Neonatal Abstinence Syndrome - solutions.aap.org Dec... · Treat with confidence. Trusted answers from the American Academy of Pediatrics. Clinical Features Complex disorder o Central

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

Neonatal Abstinence Syndrome

Jatinder Bhatia, MD, FAAPMedical College of GeorgiaAugusta UniversityAugusta, GA


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.


Objectives Define Neonatal Abstinence Syndrome (NAS)

Incidence

Commonly used/abused drugs

Signs and symptoms

Complications

Testing

Prevention and treatment



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


Introduction to Opioids Chemical class: Opioid vs opiate

o Opiates are from poppy plantso Opioid means they act like an opiate

Functional class: Narcotic analgesic


Opioid Receptors Found in the brain, spinal cord, gastrointestinal (GI)

tract, and other organso μ (mu) receptors – respiratory depressant + GIo Δ, δ (delta) receptors – development of toleranceo Κ (kappa) receptors – involved in sedation + GI

Activation of the receptors:o Supraspinal analgesiao Release of dopamine (brain’s reward system)


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 repackageo Broken down by enzymes


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


Clinical Features Complex disorder

o Central and autonomic nervous systemso 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 withdrawalKocherlakota 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


Incidence is between 55%–94% Onset depends on:

o Type of drug/additional substanceso Half life of the drugo Time of last maternal dose prior to delivery

CNS GI Autonomic• Inconsolability• High-pitched crying• Skin excoriation• Hyperactive reflexes• Tremors• Seizures

• Poor feeding• Excessive sucking• Feeding

intolerance• Vomiting• Diarrhea

• Sweating• Fever• Nasal stuffiness• Sneezing• Tachypnea• Mottling

Abbreviations: CNS, central nervous system; GI, gastrointestinal


Adapted from Cotton SW. Drug testing in the neonate. Clin Lab Med. 2012;32(3):449–466


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*NAS tool not valid

24–36 hours

Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014;134(2):e547–e561


Clinical and Other Consequences of Maternal Opioid Use

Outcomes in the pregnant womanSexually transmitted infectionsHIV infectionHepatitisEndocarditisOsteomyelitisSepsisCellulitisChaotic lifestyle (eg, prostitution, violence, and theft)Decreased commitment to health careDecreased receptiveness to social servicesOutcomes in the fetusGrowth restrictionAbruptio placentaePreterm laborAbnormal heart patternsDeathOutcomes in the newbornLow birth weightPreterm deliverySmall head circumferenceSleep myoclonusChild maltreatmentVisual disturbances

The information provided in the table is from Wong S, Ordean A, Kahan M, et al. Substance use in pregnancy. J ObstetGynaecol Can. 2011;33(4):367–384; Patrick SW, Dudley J, Martin PR, et al. Prescription opioid epidemic and infant outcomes. Pediatrics. 2015;135(5):842–850; ACOG Committee on Health Care for Underserved Women and American Society of Addiction Medicine. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy. Obstet Gynecol. 2012;119(5):1070–1076; Visconti KC, Hennessy KC, Towers CV, Howard BC. Chronic opiate use in pregnancy and newborn head circumference. Am J Perinatol. 2015;3(1)2:27–32; Jansson LM, Velez ML. Infants of drug-dependent mothers. Pediatr Rev. 2011;32(1):5–12; Lee J, Hulman S, Musci M Jr, Stang E. Neonatal abstinence syndrome: influence of a combined inpatient/outpatient methadone treatment regimen on the average length of stay of a Medicaid NICU population. Popul Health Manag. 2015;18(5):392–397; and O’Donnell M, Nassar N, Leonard H, et al. Increasing prevalence of neonatal withdrawal syndrome: population study of maternal factors and child protection involvement. Pediatrics. 2009;123(4):e614–621


Adapted from Finnegan LP, Connaughton JF Jr, KronRE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2(1–2):141–158


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


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 = 5.5o 95th percentile on DOL 2 = 7.0

Circadian rhythm established by 5–6 weekso Median day score = 5.0o Median night score = 2.0

Scores >8 can be considered pathologicZimmermann-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


Supportive Care

Scores <8 can generally be managed with non-pharmacologic, comfort care.


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)


Breastfeeding Encouraged:

o Promote bondingo Optimal nutritiono Passive immunityo ↓ severity of NAS

Contraindications:o HIV+o Not in treatmento 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

Miniscule amounts of drug in breastmilk:o Methadone = Hale category = L2o Buprenorphine transdermal = L2o Buprenorphine + Naloxone = L3


Nursing Experience Parents may fear exposure as a “bad” person or losing

child to welfare systemo Parents may detach or distance from the infanto Nurse becomes surrogate mother

Nursing role conflicto Nurses have advanced training and specialized skillso Spend a considerable time soothing the affected infant,

and educating and consoling the familyo 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


AAP Guidelines

Drug therapy is indicated to relieve moderate to severe signs of NAS andto prevent complications such as fever, weight loss, and seizures if an infant does not respond to a committed program of non-pharmacologic support.


First Line


Morphine MethadoneClass Opiate Synthetic opiateAction μ (mu) agonist μ (mu) agonistT½ 8 h

Allows for rapid titration

26 hMaintains more consistent serum concentrations

Watch for Respiratory depression

Prolonged Q-T interval


Second Line


Phenobarbital ClonidineClass Barbiturate Centrally acting

adrenergicAdd if Majority of score due

to CNSPolydrug abuse

Majority of score due to autonomic(RR, BP, sweating, etc.)

Watch for Over-sedationImpaired suck reflex

HypotensionBradycardia

Requires therapeutic monitoring of drug levels

Careful taper due to rebound hypertension


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.


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


Remember, Narcan (naloxone) has been removed from NRP as a resuscitation medication.


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


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.


Discharge Education How to provide supportive care and soothing behaviors:

o Modify environment to ↓ sensory stimulationo Appropriate feedingo 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


From Centers for Disease Control and Prevention (CDC). Vital Signs. Opioid Painkiller Prescribing infographic. www.cdc.gov/vitalsigns/opioid-prescribing. Accessed September 7, 2017.


State Policies in Brief Substance abuse during pregnancy is considered:

o Criminal act (1 state) – allowed to “sunset” July 1, 2016o 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


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) andRobinson v California, 370 US 660 (1962)o Addiction is an illness and criminalization is a

violation of the 8th amendment (cruel andunusual punishment).

Harris LH, Paltrow L. MSJAMA. The status of pregnant women and fetuses in US criminal law. JAMA. 2003;289(13):1697–1699


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.


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


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Neonatal Abstinence Syndrome - solutions.aap.org Dec... · Treat with confidence. Trusted answers from the American Academy of Pediatrics. Clinical Features Complex disorder o Central