Neonatal Opioid Withdrawal Syndrome · presentation, assessment, treatment, and discharge....

CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care

Neonatal Opioid Withdrawal SyndromeStephen W. Patrick, MD, MPH, MS, FAAP,a Wanda D. Barfield, MD, MPH, FAAP,b Brenda B. Poindexter, MD, MS, FAAP,c COMMITTEEON FETUS AND NEWBORN, COMMITTEE ON SUBSTANCE USE AND PREVENTION

abstractThe opioid crisis has grown to affect pregnant women and infants across theUnited States, as evidenced by rising rates of opioid use disorder amongpregnant women and neonatal opioid withdrawal syndrome among infants.Across the country, pregnant women lack access to evidence-based therapies,including medications for opioid use disorder, and infants with opioidexposure frequently receive variable care. In addition, public systems, such aschild welfare and early intervention, are increasingly stretched by increasingnumbers of children affected by the crisis. Systematic, enduring, coordinated,and holistic approaches are needed to improve care for the mother-infantdyad. In this statement, we provide an overview of the effect of the opioidcrisis on the mother-infant dyad and provide recommendations formanagement of the infant with opioid exposure, including clinicalpresentation, assessment, treatment, and discharge.

INTRODUCTION

The United States has experienced a surge in opioid use and opioid-relatedcomplications. From 1999 to 2009, there was a quadrupling of opioid painreliever prescription sales nationwide.1 By 2015, 3 times as manyprescriptions for opioid pain relievers were filled than in 1999,2 reaching.37% of US adults using opioid pain relievers in 2015.3 The rapidincrease in opioid pain reliever use in the early 2000s was associated witha parallel increase in opioid pain reliever–related treatment facilityadmissions and overdose deaths.1 Since 2011, however, deaths fromopioid pain relievers have plateaued, whereas deaths from heroin andfentanyl have grown exponentially.4 In 2017, .47 600 Americans died ofopioid-related overdoses (including opioid pain relievers, heroin, andfentanyl), outnumbering deaths from car crashes and firearms.5

As the opioid crisis grew in scope and complexity in the population atlarge, opioid use6 and opioid use disorder (OUD)7–9 among pregnantwomen also increased. Opioid use in pregnancy can lead to a withdrawalsyndrome in the newborn shortly after birth. The syndrome has beentraditionally called neonatal abstinence syndrome but more recently hasbeen called neonatal opioid withdrawal syndrome (NOWS) by federal

aDivision of Neonatology, Department of Pediatrics and Health Policy,School of Medicine, Vanderbilt University and Vanderbilt Center forChild Health Policy, Vanderbilt University Medical Center, Nashville,Tennessee; bCenters for Disease Control and Prevention, Atlanta,Georgia; and cDepartment of Pediatrics, College of Medicine, Universityof Cincinnati and Cincinnati Children’s Medical Hospital Center,Cincinnati, Ohio

Clinical reports from the American Academy of Pediatrics benefit fromexpertise and resources of liaisons and internal (AAP) and externalreviewers. However, clinical reports from the American Academy ofPediatrics may not reflect the views of the liaisons or theorganizations or government agencies that they represent.

Drs Patrick, Barfield, and Poindexter were directly involved in theplanning, researching, and writing of this report and approved thefinal manuscript as submitted.

The guidance in this report does not indicate an exclusive course oftreatment or serve as a standard of medical care. Variations, takinginto account individual circumstances, may be appropriate.

All clinical reports from the American Academy of Pediatricsautomatically expire 5 years after publication unless reaffirmed,revised, or retired at or before that time.

The findings and conclusions in this report are those of the authorsand do not necessarily represent the views of the US Centers forDisease Control and Prevention.

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authors have filedconflict of interest statements with the American Academy ofPediatrics. Any conflicts have been resolved through a processapproved by the Board of Directors. The American Academy ofPediatrics has neither solicited nor accepted any commercialinvolvement in the development of the content of this publication.

DOI: https://doi.org/10.1542/peds.2020-029074

Address correspondence to Stephen W. Patrick, MD, MPH, MS, FAAP.E-mail: [email protected]

To cite: Patrick SW, Barfield WD, Poindexter BB, AAP COMMITTEEON FETUS AND NEWBORN, COMMITTEE ON SUBSTANCE USE ANDPREVENTION. Neonatal Opioid Withdrawal Syndrome. Pediatrics.2020;146(5):e2020029074

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https://doi.org/10.1542/peds.2020-029074

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agencies, including the US Food andDrug Administration.10 Althoughneonatal abstinence syndrome isa more general term for neonatalwithdrawal that, in the literature, mayinclude nonopioid exposures (eg,benzodiazepines),11 evidencesuggests that the recent growth ofneonatal drug withdrawal has beenprimarily from in utero opioidexposure either in isolation or incombination with other substances.8

