Neonatal Opioid Withdrawal SyndromeOBOENCT04149509
ACT NOW Longitudinal Study: Outcomes of Babies With Opioid Exposure Study
An observational study of Neonatal Opioid Withdrawal Syndrome, run by Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program at 6 sites in United States.
Trial summary
The objective of this longitudinal cohort study is to quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal… Read more about this study
- Who is it for?
- Ages Up to 1 monthHealthy volunteers can take part
- Conditions the study is for
- Neonatal Opioid Withdrawal Syndrome
- How many people
- 300 participants
- Where
- 6 sitesUnited States
- Study dates
- 19 Aug 2020to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 month
- All sexes
- Healthy volunteers accepted
- Child
Study population: Infants will be prescreened at participating birth hospitals using the inclusion and exclusion criteria listed below.
Who may be able to join
- Exposed infants: Born ≥37 weeks gestation with second or third trimester opioid exposure
- Control infants: Born ≥37 weeks gestation with no antenatal drug exposure
Who cannot join
- Infants with known chromosomal or congenital anomalies potentially affecting the central nervous system
- Apgar score at 5 minutes of <5
- Any requirement for positive pressure ventilation in the NICU
- Inability to return for outpatient MRI and/or follow-up
- IUGR <3rd percentile
- Heavy alcohol use during pregnancy (8+ drinks per week).
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
RTI International
Durham, North Carolina, 27705
Univeristy of Pennsylvania
Philadelphia, Pennsylvania, 19104
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
The objective of this longitudinal cohort study is to quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects
Read the detailed description
This objective of this longitudinal cohort study is to prospectively examine the medical, neuroanatomical, neurodevelopmental, behavioral, and social/family/home outcomes of infants who were exposed to opioids in utero. Match control infants will be recruited into the study and based on birth hospital and birth month of the exposed infants. The study will quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects. The investigators hypothesize that neural connectivity and neuroanatomical volumes are altered by antenatal opioid exposure and that the magnitude of these alterations correlates with developmental and behavioral outcomes. Further, maternal and environmental factors interact with antenatal opioid exposure to influence the trajectories of connectivity, development, and behavior over the first 2 years of life.
- Conditions
- Neonatal Opioid Withdrawal Syndrome
- Keywords
- NOWS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Exposed | Infants born ≥ 37 weeks gestation with second or third trimester opioid exposure as determined by maternal urine toxicology screen at delivery; maternal history; and/or infant urine, meconium, or umbilical cord toxicology screen. | |
| Unexposed - Controls | Infants born ≥ 37 weeks gestation with no antenatal drug exposure as determined by maternal urine toxicology screen at delivery and/or maternal history. We will match control infants to exposed infants based on Clinical Site and up to 60 days after the date of birth of the exposed infant , recruiting 1 control for every other exposed infant at each site. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome related to brain development: White Matter Volume
Volumetric analysis will be done with the white matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Measured: Birth to 22-24 months of age
Primary outcome related to brain development: Cortical Gray Matter Volume
Volumetric analysis will be done with the cortical gray matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Measured: Birth to 22-24 months of age
Primary outcome related to brain development: Deep Gray Matter Volume
Volumetric analysis will be done with the deep gray matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Measured: Birth to 22-24 months of age
Primary outcome related to brain development: Lateral Ventricle Volume
Volumetric analysis will be done with the lateral ventricle volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Measured: Birth to 22-24 months of age
Primary outcome related to brain development: External cerebrospinal fluid
Volumetric analysis will be done with the external cerebrospinal fluid volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Measured: Birth to 22-24 months of age
Primary outcome related to behavioral and development: Bayley Scales of Infant Development
The Bayley Scales of Infant Development is considered the gold standard assessment of early child development and includes cognitive, language, fine motor, and gross motor subscales. Subscale scores each range from 1 - 19, with higher scores indicating higher performance.
Measured: 22-24 months of age
Primary outcome related to behavioral and development: Spot Vision Screener
The vision screener and auto-refractor detects amblyopia risk factors such as myopia, hyperopia, astigmatism, anisometropia, gaze, and anisocoria. Results are reported as "all measurements in range-pass" or "complete eye exam recommended-fail" based on manufacturer criteria for age. If the screen recommends a complete eye exam, the reason for failure (of the 6 factors listed above) and affected eye(s) will be recorded.
Measured: 22-24 months of age
Primary outcome related to behavioral and development: BITSEA
Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit.
