ACT NOW Longitudinal Study: Outcomes of Babies with Opioid Exposure Study

Active, not recruiting

• Conditions: Neonatal Opioid Withdrawal Syndrome

• Registration Number: NCT04149509
• Lead Sponsor: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program

Brief 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 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 Timeline

• Study First Submitted: 2019-10-24
• Study First Submitted QC: 2019-10-31
• Study First Posted: 2019-11-04
• Study Start: 2020-08-19
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 300

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary outcome related to brain development: Lateral Ventricle Volume	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	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 brain development: White Matter Volume	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	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	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 behavioral and development: BITSEA	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.
Primary outcome related to behavioral and development: Bayley Scales of Infant Development	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	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.

Trial Locations

Locations (6)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Children's National Medical Center; 🇺🇸 Washington, D.C., District of Columbia, United States

RTI International; 🇺🇸 Durham, North Carolina, United States

Cincinnati Children's Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Case Western Reserve University, Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Univeristy of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States