Related Experiment Video
Updated: Aug 27, 2025

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
MRI Findings in Third-Trimester Opioid-Exposed Fetuses, With Focus on Brain Measurements: A Prospective Multicenter
Usha D Nagaraj1,2, Beth M Kline-Fath1,2, Bin Zhang3,4
1Department of Radiology and Medical Imaging, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3026.
Insights
Prenatal opioid exposure in fetuses is linked to smaller brain size and altered fetal physiology. This research highlights the impact of maternal opioid use on fetal brain development.
Area of Science:
- Neurology
- Obstetrics
- Pediatrics
Background:
- The opioid epidemic significantly impacts infants, with in utero opioid exposure increasing risks for cognitive and behavioral issues.
- Limited research exists on prenatal brain development in opioid-exposed fetuses.
- This study addresses the gap in understanding the effects of prenatal opioid exposure on fetal brain development.
Purpose of the Study:
- To compare fetal brain 2D biometric measurements between opioid-exposed and unexposed fetuses using MRI.
- To evaluate additional pregnancy-related assessments in opioid-exposed versus unexposed fetuses.
- To investigate the impact of prenatal opioid exposure on fetal brain development.
Main Methods:
- A prospective case-control study involving third-trimester fetal MRI.
- Comparison of 14 2D brain biometric measurements and four derived indexes between opioid-exposed (n=28) and unexposed (n=37) fetuses.
- Multivariable linear regression adjusted for gestational age, fetal sex, and nicotine exposure.
Main Results:
- Opioid-exposed fetuses showed significantly smaller measurements in seven brain areas, including cerebral frontooccipital diameter and corpus callosum length.
- A larger frontooccipital index was observed in opioid-exposed fetuses.
- Opioid-exposed fetuses had higher frequencies of breech position and increased amniotic fluid volume.
Conclusions:
- Fetuses exposed to opioids in utero exhibit smaller brain size compared to unexposed fetuses.
- Prenatal opioid exposure is associated with altered fetal physiology, including position and amniotic fluid volume.
- Findings provide crucial insights into the neurological impact of prenatal opioid exposure.
Abstract:
BACKGROUND. The opioid epidemic has profoundly affected infants born in the United States, as in utero opioid exposure increases the risk of cognitive and behavioral problems in childhood. Scarce literature has evaluated prenatal brain development in fetuses with opioid exposure in utero (hereafter opioid-exposed fetuses). OBJECTIVE. The purpose of this study is to compare opioid-exposed fetuses and fetuses without opioid exposure (hereafter unexposed fetuses) in terms of 2D biometric measurements of the brain and additional pregnancy-related assessments on fetal MRI. METHODS. This prospective case-control study included patients in the third trimester of pregnancy who underwent investigational fetal MRI at one of three U.S. academic medical centers from July 1, 2020, through December 31, 2021. Fetuses were classified as opioid exposed or unexposed in utero. Fourteen 2D biometric measurements of the fetal brain were manually assessed and used to derive four indexes. Measurements and indexes were compared between the two groups by use of multivariable linear regression models, which were adjusted for gestational age (GA), fetal sex, and nicotine exposure. Additional pregnancy-related findings on MRI were evaluated. RESULTS. The study included 65 women (mean age, 29.0 ± 5.5 [SD] years). A total of 28 fetuses (mean GA at the time of MRI, 32.2 ± 2.5 weeks) were opioid-exposed, and 37 fetuses (mean GA at the time of MRI, 31.9 ± 2.7 weeks) were unexposed. In the adjusted models, seven measurements were smaller (p < .05) in opioid-exposed fetuses than in unexposed fetuses: cerebral frontooccipital diameter (93.8 ± 7.4 vs 95.0 ± 8.6 mm), bone biparietal diameter (79.0 ± 6.0 vs 80.3 ± 7.1 mm), brain biparietal diameter (72.9 ± 7.7 vs 74.1 ± 8.6 mm), corpus callosum length (37.7 ± 4.0 vs 39.4 ± 3.7 mm), vermis height (18.2 ± 2.7 vs 18.8 ± 2.6 mm), anteroposterior pons measurement (11.6 ± 1.4 vs 12.1 ± 1.4 mm), and transverse cerebellar diameter (40.4 ± 5.1 vs 41.4 ± 6.0 mm). In addition, in the adjusted model, the frontoocccipital index was larger (p = .02) in opioid-exposed fetuses (0.04 ± 0.02) than in unexposed fetuses (0.04 ± 0.02). Remaining measures and indexes were not significantly different between the two groups (p > .05). Fetal motion, cervical length, and deepest vertical pocket of amniotic fluid were not significantly different (p > .05) between groups. Opioid-exposed fetuses, compared with unexposed fetuses, showed higher frequencies of both breech position (21% vs 3%, p = .03) and increased amniotic fluid volume (29% vs 8%, p = .04). CONCLUSION. Fetuses with opioid exposure in utero had a smaller brain size and altered fetal physiology. CLINICAL IMPACT. The findings provide insight into the impact of prenatal opioid exposure on fetal brain development.

