Tag Archive for: opioid

New study finds prenatal opioid exposure linked to smaller newborn brain volumes

brain scans of newbornA new study out of the Center for Prenatal, Neonatal & Maternal Health Research, directed by Catherine Limperopoulos, PhD, led by Yao Wu, PhD and Stephanie Merhar, MD, MS, out of Cincinnati Children’s Hospital Medical Center, sought answers to the question: “Do brain volumes differ in opioid-exposed vs. unexposed newborns?” In one of the largest studies of this kind, researchers found that prenatal exposure to opioids is associated with smaller brain volumes in newborns. These findings from the landmark Outcomes of Babies with Opioid Exposure (OBOE) study build on, reinforce smaller studies, and achieve a better understanding of the impacts of prenatal opioid exposure (POE).

Dive Deeper

The Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT-NOW)’s OBOE study is a multi-site observational study of newborns with prenatal opioid exposure and a control group of unexposed newborns from four different sites in the United States – Case Western Reserve University, Cincinnati Children’s Hospital Medical Center, University of Alabama at Birmingham, and Children’s Hospital of Philadelphia.

In a study involving 173 newborns who were exposed to opioids during pregnancy and 96 newborns not exposed to opioids prenatally showed smaller brain sizes in several key areas. Specifically, these exposed babies had smaller total brain volumes, as shown through MRI, as well as reduced volumes in important parts of the brain, including the cortex (outer layer of the brain), deep gray matter (areas that control movement and emotions), white matter (which helps transmit signals in the brain), cerebellum (responsible for coordination and movement), brainstem (controls basic functions like breathing), and the amygdala (involved in emotions and memory).

Further details showed that newborns exposed to medication for opioid use disorder (MOUD) during pregnancy with methadone, had smaller white matter volumes, while those exposed to MOUD with buprenorphine had smaller volumes specifically in the right amygdala. Additionally, newborns who were exposed to opioids plus additional substances such as THC and gabapentin had smaller volumes in even more brain areas compared to those who were only exposed to opioids.

What’s Next

The OBOE study sets the groundwork for further research into the long-term impact of opioid exposure during pregnancy. Additional work is necessary to expand on these findings and how they relate to functions in childhood – including exploring the way these reduced brain volumes may impact cognitive, behavioral, and motor impairments. The study raises important questions about how current guidelines for MOUD during pregnancy – specifically with methadone and buprenorphine – might evolve considering these findings. This study highlights the need for further research to assess the long-term effects of MOUD regimens on both maternal and infant outcomes.

This significant study underscores the importance of multi-disciplinary collaboration in opioid exposure research, effective regulation, and policy interventions – involving healthcare providers, researchers, policymakers, and affected families – to best mitigate the consequences and improve the health outcomes of children affected by prenatal opioid exposure.

You can read the full study, Antenatal Opioid Exposure and Global and Regional Brain Volumes in Newborns, and its companion editorial, Following the Developing Brain Affected by Opioid Exposure, in the Journal of the American Medical Association.

Additional authors from Children’s National include Kushal Kapse, BS, MS, and Josepheen De Asis-Cruz, MD, PhD. Other authors include Carla M. Bann, PhD, Jamie E. Newman, PhD4, Nicole Mack, MS, Sara B. De Mauro, MD, MSCE, Namasivayam Ambalavanan, MD, Jonathan M. Davis, MD, Scott A. Lorch, MD, MSCE5, Deanne Wilson-Costello, MD, Brenda B. Poindexter, MD and Myriam Peralta-Carcelen, MD.

In the News: Battling fentanyl addiction in pediatrics

“Intervening quite early in a developmentally proper manner within the pediatric health system can go a long way.”

In a recent video with CNN, Sivabalaji Kaliamurthy, M.D., director of our Addictions Program, and one of his patients struggling with a severe addiction to fentanyl, talk about this deadly opioid that has become a leading cause of overdose among young people in the U.S. Dr. Kaliamurthy talks about the critical shortage of addiction programs specifically designed for teens and sheds light on our program at Children’s National Hospital. The program is one of the only ones in the country working to address this urgent need with specialized support tailored to younger patients grappling with substance use disorders. Watch the video on CNN.

parent regards child with concern

Racial and ethnic disparities in ED opioid prescriptions have decreased

pill bottles and pills

Whereas in 2012, there were clear racial and ethnic differences in opioid prescription rates. By 2019, those differences were no longer statistically significant overall or within sites.

As the provision of opioid prescriptions declined over time, previously marked racial and ethnic disparities in opioid prescription rates at the time of Emergency Department (ED) discharge also attenuated, according to new findings led by Monika Goyal, M.D., M.S.C.E., associate division chief of Emergency Medicine and Trauma Services at Children’s National Hospital, and others.

The research, published in Pediatrics, investigated whether racial and ethnic differences in the delivery of outpatient opioid prescriptions for children discharged from the ED with long-bone fractures diminished over time.

“In 2012 compared to 2019, although rates of opioid prescribing were higher across all racial/ethnic groups, they were highest for NH-white youth,” said Dr. Goyal. “It’s reassuring to see that as rates of opioid prescribing declined over time, such racial and ethnic differences have attenuated.”

Whereas in 2012, there were clear racial and ethnic differences in opioid prescription rates. By 2019, those differences were no longer statistically significant overall or within sites.

However, as clinicians prescribed fewer opioids, sites continued to have moderate racial and ethnic variability in opioid prescribing rates for non-Hispanic white, non-Hispanic Black and Hispanic children.

The authors caution that the reduction of opioid prescription is possibly attributed to the response against the opioid epidemic.  There is also a need for more studies that seek to identify optimal outpatient pain management for children with fractures and ensure suitable post-discharge pain control for all children, regardless of race and/or ethnicity.

The retrospective cross-sectional study sampled children 4-18 years with long bone fractures using the Pediatric Emergency Care Applied Research Network (PECARN) Registry, an electronic health record registry of four geographically diverse pediatric EDs, from January 1, 2012, to December 31, 2019.

Patient race and ethnicity were categorized as non-Hispanic (NH) white, NH-Black, Hispanic or other. The investigators performed bivariable and multivariable logistic regression to measure the association between patient race and ethnicity and outpatient prescription. Out of the 42,803 ED eligible visits to analyze, 6,441 received an opioid prescription at ED discharge. This data showed that disparities when prescribing an opioid decreased over a 7-year period.

Breakthrough device objectively measures pain type, intensity and drug effects

AlgometRX

Clinical Research Assistant Kevin Jackson uses AlgometRx Platform Technology on Sarah Taylor’s eyes to measure her degree of pain. Children’s National is testing an experimental device that aims to measure pain according to how pupils react to certain stimuli. (AP Photo/Manuel Balce Ceneta)

Pediatric anesthesiologist Julia C. Finkel, M.D., of Children’s National Health System, gazed into the eyes of a newborn patient determined to find a better way to measure the effectiveness of pain treatment on one so tiny and unable to verbalize. Then she realized the answer was staring back at her.

Armed with the knowledge that pain and analgesic drugs produce an involuntary response from the pupil, Dr. Finkel developed AlgometRx, a first-of-its-kind handheld device that measures a patient’s pupillary response and, using proprietary algorithms, provides a diagnostic measurement of pain intensity, pain type and, after treatment is administered, monitors efficacy. Her initial goal was to improve the care of premature infants. She now has a device that can be used with children of any age and adults.

“Pain is very complex and it is currently the only vital sign that is not objectively measured,” says Dr. Finkel, who has more than 25 years of experience as a pain specialist. “The systematic problem we are facing today is that healthcare providers prescribe pain medicine based on subjective self-reporting, which can often be inaccurate, rather than based on an objective measure of pain type and intensity.” To illustrate her point, Dr. Finkel continues, “A clinician would never prescribe blood pressure medicine without first taking a patient’s blood pressure.”

The current standard of care for measuring pain is the 0-to-10 pain scale, which is based on subjective, observational and self-reporting techniques. Patients indicate their level of pain, with zero being no pain and ten being highest or most severe pain. This subjective system increases the likelihood of inaccuracy, with the problem being most acute with pediatric and non-verbal patients. Moreover, Dr. Finkel points out that subjective pain scores cannot be standardized, heightening the potential for misdiagnosis, over-treatment or under-treatment.

Dr. Finkel, who serves as director of Research and Development for Pain Medicine at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, says that a key step in addressing the opioid crisis is providing physicians with objective, real-time data on a patient’s pain level and type, to safely prescribe the right drug and dosage or an alternate treatment.,

She notes that opioids are prescribed for patients who report high pain scores and are sometimes prescribed in cases where they are not appropriate. Dr. Finkel points to the example of sciatica, a neuropathic pain sensation felt in the lower back, legs and buttocks. Sciatica pain is carried by touch fibers that do not have opioid receptors, which makes opioids an inappropriate choice for treating that type of pain.

A pain biomarker could rapidly advance both clinical practice and pain research, Dr. Finkel adds. For clinicians, the power to identify the type and magnitude of a patient’s nociception (detection of pain stimuli) would provide a much-needed scientific foundation for approaching pain treatment. Nociception could be monitored through the course of treatment so that dosing is targeted and personalized to ensure patients receive adequate pain relief while reducing side effects.

“A validated measure to show whether or not an opioid is indicated for a given patient could ease the health care system’s transition from overreliance on opioids to a more comprehensive and less harmful approach to pain management,” says Dr. Finkel.

She also notes that objective pain measurement can provide much needed help in validating complementary approaches to pain management, such as acupuncture, physical therapy, virtual reality and other non-pharmacological interventions.

Dr. Finkel’s technology, called AlgometRx, has been selected by the U.S. Food and Drug Administration (FDA) to participate in its “Innovation Challenge: Devices to Prevent and Treat Opioid Use Disorder.” She is also the recipient of Small Business Innovation Research (SBIR) grant from the National Institute on Drug Abuse.