The recent increase in OUD inpregnancy and NOWS revealsdeficiencies in the continuum of carefor the maternal-infant dyad inclinical and public systems. The childwelfare system, for example, reportedan increase of .10 000 infants infoster care from 2011 to 2017, mostbecause of parental substanceuse.12,13 Systematic, enduring,coordinated, and holistic approachesare needed to improve care for themother-infant dyad. Optimizing thehealth and well-being of a pregnantwoman gives her infant the highestlikelihood of an ideal outcome. Carefor the mother-infant dyad should becomprehensive and should considerthe needs of both the mother andinfant, as is outlined in the AmericanAcademy of Pediatrics (AAP) policystatement “A Public Health Responseto Opioid Use in Pregnancy.”14 Thisstatement builds on previous AAP-released clinical recommendations,including “Recommendations to theIndian Health Service on NeonatalOpioid Withdrawal Syndrome,”15 andfocuses primarily on the clinicalpresentation, assessment, andtreatment of infants with opioidexposure and those with NOWS. Thestatement also discusses how thedischarge process can be used toconnect infants to importantpostdischarge services.

OUD IN PREGNANCY AND NOWS

Use of opioids, even as directed, canheighten risk of developing OUD,defined as a problematic pattern of

opioid use that leads to clinicallysignificant impairment or distress.16

Rates of OUD in pregnancy grewsubstantially from 1999 to 2014,7

with disproportionally higher rates inrural areas of the country.9 UntreatedOUD in pregnant women can result indire consequences for the mother-infant dyad, including overdose death,fetal loss, and preterm birth. Ashighlighted by the recent report fromthe National Academies of Sciences,Engineering, and Medicine,“Medications for Opioid Use DisorderSave Lives,”17 optimal care forpregnant women with OUD includestreatment with methadone orbuprenorphine. Methadone is a fullm-opioid receptor agonist, which isdispensed from federally licensedopioid treatment programs. Incontrast, buprenorphine is a partialm-opioid receptor agonist and partialk-opioid receptor antagonist that canbe obtained from an opioid treatmentprogram or from a provider who hasobtained a waiver to prescribethrough the Drug AddictionTreatment Act of 2000. Despiteliterature to support the use ofmedications for OUD in pregnancy,there remain substantial barriers inobtaining medications for OUDamong pregnant women.18,19 Thesebarriers may, in part, be why themajority of pregnant women whoare able to obtain treatment ofOUD do not receive medicationsfor OUD, despite evidence of theirbenefit.18,20

Opioid use typically does not occur inisolation and frequently involvesother substances. In a recent study,using data from the National Surveyof Drug Use and Health from 2005to 2014, authors found that 5.1% ofUS pregnant women reportednonmedical use of an opioid painreliever in the last year. Comparedwith pregnant women who did notreport nonmedical use of an opioidpain reliever in the last 30 days,pregnant women who reportednonmedical use of an opioid pain

reliever were more likely (P , .001)to also report last-30-day use ofalcohol (49.2% vs 8.6%), tobacco(59.3% vs 15.6%), and marijuana(41.6% vs 3.3%).21 Importantly, useof other substances (eg, tobacco)22 orprescription sedatives (eg,benzodiazepines)23 along with anopioid may increase risk and/orseverity of NOWS. In addition, alcoholuse in pregnancy is particularlyproblematic because alcohol,a teratogen, can cause fetal alcoholspectrum disorders and is the leadingcause of preventable intellectualdisability in the United States.24 It isdifficult for clinicians to disentanglethe short- and long-term effects ofexposure to opioids from othersubstances. Finally, social andeconomic factors,25 systemicracism,26 maternal physical andmental health, genetic and/orepigenetic, nutritional, andenvironmental factors may adverselyaffect infant developmentindependent of maternal substanceuse disorder.27

Increases in maternal opioid use wereaccompanied by a parallel increase inNOWS.8,9 From 2000 to 2016, theincidence of NOWS increased from1.2 to 8.8 per 1000 hospitalbirths.8,28–30 These increases havebeen steeper in rural and tribal areas9

and among infants enrolled in theMedicaid program.29 In addition,there is remarkable state-to-statevariation in NOWS. For example, WestVirginia has the highest reported rateof NOWS at 33.4 per 1000 hospitalbirths, compared with Hawaii at0.7 per 1000 hospital births.31

American Indian and Alaskannative populations have beendisproportionately affected by NOWS.In 2016, American Indian andAlaskan native infants had the highestrate of NOWS at 15.9 per 1000hospital births, compared with whiteinfants at 10.5 per 1000 hospitalbirths, Black infants at 3.4 per 1000hospital births, and Hispanic infantsat 2.5 per 1000 hospital births.32

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ASSESSMENT AND CLINICALPRESENTATION

Assessment of infants with opioidexposure by the health care teamshould include a thorough maternalhistory, including informationgathered on substance use, additionalmedication use (prescribed andunprescribed), adversitiesexperienced in childhood, culturalbeliefs, trauma and violenceexposures past and present, mentalhealth disorders, and infectiousdiseases (including HIV and hepatitisC virus [HCV] infections). Ideally,clinicians should also assess theneeds of the family, including thestatus of significant others andchildren as well as food and housinginsecurity. When evaluating aninfant with clinical signs consistentwith NOWS, it is also importantto consider other diagnoses thatpresent similarly (eg, sepsis,hypoglycemia, hypocalcemia, andneurologic injury).

