Neonatal outcomes and immune reprogramming induced by prenatal opioid and hepatitis C exposure

Prenatal opioid exposure (POE) is an escalating public health concern. However, its impact on neonatal immune development remains poorly defined. This study examined how POE, with or without maternal hepatitis C (hepatitis C virus, HCV) infection, shapes neonatal immunity.

Umbilical cord blood was collected from pregnancies included uncomplicated term controls (n=38) and deliveries in patients with severe opioid use disorder on medication-assisted treatment, with (n=41) or without HCV (n=34) infection. Flow cytometry was used to characterize cell phenotype and functional response to stimulation. Single-cell RNA sequencing was used to investigate transcriptomics changes.

POE was associated with smaller birth size, higher rates of congenital anomalies, and longer intensive care admissions. Immune profiling showed a proinflammatory milieu, reduced circulating levels of neuroprotective factors, expanded memory/effector T and B cells, blunted T-cell responses, and markedly reduced natural killer (NK) cell frequency and cytotoxicity, especially in POE HCV+ newborns. Monocytes exhibited inflammatory reprogramming with impaired antiviral and tissue repair pathways and disrupted lymphoid-innate immune cell communication.

These findings suggest that POE-driven immune disequilibrium may underlie adverse early-life outcomes and highlight monitoring and intervention targets.