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

NCT04149509 | Active Not Recruiting DMC

• 6 other identifiers: ACTNOW-031PL1HD101059-01RL1HD104251RL1HD104252RL1HD104253RL1HD104254
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 6

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

Conditions

Neonatal Opioid Withdrawal Syndrome

Keywords

NOWS

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (2)

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.

Eligibility Criteria

• Age: Up to 1 Month
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (5)

• 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.

  PMID: 40414418 DERIVED

• Wu 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.

  PMID: 40193106 DERIVED

• Parlberg 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.

  PMID: 40186111 DERIVED

• Merhar 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.

  PMID: 40057022 DERIVED

• Parlberg 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.

  PMID: 38585728 DERIVED

Study Officials

• Carla Bann, PhD

  RTI International

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: November 4, 2019
• Study Start: August 19, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (6)