Abstract
BACKGROUND: The neural bases of adverse neurodevelopmental outcomes in antenatal opioid exposure are poorly understood. Very limited in vivo human newborn imaging studies have reported disrupted functional connectivity (FC) in limbic and reward-related brain regions, but these studies used small samples and lacked matched controls. Our objective was to compare brain FC in antenatal opioid-exposed and unexposed newborns to study the impact of opioid exposure on early brain development. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected using 3T MRI at 4 centers as part of the prospective, observational OBOE (Outcomes of Babies with Opioid Exposure) study. We used seed-based correlation analysis to estimate the FC of 93 brain regions. Voxelwise linear regression with covariate adjustment and correction for multiple comparisons was used to determine significant between-group differences. FC differences based on opioid type were also investigated. RESULTS: We evaluated 248 rs-fMRI scans (158 opioid-exposed/90 unexposed). Canonical sensorimotor and higher-order resting-state network maps in exposed newborns (mean ± SD postmenstrual age at MRI = 42.80 ± 2.2 weeks, 53 male) were comparable to control newborns (42.82 ± 1.9 weeks, 88 male; Dice indices > 0.9 across 7 networks). Exposed newborns showed decreased FC from seeds in bilateral pre- and left postcentral gyri, bilateral orbitofrontal regions, and cerebellum and increased FC from seeds in peri-opercular, subcortical (e.g., amygdala, hippocampus, and putamen), and mid-to-superior occipital regions (familywise error rate, α < 0.05). Connectivity from 23 of 93 (24.7%) seeds differed between groups. Methadone- and buprenorphine-exposed newborns showed disrupted regional FC compared with control newborns, but there were no FC differences between them. CONCLUSIONS: In a large sample of antenatally opioid-exposed newborns, we found altered organization of brain functional networks, particularly in integrative sensorimotor-affective circuits.