CLINICAL PRESENTATION OF NOWS INNEONATES

NOWS occurs after chronic exposureto opioids (Table 1); therefore,exposure to opioids around the timeof delivery, including opioids in anepidural or intravenous agonistand/or antagonist therapies (eg,nalbuphine, butorphanol), doesnot cause NOWS. The clinical

presentation or risk of NOWS variesby opioid type (eg, immediate release,sustained release, maintenance),22

the maternal drug history (includingtiming of the most recent use ofdrugs before delivery), maternalmetabolism, net transfer of drugsacross the placenta, placentalmetabolism, infant metabolism andexcretion, and other factors.11 Inaddition, maternal use of othersubstances, such as cigarettes,benzodiazepines, and gabapentin,may influence the onset, severity,or duration of the withdrawalsyndrome.22,23,33 Higher cumulativeopioid exposure may increase therisk of NOWS among infantsexposed to immediate-releaseprescription opioids22; however,studies of the relationshipbetween maternal methadone34,35

and buprenorphine22,36 dosageand risk or severity of NOWShave generally found norelationship.

Because opioid receptors areconcentrated in the central nervoussystem and the gastrointestinal tract,the predominant clinical signs reflectthese systems (eg, tremors, loosestools; Table 2). Onset of clinical signsof withdrawal tend to reflect the half-life of the opioid involved. Forexample, withdrawal from heroinoften begins within 24 hours of birth,whereas withdrawal from methadone

usually begins at ∼24 to 72 hours ofage.11 Withdrawal, however, may bedelayed until 5 to 7 days of age, whichis typically after hospital dischargefor uncomplicated term infants.11

Subacute signs of opioid withdrawalmay last up to 6 months.11,37

SCREENING

Screening for substance use is distinctfrom testing for substance use.Screening generally refers to the useof a validated instrument to assesssubstance use, whereas testing refersto the use of a diagnostic test (eg,urine toxicology). Ideally, screeningfor substance use occurs in the firsttrimester by a prenatal provider(eg, family medicine, obstetrician,midwife) using a validated screeningtool, as endorsed by the AmericanCollege of Obstetricians andGynecologists (ACOG). The ACOGrecommends early universalscreening for substance use at thetime of the first prenatal visit.38

During this time, other risks shouldbe assessed, including HIV, HCV, andsyphilis infection, and, if identified,appropriate planning for treatment(eg, HIV antiviral therapy) shouldoccur in the perinatal period. AnACOG committee opinion mentionsthat screening tools include the “4P’s” for adults and the “CRAFFT” toolfor adolescents (Table 3).38 Clinicalguidance from the AAP for screening

TABLE 1 Common Immediate-Release, Sustained-Release, and Maintenance Opioids

Drug Immediate Release Sustained Release Maintenance

Buprenorphine — — XCodeine X — —

Dihydrocodeine X — —

Fentanyl X X —

Hydrocodone X — —

Hydromorphone X X —

Levorphanol X — —

Meperidine X — —

Methadone — — XMorphine X X —

Oxycodone X X —

Oxymorphone X X —

Tramadol X — —

Adapted from Argoff CE, Silvershein DI. A comparison of long- and short-acting opioids for the treatment of chronic noncancer pain: tailoring therapy to meet patient needs. Mayo ClinProc. 2009;84(7):602–612. —, not applicable.

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adolescents for substance use can befound in the clinical report on

substance use screening, briefintervention, and referral totreatment.39 Prenatal clinicians canalso use their state’s prescriptiondrug monitoring program asa resource for filled prescriptionsbecause it may capture some high-risk patient behaviors, such aspatients seeking controlledsubstances from different clinicians.40

A complete summary of ACOG-recommended screening is beyondthe scope of this statement but can befound online (https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Opioid-Use-and-Opioid-Use-Disorder-in-Pregnancy).Ideally, pediatric clinicians shouldwork collaboratively with obstetriccolleagues to obtain relevant clinicalinformation (eg, screening results) tominimize care duplication. Pregnantwomen with OUD should also receiveantenatal counseling by a pediatrichealth care provider to assess infantrisks of NOWS and provide educationon the clinical signs of withdrawaland need for nonpharmacologic andpharmacologic interventions.

SCREENING AND TESTING: MOTHER ANDINFANT

Given the challenges in identifyinginfants at risk for NOWS withmaternal screening, some haveadvocated for universal urinetoxicology testing of mothers at thetime of delivery. In a recent cohortstudy from a single center, theefficacy of a universal testing protocolfor all mothers was assessed ina community hospital setting. In thisstudy, 5.4% of pregnant women hada positive drug test result at the timeof admission (3.2% were positive foropioids). Of the pregnant women witha positive urine drug test result foropioids, 20% had a negative risk-based screen result.41 However,screening and testing processes arecomplex and have potential legalramifications, and the AAP endorsesinformed consent for toxicologytesting of pregnant women.14 Notablyuniversal testing has resulted indisproportionately higher childprotective services referrals for Blackwomen compared with whitewomen42,43 Pediatricians should beaware of and reduce institutionalbiases in implementing universaltoxicology testing for infants, whichcould result in unequal consequencesfor mothers and infants on the basisof race, ethnicity, and/orsocioeconomic status.

