Fetal brain volumes and brain gyrification index associated with opioid exposure

Abstract Opioid use during pregnancy continues to be a significant public health challenge, with antenatal opioid exposure suggesting adverse infant and child health outcomes. Early identification of risk of future neurodevelopmental disorders could help improve long-term health outcomes in these children. In this study, we assess whether prenatal opioid exposure is associated with early alterations in human fetal brain development identifiable on fetal MRI. This was a prospective, institutional review board approved, multicenter study that recruited pregnant women on medication assisted treatment (MAT) for opioid use disorder (OUD) and a control cohort of non-OUD pregnant women. Fetal brain MRI was performed in the second or third trimester of gestation. Semiautomated pipelines were used to create super resolution 3D isotropic anatomic brain magnetic resonance images from 2D fetal brain images and segmented into different tissue types. Fetal brain gyrification indices were also calculated. Differences between fetuses with opioid exposure and control fetuses were assessed. There were 63 fetuses in this study – 31 with opioid exposure and 32 without opioid exposure (controls). Fetuses with opioid exposure had significantly smaller fetal brain total volumes, fetal brain white matter volume, and significantly lower fetal brain gyrification index compared to control fetuses. In opioid exposed fetuses, fetal brain volumetric and surface-based metrics did not correlate with severity of neonatal opioid withdrawal syndrome (NOWS) requiring longer hospitalization or postnatal opioid medication treatment. Additional and larger prospective studies are needed to understand how fetal brain development may be associated with short- and long-term outcomes.