Treat with confidence. Trusted answers from the American Academy of Pediatrics.

Neonatal Abstinence Syndrome

Jatinder Bhatia, MD, FAAP Medical College of Georgia Augusta University Augusta, GA Treat with confidence. Trusted answers from the American Academy of Pediatrics. Disclosures & Disclaimers . Consultant for Nestlé USA . CME lectures for Mead Johnson Nutrition . Grant support from Chiesi, Duke (NIH) . Statements and opinions expressed are those of the author and not necessarily those of the American Academy of Pediatrics. . Mead Johnson sponsors programs such as this to give healthcare professionals access to scientific and educational information provided by experts. The presenter has complete and independent control over the planning and content of the presentation, and is not receiving any compensation from Mead Johnson for this presentation. The presenter’s comments and opinions are not necessarily those of Mead Johnson. In the event that the presentation contains statements about uses of drugs that are not within the drugs' approved indications, Mead Johnson does not promote the use of any drug for indications outside the FDA-approved product label. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Objectives . Define Neonatal Abstinence Syndrome (NAS) . Incidence . Commonly used/abused drugs . Signs and symptoms . Complications . Testing . Prevention and treatment Treat with confidence. Trusted answers from the American Academy of Pediatrics. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Terminology . NAS refers to a postnatal opioid withdrawal syndrome. . 55%–94% of newborns are affected when mothers are addicted to or treated with opioids during pregnancy. . Other terms: Neonatal withdrawal syndrome; neonatal drug withdrawal syndrome; neonatal withdrawal . A more liberal definition includes exposure to non-opioid substances; however, assessment tools for NAS were developed for infants exposed to opioids. . Polysubstance use is common among those who use opioids.

McQueen K, Murphy-Oikonen J. Neonatal abstinence syndrome. N Engl J Med. 2016;375(25):2468–2479; Finnegan LP, Connaughton JF Jr, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2(1–2):141–158; Hudak ML, Tan RC, American Academy of Pediatrics Committee on Drugs, Committee on Fetus and Newborn. Neonatal drug withdrawal. Pediatrics. 2012;129(2):e540–e560; Davies H, Gilbert R, Johnson K, et al. Neonatal drug withdrawal syndrome: cross-country comparison using hospital administrative data in England, the USA, Western Australia and Ontario, Canada. Arch Dis Child Fetal Neonatal Ed. 2016;101(1):F26–F30; Kaltenbach K, Jones HE. Neonatal abstinence syndrome: presentation and treatment considerations. J Addict Med. 2016;10(4):217–223; and Krans EE, Cochran G, Bogen DL. Caring for opioid-dependent pregnant women: prenatal and postpartum care considerations. Clin Obstet Gynecol. 2015;58(2):370–379 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Introduction to Opioids . Chemical class: Opioid vs opiate o Opiates are from poppy plants o Opioid means they act like an opiate . Functional class: Narcotic analgesic Treat with confidence. Trusted answers from the American Academy of Pediatrics. Opioid Receptors . Found in the brain, spinal cord, gastrointestinal (GI) tract, and other organs o μ (mu) receptors – respiratory depressant + GI o Δ, δ (delta) receptors – development of tolerance o Κ (kappa) receptors – involved in sedation + GI . Activation of the receptors: o Supraspinal analgesia o Release of dopamine (brain’s reward system) Treat with confidence. Trusted answers from the American Academy of Pediatrics. Normal Neurotransmission . Synthesized from precursors . Packaged into vesicles . Released in response to presynaptic action potential . Activates postsynaptic receptor . Released back into synapse . Removed from synapse o Reuptake and repackage o Broken down by enzymes Treat with confidence. Trusted answers from the American Academy of Pediatrics. All Addictions Can be Traced to Dopamine