Toxicology testing for an infant canoccur from multiple modalities,including urine, meconium, andumbilical cord tissue.11 A urinesample should be collected as soon aspossible after birth if the clinician isconcerned because many drugs arerapidly metabolized andeliminated.44–46 For example, after inutero exposure, opioids and theirmetabolites may no longer bedetectable in an infant’s urine afterthe first few days of life. Similarly,a positive urine screening result mayonly reflect recent exposure for mostsubstances and may not reflectprevious, more remote in uteroexposure. Drugs that are excreted in

the hepatobiliary system as well asdrugs excreted by the fetal kidneysinto the amniotic fluid areconcentrated in meconium.Meconium testing provides a longerwindow of time throughout thepregnancy, beginning as early as 20weeks’ gestation, and is generallyconsidered the gold standard forinfant toxicology testing.47–49

Meconium collection, however, can belabor intensive, requiring collectionfor several days, and does not reflectperiods of abstinence close todelivery. Meconium must be collectedbefore it is contaminated bynonmeconium stools (ie, after theinfant receives colostrum ortransitional milk, mature human milk,or formula). More recently, umbilicalcord tissue testing has emerged as analternative to meconium collection;given that umbilical cord tissue isreadily available at the time of birth,it has logistic advantages tomeconium collection.49–53 Althoughsome studies have suggestedequivalence between meconium andumbilical cord tissue testing,53 othersstudies have found the paired testingof meconium and umbilical cordtissue to be discordant.54 Cliniciansshould be mindful of the differencesin testing modalities whenconsidering their needs for testingand work with their laboratories todetermine the best testing modalityin their setting.

Infant toxicology testing should becompleted when it will inform clinicalmanagement. In some instances,testing of the infant provides noadditional clinical information andwould not be recommended. Forexample, for women in treatment forOUD who are closely monitored withfrequent toxicology testing,meconium and/or umbilical cordtissue testing would not likelyprovide any additional clinicalinformation if this information isreadily available to the pediatrician.Testing can be helpful, however, whenclinical details are lacking (eg, late or

TABLE 2 Signs of NOWS

Signs of NOWS

Central nervous system irritabilityHigh-pitched, continuous cryingDecreased sleepTremorsIncreased muscle toneHyperactive Moro reflexSeizures

Gastrointestinal dysfunctionFeeding difficultiesVomitingLoose or watery stools

Autonomic nervous system activationSweatingFeverFrequent yawning and sneezingIncreased respiratory rateNasal stuffiness and flaring

Adapted from Ko JY, Wolicki S, Barfield WD, et al. CDCGrand Rounds: public health strategies to prevent neo-natal abstinence syndrome. MMWR Morb Mortal WklyRep. 2017;66(9):242–245.


https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Opioid-Use-and-Opioid-Use-Disorder-in-Pregnancy





no prenatal care, placental abruption)and should be considered.

DIAGNOSIS, ASSESSMENT, ANDTREATMENT

In the 1970s, several scoring systemswere developed to guide thediagnosis and treatment of neonatalabstinence syndrome.55,56 Still today,however, there is not one agreed-onscoring tool, and each scoring tool isprone to challenges of interraterreliability because each containsclinical signs that can be subjective orrelated to infant adaptation toextrauterine life.

The most commonly used scoringtool in the United States today isa modification of the originalFinnegan score, developed inthe early 1970s by Dr LorettaFinnegan.55,57 Another commonlyused score is a Finnegan scalemodification created from theMaternal Opioid Treatment: HumanExperimental Research (MOTHER)Neonatal Abstinence Measure trial(Fig 1).58 Similar to other tools, theMOTHER modification includescommon central nervous system,gastrointestinal tract, and autonomicclinical signs. Clinical signs areweighted to reflect severity; forexample, sleeping ,1 hour after

feeding reflects a score of 3, whereassleeping ,3 hours after feedingreflects a score of 1. The score is usedfor initiation, advancement, andweaning of pharmacotherapy forNOWS on the basis of severity. TheMOTHER modification suggestsinitiating pharmacotherapy if there isa consistent score of 9 to 12 ora single score of 13.

