Maternal Buprenorphine-naloxone Treatment and the Infant

Maternal Buprenorphine-naloxone Treatment During the Perinatal Period: Fetal and Infant Effects

The purpose of this mechanistic study is to evaluate the effects that maternal buprenorphine-naloxone maintenance have on the neurobehavioral development of the fetus and infant. To accomplish this, the investigators will study a sample of 120 opioid dependent pregnant women that will receive buprenorphine-naloxone as part of substance abuse treatment at a comprehensive care treatment facility for pregnant and parenting women with substance use disorders. Fetal neurobehavior and maternal physiology will be assessed, via an established maternal-fetal data acquisition system, at 4 points during gestation: 24, 28, 32 and 36 weeks. Infant birth parameters and Neonatal Abstinence Syndrome (NAS) spectrum display will be evaluated at birth, and infant neurodevelopment will be assessed during the first month of life.

Study Overview

• Status: Completed
• Conditions: Maternal Opioid Use Disorder; Opioid Exposed Infant
• Intervention / Treatment: Device: fetal monitoring; Drug: Buprenorphine Naloxone

Detailed Description

The project population will be 40 pregnant women with opioid use disorder inducted as outpatients to buprenorphine-naloxone maintenance. Subject treatment data, including medical and obstetric histories, drug use histories, demographic information and psychosocial information will be extracted from patient charts. Weekly urine toxicology testing will provide information regarding other substance use/misuse during the time of study participation. Study participants will undergo 2 60 minute maternal and fetal neurophysiologic monitoring sessions on one day at 4 points during gestation: 24, 28, 32 and 36 weeks, at times of trough (just before sublingual buprenorphine-naloxone or methadone daily dose) and peak (2 1/2 hours after dosing) maternal drug levels. Fetal cardiac (heart rate, heart rate variability, heart rate accelerations) and movement (total fetal movement, number and duration of movement bouts) and the correlation between the two (fetal heart rate-movement coupling) will be determined. Maternal physiologic measures will include heart period and variability, vagal tone, skin conductance and respiratory data. All maternal and fetal measures, with the exception of blood pressure, will be computed in 1-minute intervals and averaged over the 60 min recording. Infant birth data and birth parameters, and neonatal abstinence syndrome scores will be extracted from patient charts. Infants will undergo neurobehavioral testing using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale, a 30 minute harmless assessment of infant functioning, on days 3, 14 and 30 of life.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 44 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Current opioid use disorder (OUD) as defined by DSM V criteria
• singleton pregnancies, generally uncomplicated by conditions that jeopardize pregnancy outcome
• Gestation less than 24 weeks

Exclusion Criteria:

• Complications of pregnancy, including gestational diabetes, polyhydramnios, hypertension, placenta previa or significant risk of preterm delivery;
• Evidence of fetal malformation detected by prenatal ultrasound;
• Significant general maternal health problems that can affect fetal functioning, including Type I or gestational diabetes, alterations in thyroid functioning, HIV infection or hypertension;
• Significant maternal psychopathology that would preclude informed consent;
• Alcohol use disorder per DSM V criteria (see ascertainment methods below)
• Women stable on methadone maintenance (defined as more than 3 consecutive days of dosing)
• Women coming to treatment reporting "street" methadone use (for more than 3 consecutive days
• Women not planning to receive obstetric care at the Center for Addiction and Pregnancy; - Women not planning to deliver their infants at Johns Hopkins Bayview Medical center
• Women planning for adoption of their infant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buprenorphine-naloxone treated; Participants receiving buprenorphine-naloxone treatment for opioid use disorder during pregnancy	Device: fetal monitoring; Maternal fetal monitoring; Other Names: maternal physiology monitoring; Drug: Buprenorphine Naloxone; Treatment for opioid use disorder; Other Names: Suboxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal Heart Rate at 24 Weeks	Fetal heart rate in beats per minute, mean over 60 minutes gestation. Fetal heart rate in msec at 24 weeks of gestation at times of peak maternal plasma drug concentrations	24 weeks of gestation
Fetal Heart Rate at 28 Weeks Gestation	Fetal heart rate in beats per minute, mean over 60 minutes gestation. Fetal heart rate at 28 weeks of gestation at times of tpeak maternal plasma drug concentrations.	28 weeks of gestation
Fetal Heart Rate at 32 Weeks Gestation	Fetal heart rate in beats per minute, mean over 60 minutes. Fetal heart rate at 32 weeks of gestation at times of peak maternal plasma drug concentrations	32 weeks of gestation
Fetal Heart Rate at 36 Weeks Gestation	Fetal heart rate in beats per minute, mean over 60 minutes. Fetal heart rate at 36 weeks of gestation at times of peak maternal plasma drug concentrations.	36 weeks of gestation
Total Fetal Movement at 24 Weeks Gestation	Total fetal movement at 24 weeks of gestation. Total number of fetal moves over 60 minutes via fetal monitoring at time of peak maternal plasma drug concentrations at 24 weeks of gestation.	24 weeks of gestation
Total Fetal Movement at 36 Weeks Gestation	Total fetal movement over 60 minutes via fetal monitoring at 36 weeks of gestation. Nimber of fetal movements over 60 minutes via fetal monitoring at times of peak maternal plasma drug concentrations at 36 weeks of gestation.	36 weeks of gestation
Total Fetal Movement at 28 Weeks Gestation	Total fetal movement over 60 minutes via fetal monitoring. Total fetal movement over 60 minutes via fetal monitoring at times of trough and peak maternal plasma drug concentrations at 28 weeks of gestation.	28 weeks of gestation
Total Fetal Movement at 32 Weeks Gestation	Total fetal movement over 60 minutes via fetal monitoring at 32 weeks of gestation. Number of fetal moves over 60 minutes via fetal monitoring at times of peak maternal plasma drug concentrations at 32 weeks of gestation.	32 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal abstinence syndrome severity score (NAS)1	NAS lists 21 symptoms most frequently observed in opiate-exposed infants. Baseline score is recorded two hours after birth or admission to the nursery. If the infant's score at any scoring interval is ≥ 8, scoring is increased to 2-hourly and continued for 24 hours from the last total score of 8 or higher. If the 2-hourly score is ≤ 7 for 24 hours then 4-hourly scoring intervals may be resumed. If pharmacotherapy is not needed the infant is scored for the first 4 days of life at 4-hourly intervals. If pharmacotherapy is required the infant is scored at 2- or 4-hourly intervals, depending on whether the abstinence score is less than or greater than 8 throughout the duration of therapeutic period. If after cessation of pharmacotherapy the score is less than 8 for the following 3 days, scoring may be discontinued.	day 1 of life
NAS2	Neonatal abstinence syndrome severity score	day 2 of life
NAS3	Neonatal abstinence syndrome severity score	day 3 of life
NAS4	Neonatal abstinence syndrome severity score	day 4 of life

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Lauren M Jansson, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): December 27, 2022
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: maternal opioid use; neonatal abstinence syndrome; buprenorphine-naloxone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Naloxone; Buprenorphine, Naloxone Drug Combination
• Other Study ID Numbers: IRB00093171; 1R01DA041367-01A1 (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: Yes
• Studies a U.S. FDA-regulated device product: No