News Release

Study finds increase in maternal opiate use, infants born with drug withdrawal syndrome

Peer-Reviewed Publication

JAMA Network

CHICAGO – Between 2000 and 2009 in the United States, the annual rate of maternal opiate use increased nearly 5-fold, while diagnosis of the drug withdrawal syndrome among newborns, neonatal abstinence syndrome (NAS), increased almost 3-fold, accompanied by a substantial increase in hospital charges related to NAS, according to a study published online by JAMA. The study is being released early to coincide with its presentation at the Pediatric Academic Societies Annual Meeting.

A recent national study indicated that 16.2 percent of pregnant teens and 7.4 percent of pregnant women aged 18 to 25 years use illicit drugs, according to background information in the article. Neonatal abstinence syndrome "most commonly occurs in the context of antepartum [before birth] opiate use, although other drugs have also been implicated. In addition to NAS, illicit drug use (specifically opioid dependence) during pregnancy is associated with a significantly increased risk of adverse neonatal outcomes such as low birthweight (<2,500 grams [5.5 lbs]) and mortality," the authors write. Neonatal abstinence syndrome is characterized by a wide array of signs and symptoms including increased irritability, hypertonia (heightened muscle tone), tremors, feeding intolerance, seizures, and respiratory distress. Symptoms of withdrawal associated with NAS have been described in 60 percent to 80 percent of newborns exposed to heroin or methadone in utero. To date, there have been no estimates of the national incidence of NAS across the United States in the context of opiate use during pregnancy.

Stephen W. Patrick, M.D., M.P.H., M.S., of the University of Michigan Health System, Ann Arbor, Mich., and colleagues conducted a study to examine patterns in the national incidence of NAS and maternal opiate use at the time of delivery and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1,000 hospital births. All hospital charges were adjusted for inflation to 2009 U.S. dollars.

Between 2000 and 2009, the rate of newborns diagnosed with NAS increased from 1.20 to 3.39 per 1,000 hospital births per year. Also during this time period, the number of mothers using or dependent on opiates increased from 1.19 to 5.63 per 1,000 hospital births per year. "Compared with all other hospital births, newborns with NAS were significantly more likely to have respiratory diagnoses (30.9 percent), to have low birthweight (19.1 percent), have feeding difficulties (18.1 percent), and have seizures (2.3 percent). Newborns with NAS were also more likely to be covered by Medicaid (78.1 percent) and reside in zip codes within the lowest income quartile (36.3 percent)," the authors write.

Average hospital charges for newborns diagnosed with NAS increased between 2000 and 2009 from $39,400 to $53,400, a 35 percent increase. The hospital length of stay (LOS) for newborns diagnosed with NAS averaged 16 days, and remained relatively unchanged during the study period. Between 2000 and 2009, total hospital charges for NAS are estimated to have increased from $190 million to $720 million, adjusted for inflation. The researchers write that in 2009, the estimated number of newborns with NAS was 13,539 -- or approximately 1 infant born per hour in the United States with signs of drug withdrawal.

"In conclusion, newborns with NAS experience longer, often medically complex and costly initial hospitalizations. The increasing incidence of NAS and its related health care expenditures call for increased public health measures to reduce antenatal exposure to opiates across the United States. In addition, further innovation and standardization of treatment of NAS may mitigate NAS symptoms and reduce hospital LOS. States are poised to seek innovative solutions to decreasing the burden of NAS, because the majority of hospital expenditures for this condition are shouldered by state Medicaid programs."

(doi:10.1001/JAMA.2012.3951. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This work was supported by a grant from the Robert Wood Johnson Foundation Clinical Scholars Program. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3:15 p.m. CT Monday, April 30 at this link.

Editorial: Epidemic of Prescription Opiate Abuse and Neonatal Abstinence

In an accompanying editorial, Marie J. Hayes, Ph.D., of the University of Maine, Orono, and Mark S. Brown, M.D., of Eastern Maine Medical Center, Bangor write that "future directions in NAS research must address the need for clinical trials of new medications to establish optimal protocols for maternal opiate dependence with particular focus on methadone treatment induction of the mother early in pregnancy, maternal adherence to treatment, ancillary alcohol use monitoring, and psychiatric care."

"Postnatally, early identification and aggressive opiate replacement in infants with early signs of NAS may help to decrease severity and LOS. As suggested by Patrick et al and other studies, breastfeeding may reduce treatment rate and LOS in opiate-exposed infants in all categories. Clues to fetal-neonatal dependence and NAS risk are emerging from studies of placental transfer of opiates across gestation, relation to maternal dose change, infant pharmacogenomics, and meconium [stool of an infant] metabolites to determine other exposures. This additional information may lead to better postnatal care of infants with NAS."

(doi:10.1001/JAMA.2012.4526. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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To contact Stephen W. Patrick, M.D., M.P.H., M.S., call Mary Masson at 734-764-2220 or email mfmasson@umich.edu. To contact editorial co-author Marie J. Hayes, Ph.D., call Ron Lisnet at 207-581-3779 or email ron.lisnet@umit.maine.edu.


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