More recently, a new scoring tool hasemerged, called Eat, Sleep, Console(ESC), which aims to guide treatmentof NOWS.59 The tool is guided by theinfant’s clinical signs of withdrawalthrough evaluation of an infant’sability to eat $1 oz or breastfeedwell, sleep undisturbed $1 hour, andbe consoled. If these criteria arenot met, the medical team meets,assesses the environment andnonpharmacologic approaches, andconsiders initiating or escalatingpharmacotherapy. ESC is appealingbecause of its ease of use andsimplicity but has not been studiedoutside of quality improvementinitiatives. It remains somewhatunclear, for example, if improvementsin length of hospital stay areattributable to the ESC approach itselfor to better adherence tononpharmacologic approaches, whichcan also reduce length of stay.59

Despite challenges presented byscoring tools, data suggest thatstandardizing institutional scoringprocesses (ie, by using the same toolthe same way with each patient) andtraining to improve interraterreliability improves clinical outcomes,including decreasing length ofhospital stay.60 For example, duringthe 2-year Vermont Oxford NeonatalAbstinence Syndrome Collaborative,standardized scoring processes wereassociated with a shorter length ofstay (–3.3 days; 95% confidenceinterval [CI], –4.9 to –1.4).60 The AAPdoes not endorse one scoring systemover another because there is notsignificant evidence to support onetool’s superiority. However, givenevidence to suggest that establishinga consistent protocol and approach toscoring improves outcomes, everyhospital should have a writtenprotocol and optimize provideradherence. More research to supportthe optimal assessment of an infantwith opioid exposure is needed.

CLINICAL MANAGEMENT OF NOWS

Observation

All infants with chronic opioidexposure should be observed for atleast 72 hours to monitor for thedevelopment of withdrawal. Although

TABLE 3 Screening for Substance Use

Screening for Substance Use

4 P’sa

Parents: Did any of your parents have a problem with alcohol or other drug use?Partner: Does your partner have a problem with alcohol or drug use?Past: In the past, have you had difficulties in your life because of alcohol or other drugs, including prescription medications?Present: In the past month, did you drink any alcohol or use any other drugs?Any “yes” answer indicates that additional assessment is needed.

CRAFFTb,c

C: Have you ever ridden in a car driven by someone (including yourself) who was high or had been using alcohol or drugs?R: Do you ever use alcohol or drugs to relax, feel better about yourself, or fit in?A: Do you ever use alcohol or drugs while you are by yourself or alone?F: Do you ever forget things you did while using alcohol or drugs?F: Does your family or friends ever tell you that you should cut down on your drinking or drug use?T: Have you ever gotten in trouble while you were using alcohol or drugs?Two or more “yes” answers indicate that additional assessment is needed.

a Ewing H. A practical guide to intervention in health and social services with pregnant and postpartum addicts and alcoholics: theoretical framework, brief screening tool, key interviewquestions, and strategies for referral to recovery resources. Martinez, CA: The Born Free Project, Contra Costa County Department of Health Services; 1990.b Notice to clinic staff and medical records: The information on this page is protected by special federal confidentiality rules (42 CFR x2), which prohibit disclosure of this informationunless authorized by specific written consent. A general authorization for release of medical information is not sufficient.c Copyright John R. Knight, MD, Boston Children’s Hospital, 2018. All rights reserved. Reproduced with permission. For more information, contact [email protected].


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FIGURE 1MOTHER Trial Modification of the Finnegan Score. (Reprinted with permission from Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndromeafter methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320–2331.)


there is increasing evidence thatmultiple factors may increase anopioid-exposed infant’s risk ofwithdrawal (eg, gestational age,specific genotypes, cigarette use,benzodiazepine and gabapentin use),there remains insufficient evidence ofhow to use these exposures to tailoran infant’s postnatal observationperiod. Institutions should considerobserving infants exposed toimmediate-release opioids forat least 3 days, infants exposed tobuprenorphine and sustained-releaseopioids for 4 to 7 days, and infantsexposed to methadone for 5 to 7 days.Notably, however, there remainslimited evidence to informobservation periods, and excessobservation could result in separationof the mother-infant dyad. Additionalresearch is needed to informappropriate hospital observationperiods for infants with opioidexposure.

Setting

Traditionally, NOWS in the UnitedStates has been managed in theNICU61; however, many infants at riskfor or with NOWS do not need NICU-level care. Depending on the physicaldesign of the unit, care in a NICU mayresult in separation of the mother-infant dyad, which can furtherexacerbate infant clinical signs ofwithdrawal and can be traumatic formothers during this vulnerablepostpartum period. In addition, forinfants going through withdrawal, theNICU environment, which can be loudand overly stimulating, may not beoptimal. Recently, models of care haveemerged that are focused on enablingthe new mother to “room-in” with hernewborn (in many cases, outside theNICU environment).62 In a recentmeta-analysis, it was found thatrooming-in was associated with lowerrates of pharmacotherapy forwithdrawal (relative risk, 0.37; 95%CI, 0.19 to 0.71; I2, 85%) and shorterlengths of hospital stay (weightedmean difference, –10.41 days; 95%CI, –16.84 to –3.98 days; I2, 91%).63

Keeping the mother-infant dyadtogether may promote bonding andfacilitate breastfeeding, and rooming-in should be considered the preferredmodel, including in the NICU, forinfants with opioid exposure. Inaddition, the environment and infanthandling should be modified so that itis not overly stimulating, which canexacerbate clinical signs ofwithdrawal (eg, loud noises, brightlights). In addition, it is importantthat care clinicians (eg, nurses, nursepractitioners, physicians) cluster careinterventions together temporally soas not to unnecessarily disturb theinfant, which may also aggravatesigns of withdrawal.

