Diagnosing the tiniest victims of the opioid epidemic

The opioid epidemic doesn’t discriminate—people of all ages, races, and genders are affected. However, perhaps the most vulnerable population may be the newborn babies born to women who were taking opioids during their pregnancy—two groups that researchers don’t yet completely understand. More than 20,000 babies in the United States were born addicted to opioids in 2012 (the most recent year with data available). As their bodies suddenly adjust to life without the drug postpartum, they experience a range of opioid withdrawal symptoms collectively called neonatal opioid withdrawal syndrome (NOWS). One symptom is seizures, which—if they are severe enough—can cause permanent cognitive impairment.

That’s why Rajesh C. Miranda, PhD, a professor at the Texas A&M College of Medicine, and his colleague Ludmila Bakhireva, MD, PhD, MPH, a professor and epidemiologist at the University of New Mexico College of Pharmacy, are leading a new study to find the mechanisms behind why some infants develop NOWS and others—even those whose mothers took the same doses of opioids during pregnancy—do not. There is great variability in the severity and duration of symptoms, and the causes of these differences remain unknown.

“With this study we are trying to identify biomarkers to predict which opioid-exposed infants are likely to undergo NOWS before they exhibit any symptoms,” Miranda said. “The idea is to identify and proactively treat infants at high risk for developing NOWS.”

The current standard of care for infants born to women who have been using opioids is to watch and wait to determine whether symptoms appear. If they do, then they are given small doses of an opioid like morphine, which are slowly tapered to wean them off the drug safely. Of course, giving a powerful opioid to every newborn who might experience NOWS isn’t a good idea either—thus the importance of being able to predict which infants are most at risk.

“In previous research, we found that tiny epigenetic markers called micro-RNAs circulating in the mother’s blood may help predict which children are likely to have fetal alcohol spectrum disorders,” Miranda said. “We then started wondering if the same might be true for the effects of other drugs, like opioids, on the infant.”

Miranda and Bakhireva will test this in 70 infants of women who are taking methadone or buprenorphine as part of medication-assisted treatment for opioid use disorder. “Dr. Bakhireva already had an established, well-characterized cohort she followed for other research, and since these women are actively getting help for their disease, they tend to have fewer exposures to illegal drugs and alcohol, which can complicate the findings,” Miranda said.

Once the infants are born, the research team takes a sample of blood from the umbilical cord to assess for micro-RNAs. They hope to determine which ones serve as surrogate markers for brain health at birth and thus which infant micro-RNA “signature” can predict severity of NOWS before withdrawal symptoms begin.

“We hope that once we have found the relevant micro-RNAs that they can be used not only as diagnostic biomarkers for drug exposure and effects, but also manipulated to diminish effects of drug exposure and to provide protection to the brain,” Miranda said.

The study is supported by a two-year grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), part of the National Institutes of Health.