Newborns who have been exposed to opioid drugs in the womb routinely receive medical treatment to help them overcome withdrawal symptoms, but no one knows for sure whether their prenatal exposure might harm their health later in life.
Now, University of New Mexico researchers are joining in a large multi-site study to explore the long-term impact of prenatal opioid exposure on children’s brain, cognitive, behavioral, social and emotional development.
A team from the UNM Health Sciences Center and the Mind Research Network (MRN) are part of a five-university consortium planning grant from the National Institutes of Health (NIH) under its Helping to End Addiction Long-Term (HEAL) Initiative, said Ludmila Bakhireva, MD, PhD, MPH, director of the UNM College of Pharmacy Substance Use Research & Education Center and a principal investigator on the grant.
The UNM/MRN site received $542,000 for the Phase I of the initiative. It is intended to lay the groundwork for a planned Phase II of the project, which will follow thousands of children from before birth to pre-adolescence. Researchers will use neuroimaging and neurodevelopmental assessments to gauge the impact of prenatal substance exposure. Many of the participants will be recruited through UNM’s Milagro Program – a specialty clinic that provides care to pregnant women with substance use disorders.
There have been no large, long-term multi-center studies in the U.S. on child behavioral and cognitive development resulting from exposure to opioids, Bakhireva said.
“Pregnant women and young children are the most vulnerable population affected by the opioid epidemic,” she said. “It’s exciting to see the NIH recognize that we need to do an extensive study to characterize developmental trajectories in exposed children. Sometimes when you get to young adulthood it's already too late. I feel like it’s a missed opportunity not to intervene earlier in life.”
Often, she adds, exposure to opioids and other substances co-occurs with poverty, the psychological impact of stigmatization and racism and other risk factors that affect development, although children of all social status and racial groups are affected by the opioid epidemic.
“It’s really hard to disentangle these factors,” Bakhireva said. “A long-term study would allow us to identify not just risk factors, but also resilience factors – how can we ameliorate prenatal exposure to allow children to achieve the best outcomes?”
Bakhireva will be joined in the study by fellow principal investigators Lawrence Leeman, MD, MPH, a professor in UNM’s Department of Family & Community Medicine and director of the Milagro Program, and Julia Stephen, PhD, professor of translational neuroscience at the Mind Research Network.
The trio has partnered with teams from the University of California, San Diego, Emory University, Case Western Reserve University and Oklahoma State University for the 18-month planning grant to map out the long-term child development study.
The study is part of the larger HEAL Initiative, launched by the NIH in April 2018 to improve prevention and treatment strategies for opioid misuse and addiction and enhance pain management. The initiative aims to improve treatments for chronic pain, curb the rates of opioid use disorder and overdose and achieve long-term recovery from opioid addiction. The UNM/MRN award is one of 375 NIH grant awards across 41 states made in FY 2019 to apply scientific solutions to reverse the national opioid crisis.
The comprehensive study of infants and younger children complements the HEAL Adolescent Brain Cognitive Development (ABCD) study, which is already underway and focuses on ages 9 to 22, said Stephen, an expert in neuroimaging.
“Both of these are focused on trying to understand the risk of addiction and the effects of addiction,” Stephen said. “The ABCD study is really looking at normal development as well, and trying to understand the factors that impact long-term development in kids.”
The Mind Research Network is equipped to scan children’s brains using magnetic resonance imaging (MRI), magnetic encephalography (MEG) and electroencephalography (EEG), Stephen said.
The team hopes to identify characteristic changes in brain structure or function that mirror behavioral abnormalities in children affected by opioid exposure, Bakhireva says, but it will also be looking for other telltale signs, including epigenetic changes and physiological measures.
During the Phase I planning stage, the team will start by working out the best way to recruit mothers willing to participate in years-long research, assessing the feasibility of multi-modal infant assessments, how to report test results to parents and a mechanism to provide access to services for children identified as being at risk.
The study has great relevance for the Milagro Program, which provides care for close to 200 women each year, Leeman said.
“We are acutely aware of the limited information regarding the effects of opioids, stimulants and other drugs on fetal, neonatal and pediatric development,” he said, adding that the study will “provide information to counsel women in pregnancy and lead to the development of optimal care plans for infants exposed to perinatal substance use.”
The planning phase will also consider smaller hospitals and clinics in rural New Mexico from which study participants who are routinely underrepresented in research might be recruited, Bakhireva said.
In a previous small study of children whose mothers received care at the Milagro Program, it was “reassuring” that at six months, infants who had undergone opioid withdrawal following delivery did not show pronounced differences, Bakhireva said.
But there are suspicions that prenatal drug exposure, alone or in combination with environmental factors, could lead to problems later in life, such as heightened pain sensitivity, inflammation and emotional dysregulation, she said. The new study should shed light in these areas.
“There are a lot of questions to be addressed in the next 18 months,” Bakhireva said. “This is a great opportunity for UNM, because it builds on our previous solid track record in this field and our established multi-disciplinary collaborations. It will allow New Mexicans to be represented in a national study, making future results more applicable to our population.”