Disrupted Brain Connectivity in Newborns Following Antenatal Opioid Exposure

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 MRI data were collected using 3T MRIs at four centers as part of the prospective, observational Outcomes of Babies with Opioid Exposure study. We used seed-based correlation analysis to estimate the FC of 93 brain regions. Voxel-wise 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 performed 248 scans (158 opioid-exposed/90 unexposed). Canonical sensorimotor and higher-order resting state network maps in exposed newborns (mean postmenstrual age at MRI±sd:42.80±1.9wks,52M) were comparable to controls (42.82±2.2, 88; Dice indices>0.9 across seven 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 (family-wise error rate,α<0.05). Connectivity from 23/93 (24.7%) seeds differed between groups. Methadone- and buprenorphine-exposed newborns showed disrupted regional FC compared to controls, but no FC differences between them.

CONCLUSIONS: In a large sample of antenatally opioid-exposed newborns, we report altered organization of brain functional networks, particularly in integrative sensorimotor-affective circuits.