Measured: 22-24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start19 Aug 2020
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Neonatal Opioid Withdrawal SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
- Sponsor type
- Research network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Carla Bann, PhD, Study director, RTI International
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04149509
- Sponsor's protocol ID
- ACTNOW-03
- Other IDs
- 1PL1HD101059-01, RL1HD104251, RL1HD104252, RL1HD104253, RL1HD104254
- Acronym
- OBOE
- Status last verified
- Jan 2025
- First submitted
- 24 Oct 2019
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plan to Share IPD
Publications
Merhar SL, Bann CM, Mack N, Newman JE, Limperopoulos C, Ambalavanan N, Davis JM, DeMauro SB, Lorch SA, Wilson-Costello DE, Peralta-Carcelan M, Parlberg LM, Poindexter BB, Kapse K, Kline-Fath BM, Murnick JG. Prenatal Opioid Exposure Is Associated with Punctate White Matter Lesions in Term Newborns. J Pediatr. 2025 Sep;284:114669. doi: 10.1016/j.jpeds.2025.114669. Epub 2025 May 23.
PubMed 40414418Wu Y, Merhar SL, Bann CM, Newman JE, Kapse K, De Asis-Cruz J, Mack N, De Mauro SB, Ambalavanan N, Davis JM, Lorch SA, Wilson-Costello D, Poindexter BB, Peralta-Carcelen M, Limperopoulos C. Antenatal Opioid Exposure and Global and Regional Brain Volumes in Newborns. JAMA Pediatr. 2025 Jun 1;179(6):639-646. doi: 10.1001/jamapediatrics.2025.0277.
PubMed 40193106Parlberg LM, Newman JE, Merhar SL, Poindexter B, DeMauro SB, Lorch SA, Peralta-Carcelen M, Wilson-Costello DE, Ambalavanan N, Limperopoulos C, Mack N, Davis JM, Walsh MC, Bann CM; ACT NOW OBOE Study Consortium. Risk factors for food insecurity and association with prenatal care utilization among women who took opioids during pregnancy and unexposed controls. BMC Pregnancy Childbirth. 2025 Apr 4;25(1):396. doi: 10.1186/s12884-025-07499-y.
PubMed 40186111Merhar SL, Yolton K, DeMauro SB, Beiersdorfer T, Newman JE, Lorch SA, Wilson-Costello D, Ambalavanan N, Bangdiwala A, Peralta-Carcelen M, Poindexter BB, Davis JM, Limperopoulos C, Bann CM. Neurobehavioral Profiles in Opioid-Exposed and Unexposed Neonates. J Pediatr. 2025 Jun;281:114527. doi: 10.1016/j.jpeds.2025.114527. Epub 2025 Mar 7.
PubMed 40057022Parlberg LM, Newman JE, Merhar S, Poindexter B, DeMauro S, Lorch S, Peralta-Carcelen M, Wilson-Costello D, Ambalavanan N, Limperopoulos C, Mack N, Davis JM, Walsh M, Bann CM. Risk factors for food insecurity and association with prenatal care utilization among women who took opioids during pregnancy. Res Sq [Preprint]. 2024 Mar 25:rs.3.rs-3921909. doi: 10.21203/rs.3.rs-3921909/v1.
PubMed 38585728
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ACT NOW Longitudinal Study: Outcomes of Babies With Opioid Exposure Study
- ClinicalTrials.gov ID
- NCT04149509
- Acronym / sponsor ID
- OBOE / ACTNOW-03
- Conditions
- Neonatal Opioid Withdrawal Syndrome
- Keywords
- NOWS
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) ProgramResearch network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 4 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this longitudinal cohort study is to quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects
Detailed description
This objective of this longitudinal cohort study is to prospectively examine the medical, neuroanatomical, neurodevelopmental, behavioral, and social/family/home outcomes of infants who were exposed to opioids in utero. Match control infants will be recruited into the study and based on birth hospital and birth month of the exposed infants. The study will quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects. The investigators hypothesize that neural connectivity and neuroanatomical volumes are altered by antenatal opioid exposure and that the magnitude of these alterations correlates with developmental and behavioral outcomes. Further, maternal and environmental factors interact with antenatal opioid exposure to influence the trajectories of connectivity, development, and behavior over the first 2 years of life.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed | – | –Infants born ≥ 37 weeks gestation with second or third trimester opioid exposure as determined by maternal urine toxicology screen at delivery; maternal history; and/or infant urine, meconium, or umbilical cord toxicology screen. |
| Unexposed - Controls | – | –Infants born ≥ 37 weeks gestation with no antenatal drug exposure as determined by maternal urine toxicology screen at delivery and/or maternal history. We will match control infants to exposed infants based on Clinical Site and up to 60 days after the date of birth of the exposed infant , recruiting 1 control for every other exposed infant at each site. |
Who may qualify
- Ages
- Up to 1 month
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Infants will be prescreened at participating birth hospitals using the inclusion and exclusion criteria listed below.
