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2024 Fetal Care Center Frontiers in Fetal Neurology Day 2 - Dr. Usha Nagaraj
With Dr. Usha Nagaraj
Educational content from recorded physician discussions — not medical advice. Talk to your (or your child's) care team about your situation.
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What the experts said
1 infant is born with prenatal opioid exposure every 15 minutes in the United States
Opioid-exposed children tend to have lower school achievement and higher rates of severity of behavioral problems
The underlying neurocognitive mechanisms for poor outcomes in opioid-exposed children are unknown
Patients enrolled in the IMPAC study had to be at least 26 weeks gestational age at the time of imaging
The research imaging protocol used 2 millimeter thick slices acquired in 3 planes, with each run through the brain taking about 4 minutes to obtain
65 women were enrolled in the study: 28 opioid-exposed fetuses and 37 unexposed fetuses
Breech presentation was more common in opioid-exposed fetuses (21% versus 3%)
Subjective assessment of amniotic fluid was increased in opioid-exposed fetuses compared to unexposed fetuses
Fetal motion, cervical length on fetal MRI, and deepest vertical pocket of amniotic fluid were not significantly different between opioid-exposed and unexposed groups
Nicotine exposure was significantly higher in opioid-exposed fetuses and was controlled for in the analysis
Birth weight and head circumference at birth were not significantly different between opioid-exposed and unexposed groups
Seven measurements were significantly smaller in opioid-exposed fetuses: brain frontal occipital diameter, brain biparietal diameter, bone biparietal diameter, transverse cerebellar diameter, vermis height, and anteroposterior measurement of the pons
Breech presentation in opioid-exposed fetuses might suggest abnormality in fetal movements
Increased amniotic fluid in opioid-exposed fetuses may be related to fetal swallowing
Smaller brains in opioid-exposed fetuses fit with theories around impact on neuronal proliferation by opioid exposure
Fractional anisotropy (FA) is a measure of the strength of directionality of water molecules
Mean diffusivity (MD) is the strength of water movement
FA and MD values can vary based on scanner hardware and acquisition parameters and need to be interpreted with caution
DTI has shown microstructural differences in white matter in children with prenatal opioid exposures and other prenatal illicit drug exposures
Historically, DTI was not possible in the fetus due to fetal motion, but slice-to-volume registration techniques now allow it to be done in a robust manner
The DTI protocol used 20 non-colinear diffusion weighted directions with a B value of 800
Slice-to-volume registration automatically removes motion corrupted slices and realigns non-motion corrupted slices so they are anatomically aligned
Combat harmonization is a statistical correction strategy that minimizes inter-center effects in DTI from scanner differences while preserving physiologic features
More than half of the 28 patients from Cincinnati Children's and Arkansas Medical Center with DTI data had to be excluded due to excessive fetal motion
15 controls and 11 opioid-exposed fetuses had analyzable DTI data
There was no statistically significant difference in fetal motion measured by average framewise displacement in millimeters between opioid-exposed and control groups
Statistically significant higher FA values were found in opioid-exposed fetuses in bilateral medial lemnisci and middle cerebellar peduncles
Opioid exposure may potentially cause inflammation affecting normal white matter development
Gyrification index is a ratio between the surface area and the convex hull, where increased gyrification index indicates increased convolutional markings in the brain
The 3D reconstruction and cortical surface extraction process takes hours per patient and is very labor intensive
Of 63 patients from all three sites, over half had to be excluded for inadequate image quality due to fetal motion challenges with accurate fetal brain extraction
29 patients were included in the 3D analysis: 14 opioid-exposed and 15 unexposed
The 3D analysis corrected for gestational age, fetal sex, maternal education, polysubstance use, high blood pressure, and the site at which the MRI was scanned
All assessed parameters were lower in the opioid-exposed group: total brain volume, cortical plate volume, surface area, sulcal depth, mean curvature, and gyrification index
Decreased surface area in opioid-exposed fetuses showed regional preference for perisylvian regions and central sulci
Decreased sulcal depth in opioid-exposed fetuses was more widespread but showed regional preferences for bilateral perisylvian regions, bilateral central sulci, and parieto-occipital features
Mean curvature showed no statistically significant regional differences between groups
Decreased volumes and gyration in opioid-exposed fetuses are possibly related at least in part to opioids causing impaired neurogenesis in the developing brain