Nonpharmacologic Care

The literature to support specificnonpharmacologic approaches issparse; however, evolving evidencesuggests that effectivenonpharmacologic care that engagesthe mother is an essential foundationto the care of an infant with opioidexposure. Nonpharmacologic carethat is individualized should beapplied beginning at birth for allinfants with substance exposure andcontinued throughout hospitalizationand beyond, regardless of the needfor pharmacotherapeuticintervention. Engaging and coachingcaregivers in nonpharmacologic carepromotes bonding and may improveoutcomes, beginning with educationabout the infant-specific signs ofNOWS and helping the family tointerpret what triggers the clinicalsigns the infant is experiencing andeducation about how to support hisor her regulation. Clinical features ofNOWS, such as irritability,uncontrolled movements, andfragmented sleep, can be challengingfor the new mother. Providingsupport to the mother as sheresponds to these clinical features isimportant. Mothers frequentlyexperience overwhelming feelings ofguilt and anxiety in response to thedysregulated neurobehaviorsassociated with NOWS, and

pediatricians are uniquely positionedto support mothers to manage theiremotions while supporting thehealing and development of theirinfants.64 Nonpharmacologic careshould also include a thoroughassessment of the hospitalenvironment and infant handlingand adaptations by the infantto each to minimize NOWSexpression.

Nonpharmacologic treatment mayinclude a variety of supportive careapproaches. As described by Velezand Jansson,64 approaches tononpharmacologic care should betailored to the clinical behavioral andphysiologic signs the infant isexperiencing. Velez and Jansson64

note 4 specific domains: (1) reactivityto sensory stimulation and regulatoryissues, (2) behavioral states and statecontrol, (3) motor and tone control,and (4) autonomic signs of stress. Forexample, an infant experiencingoverreactivity to visual stimulationmay benefit from a dimly litenvironment, whereas an infant withhypertonia may benefit fromswaddling (Fig 2).

Breastfeeding

Perhaps the most studiednonpharmacologic intervention isbreastfeeding.65 In general,breastfeeding is safe for mothers whotake methadone or buprenorphineand may reduce clinical signs ofNOWS and length of hospital stay;thus, in many settings, breastfeedinghas become a critical foundation incare for the mother-infant dyad.Methadone and buprenorphine areexcreted into human milk at lowconcentrations. The Academy ofBreastfeeding Medicine has publishedconsensus breastfeeding guidelinesthat suggest that breastfeedingshould be encouraged if the motherhas not had a relapse in .90 days butdiscouraged if there has beena relapse in the last 30 days.66 BeingHIV-positive is a contraindication tobreastfeeding in high-income


countries, such as the United States,and HCV-positive mothers withbleeding or cracked nipples shouldalso consider abstaining frombreastfeeding.67 Clinicians andpatients should be cautious withsudden discontinuation ofbreastfeeding because somehave reported signs of infantwithdrawal.68

In a recent survey of women intreatment of OUD, it was found thatalthough most mothers desire andattempt to establish breastfeeding,they encounter significant challenges(eg, long NICU stays, lack of supportand education) that compromise theirsuccess. For these reasons, rates ofbreastfeeding initiation, exclusivity,and duration remain low amongmothers with OUD. In addition, somemother-infant dyads may havedifficulty with latching because ofwithdrawal and may requirefortification of milk because of infantweight loss, which can lead to fewerbreastfeeding attempts and lowersustainment of breastfeeding. Lastly,breastfeeding counseling and supportshould be trauma informed becausemothers with OUD report high ratesof trauma, including sexual trauma,

which may influence their desire tobreastfeed.69–71

PHARMACOTHERAPY

For infants with severe NOWS, use ofa medication in addition tononpharmacologic measures isnecessary to improve clinical signs ofwithdrawal and minimizecomplications from withdrawal (eg,severe weight loss). Ideally,pharmacotherapy minimizes clinicalsigns of withdrawal, and then theinfant is weaned off the medicationusing a standardized protocol tominimize total medicationexposure.72 Pharmacologic therapyshould be considered for severeopioid withdrawal despitenonpharmacologic interventions.Vomiting and loose stools areassociated with dehydration and poorweight gain and are relativeindications for treatment. Naloxoneshould never be administered to aninfant with NOWS because it willexacerbate the underlying withdrawalsyndrome.

The literature supports the use of anopioid for opioid withdrawal asa first-line agent.73 In the UnitedStates, the most common first-line

therapy for NOWS is morphine.61 Inseveral recently published studies, itwas found that longer-acting opioidsmay reduce length of stay whencompared with morphine. Kraftet al74 found that when comparedwith morphine, buprenorphine usedfor NOWS resulted in a shortermedian duration of treatment (15 vs18 days; P , .001) and length ofhospital stay (21 vs 33 days; P ,.001). Similarly, Davis et al75 foundthat when compared with morphine,methadone resulted in a shorterduration of treatment (11.5 vs 15days; P = .009) and length of stay(16 vs 20 days; P = .005). Importantly,both clinical trials occurred in thecontext of rigorous study protocolsand included only women intreatment of OUD to test the efficacyof these medications; therefore, onelimitation of these clinical trials maybe generalizability to otherpopulations (ie, infants of mothersnot in treatment of OUD).

