DTI of Opioid-Exposed Fetuses Using ComBat Harmonization: A Bi-Institutional Study

Abstract

BACKGROUND AND PURPOSE: The underlying mechanisms leading to altered cognitive, behavioral, and vision outcomes in children with prenatal opioid exposure are yet to be fully understood. Some studies suggest WM alterations in infants and children with prenatal opioid exposure; however, the time course of WM changes is unknown. We aimed to evaluate differences in diffusion tensor imaging MRI parameters in the brain between opioid exposed fetuses and normal controls. MATERIALS AND METHODS: This is a pilot, prospective cohort study in which subjects in the third trimester of pregnancy underwent fetal DTI of the brain with 20 noncolinear diffusion directions and a b-value of 500 s/mm2 at 2.5-mm isotropic resolution. RESULTS: The study included a total of 26 fetuses, 11 opioid-exposed (mean gestational age, 32.61 [SD, 2.35] weeks) and 15 unexposed controls (mean gestational age, 31.77 [SD, 1.68] weeks). After we adjusted for gestational age, fractional anisotropy values were significantly higher in opioid-exposed fetuses relative to controls in 8 WM tracts: the bilateral lemniscus (left: P ¼ .017; right: P ¼ .020), middle cerebellar peduncle (P ¼ .027), left inferior cerebellar peduncle (P ¼ .026), right sagittal stratum (P ¼ .040), right fornix stria terminalis (P ¼ .022), right inferior fronto-occipital fasciculus (P ¼ .011), and the right uncinate fasciculus (P ¼ .033). Significant alteration was also identified in other DTI indices involving a series of brain regions. CONCLUSIONS: Our data demonstrate initial evidence of cerebral WM microstructural differences between opioid-exposed fetuses and unexposed controls. Further studies in larger patient populations will be needed to fully understand these findings.