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Jefferson study finds more effective drug shortens therapy for addicted newborns

As the opioid epidemic rages on, more babies are being born addicted to the drugs their mothers took.

As the opioid epidemic rages on, more babies are being born addicted to the drugs their mothers took. Many of these infants spend weeks in the hospital, carefully being weaned from opioid dependence with gradually decreasing doses of oral morphine or methadone.

Their treatment time could be cut nearly in half by giving them buprenorphine, a milder opioid addiction treatment, concludes a study by Thomas Jefferson University researchers published online Thursday in the New England Journal of Medicine.

While the researchers did not consider costs, the health-care savings could be huge. A recent study found that on average, addicted babies need 23 days of intensive care at a  cost of $93,400. That adds up to a $1.5 billion tab for the estimated 23,000 infants born each year suffering withdrawal, called neonatal abstinence syndrome (NAS).

"This is a practice-changing advance for treatment of babies with NAS," said Walter K. Kraft, the physician and clinical pharmacologist who led the Jefferson study. "We predict that buprenorphine will become the new standard of care for NAS."

Neonatologist Mark Hudak, lead author of the American Academy of Pediatrics' guidelines on NAS treatment, praised the study as "exciting," but not automatically enough to change practice.

"Some institutions may switch to buprenorphine as an alternative that is very acceptable," said Hudak, chair of pediatrics at the University of Florida College of Medicine in Jacksonville. "Whether there's enough evidence to say this should be the standard of care — that is, everyone agrees this is unequivocally the best method — I'd personally like to see one more confirmatory study."

Gerard M. Cleary, medical director of neonatal intensive care at Abington Hospital-Jefferson Health, noted a limitation of the study: It excluded premature infants, so the results can't be generalized to such babies.

"Safely shortening the hospital stay and treatment duration would be a great benefit to newborns and their families," Cleary said in an email. "This study demonstrated promise … and invites further investigation of the benefits of buprenorphine on NAS."

Buprenorphine is one of three types of medications used to help adults kick their opioid addiction, and many experts say it is underused.

About seven years ago, Jefferson researchers wondered if it could benefit newborns. Like adults in withdrawal, infants feel the effects in every organ system. Their symptoms include tremors, muscle spasms, shrill crying, irritability, sweating, indigestion, diarrhea, vomiting, poor sleeping, and fever.

Buprenorphine, approved by the FDA in 2002,  is longer-acting and has less risk of toxic effects – such as suppressing breathing — than liquid morphine, used by about 80 percent of neonatal intensive care units in the United States.

"Buprenorphine may have a built-in safety effect. Giving more of the drug won't lead to a corresponding increase in toxicity," Kraft explained.

The new study, which builds on two pilot trials, was relatively small — 63 infants — but rigorously designed to minimize the chance of biased results. Medical staff did not know which drug the babies were treated with because the medications looked the same, and each administration  involved two liquids — morphine plus a placebo or buprenorphine plus a placebo.

When the results were analyzed, buprenorphine's effect "was larger than expected," Kraft said. Babies on that drug had a median of 15 days of treatment, compared with 28 for those on morphine  — a 47 percent reduction. The median hospital stay with buprenorphine was 21 days, compared to 33 with morphine.

The problem of NAS shows no signs of lessening. Even women who want to get off drugs when they learn they are pregnant may not be able to protect their babies; going cold turkey while pregnant increases the risk of miscarriage, so women seeking treatment are usually put on methadone as an opioid replacement therapy. Methadone is less harmful to infants than stronger opioids such as oxycodone or heroin, but it still leads to NAS.

Pennsylvania mirrors the national trend. The rate of newborn hospital stays for substance-abuse problems soared 250 percent from 2000 to 2015, when nearly 20 out of every 1,000 newborns faced withdrawal issues, according to a recent report by the Pennsylvania Health Care Cost Containment Council.

Hudak said the pediatricians' academy is reviewing new research and considering revisions to its guidelines.

"Very little careful research has been done to look at what you'd think is a straightforward and simple question: Which medication is more effective?" Hudak said. "I think this Jefferson paper will be important to look at."