As the number of pregnant women using opioid drugs continues to rise, questions have been raised about the long-term health effects on children exposed to these drugs in the womb. Researchers at the University of Maryland School of Medicine now have preliminary but striking evidence that suggests that such exposure can cause long-lasting impairment in the brain's ability to process sensory information. These impairments may give rise to autism, attention deficit hyperactivity disorder, and substance use disorders during adolescence. The landmark study, recently published in Journal of Neuroscience, used a preclinical model to study the issue and found that newborn mice exposed to the opioid fentanyl in the womb developed withdrawal symptoms and sensory processing disorders that lasted at least until adolescence.
"While we had evidence on the effects of fentanyl exposure in newborns, such as premature birth and low birthweight, our study provides new preliminary evidence that the effects of fentanyl last well into adolescence and beyond," said study author Asaf Keller, PhD, Interim Chair of the Department of Anatomy & Neurobiology. "It is a novel and important finding, but one that needs to be replicated in clinical studies."
The experiments were led by graduate students Jason Alipio, Catherine Haga, and other colleagues in Dr. Keller's laboratory, and in the laboratory of Mary Kay Lobo, PhD, Professor of Anatomy and Neurobiology at UMSOM. The work was supported by the Substance Use in Pregnancy Center at UMSOM and by MPowering The State Opioid Use Disorders Research Collaboration.
An estimated seven percent of women reported using prescription opioid pain relievers during pregnancy, with one in five of them reporting that they misused these drugs outside of a provider's care, according to 2019 data from the Centers for Disease Control and Prevention (CDC). The problem likely has grown worse during the COVID-19 pandemic. Drug overdose deaths - primarily caused by the illicit use of fentanyl - have skyrocketed to their highest level ever recorded during the 2020 pandemic, according to the CDC.
To conduct the study, Dr. Keller and his colleagues exposed pregnant mice to various doses of fentanyl throughout their pregnancies and evaluated the newborn pups through their first few weeks of life (adolescence). They found that newborn mice exposed to the highest levels of fentanyl exhibited the most profound neurological effects, exhibiting anxiety-like behaviors when exposed to low levels of stress. They also found differences in their brain circuitry and found the mechanisms cells used to communicate with each other had been permanently altered.
"There were weaker connections in the regions of the brain involved in sensory processing, and stronger connections in regions associated with higher brain processing," Dr. Keller said. "We are not at the point of proving causality from the fentanyl exposure, but it is a strong correlation."
Next steps in the investigation include the design of a study to demonstrate that these changes in the brain lead to behavior changes. Once that connection is established, researchers can begin to evaluate therapies, either drug or behavioral, to determine what steps can help to alleviate any long-lasting impact on children exposed to opioids in the womb.
"This is a significant finding that underscores how much we still do not understand about the long-lasting effects of drug exposure to the developing fetus and newborn," said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore; and the John Z. and Akiko K. Bowers Distinguished Professor; and Dean, University of Maryland School of Medicine. "It clearly demonstrates the need for more research to understand fully how such exposure disrupts normal brain development, and to identify therapies that can work to help these children."
About the University of Maryland School of Medicine
Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 45 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has more than $563 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu