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EVIDENCE- Neonatal Abstinence Syndrome BASED CARE SHEET What We Know › Use or abuse of psychoactive substances—including prescription and nonprescription drugs, , and illicit drugs—by a woman during places her newborn at risk for neonatal abstinence syndrome (NAS; also called neonatal withdrawal syndrome)(1,2,4,7,8,10,12,13) • These substances cross the placenta and can cause dependency in the fetus; when fetal exposure to the substance(s) terminates at birth, the newborn is at risk for a spectrum of withdrawal manifestations (e.g., autonomic dysfunction, respiratory distress, gastrointestinal compromise) that can necessitate prolonged treatment, intensive monitoring, and extended hospitalization and can result in impaired maternal- bonding, as well as short- and long-term adverse effects on neurodevelopment(1,3,4,7,9,12) • The incidence of NAS appears to be increasing in the United States(1,7,12,13) –Prevalence of NAS has increased five-fold from 2002–2017(12) –In the U.S., one infant is born each hour requiring treatment for NAS › Opiates, including heroin and methadone, are commonly associated with NAS, which occurs in 50–95% of exposed to these drugs in utero(2,4,8) • Other substances associated with NAS include , , , diphenhydrAMINE, chlordiazePOXIDE, phencyclidine, , and (4) ICD-9 • Withdrawal signs and manifestations can develop in neonates after in utero exposure 779.5 late in the pregnancy to antidepressant medication (e.g., selective serotonin reuptake inhibitors [SSRIs])(3,4,5) ICD-10 P96.1 › Manifestations of NAS include tremor, hyperirritability, jitteriness, excessive and often high-pitched crying, hypertonicity, fever, poor sucking, vomiting, diarrhea, sweating, sneezing, fever, nasal congestion, difficulty sleeping, respiratory distress, tachypnea, and Authors (2,4,5,7,9,12) Tanja Schub, BS • NAS onset and severity depend on the substance the infant is withdrawing from, the Cinahl Information Systems, Glendale, CA (5,16) Arsi L. Karakashian, RN, BSN combination of substances used, and the of the infant Armenian American Medical Society of –The short half-lives of opiates are responsible for a rapid onset of NAS, usually within California 72 hours after birth, in neonates born to who abused opiates.(4)The dose of Reviewers opiate the neonate was exposed to in utero does not seem to correlate with the severity (9,16) Darlene Strayer, RN, MBA of NAS Cinahl Information Systems, Glendale, CA – maintenance therapy is the standard of care for opioid-dependent pregnant Sara Richards, MSN, RN (1) Cinahl Information Systems, Glendale, CA women Nursing Practice Council - NAS associated with in utero exposure is less severe than NAS Glendale Adventist Medical Center, associated with in utero exposure to methadone, suggesting that buprenorphine may Glendale, CA be a superior treatment option for opioid dependence during pregnancy(5) Editor - Researchers are investigating pharmacologic alternatives to opioid agonist Diane Pravikoff, RN, PhD, FAAN substitution therapy for opioid dependence during pregnancy, including opioid Cinahl Information Systems, Glendale, CA vaccines and drugs that target the serotonergic system(10) - Investigators in Norway found evidence that medically supervised detoxification of opioid-dependentpregnant women may be an alternative to opioid maintenance June 23, 2017 therapy. Infants born to women who underwent detoxification in a residential setting

Published by Cinahl Information Systems, a division of EBSCO Information Services. Copyright©2017, Cinahl Information Systems. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the publisher. Cinahl Information Systems accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional. Cinahl Information Systems, 1509 Wilson Terrace, Glendale, CA 91206 during pregnancy experienced less prenatal drug exposure and had better perinatal outcomes, with no NAS. Risk of and other complications was not increased in women who underwent detoxification(1) –- (e.g., and barbiturates) have longer half-lives than opiates; manifestations of NAS that result from maternal abuse of sedative-hypnotics do not develop for 2–4 weeks after birth(4) –Polysubstance abuse produces more intense manifestations of NAS than abuse of a single substance(4,8) –Preterm infants experience a shorter, less severe course of opiate-related NAS (e.g., from maternal methadone use), and have significantly fewer central nervous system manifestations compared with full-term infants - In a study of 129 infants who were exposed to methadone or buprenorphine in utero, factors associated with increased risk of NAS included later estimated gestational age, lower maternal weight at delivery, maternal use of SSRIs, vaginal delivery, and higher infant birth-weight(6) –The sex of the infant may influence the severity of NAS; in a recent study of 90 infants born to women who were treated with buprenorphine during pregnancy, researchers found that male infants experienced more severe NAS than females and were more likely to require pharmacologic therapy(11) –Genetic factors may affect the severity of NAS(7,17) - Researchers recently reported that among infants with NAS, those with variants in the μ-opioid receptor (OPRM1) and catechol-o-methyltransferase (COMT) genes had shorter lengths of hospital stay and less need for pharmacologic therapy(17) › Updated guidelines for patient evaluation and pharmacologic treatment of NAS were published in 2012 by the American Academy of (AAP); the guidelines include the following:(5) • Each healthcare facility should develop and implement a protocol for the evaluation and management of NAS –Protocol-driven weaning of infants with NAS appears to be associated with reduced duration of opioid treatment and hospital stay compared to weaning without the use of a protocol. In a study of 547 late preterm and term infants receiving inpatient pharmacologic treatment for NAS, researchers found that those who underwent protocol-drivenweaning experienced significantly shorter duration of opioid treatment (17.7 vs. 32.1 days) and shorter hospital stay (22.7 vs. 32.1 days) • Urine toxicology testing should be performed on both and newborn –Testing of meconium, tissue, and/or neonatal hair can be performed to identify the specific substance(s) involved; serum glucose, serum calcium, CBC, and HIV testing may also be indicated(4) • A standardized assessment method such as the Lipsitz Neonatal Drug-Withdrawal Scoring System (recommended by the AAP) should be administered to evaluate the extent of withdrawal manifestations in newborns(5,7,12) –Other standardized tools that can be administered include the Finnegan Neonatal Abstinence Scoring System, the Neonatal Withdrawal Inventory, and the Neonatal Narcotic Withdrawal Index(2,4,7,8,12) • Nonpharmacologic management for neonates with NAS involves reducing sensory stimulation, including the use of dimmed lighting, prone positioning, and (5,7,12,18) – and use of can help calm infants with NAS(7) – for at least 72 hours starting at birth reduces the duration and severity of NAS and decreases the need for pharmacologic treatment; breastfeeding soothes infants and the itself contains a small amount of the abused substance(s), which relieves withdrawal signs and manifestations(5,7,14,18) • Up to 91% of neonates with NAS require pharmacologic therapy and an extended hospital stay(7,14) –Guidelines do not exist regarding the length of hospital stay considered sufficient to identify if NAS treatment is required following birth. In a study of 210 newborns 95% of those requiring treatment for NAS were identified within 5 days of birth prompting researchers to suggest that 5 days is adequate for routine post-natal observation for NAS(15) • Pharmacologic treatment for NAS includes the following: –Tincture of opium is the preferred treatment for opiate withdrawal; methadone may also be administered(5,10,12) - Opioid antagonists (e.g., naloxone) are contraindicated in neonates because they have the potential to cause seizures(7) – is prescribed for sedative- withdrawal and is preferred over (5,7,10,12) –Morphine has been used to treat NAS associated with heroin withdrawal(5,9,10) –Buprenorphine may be more effective than morphine in treating infants with NAS, and is associated with reduced length of hospital stay(5,10,18) – can be prescribed as adjunctive therapy for the treatment of opiate withdrawal in order to reduce the duration of pharmacotherapy(4,5,10)

What We Can Do › Learn about NAS so you can accurately assess your neonatal patients’ personal characteristics and the health education needs of the mother; share this information with your colleagues • Become familiar with maternal risk factors for , including incarceration, prostitution, mental health disorders, and a history of domestic violence • Review newly published information regarding maternal factors that could suggest fetal substance exposure; these factors include failure to obtain prenatal care; history of placental abruption, fetal demise, or spontaneous abortion; severe mood swings; cerebrovascular accident; and myocardial infarction • Monitor for signs of NAS in newborns(5) • Keep current with the latest recommendations for the treatment of NAS › Communicate with empathy when talking about substance use with pregnant women, and use nonjudgmental, direct language • When possible, provide written information regarding the effects of substance abuse on the fetus/newborn to reinforce verbal education(4) › Follow facility protocols regarding the screening of pregnant women and at-risk newborns › Promote and assist with prompt treatment and close monitoring of newborns with NAS › Promote breastfeeding (unless the mother has HIV infection) and healthy lifestyle practices to increase the chance of optimum infant outcome(5) › Request referral to a social worker for identification of local resources for classes (e.g., child development, nutrition); subsidized mental health services; vocational counseling; shelters (e.g., for the homeless, victims of domestic violence); HIV counseling; childcare and transportation assistance; Women, Infant, and Children (WIC) programs; and substance abuse programs, as appropriate

Coding Matrix References are rated using the following codes, listed in order of strength:

M Published meta-analysis RV Published review of the literature PP Policies, procedures, protocols SR Published systematic or integrative literature review RU Published research utilization report X Practice exemplars, stories, opinions RCT Published research (randomized controlled trial) QI Published quality improvement report GI General or background information/texts/reports R Published research (not randomized controlled trial) L Legislation U Unpublished research, reviews, poster presentations or C Case histories, case studies PGR Published government report other such materials G Published guidelines PFR Published funded report CP Conference proceedings, abstracts, presentation

References 1. Brandt, L., & Finnegan, L. P. (2017). Neonatal abstinence syndrome: Where are we, and where do we go from here? Current Opinion In Psychiatry, 30(4), 268-274. doi:10.1097/YCO.0000000000000334 (RV) 2. Dickes, L., Summery, J., Mayo, R., Hudson, J., Sherrill, W. W., & Chen, L. (2017). Potential for medicaid savings: A state and national comparison of an innovative neonatal abstinence syndrome treatment model. Population Health Management. Advance online publication. doi:10.1089/pop.2016.0158 (M) 3. Gentile, S. (2011). Neonatal withdrawal reactions following late in utero exposure to antidepressant medications. Current Women's Health Reviews, 7(1), 18-27. doi:10.2174/157340411794474793 (SR) 4. Hamdan, A. H. (2016, November 27). Neonatal abstinence syndrome. Medscape. Retrieved May 19, 2017, from http://emedicine.medscape.com/article/978763-overview (GI) 5. Hudak, M. L., Tan, R. C., & Committee on Fetus and Newborn, American Academy of Pediatrics. (2012). Neonatal . Pediatrics, 129(2), e540-e560. doi:10.1542/peds.2011-3212 (G) 6. Kaltenbach, K., Holbrook, A. M., Coyle, M. G., Heil, S. H., Salisbury, A. L., Stine, S. M., ... Jones, H. E. (2012). Predicting treatment of neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication. Addiction, 107(Suppl 1), 45-52. doi:10.1111/j.1360-0443.2012.04038.x (R) 7. Kocherlakota, P. (2014). Neonatal abstinence syndrome. Pediatrics, 134(2), e547-e561. doi:10.1542/peds.2013-3524 (RV) 8. Lucas, K., & Knobel, R. B. (2012). Implementing practice guidelines and education to improve care of infants with neonatal abstinence syndrome. Advances in Neonatal Care, 12(1), 40-45. doi:10.1097/ANC.0b013e318241bd73 (R) 9. Mccarthy, J. J., Leamon, M. H., Willits, N. H., & Salo, R. (2015). The effect of methadone dose regimen on neonatal abstinence syndrome. Journal of Addiction Medicine, 9(2), 105-110. doi:10.1097/adm.0000000000000099 (R) 10. McLemore, G. L., Lewis, T., Jones, C. H., & Gauda, E. B. (2013). Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome. Seminars in Fetal and Neonatal Medicine, 18(1), 35-41. doi:10.1016/j.siny.2012.09.002 (RV) 11. O'Connor, A. B., O'Brien, L., & Alto, W. A. (2013). Are there gender related differences in neonatal abstinence syndrome following exposure to buprenorphine during pregnancy? Journal of Perinatal Medicine, 41(5), 621-623. doi:10.1515/jpm-2012.0288 (R) 12. Patrick, S. W., Schiff, D. M., & Committee on Substance Use and Prevention. (2017). A public health response to opioid use in pregnancy. Pediatrics, 139(3), 1-7. doi:10.1542/peds.2016-4070 (G) 13. Patrick, S. W., Schumacher, R. E., Benneyworth, B. D., Krans, K. E., McAllister, J. M., & Davis, M. M. (2012). Neonatal abstinence syndrome and associated health expenditures: United States, 2000-2009. Journal of the American Medical Association, 307(18), 1934-1940. doi:10.1001/jama.2012.3951 (R) 14. Pritham, U. A. (2013). Breastfeeding promotion for management of neonatal abstinence syndrome. JOGNN: Journal of Obstetric, Gynecologic & Neonatal Nursing, 42(5), 517-526. doi:10.1111/1552-6909.12242 (SR) 15. Smirk, C. L., Bowman, E., Doyle, L. W., & Kamlin, C. O. F. (2014). How long should infants at risk of drug withdrawal be monitored after birth? Journal of Paediatrics & Child Health, 50(5), 352-355. doi:10.111/jpc.12513 (R) 16. Thajam, D., Atkinson, D. E., Sibley, C. P., & Lavender, T. (2010). Is neonatal abstinence syndrome related to the amount of opiate used? Journal of Obstetric, Gynecologic, and Neonatal Nursing, 39(5), 503-509. doi:10.1111/j.1552-6909.2010.01174.x (SR) 17. Wachman, E. M., Hayes, M. J., Brown, M. S., Paul, J., Harvey-Wilkes, K., Terrin, N., ... Davis, J. M. (2013). Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA: Journal of the American Medical Association, 309(17), 1821-1827. doi:10.1001/ jama.2013.3411 (R) 18. Wang, M. (2014, January 29). Perinatal drug abuse and neonatal drug withdrawal. Medscape. Retrieved February 29, 2016, from http://emedicine.medscape.com/article/978492-overview (GI)