. Cocaine – blocks transporters to inhibit reuptake . Amphetamines – stimulate dopamine producing cells . Opiates – trigger a complex chemical cascade (involving gamma-aminobutyric acid [GABA]) that increases rate of release Treat with confidence. Trusted answers from the American Academy of Pediatrics. Clinical Features . Complex disorder o Central and autonomic nervous systems o GI symptoms • Clinical signs within the first few days after birth, but variable in timing and severity • Mild tremors, irritability, fever • Excessive weight loss • Seizures • Type of opioid, dose, and timing of exposure alters risk of withdrawal Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014;134(2):e547–e561; and Wiles JR, Isemann B, Ward LP, Vinks AA, Akinbi H. Current management of neonatal abstinence syndrome secondary to intrauterine opioid exposure. J Pediatr. 2014;165(3):440–446 Treat with confidence. Trusted answers from the American Academy of Pediatrics.

CNS GI Autonomic • Inconsolability • Poor feeding • Sweating • High-pitched crying • Excessive sucking • Fever • Skin excoriation • Feeding • Nasal stuffiness • Hyperactive reflexes intolerance • Sneezing • Tremors • Vomiting • Tachypnea • Seizures • Diarrhea • Mottling

Abbreviations: CNS, central nervous system; GI, gastrointestinal . Incidence is between 55%–94% . Onset depends on: o Type of drug/additional substances o Half life of the drug o Time of last maternal dose prior to delivery Treat with confidence. Trusted answers from the American Academy of Pediatrics.

Adapted from Cotton SW. Drug testing in the neonate. Clin Lab Med. 2012;32(3):449–466 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Symptoms Usually Occur by Day 5 Drug Onset Heroin Within 24 hours Methadone 3–5 days Buprenorphine 3–5 days Prescription Opioids 24–36 hours Cocaine, Meth 24–36 hours *NAS tool not valid Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014;134(2):e547–e561 Treat with confidence. Trusted answers from the American Academy of Pediatrics.

Clinical and Other Consequences of Maternal Opioid Use

Outcomes in the pregnant woman The information provided in the table is Sexually transmitted infections from Wong S, Ordean A, Kahan M, et al. HIV infection Substance use in pregnancy. J Obstet Gynaecol Can. 2011;33(4):367–384; Hepatitis Patrick SW, Dudley J, Martin PR, et al. Prescription opioid epidemic and infant Endocarditis outcomes. Pediatrics. 2015;135(5):842– 850; ACOG Committee on Health Care Osteomyelitis for Underserved Women and American Sepsis Society of Addiction Medicine. ACOG Committee Opinion No. 524: Opioid Cellulitis abuse, dependence, and addiction in pregnancy. Obstet Gynecol. Chaotic lifestyle (eg, prostitution, violence, and theft) 2012;119(5):1070–1076; Visconti KC, Decreased commitment to health care Hennessy KC, Towers CV, Howard BC. Chronic opiate use in pregnancy and Decreased receptiveness to social services newborn head circumference. Am J Perinatol. 2015;3(1)2:27–32; Jansson LM, Outcomes in the fetus Velez ML. Infants of drug-dependent mothers. Pediatr Rev. 2011;32(1):5–12; Growth restriction Lee J, Hulman S, Musci M Jr, Stang E. Abruptio placentae Neonatal abstinence syndrome: influence of a combined Preterm labor inpatient/outpatient methadone treatment regimen on the average Abnormal heart patterns length of stay of a Medicaid NICU Death population. Popul Health Manag. 2015;18(5):392–397; and O’Donnell M, Outcomes in the newborn Nassar N, Leonard H, et al. Increasing prevalence of neonatal withdrawal Low birth weight syndrome: population study of maternal Preterm delivery factors and child protection involvement. Pediatrics. Small head circumference 2009;123(4):e614–621 Sleep myoclonus Child maltreatment Visual disturbances Treat with confidence. Trusted answers from the American Academy of Pediatrics.

Adapted from Finnegan LP, Connaughton JF Jr, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2(1–2):141–158 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Scoring Frequency . Allow baby to transition before scoring begins (generally within 2 hours) . Then score q 3–4 h . If total score >8, score q 2 h . Score before feeding . Consistent schedule Treat with confidence. Trusted answers from the American Academy of Pediatrics. What’s “Normal”? . Healthy neonates with no opioid exposure . On DOL 1–3, the median score = 2.0 . Variability increased with age o 95th percentile on DOL 1 = 5.5 o 95th percentile on DOL 2 = 7.0 . Circadian rhythm established by 5–6 weeks o Median day score = 5.0 o Median night score = 2.0 . Scores >8 can be considered pathologic

Zimmermann-Baer U, Nötzli U, Rentsch K, Bucher HU. Finnegan neonatal abstinence scoring system: normal values for first 3 days and weeks 5-6 in non-addicted infants. Addiction. 2010;105(3):525–528 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Supportive Care Scores <8 can generally be managed with non-pharmacologic, comfort care. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Calm Environment . Quiet, dim room with low activity o Rooming-in: ↓Rx, ↓LOT, ↓LOS, ↓cost of NICU beds, promotes family-centered care . Away from high traffic areas (phone, sink, etc.) . Prepare everything before disturbing and “cluster” care . Limit visitors . Avoid excessive handling . Present one stimulus at a time (do not walk or sway while feeding) Treat with confidence. Trusted answers from the American Academy of Pediatrics. Breastfeeding . Encouraged: . Miniscule amounts of drug in o Promote bonding breastmilk: o Optimal nutrition o Methadone = Hale category = L2 o Passive immunity o Buprenorphine transdermal = L2 o ↓ severity of NAS o Buprenorphine + Naloxone = L3 . Contraindications: o HIV+ o Not in treatment o Polydrugs?? (beware THC)

Cleveland LM. Breastfeeding recommendations for women who receive medication-assisted treatment for opioid use disorders: AWHONN Practice Brief Number 4. J Obstet Gynecol Neonatal Nurs. 2016;45(4):574–576; Pritham UA. Breastfeeding promotion for management of neonatal abstinence syndrome. J Obst Gynecol Neonatal Nurs. 2013;43(5):517–526; and Reece-Stremtan S, Marinelli KA. ABM clinical protocol #21: guidelines for breastfeeding and substance use or substance use disorder, revised 2015. Breastfeed Med. 2015;10(3):135–141 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Nursing Experience . Parents may fear exposure as a “bad” person or losing child to welfare system o Parents may detach or distance from the infant o Nurse becomes surrogate mother . Nursing role conflict o Nurses have advanced training and specialized skills o Spend a considerable time soothing the affected infant, and educating and consoling the family o Perception that babies are less sick but very demanding Murphy-Oikonen J, Montelpare WJ, Southon S, Bertoldo L, Persichino N. Identifying infants at risk for neonatal abstinence syndrome: a retrospective cohort comparison study of 3 screening approaches. J Perinat Neonatal Nurs. 2010;24(4):366–372 and Maguire D, Webb M, Passmore D, Cline G. NICU nurses’ lived experience: caring for infants with neonatal abstinence syndrome. Adv Neonatal Care. 2012;12(5):281–285 Treat with confidence. Trusted answers from the American Academy of Pediatrics. AAP Guidelines Drug therapy is indicated to relieve moderate to severe signs of NAS and to prevent complications such as fever, weight loss, and seizures if an infant does not respond to a committed program of non-pharmacologic support. Treat with confidence. Trusted answers from the American Academy of Pediatrics. First Line Morphine Methadone Class Opiate Synthetic opiate Action μ (mu) agonist μ (mu) agonist T½ 8 h 26 h Allows for rapid Maintains more titration consistent serum concentrations Watch for Respiratory Prolonged Q-T depression interval Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014;134(2):e547–e571 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Second Line Phenobarbital Clonidine Class Barbiturate Centrally acting adrenergic Add if Majority of score due Majority of score due to CNS to autonomic Polydrug abuse (RR, BP, sweating, etc.) Watch for Over-sedation Hypotension Impaired suck reflex Bradycardia Requires therapeutic Careful taper due to monitoring of drug rebound hypertension levels Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014;134(2):e547–e571 Treat with confidence. Trusted answers from the American Academy of Pediatrics.

