Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure.

Rupa Radhakrishnan,Ramana V Vishnubhotla,Yi Zhao,Bing He,Jingwen Yan,Gregory M Sokol,David M Haas,Senthilkumar Sadhasivam,Nicole Steinhardt

doi:10.3389/fped.2022.847037

Abstract

BackgroundInfants with prenatal opioid and substance exposure are at higher risk of poor neurobehavioral outcomes in later childhood. Early brain imaging in infancy has the potential to identify early brain developmental alterations that may help predict behavioral outcomes in these children. In this study, using resting-state functional MRI in early infancy, we aim to identify differences in global brain network connectivity in infants with prenatal opioid and substance exposure compared to healthy control infants.Methods and MaterialsIn this prospective study, we recruited 23 infants with prenatal opioid exposure and 29 healthy opioid naïve infants. All subjects underwent brain resting-state functional MRI before 3 months postmenstrual age. Covariate Assisted Principal (CAP) regression was performed to identify brain networks within which functional connectivity was associated with opioid exposure after adjusting for sex and gestational age. Associations of these significant networks with maternal comorbidities were also evaluated. Additionally, graph network metrics were assessed in these CAP networks.ResultsThere were four CAP network components that were significantly different between the opioid exposed and healthy control infants. Two of these four networks were associated with maternal psychological factors. Intra-network graph metrics, namely average flow coefficient, clustering coefficient and transitivity were also significantly different in opioid exposed infants compared to healthy controls.ConclusionPrenatal opioid exposure is associated with alterations in global brain functional networks compared to non-opioid exposed infants, with intra-network alterations in graph network modeling. These network alterations were also associated with maternal comorbidity, especially mental health. Large-scale longitudinal studies can help in understanding the clinical implications of these early brain functional network alterations in infants with prenatal opioid exposure.

Highlights

Opioid use and misuse is an ongoing public health crisis
Recruitment of pregnant women in the opioid exposed group occurred primarily through the antenatal opioid use disorder clinic at Indiana University (IU) health, where buprenorphine is prescribed for medication assisted treatment
Eighteen of the mothers of infants with prenatal opioid exposure (POE) were on buprenorphine therapy in pregnancy (2–20 mg per day), four were on methadone, and one was not on any opioid maintenance in pregnancy

Summary

Introduction

Opioid use disorder (OUD) in pregnant women in the U.S has increased considerably over the last few decades [1, 2]. In pregnant women with untreated OUD, fluctuating opioid levels in the maternal bloodstream and periods of withdrawal lead to fetal distress, negatively impacting fetal development and increasing the odds of still birth, poor fetal growth and preterm birth [8– 12]. Infants with prenatal opioid exposure (POE) are at a high risk for developing withdrawal symptoms after birth–neonatal opioid withdrawal syndrome (NOWS)–which occurs in 55–94% of these infants, and results in prolonged and expensive hospital stays [12–17]. Infants with prenatal opioid and substance exposure are at higher risk of poor neurobehavioral outcomes in later childhood. In this study, using resting-state functional MRI in early infancy, we aim to identify differences in global brain network connectivity in infants with prenatal opioid and substance exposure compared to healthy control infants

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