The impact of opioid exposure during pregnancy on the human neonatal immune profile

BACKGROUND: The increasing magnitude of the opioid crisis and rising rates of neonatal abstinence syndrome (NAS) diagnoses highlight the need for increased research into how maternal substance use during pregnancy can impact the neonatal immune profile and its functionality. We hypothesized that neonates with opioid exposure would have reduced proportions of some immune cells, an anti-inflammatory cytokine profile, reduced T cell proliferation, and monocyte bacterial killing activity compared to the control population. METHODS: The present study compares immune cell populations, inflammatory and anti-inflammatory cytokine and chemokine levels in the serum, and monocyte and T cell functional activity using umbilical cord samples from neonates with known opioid exposure during gestation and from control neonates without known exposure. RESULTS: Our findings demonstrated a significant reduction in neutrophils, decreased levels of inflammatory cytokines in the serum, and reduced IL-2 production during in vitro CD4(+) T cell proliferation in neonates exposed to opioids compared to controls. The neutrophil findings were supported by retrospective analysis of an extended network of deidentified patient records. CONCLUSIONS: This study is the first of its kind to evaluate differences in neonatal immunity as a result of opioid exposure in the human population that will inform continued mechanistic studies. IMPACT: The opioid epidemic has become a public health crisis in the United States, and the corresponding incidence of neonatal abstinence syndrome (NAS) have risen accordingly. New research is required to understand the short and long-term health impacts of opioid exposure to the neonate. This is the first human study to investigate the immunologic profile and functionality in neonates with known opioid exposure in utero. The abundance of neutrophils and the ratio of neutrophils to lymphocytes is significantly reduced along with inflammatory cytokines and chemokines following opioid exposure during pregnancy. The immune profile in opioid-exposed neonates may promote susceptibility to infection.