Key inclusion criteria (2 listed)
- Exposed infants: Born ≥37 weeks gestation with second or third trimester opioid exposure
- Control infants: Born ≥37 weeks gestation with no antenatal drug exposure
Key exclusion criteria (6 listed)
- Infants with known chromosomal or congenital anomalies potentially affecting the central nervous system
- Apgar score at 5 minutes of <5
- Any requirement for positive pressure ventilation in the NICU
- Inability to return for outpatient MRI and/or follow-up
- IUGR <3rd percentile
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Primary outcome related to brain development: White Matter Volume
Time frame: Birth to 22-24 months of age
Volumetric analysis will be done with the white matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Primary outcome related to brain development: Cortical Gray Matter Volume
Time frame: Birth to 22-24 months of age
Volumetric analysis will be done with the cortical gray matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Primary outcome related to brain development: Deep Gray Matter Volume
Time frame: Birth to 22-24 months of age
Volumetric analysis will be done with the deep gray matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Primary outcome related to brain development: Lateral Ventricle Volume
Time frame: Birth to 22-24 months of age
Volumetric analysis will be done with the lateral ventricle volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Primary outcome related to brain development: External cerebrospinal fluid
Time frame: Birth to 22-24 months of age
Volumetric analysis will be done with the external cerebrospinal fluid volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
Primary outcome related to behavioral and development: Bayley Scales of Infant Development
Time frame: 22-24 months of age
The Bayley Scales of Infant Development is considered the gold standard assessment of early child development and includes cognitive, language, fine motor, and gross motor subscales. Subscale scores each range from 1 - 19, with higher scores indicating higher performance.
Primary outcome related to behavioral and development: Spot Vision Screener
Time frame: 22-24 months of age
The vision screener and auto-refractor detects amblyopia risk factors such as myopia, hyperopia, astigmatism, anisometropia, gaze, and anisocoria. Results are reported as "all measurements in range-pass" or "complete eye exam recommended-fail" based on manufacturer criteria for age. If the screen recommends a complete eye exam, the reason for failure (of the 6 factors listed above) and affected eye(s) will be recorded.
Primary outcome related to behavioral and development: BITSEA
Time frame: 22-24 months of age
Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Derived from this study: PubMed 40414418Merhar SL, Bann CM, Mack N, Newman JE, Limperopoulos C, Ambalavanan N, Davis JM, DeMauro SB, Lorch SA, Wilson-Costello DE, Peralta-Carcelan M, Parlberg LM, Poindexter BB, Kapse K, Kline-Fath BM, Murnick JG. Prenatal Opioid Exposure Is Associated with Punctate White Matter Lesions in Term Newborns. J Pediatr. 2025 Sep;284:114669. doi: 10.1016/j.jpeds.2025.114669. Epub 2025 May 23.
- Derived from this study: PubMed 40193106Wu Y, Merhar SL, Bann CM, Newman JE, Kapse K, De Asis-Cruz J, Mack N, De Mauro SB, Ambalavanan N, Davis JM, Lorch SA, Wilson-Costello D, Poindexter BB, Peralta-Carcelen M, Limperopoulos C. Antenatal Opioid Exposure and Global and Regional Brain Volumes in Newborns. JAMA Pediatr. 2025 Jun 1;179(6):639-646. doi: 10.1001/jamapediatrics.2025.0277.
- Derived from this study: PubMed 40186111Parlberg LM, Newman JE, Merhar SL, Poindexter B, DeMauro SB, Lorch SA, Peralta-Carcelen M, Wilson-Costello DE, Ambalavanan N, Limperopoulos C, Mack N, Davis JM, Walsh MC, Bann CM; ACT NOW OBOE Study Consortium. Risk factors for food insecurity and association with prenatal care utilization among women who took opioids during pregnancy and unexposed controls. BMC Pregnancy Childbirth. 2025 Apr 4;25(1):396. doi: 10.1186/s12884-025-07499-y.
- Derived from this study: PubMed 40057022Merhar SL, Yolton K, DeMauro SB, Beiersdorfer T, Newman JE, Lorch SA, Wilson-Costello D, Ambalavanan N, Bangdiwala A, Peralta-Carcelen M, Poindexter BB, Davis JM, Limperopoulos C, Bann CM. Neurobehavioral Profiles in Opioid-Exposed and Unexposed Neonates. J Pediatr. 2025 Jun;281:114527. doi: 10.1016/j.jpeds.2025.114527. Epub 2025 Mar 7.
- Derived from this study: PubMed 38585728Parlberg LM, Newman JE, Merhar S, Poindexter B, DeMauro S, Lorch S, Peralta-Carcelen M, Wilson-Costello D, Ambalavanan N, Limperopoulos C, Mack N, Davis JM, Walsh M, Bann CM. Risk factors for food insecurity and association with prenatal care utilization among women who took opioids during pregnancy. Res Sq [Preprint]. 2024 Mar 25:rs.3.rs-3921909. doi: 10.21203/rs.3.rs-3921909/v1.
- Individual participant dataSharing planned: Yes. Plan to Share IPD
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carla Bann, PhD study director
RTI International
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Opioid Withdrawal Syndrome, run by Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary outcome related to brain development: White Matter Volume (time frame: Birth to 22-24 months of age). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04149509, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.