Opioids affect the fetal brain: reframing the detoxification debate

Abstract

Medication-assisted treatment is recommended for individuals with an opioid use disorder, including pregnant women. Medication-assisted treatment during pregnancy provides benefits to the mother and fetus, including better pregnancy outcomes, reduced illicit drug use, and improved prenatal care. An alternative approach, medically supervised withdrawal (detoxification), has, in recent reports, demonstrated a low risk of fetal death and low rates of relapse and neonatal abstinence syndrome. The rates of relapse and neonatal abstinence syndrome are questioned by many who view medically supervised withdrawal as unacceptable based on the concern for the potential adverse consequences of relapse to mother and baby. The impact of opioids on the fetal brain have not been integrated into this debate. Studies in animals and human brain tissues demonstrate opioid receptors in neurons, astroglia, and oligodendrocytes. Age-specific normative data from infants, children, and adults have facilitated investigation of the impact of opioids on the human brain in vivo. Collectively, these studies in animals, human neural tissue, adult brains, and the brains of children and newborns demonstrate that opioids adversely affect the human brain, primarily the developing oligodendrocyte and the processes of myelinization (white matter microstructure), connectivity between parts of the brain, and the size of multiple brain regions, including the basal ganglia, thalamus, and cerebellar white matter. These in vivo studies across the human lifespan suggest vulnerability of specific fronto-temporal-limbic and frontal-subcortical (basal ganglia and cerebellum) pathways that are also likely vulnerable in the human fetal brain. The long-term impact of these reproducible changes in the fetal brain in vivo is unclear, but the possibility of lasting injury has been suggested. In light of the recent data on medically supervised withdrawal and the emerging evidence suggesting adverse effects of opioids on the developing fetal brain, a new paradigm of care is needed that includes the preferred option of medication-assisted treatment but also the option of medically supervised opioid withdrawal for a select group of women. Both these treatment options should offer mental health and social services support throughout pregnancy. More research on both opioid exposure on the developing human brain and the impact of medically supervised withdrawal is required to identify appropriate candidates, optimal dose reduction regimens, and gestational age timing for initiating medically supervised withdrawal.

Keywords: MRI; accumbens area; amygdala; astroglia; brainstem; buprenorphine; cerebellum; cerebral cortex; detoxification; fetal neurobiology; magnetic resonance imaging; medically supervised opioid withdrawal; medication-assisted treatment; methadone; neural pathways; oligodendrocytes; opioid dose reduction or elimination; opioids; pallidum; putamen; superior and inferior longitudinal fasciculus and white matter.

FIGURE 1

Multi-modal Neuroimaging tools in a Pediatric Health Controls: (1) DTI tractography (Blue) shows probabilistic tractography of white matter pathways shows to be vulnerable in opiate exposed patients including the (a) inferior longituidinal fasiculus, fasiculus, overlapping with (b) optic radiations, (c) inferior frontal occipital fasiculus, and (d) posterior thalamic radiations; (2) functional MRI (orange) study using an auditory stimulus activating primary auditory pathways; (3) two square voxels using MR spectroscopy in subcortical grey matter and grey matter structures showing metabolic changes in the brain including choline (cho), creatine (Cre), NAA and lipids.