare concentrations of blood proteins in POE group vs controls
Ages and Stages Questionnaire Scores during infancy	After birth through one year of life	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.
Placental epigenetic changes related to POE	Between 20 weeks gestation and delivery	Compare placental DNA methylation in POE group and control group
Neurocognitive and behavioral development assessment (Bayley-4) at one year of age	After birth through one year of life	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.
Neonatal Opioid Withdrawal Syndrome (NOWS) severity	After birth through one year of life	Measuring NOWs severity in the POE group using eat sleep console scores
Length of Hospital Stay	After birth through one year of life	Measuring NOWs severity in the POE group using length of hospital stay

Trial Locations

Locations (2)

Riley Hospital for Children; 🇺🇸 Indianapolis, Indiana, United States

University of Pittsburg; 🇺🇸 Pittsburgh, Pennsylvania, United States