Buprenorphine Dependence, Methadone Dependence, Narcotic-Related Disorders, Opioid Use Disorder, Pregnancy Related, Substance-Related Disorders
Conditions
Keywords
Pregnant with Opioid Use Disorder, Opioid Use Disorder, Subutex, Buprenorphine, Pregnant taking buprenorphine/subutex
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.
Interventions
DRUGBuprenorphine or Methadone Treatment
Pregnant mothers must be taking Buprenorphine or Methadone
DIAGNOSTIC_TESTFetal and Placental MRI
Two MRIs : * Second Trimester * Third Trimester
BEHAVIORALChild Developmental Assessment
At 1 year of life child will receive a developmental assessment
BEHAVIORALQuestionnaires
Participants will answer questionnaires on their medical history, pregnancy, substance use, and after birth: their child's development
OTHERBlood 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.
Sponsors
Senthil Sadhasivam
National Institute on Drug Abuse (NIDA)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Placental epigenetic changes related to POE | Between 20 weeks gestation and delivery | Compare placental DNA methylation in POE group and control group |
| Placental dysfunction biomarkers related to POE | Between 20 weeks gestation and delivery | Compare concentrations of blood proteins in POE group vs controls |
| 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 |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed