## Protocol Section
### Identification Module
**NCT ID:** NCT01561079

**Brief Title:** Fetal and Infant Effects of Maternal Buprenorphine Treatment

**Official Title:** Fetal and Infant Effects of Maternal Buprenorphine Treatment

#### Organization Study ID Info
**ID:** 00051600
#### Organization
**Class:** OTHER
**Full Name:** Johns Hopkins University
### Status Module
#### Completion Date
**Date:** 2016-06

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2017-09-26

**Type:** ACTUAL

**Last Update Submit Date:** 2017-08-28

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2016-06

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2017-08-28

**Type:** ACTUAL

**Results First Submit Date:** 2017-03-08

**Results First Submit QC Date:** 2017-08-25

#### Start Date
**Date:** 2012-02

**Status Verified Date:** 2017-08

#### Study First Post Date
**Date:** 2012-03-22
**Type:** ESTIMATED
**Study First Submit Date:** 2012-03-19
**Study First Submit QC Date:** 2012-03-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Johns Hopkins University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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.

**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.

### Conditions Module

**Conditions:**

- Neonatal Abstinence Syndrome

**Keywords:**

- Buprenorphine

- Methadone

- Fetal neurobehavior

- Infant neurobehavior

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 127

**Type:** ACTUAL

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Buprenorphine maintenance during pregnancy

**Intervention Names:**

- Drug: Buprenorphine

**Label:** Maternal buprenorphine treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Maternal buprenorphine treatment

**Description:** Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.

**Name:** Buprenorphine

**Other Names:**

- Subutex

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Fetal heart rate in beats per minute at time of trough and peak maternal buprenorphine levels

**Measure:** Fetal Heart Rate

**Time Frame:** 24, 28, 32 and 36 weeks of gestation

**Description:** Fetal heart rate variability at 24, 28, 32 and 36 weeks of gestation at times of trough and peak maternal buprenorphine levels

**Measure:** Fetal Heart Rate Variability

**Time Frame:** 24, 28, 32 and 36 weeks of gestation

**Description:** Number of accelerations of fetal heart rate exhibited during the 60 minute recordings

**Measure:** Accelerations of Fetal Heart Rate

**Time Frame:** 24, 28, 32 36 weeks of gestation

**Description:** Fetal movement (number x duration of fetal movements) during the 60 minute recordings at times of trough and peak maternal buprenorphine levels

**Measure:** Fetal Movement

**Time Frame:** 24, 28, 32, 36 weeks of gestation

**Description:** 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.

**Measure:** Fetal Movement - Fetal Heart Rate Coupling

**Time Frame:** 24, 28, 32, 36 weeks of gestation

### Eligibility Module

**Eligibility Criteria:** 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)

**Maximum Age:** 40 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Baltimore

**Country:** United States

**Facility:** Center for Addiction and Pregnancy

**State:** Maryland

**Zip:** 21224

**Location 2:**

**City:** Baltimore

**Country:** United States

**Facility:** Johns Hopkins Bayview Medical Center

**State:** Maryland

**Zip:** 21224

#### Overall Officials

**Official 1:**

**Affiliation:** Johns Hopkins University

**Name:** Lauren M Jansson, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Jansson LM, Dipietro JA, Velez M, Elko A, Williams E, Milio L, O'Grady K, Jones HE. Fetal neurobehavioral effects of exposure to methadone or buprenorphine. Neurotoxicol Teratol. 2011 Mar-Apr;33(2):240-3. doi: 10.1016/j.ntt.2010.09.003. Epub 2010 Sep 22.

**PMID:** 20868741

**Citation:** Velez ML, McConnell K, Spencer N, Montoya L, Tuten M, Jansson LM. Prenatal buprenorphine exposure and neonatal neurobehavioral functioning. Early Hum Dev. 2018 Feb;117:7-14. doi: 10.1016/j.earlhumdev.2017.11.009. Epub 2017 Dec 7.

**PMID:** 29223912

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007232

- Term: Infant, Newborn, Diseases

- ID: D000019966

- Term: Substance-Related Disorders

- ID: D000064419

- Term: Chemically-Induced Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC25

- Name: Substance Related Disorders

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M12302

- Name: Neonatal Abstinence Syndrome

- Relevance: HIGH

- As Found: Neonatal Abstinence Syndrome

- ID: M10276

- Name: Infant, Newborn, Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21837

- Name: Substance-Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M30302

- Name: Chemically-Induced Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009357

- Term: Neonatal Abstinence Syndrome

### Intervention Browse Module - Ancestors

- ID: D000000701

- Term: Analgesics, Opioid

- ID: D000009294

- Term: Narcotics

- ID: D000002492

- Term: Central Nervous System Depressants

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000009292

- Term: Narcotic Antagonists

### Intervention Browse Module - Browse Branches

- Abbrev: Analg

- Name: Analgesics

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: NarcAntag

- Name: Narcotic Antagonists

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AnTuAg

- Name: Antitussive Agents

- Abbrev: Resp

- Name: Respiratory System Agents

### Intervention Browse Module - Browse Leaves

- ID: M5317

- Name: Buprenorphine

- Relevance: HIGH

- As Found: Aortic

- ID: M11671

- Name: Methadone

- Relevance: LOW

- As Found: Unknown

- ID: M4033

- Name: Analgesics, Opioid

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M12245

- Name: Narcotics

- Relevance: LOW

- As Found: Unknown

- ID: M12243

- Name: Narcotic Antagonists

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000002047

- Term: Buprenorphine

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Maternal Buprenorphine Treatment

**Deaths Num At Risk:** 49

**Description:** Buprenorphine maintenance during pregnancy

Buprenorphine: Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.

Two severe adverse events were reported in the same infant patient. One infant had congenital heart disease and polydactyly

**ID:** EG000

**Other Num Affected:** 15

**Other Num at Risk:** 49

**Serious Number Affected:** 1

**Serious Number At Risk:** 49

**Title:** Maternal Buprenorphine Treatment

**Frequency Threshold:** 0

#### Other Events

**Term:** Cholestasis of pregnancy

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** Three participants developed cholestasis of pregnancy. All three had concurrent Hepatitis C infection and were therefore at increased risk for this condition.

**Organ System:** Hepatobiliary disorders

**Source Vocabulary:** 

**Term:** Bacterial vaginosis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One subject developed bacterial vaginosis

**Organ System:** Infections and infestations

**Source Vocabulary:** 

**Term:** choroid plexus cysts

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One fetal subject had choroid plexus cysts on fetal sonogram

**Organ System:** Nervous system disorders

**Source Vocabulary:** 

**Term:** cardiomegaly

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** 2 fetal subjects had mild cardiomegaly on fetal sonogram

**Organ System:** Cardiac disorders

**Source Vocabulary:** 

**Term:** pneumonia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One infant was born with congenital pneumonia

**Organ System:** Infections and infestations

**Source Vocabulary:** 

**Term:** fetal growth restriction

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One fetus was diagnosed with fetal growth restriction (but was average for gestational age at delivery)

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** chorioamnionitis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** Two maternal subjects had chorioamnionitis at delivery

**Organ System:** Pregnancy, puerperium and perinatal conditions

**Source Vocabulary:** 

**Term:** Fetal stress at delivery

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** Two fetuses exhibited fetal stress at the time of delivery

**Organ System:** Pregnancy, puerperium and perinatal conditions

**Source Vocabulary:** 

**Term:** psychiatric concern

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One maternal subject developed a psychiatric concern warranting hospitalization

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** fetal arrythmia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One fetus had a cardiac arrhythmia

**Organ System:** Cardiac disorders

**Source Vocabulary:** 

**Term:** maternal dehydration

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One maternal subject developed decreased fetal HRV and fetal tachycardia, was dx with dehydration

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** nonreactive fetal tracing, fetal hear rate deceleration

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Pregnancy, puerperium and perinatal conditions

**Source Vocabulary:** 

#### Serious Events

**Term:** Severe adverse event

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One infant born to a buprenorphine maintained mother in the protocol had polydactyly The infant had a family history of polydactyly

**Organ System:** Congenital, familial and genetic disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 49

**Num Events:** 1

**Term:** congenital heart disease

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** One infant born to a buprenorphine maintained mother was born with a congenital heart disease. The infant had a family history of congenital heart disease.

**Organ System:** Cardiac disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 49

**Num Events:** 1

**Time Frame:** 3 years, 3 months

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 49

**Units:** Participants

### Group

**ID:** BG000

**Title:** Fetal

**Description:** Daily sublingual buprenorphine treatment of pregnant, opioid dependent women Subjects completing any maternal-fetal monitoring at any combination of the following gestational ages: 24, 28, 32 36 weeks

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 4.4

**Value:** 27.6

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 49

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 6

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 43

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 1.9

**Value:** 11.5

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 4.8

**Value:** 19.8

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 4.6

**Value:** 21.0

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 4.4

**Value:** 6.5

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 7.0

**Value:** 21.3

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 56.7

**Value:** 121.1

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 7.1

**Value:** 12.0

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 6.0

**Value:** 12.3

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 6.3

**Value:** 12.7

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 6.5

**Value:** 12.8

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 8.0

**Value:** 16.4

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 25.6

**Value:** 19.7

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Education
**Unit of Measure:** years
### Measure 5
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age at first substance use
**Unit of Measure:** years
### Measure 6
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age at regular substance use
**Unit of Measure:** years
### Measure 7
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Duration of regular substance use upon treatment entry
**Unit of Measure:** years
### Measure 8
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Gestational age upon treatment entry
**Unit of Measure:** weeks
### Measure 9
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Length of time in treatment prior to delivery
**Unit of Measure:** days
### Measure 10
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Buprenorphine dose at 24 weeks if gestation
**Unit of Measure:** mg
### Measure 11
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Buprenorphine dose at 28 weeks if gestation
**Unit of Measure:** mg
### Measure 12
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Buprenorphine dose at 32 weeks if gestation
**Unit of Measure:** mg
### Measure 13
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Buprenorphine dose at 36 weeks if gestation
**Unit of Measure:** mg
### Measure 14
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Urine toxicology screenings during treatment
**Unit of Measure:** number of screenings
### Measure 15
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Positive research urine toxicology screening at delivery
**Unit of Measure:** percent positive urine tox. screenings
## Results Section - More Information Module
### Certain Agreement
### Limitations and Caveats
**Description:** Small sample size
### Point of Contact
**Email:** ljansson@jhmi.edu
**Organization:** Johns Hopkins University School of Medicine
**Phone:** 410-550-5438
**Title:** Dr. Lauren M Jansson
## Results Section - Outcome Measures Module
### Outcome Measure 1
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** 
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** 0.001
**P-Value Comment:** The p values were not adjusted for multiplicity The a priori threshold = .05
**Parameter Type:** 
**Parameter Value:** 
**Statistical Comment:** The p-value was calculated
**Statistical Method:** Hierarchical Linear Modeling
**Tested Non-Inferiority:** 
### Outcome Measure 2
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** 
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** <.002
**P-Value Comment:** 
**Parameter Type:** 
**Parameter Value:** 
**Statistical Comment:** 
**Statistical Method:** Hierarchical Linear Modeling
**Tested Non-Inferiority:** 
### Outcome Measure 3
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** 
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** 0.0001
**P-Value Comment:** 
**Parameter Type:** 
**Parameter Value:** 
**Statistical Comment:** 
**Statistical Method:** Hierarchical Linear Modeling
**Tested Non-Inferiority:** 
### Outcome Measure 4
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** 
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** .008
**P-Value Comment:** 
**Parameter Type:** 
**Parameter Value:** 
**Statistical Comment:** The reported p-value was calculated
**Statistical Method:** Hierarchical Linear Modeling
**Tested Non-Inferiority:** 
### Outcome Measure 5
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** 
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** 
**Dispersion Value:** 
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY_OR_OTHER
**Other Analysis Description:** 
**P-Value:** .002
**P-Value Comment:** 
**Parameter Type:** 
**Parameter Value:** 
**Statistical Comment:** 
**Statistical Method:** Hierarchical Linear Modeling
**Tested Non-Inferiority:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 5.8
- **Upper Limit:** 
- **Value:** 145.7
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 5.4
- **Upper Limit:** 
- **Value:** 143.3
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 6.0
- **Upper Limit:** 
- **Value:** 138.6
- **Comment:** 
- **Group ID:** OG003
- **Lower Limit:** 
- **Spread:** 7.1
- **Upper Limit:** 
- **Value:** 136.3
- **Comment:** 
- **Group ID:** OG004
- **Lower Limit:** 
- **Spread:** 6.4
- **Upper Limit:** 
- **Value:** 143.9
- **Comment:** 
- **Group ID:** OG005
- **Lower Limit:** 
- **Spread:** 4.8
- **Upper Limit:** 
- **Value:** 141.0
- **Comment:** 
- **Group ID:** OG006
- **Lower Limit:** 
- **Spread:** 6.3
- **Upper Limit:** 
- **Value:** 135.4
- **Comment:** 
- **Group ID:** OG007
- **Lower Limit:** 
- **Spread:** 6.1
- **Upper Limit:** 
- **Value:** 131.3
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.3
- **Upper Limit:** 
- **Value:** 5.4
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.9
- **Upper Limit:** 
- **Value:** 6.7
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 3.0
- **Upper Limit:** 
- **Value:** 7.5
- **Comment:** 
- **Group ID:** OG003
- **Lower Limit:** 
- **Spread:** 2.1
- **Upper Limit:** 
- **Value:** 7.9
- **Comment:** 
- **Group ID:** OG004
- **Lower Limit:** 
- **Spread:** 1.5
- **Upper Limit:** 
- **Value:** 4.9
- **Comment:** 
- **Group ID:** OG005
- **Lower Limit:** 
- **Spread:** 1.8
- **Upper Limit:** 
- **Value:** 7.3
- **Comment:** 
- **Group ID:** OG006
- **Lower Limit:** 
- **Spread:** 2.7
- **Upper Limit:** 
- **Value:** 7.0
- **Comment:** 
- **Group ID:** OG007
- **Lower Limit:** 
- **Spread:** 2.1
- **Upper Limit:** 
- **Value:** 6.3
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 3
- **Value:** 0.52
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 8
- **Value:** 1.59
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 15
- **Value:** 3.57
- **Comment:** 
- **Group ID:** OG003
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 17
- **Value:** 5.28
- **Comment:** 
- **Group ID:** OG004
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 3
- **Value:** 0.43
- **Comment:** 
- **Group ID:** OG005
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 7
- **Value:** 2.12
- **Comment:** 
- **Group ID:** OG006
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 9
- **Value:** 2.29
- **Comment:** 
- **Group ID:** OG007
- **Lower Limit:** 0
- **Spread:** 
- **Upper Limit:** 9
- **Value:** 2.25
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 752.0
- **Upper Limit:** 
- **Value:** 1496.2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 795.4
- **Upper Limit:** 
- **Value:** 1390.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 674.6
- **Upper Limit:** 
- **Value:** 1458.7
- **Comment:** 
- **Group ID:** OG003
- **Lower Limit:** 
- **Spread:** 979.5
- **Upper Limit:** 
- **Value:** 1446.7
- **Comment:** 
- **Group ID:** OG004
- **Lower Limit:** 
- **Spread:** 575.6
- **Upper Limit:** 
- **Value:** 1613.0
- **Comment:** 
- **Group ID:** OG005
- **Lower Limit:** 
- **Spread:** 674.5
- **Upper Limit:** 
- **Value:** 1385.7
- **Comment:** 
- **Group ID:** OG006
- **Lower Limit:** 
- **Spread:** 830.7
- **Upper Limit:** 
- **Value:** 1381.2
- **Comment:** 
- **Group ID:** OG007
- **Lower Limit:** 
- **Spread:** 756.2
- **Upper Limit:** 
- **Value:** 1038.2
**Title:** 
#### Outcome Measure 5
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.06
- **Upper Limit:** 
- **Value:** 0.13
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** .07
- **Upper Limit:** 
- **Value:** 0.21
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.10
- **Upper Limit:** 
- **Value:** 0.23
- **Comment:** 
- **Group ID:** OG003
- **Lower Limit:** 
- **Spread:** 0.11
- **Upper Limit:** 
- **Value:** 0.25
- **Comment:** 
- **Group ID:** OG004
- **Lower Limit:** 
- **Spread:** 0.06
- **Upper Limit:** 
- **Value:** 0.09
- **Comment:** 
- **Group ID:** OG005
- **Lower Limit:** 
- **Spread:** 0.09
- **Upper Limit:** 
- **Value:** 0.20
- **Comment:** 
- **Group ID:** OG006
- **Lower Limit:** 
- **Spread:** 0.10
- **Upper Limit:** 
- **Value:** 0.21
- **Comment:** 
- **Group ID:** OG007
- **Lower Limit:** 
- **Spread:** 0.10
- **Upper Limit:** 
- **Value:** 0.20
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** Fetal heart rate in beats per minute at time of trough and peak maternal buprenorphine levels
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** Participants active in the protocol at 24, 28, 32 and 36 weeks, respectively
**Reporting Status:** POSTED
**Time Frame:** 24, 28, 32 and 36 weeks of gestation
**Title:** Fetal Heart Rate
**Type:** PRIMARY
**Unit of Measure:** beats per minute
##### Group
**Description:** Fetal heart rate in beats per minute at 24 weeks of gestation at trough
**ID:** OG000
**Title:** FHR 24 Weeks Trough
##### Group
**Description:** Fetal heart rate in beats per minute at 28 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG001
**Title:** FHR 28 Weeks Trough
##### Group
**Description:** Fetal heart rate in beats per minute at 32 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG002
**Title:** FHR 32 Weeks Trough
##### Group
**Description:** Fetal heart rate in beats per minute at 36 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG003
**Title:** FHR 36 Weeks Trough
##### Group
**Description:** Fetal heart rate in beats per minute at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG004
**Title:** FHR 24 Weeks Peak
##### Group
**Description:** Fetal heart rate in beats per minute at 28 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG005
**Title:** FHR 28 Weeks Peak
##### Group
**Description:** Fetal heart rate in beats per minute at 32 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG006
**Title:** FHR 32 Peak
##### Group
**Description:** Fetal heart rate in beats per minute at 36 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG007
**Title:** FHR 36 Peak
#### Outcome Measure 2
**Description:** Fetal heart rate variability at 24, 28, 32 and 36 weeks of gestation at times of trough and peak maternal buprenorphine levels
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** Per protocol
**Reporting Status:** POSTED
**Time Frame:** 24, 28, 32 and 36 weeks of gestation
**Title:** Fetal Heart Rate Variability
**Type:** PRIMARY
**Unit of Measure:** msec
##### Group
**Description:** Fetal heart rate variability at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG000
**Title:** FHRV 24 Trough
##### Group
**Description:** Fetal heart rate variability at 28 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG001
**Title:** FHRV 28 Trough
##### Group
**Description:** Fetal heart rate variability at 32 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG002
**Title:** FHRV 32 Trough
##### Group
**Description:** Fetal heart rate variability at 36 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG003
**Title:** FHRV 36 Trough
##### Group
**Description:** Fetal heart rate variability at 24 weeks gestation at the time of peak maternal buprenorphine levels
**ID:** OG004
**Title:** FHRV 24 Peak
##### Group
**Description:** Fetal heart rate variability at 28 weeks gestation at the time of peak maternal buprenorphine levels
**ID:** OG005
**Title:** FHRV 28 Peak
##### Group
**Description:** Fetal heart rate variability at 32 weeks gestation at the time of peak maternal buprenorphine levels
**ID:** OG006
**Title:** FHRV 32 Peak
##### Group
**Description:** Fetal heart rate variability at 36 weeks gestation at the time of peak maternal buprenorphine levels
**ID:** OG007
**Title:** FHRV 36 Peak
#### Outcome Measure 3
**Description:** Number of accelerations of fetal heart rate exhibited during the 60 minute recordings
**Dispersion Type:** 95% Confidence Interval
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 24, 28, 32 36 weeks of gestation
**Title:** Accelerations of Fetal Heart Rate
**Type:** PRIMARY
**Unit of Measure:** accelerations
##### Group
**Description:** Accelerations in fetal heart rate at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG000
**Title:** Accelerations 24 Trough
##### Group
**Description:** Accelerations in fetal heart rate at 28 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG001
**Title:** Accelerations 28 Trough
##### Group
**Description:** Accelerations in fetal heart rate at 32 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG002
**Title:** Accelerations 32 Trough
##### Group
**Description:** Accelerations in fetal heart rate at 36 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG003
**Title:** Accelerations 36 Trough
##### Group
**Description:** Accelerations in fetal heart rate at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG004
**Title:** Accelerations 24 Peak
##### Group
**Description:** Accelerations in fetal heart rate at 28 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG005
**Title:** Accelerations 28 Peak
##### Group
**Description:** Accelerations in fetal heart rate at 32 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG006
**Title:** Accelerations 32 Peak
##### Group
**Description:** Accelerations in fetal heart rate at 36 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG007
**Title:** Accelerations36 Peak
#### Outcome Measure 4
**Description:** Fetal movement (number x duration of fetal movements) during the 60 minute recordings at times of trough and peak maternal buprenorphine levels
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 24, 28, 32, 36 weeks of gestation
**Title:** Fetal Movement
**Type:** PRIMARY
**Unit of Measure:** seconds
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG000
**Title:** Fetal Movement 24 Trough
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG001
**Title:** Fetal Movement 28 Trough
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG002
**Title:** Fetal Movement 32 Trough
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG003
**Title:** Fetal Movement 36 Trough
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG004
**Title:** Fetal Movement 24 Peak
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG005
**Title:** Fetal Movement 28 Peak
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG006
**Title:** Fetal Movement 32 Peak
##### Group
**Description:** Fetal movement during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG007
**Title:** Fetal Movement 36 Peak
#### Outcome Measure 5
**Description:** 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.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 24, 28, 32, 36 weeks of gestation
**Title:** Fetal Movement - Fetal Heart Rate Coupling
**Type:** PRIMARY
**Unit of Measure:** percentage of time FM assoc w FHR change
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG000
**Title:** FM-FHR 24 Trough
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG001
**Title:** FM-FHR 28 Trough
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG002
**Title:** FM-FHR 32 Trough
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of trough maternal buprenorphine level
**ID:** OG003
**Title:** FM-FHR 36 Trough
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG004
**Title:** FM-FHR 24 Peak
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG005
**Title:** FM-FHR 28 Peak
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG006
**Title:** FM-FHR 32 Peak
##### Group
**Description:** Fetal movement-fetal heart rate coupling during the 60 minute recordings at 24 weeks of gestation at time of peak maternal buprenorphine level
**ID:** OG007
**Title:** FM-FHR 36 Peak
### Participant Flow Module
#### Group
**Description:** Daily sublingual buprenorphine treatment of pregnant, opioid dependent women Subjects undergo maternal-fetal monitoring at any combination of the following gestational time periods: 24, 28,32, 36 weeks of gestation
**ID:** FG000
**Title:** Maternal Buprenorphine Treatment
#### Period
**Title:** Overall Study
##### Withdraw
**Type:** Physician Decision
###### Reason
**Group ID:** FG000
**Number of Subjects:** 17
##### Withdraw
**Type:** Withdrawal by Subject
###### Reason
**Group ID:** FG000
**Number of Subjects:** 59
##### Withdraw
**Type:** Protocol Violation
###### Reason
**Group ID:** FG000
**Number of Subjects:** 2
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 127
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 49
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 78
**Pre-Assignment Details:** Participants must have an opioid use disorder, a singleton, generally uncomplicated pregnancy, be between 18 and 40 years of age, have accurate gestational age dating of less than 34 weeks, willing to receive obstetric care at the center and deliver their infant at the hospital affiliated with the treatment facility.
**Recruitment Details:** Participants were recruited from a comprehensive care treatment facility for pregnant and postpartum women with substance use disorders between Feb 2012 and March 2016
**Has Results:** True