If the infant is asleep when a dose is due, do not wake or skip the dose. Give dose in the inner cheek while offering a pacifier. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Oral Sucrose . Infants have a poorly functioning endogenous opioid system. . Sucrose is ineffective in calming methadone exposed infants suffering from withdrawal signs and should not be used to treat abstinence. . May be helpful for minor procedural pain.

Marceau LD, Link CL, Smith LD, Carolan SJ, Jamison RN. In-clinic use of electronic pain diaries: barriers of implementation among pain physicians. J Pain Symptom Manage. 2010;40(3):391–404 Treat with confidence. Trusted answers from the American Academy of Pediatrics.

Remember, Narcan (naloxone) has been removed from NRP as a resuscitation medication. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Weaning . Stable NAS score (all scores <8 in the preceding 24–48 hours) . Allow 24–48 hours between medication weans . After discontinuing treatment, continue NAS scoring . Discharge when all scores are <8 for at least 24 hours Treat with confidence. Trusted answers from the American Academy of Pediatrics. Risk of Readmission Infants diagnosed with NAS are nearly 2.5x as likely to be readmitted to the hospital in the first month after being discharged compared with full-term infants born without complications.

The most common cause is withdrawal. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Discharge Education . How to provide supportive care and soothing behaviors: o Modify environment to ↓ sensory stimulation o Appropriate feeding o Good skin care . Infant and home safety . Signs and symptoms of withdrawal . How to handle stressful situations . Appropriate babysitting arrangements . Follow-up appointments and programs Treat with confidence. Trusted answers from the American Academy of Pediatrics.

From Centers for Disease Control and Prevention (CDC). Vital Signs. Opioid Painkiller Prescribing infographic. www.cdc.gov/vitalsigns/opioid-prescribing. Accessed September 7, 2017. Treat with confidence. Trusted answers from the American Academy of Pediatrics. State Policies in Brief . Substance abuse during pregnancy is considered: o Criminal act (1 state) – allowed to “sunset” July 1, 2016 o Child abuse (18 states) . When prenatal drug abuse is suspected: o Reporting is mandatory (18 states) • Testing is mandatory (4 states) o Pregnant women given priority access to state-funded treatment (13 states)

Guttmacher Institute. www.guttmacher.org Treat with confidence. Trusted answers from the American Academy of Pediatrics. Maternal Testing Requires Informed Consent . Ferguson v City of Charleston, 532 US 67 (2001) o Involuntary drug testing of pregnant women violates a person’s 4th amendment right (unreasonable search and seizure). . Linder v United States, 268 US 5 (1925) and Robinson v California, 370 US 660 (1962) o Addiction is an illness and criminalization is a violation of the 8th amendment (cruel and unusual punishment).

Harris LH, Paltrow L. MSJAMA. The status of pregnant women and fetuses in US criminal law. JAMA. 2003;289(13):1697–1699 Treat with confidence. Trusted answers from the American Academy of Pediatrics. Newborn Testing Does Not Require Maternal Consent . Individuals with Disabilities Education Act (IDEA) Part C: Early Intervention for Babies and Toddlers (1986) o Includes prenatal drug and alcohol exposure as a risk factor for adverse developmental outcomes and therefore qualifies these children for evaluation and developmental services as needed. . Parents should be notified of the need for testing based on hospital policy and should be notified of the results. Treat with confidence. Trusted answers from the American Academy of Pediatrics. Conclusions . A dramatic increase in prevalence, exposure substances, and polypharmacy . Effective management strategies have been developed . Prevention strategies . Gaps exist: lack of clarity in definition and consistency . Treatment largely focused on isolation from mother/family . Follow-up of paramount importance Treat with confidence. Trusted answers from the American Academy of Pediatrics.

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