ACT NOW Longitudinal Study: Outcomes of Babies with Opioid Exposure Study (OBOE)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Neonatal Opioid Withdrawal Syndrome

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 Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Cincinnati Children's Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univeristy of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Infants will be prescreened at participating birth hospitals using the inclusion and exclusion criteria listed below.

Description

Inclusion Criteria:

• Exposed infants: Born ≥37 weeks gestation with second or third trimester opioid exposure
• Control infants: Born ≥37 weeks gestation with no antenatal drug exposure

Exclusion Criteria:

1. Infants with known chromosomal or congenital anomalies potentially affecting the central nervous system
2. Apgar score at 5 minutes of <5
3. Any requirement for positive pressure ventilation in the NICU
4. Inability to return for outpatient MRI and/or follow-up
5. IUGR <3rd percentile
6. Heavy alcohol use during pregnancy (8+ drinks per week).

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	22-24 months of age

Collaborators and Investigators

• Sponsor: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Director: Carla Bann, PhD, RTI International

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: NOWS
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Substance Withdrawal Syndrome
• Other Study ID Numbers: ACTNOW-03; 1PL1HD101059-01 (U.S. NIH Grant/Contract); RL1HD104251 (U.S. NIH Grant/Contract); RL1HD104252 (U.S. NIH Grant/Contract); RL1HD104253 (U.S. NIH Grant/Contract); RL1HD104254 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan to Share IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No