Neonatal Abstinence Syndrome (NAS), a narcotic withdrawal disorder affecting the digestive, breathing, and nervous systems of newborn babies, has become a serious problem in the United States. NAS symptoms can be variable and may include excessive crying, fever, diarrhea, poor feeding, seizures, breathing problems, tremors and stiffness. NAS cases, which are caused by a pregnant mother’s use of prescription or illegal drugs, have tripled over the past 10 years and now affect more than five of every 1,000 newborns. “That’s a pretty scary statistic, considering about four million babies are born in this country every year,” said Chief of the Division of Newborn Medicine Jonathan M. Davis, MD. “That’s 200,000 babies with NAS.”
The increasing number of NAS cases means more sick babies needing longer hospital stays, resulting in inflated health care costs – $890 million in 2009 alone, nearly four times more than 10 years ago. According to Davis, better methods for diagnosing and treating NAS could reduce the number of cases and help physicians more effectively care for NAS babies; length of stay would be reduced and the health care system, Medicaid in particular, would save millions of dollars per year. “NAS is an area that we just don’t know enough about, in prevention, diagnosis or treatment,” said Davis. “Thousands of babies spend over a month in the hospital for a problem that is potentially preventable. Clearly we need to do a better job.”
At the Forefront of Research
Davis is at the forefront of a movement to do just that. He is leading a group of researchers - including Newborn Medicine Fellow Elisha Wachman, MD, Neonatologist Karen Harvey-Wilkes, MD and Tufts Clinical and Translational Science Institute investigators Norma Terrin, PhD and Gordon Huggins, MD - that recently published a critical paper on NAS in the Journal of the American Medical Association (JAMA). The study analyzed certain genetic markers in the DNA of newborns exposed to certain drugs and found that babies with these markers needed less treatment for NAS and required a shorter hospital stay. Although currently there is no prenatal testing available for NAS, Davis and his colleagues are working to develop a mouth-swab test for the mother, which would examine gene structure and identify potential NAS risk before birth. A way to identify high-risk babies before birth would be a major breakthrough in the treatment and prevention of NAS.
The inspiration for Davis’ research began when his group noticed a tremendous increase in the number of NAS babies being treated at Tufts Children's Hospital. His colleagues around the country reported similar increases in NAS cases. However, Davis found that treatment options had not improved in 20-30 years and there was no agreement among doctors on the best medications to use for NAS; as many as 10-15 different drugs were being used in different combinations. Even some drugs that had never been FDA approved for NAS – including phenobarbital and valium – were being used, regardless of limited scientific evidence of safety or effectiveness. “Drugs are not made for babies. They are made for adults, but sometimes are used to treat babies anyway,” said Davis. “Methadone contains 20 percent alcohol as a preservative; phenobarbital contains alcohol and propylene glycol (a component of antifreeze). It’s critical that we develop medications that are safer for children.”
Research at Tufts MC
Davis and his team have also looked into potential longer-term effects of NAS. Many women who are on narcotics may also smoke cigarettes and take other psychiatric medications. The team decided to explore the effect of all these factors on the developing brain. While current NAS treatments have been used for decades, there were no previous clinical trials to prove which NAS drugs were both more effective in the short-term and result in better outcomes for kids in the future.
Davis and his colleagues are beginning a four-year, randomized clinical trial at Tufts MC and four other sites in the US, to study treating NAS babies with morphine or methadone, the two most common NAS medications. The goal of the clinical trial is to determine how these drugs affect length of hospital stay, effectiveness of treatment and need for more care. As part of the study, participating babies will be examined a year and a half after birth to check their development; the results will help Davis and his team better identify which kids might have long-term consequences of NAS. The ultimate hope is that in the future, doctors treating newborn babies will be able to more effectively predict, prevent and treat NAS, both prenatally and in newborns. “NAS is really a tough way to start out life,” said Davis. “It breaks your heart to see these poor infants so uncomfortable. We think it’s important to do everything possible to help out these little people however we can.”