Fetal and Infant Effects of Maternal Buprenorphine Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01561079
Recruitment Status : Completed
First Posted : March 22, 2012
Results First Posted : August 28, 2017
Last Update Posted : September 26, 2017
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
This research will track the longitudinal neurobehavioral development of the buprenorphine-exposed fetus across gestation through 1 month of age in an effort to determine the safety of this medication for use during gestation, the relationship between maternal physiologic changes due to buprenorphine administration and newborn functioning, and to determine potential fetal neurobehavioral markers that may predict Neonatal Abstinence Syndrome expression and infant neurobehavioral outcome. Comparisons to results from a similar project in methadone-exposed pregnancies will be made. This proposal seeks to advance the way the investigators inform the treatment of the opioid dependent woman during pregnancy and her infant after birth.

Condition or disease Intervention/treatment Phase
Neonatal Abstinence Syndrome Drug: Buprenorphine Phase 2 Phase 3

Detailed Description:
There is an increase in the prevalence of illicit opiate use among women of childbearing age in many countries today. Methadone is the treatment of choice for opioid dependency during pregnancy in the US because it markedly diminishes withdrawal symptoms and craving and blocks opioid effects, however, in utero exposure results in significant depression of fetal neurobehaviors such as fetal heart rate and heart rate variability and fetal motor activity, and significant neonatal abstinence syndrome (NAS) in the majority of exposed infants. Since its approval in 2002, the prescription of buprenorphine for opioid dependence has increased dramatically but, as with methadone, this mediation is not approved for use during pregnancy. Currently, women treated with buprenorphine prior to pregnancy are transitioned to methadone treatment due to a lack of information regarding the effects of buprenorphine on the developing fetus and infant. Pilot work by this research team suggests that buprenorphine- as compared to methadone-exposed fetuses display more optimal neurobehavioral functioning in the second and third trimesters of pregnancy. Although these results are encouraging, there is a critical need to explore fully the effects of this medication on the fetus and infant to adequately advise care providers and patients regarding its use. This is particularly true given the imminent publication of a pivotal study comparing buprenorphine to methadone treatment during pregnancy which has suggested the optimality of buprenorphine for the treatment of opioid dependence during pregnancy, and is likely to result in increasing numbers of women being treated with off-label buprenorphine during pregnancy. This proposal seeks to explore the effect of buprenorphine on maternal physiology and fetal neurobehavioral functioning longitudinally as a measure of the development of the fetal nervous system. Additionally, the neurobehavioral profile and NAS of the buprenorphine-exposed infant up to one month will be delineated in an effort to provide information necessary to provide optimal pharmacologic and non-pharmacologic treatment of NAS. Furthermore, this group has previously explored similar parameters in methadone-exposed fetuses and infants, and results of this study can be compared to those historical data. These parameters will advance our understanding of the way the investigators view and implement the future pharmacologic treatment of the opiate dependent woman during pregnancy and her infant after birth, and inform clinicians, health insurance companies and regulatory agencies in the provision of optimal care to the opioid dependent pregnant woman and her offspring before and after birth.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Fetal and Infant Effects of Maternal Buprenorphine Treatment
Study Start Date : February 2012
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Maternal buprenorphine treatment
Buprenorphine maintenance during pregnancy
Drug: Buprenorphine
Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.
Other Name: Subutex

Primary Outcome Measures :
  1. Fetal Heart Rate [ Time Frame: 24, 28, 32 and 36 weeks of gestation ]
    Fetal heart rate in beats per minute at time of trough and peak maternal buprenorphine levels

  2. Fetal Heart Rate Variability [ Time Frame: 24, 28, 32 and 36 weeks of gestation ]
    Fetal heart rate variability at 24, 28, 32 and 36 weeks of gestation at times of trough and peak maternal buprenorphine levels

  3. Accelerations of Fetal Heart Rate [ Time Frame: 24, 28, 32 36 weeks of gestation ]
    Number of accelerations of fetal heart rate exhibited during the 60 minute recordings

  4. Fetal Movement [ Time Frame: 24, 28, 32, 36 weeks of gestation ]
    Fetal movement (number x duration of fetal movements) during the 60 minute recordings at times of trough and peak maternal buprenorphine levels

  5. Fetal Movement - Fetal Heart Rate Coupling [ Time Frame: 24, 28, 32, 36 weeks of gestation ]
    The integration between fetal movements and heart rate (FM-FHR coupling) was quantified as the proportion of time individual movements were associated with a change in FHR, using previously developed criteria. FM-FHR coupling reflects coactivation of the sympathetic and parasympathetic components of the autonomic nervous system.

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Current opioid dependence as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-R criteria
  • 18-40 years of age with uncomplicated singleton pregnancies
  • Accurate gestational age dating verified by ultrasound
  • Gestation of less than 34 weeks
  • Stabilization on buprenorphine for one week prior to study procedures

Exclusion Criteria:

  • Complications of pregnancy, including gestational diabetes, polyhydramnios, hypertension, placenta previa or significant risk of preterm delivery (i.e. incompetent cervix)
  • 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 (i.e. schizophrenia)
  • Alcohol dependency per DSM IV R criteria (see ascertainment methods below)
  • Women stable on methadone maintenance (defined as more than 3 days of methadone dosing)
  • Women entering drug treatment reporting using "street" methadone (for more than 3 days)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01561079

United States, Maryland
Center for Addiction and Pregnancy
Baltimore, Maryland, United States, 21224
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Principal Investigator: Lauren M Jansson, MD Johns Hopkins University

Responsible Party: Johns Hopkins University Identifier: NCT01561079     History of Changes
Other Study ID Numbers: 00051600
First Posted: March 22, 2012    Key Record Dates
Results First Posted: August 28, 2017
Last Update Posted: September 26, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Johns Hopkins University:
Fetal neurobehavior
Infant neurobehavior

Additional relevant MeSH terms:
Neonatal Abstinence Syndrome
Infant, Newborn, Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists