Diagnosing the Tiniest Victims of the Opioid Epidemic

Which Newborns Are at Risk for Withdrawal Symptoms?

Babies born to women who were using opioids during their pregnancy are easily the most vulnerable victims of the surging opioid epidemic.

As their bodies suddenly adjust to life without the drug postpartum, infants may experience neonatal opioid withdrawal syndrome (NOWS). Symptoms can include seizures severe enough to cause permanent cognitive impairment.

Ludmila Bakhireva, MD, PhD, MPH, a professor and epidemiologist at the University of New Mexico College of Pharmacy, and her colleague Rajesh C. Miranda, PhD, a professor at the Texas A&M College of Medicine, want to know why some infants develop NOWS and others do not.

When prenatal opioid exposure is suspected, newborns undergo four days of observation in the hospital, Bakhireva said. If severe and persistent symptoms appear, the infants receive small doses of an opioid, like morphine. The drugs are slowly tapered to wean the babies off while under observation.

The researchers are trying to identify biomarkers to predict which opioid-exposed infants are likely to develop NOWS before they exhibit any symptoms, while allowing low-risk babies to be sent home earlier.

"The idea is to identify and proactively initiate non-pharmacological strategies and pharmacological management of infants at high risk for developing NOWS," Bakhireva said. The study is supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, a branch of the National Institutes of Health.

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

Bakhireva and Miranda will test their idea 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," Miranda said.

Bakhireva said a unique prospective birth cohort called ENRICH provides a trove of data ready-made for their research study. "It allows us to incorporate state-of-the-art prospective assessment of maternal exposures and interpret study findings within the complexities of social environment and medical factors," she said.

The researchers analyze a sample of blood from the umbilical cord of the newborns to assess for micro-RNAs. They hope to determine which ones might serve as surrogate markers for brain health at birth - a sort of infant micro-RNA "signature" to predict severity of NOWS before withdrawal symptoms begin.

"To date, no single factor or known combination of factors has sufficiently explained the variability in NOWS symptoms," Bakhireva said. "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."