There is evidence to support the useof secondary medications for NOWS,either when initiatingpharmacotherapy76 or, morecommonly, as an additionalmedication when clinical signscontinue to escalate despite

FIGURE 2Nonpharmacologic approaches to NOWS. Adapted from Velez M, Jansson LM. The opioid dependent mother and newborn dyad: non-pharmacologic care. JAddict Med. 2008;2(3):113–120.


pharmacotherapy with an opioid. Themost common medications used afterinitiation of an opioid for NOWS areclonidine and phenobarbital. Themajority of practitioners usephenobarbital as a second drug if theopioid does not adequately controlwithdrawal signs.77,78 In recent years,clonidine has increased in the UnitedStates as a therapy for NOWS.61

Clonidine is an a-2-adrenergicreceptor agonist that has been used incombination with an opioid or otherdrug in older children and adults toreduce withdrawal symptoms.79,80

There is not sufficient evidence tosuggest greater efficacy of clonidineover phenobarbital; however,phenobarbital has been shown tohave neurotoxicity in animalstudies,81,82 and its use has beenassociated with adversedevelopmental outcomes.83

Therefore, clinicians should consideruse of clonidine as a second-lineagent over phenobarbital, andadditional study is needed to test theeffects of both agents on infants’ long-term development.

Clinicians should be mindful thatsome drug preparations may includea high alcohol content (eg,buprenorphine), and choosingpreparations of low alcohol content ispreferred. In addition, consistent withprevious AAP statements,camphorated tincture of opium(paregoric) and/or deodorizedtincture of opioid (laudanum) shouldnot be used for NOWS.

PREPARING FOR DISCHARGE

It is important to plan effectively fora safe transition from the hospital tohome after birth for the mother-infant dyad. Families of infants withopioid exposure aredisproportionately impoverished,28

may face multiple economic andsocial challenges,12,25,84 and arefrequently involved in the childwelfare system. Adequate preparationfor hospital discharge cannot be the

pediatrician’s responsibility alone; itrequires hospital supports (eg, socialwork) to appropriately assess andassist families in this criticaltransition.

The immediate postnatal period isa time of high risk for mothers withOUD, especially if they lose access tomedications for OUD. Recent datasuggest that loss of access tomedications for OUD after delivery isassociated with overdose death.85 Inaddition, a key support to givemothers the best chance of remissionof OUD and improved dyadicrelational health is partnering withmental health clinicians to providecomprehensive treatment. Forexample, maternal screening fortreatable problems, such astraumatic stress and depression,could be addressed by referral toevidence-based, dyadic-focusedinterventions, such as child-parentpsychotherapy.86

Infants with opioid exposure are alsoat risk for adverse outcomes,including hospital readmission.87,88

Women may have to manage theirown medical follow-up needs (eg,obstetrics, addiction medicine), theirinfant’s medical follow-up needs (eg,general pediatrician, pediatricinfectious disease, lactation support),and additional services (eg, theSpecial Supplemental NutritionProgram for Women, Infants, andChildren, early intervention, childwelfare). The task of coordinatingthese multiple stakeholders,combined with the risk of adversepostdischarge outcomes (such asreadmission),88 makes formalizingthe discharge process for infants withopioid exposure critical. Use ofsimplified electronic or printchecklists can be helpful inimproving discharge processes(Table 4).89 When possible,postdischarge care for the mother-infant dyad should be coordinatedand comprehensive. Lastly, hospitalsshould ensure adequate handoffsand information transfer to

postdischarge care providers,including, pediatricians, earlyintervention providers, and home-nurse visitation programs.

Discharge Education

In addition to routine newborneducation, emphasis should be placedon the needs of the opioid-exposeddyad. Ideally, the infant caregiver hasbeen engaged in care during thepregnancy and is familiar withcommon clinical signs and scoringprocesses. The caregiver should knowwhen and how to seek help if signs ofinfant withdrawal becomeunmanageable or if additionalchallenges present (eg, maternaldepression, relapse). Infants withsubstance exposure are at anincreased risk of sleep-relateddeaths90; therefore, additionalemphasis on safe sleep and safe sleepenvironments is recommended.Similar to all infant discharges,parents of infants with opioidexposure should be providededucation on how to deal withchallenging infant behaviors (eg,subacute withdrawal signs) that mayincrease the risk of nonaccidentaltrauma.

Medical Follow-up

Infants should be observed for 24 to48 hours after finishing anymedication taper. Ideally, an infantwith opioid exposure would be seenby his or her pediatrician within48 hours of discharge from thehospital to monitor for adequateweight gain and to monitor for anycontinued signs of withdrawal. Thefrequency of pediatrician visits mayneed to be higher than that foruncomplicated term infants. Althoughthere are no data to inform the mostoptimal pediatrician visit schedule forinfants with opioid exposure, theinfant should be seen within 48 hoursof discharge, with a 1-week follow-up.Additional visits should be tailoredto the needs of the dyad. Ideally,breastfed infants should alsohave outpatient lactation support


and be assessed in the first48 hours of life.

Outpatient Pharmacotherapy

With increasing focus on reducinglength of hospital stay for infants withNOWS, many institutions begandischarging infants from the hospitalon medications. Among infantstreated in the nearly 200 centersparticipating in the Vermont OxfordNetwork collaboration focused onimproving care for NOWS, .25%were discharged from the hospital onmedications at the end of the 2-yearcollaborative.60 Consistently, theliterature suggests that discharginginfants from the hospital onpharmacotherapy reduces length ofhospital stay91–94; however,comparative outcomes, in particularduration of total treatment anddevelopment outcomes, are scant. Ina recent study, of nearly 1000 infantswith NOWS enrolled in the TennesseeMedicaid program, infants dischargedfrom the hospital on medications hada shorter median length of hospitalstay (11 vs 23 days; P , .001) butlonger median lengths of treatment(60 vs 19 days; P , .001).87 Given thelack of long-term follow-up data,clinicians should avoid outpatienttapers when possible. If outpatienttapers are used, a structuredweaning plan with comprehensivefollow-up should be implementedto minimize total medicationtime.

Hepatitis C

HCV screening among pregnantwomen is not universal in the United

States, potentially missing a windowof opportunity to identify HCV in themother-infant dyad. Even withoutuniversal screening, data suggest thatas the opioid crisis grew, rates of HCVinfection among pregnant womenincreased.95 From 2009 to 2014, therate of HCV infection among USpregnant women doubled to 3.4 per1000 live births and as high as 1 in 50births in West Virginia.96 Given thisrising risk to maternal and infanthealth, hospitals should consideruniversally screening pregnantwomen for HCV and creatingprocesses to connect the dyad totreatment postnatally.

Because vertical transmission occursin 6% of infants exposed to HCV(11% if HIV coinfection), infants mustbe tested after discharge to determineif they seroconvert. Maternalantibodies can persist for 18 months;thus, antibody testing must occurafter 18 months; however, RNApolymerase chain reaction testingmay occur earlier. Data suggest,however, that only a minority ofexposed infants are tested.97,98

Because infants with opioid exposureare at risk for HCV exposure, it isimperative that (1) all infants withopioid exposure are evaluated forHCV exposure and (2) all infantswith HCV exposure are adequatelymanaged to determine if theyacquire the virus. All infantsHCV exposure should be evaluatedand should be tested forseroconversion by using RNApolymerase chain reaction orantibody testing.

Postdischarge Services

Infants with opioid exposure,regardless of the need forpharmacotherapy for NOWS, are atincreased risk for developmentalalterations.99 In addition todevelopmental, behavioral, andmental health100 screenings by theprimary care pediatrician, all infantswith substance exposure should bereferred to early interventionservices, and developmentalscreenings in a NICU developmentalassessment clinic or equivalentshould be considered. Earlyintervention services are available inall areas of the United States as part Cof the Individuals with DisabilitiesEducation Act. Strong considerationshould also be given to referral tohome-nurse visitation programs (eg,the Maternal, Infant, and EarlyChildhood Home Visiting Program) asa resource to families.

Early Head Start programs are similarto Head Start but are targeted topregnant women and infants until age3 years. These programs supportparental and infant development andcan further enable family success,promoting housing and financialstability. Pediatricians shouldconsider referrals to Early Head Startprograms for opioid-exposed infants.Early Head Start programs can beidentified by using the Center Locator(https://eclkc.ohs.acf.hhs.gov/center-locator).

In addition, the AAP has severalresources to aid pediatricians inconnecting children to developmentalresources that are free and availableonline, including the National Centeron Early Childhood Health andWellness (https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/NCECHW/Pages/National-Center-on-Early-Childhood-Health-and-Wellness.aspx) and publicationssuch as Caring for Our Children(https://nrckids.org/CFOC/). Similarresources, such as HealthySteps(https://www.healthysteps.org/),

TABLE 4 Discharge Checklist for Infants With Opioid Exposure

Completed (Check Yes)

TaskNo significant clinical signs of withdrawal for 24–48 hParent education about NOWS and routine newborn care, emphasizing safe sleepPediatrician or primary care provider follow-up visit scheduled within 48 h of dischargeEarly intervention services referralHome-nurse visitation referralHepatitis C testing follow-up, including referral to pediatric infectious disease when appropriatePlan of safe care, coordinating with child welfare as appropriateDevelopmental-behavioral pediatrician referral as appropriate


https://eclkc.ohs.acf.hhs.gov/center-locator

https://eclkc.ohs.acf.hhs.gov/center-locator

https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/NCECHW/Pages/National-Center-on-Early-Childhood-Health-and-Wellness.aspx





https://nrckids.org/CFOC/

https://www.healthysteps.org/

may also serve pediatricians indeveloping models of care to meetthe needs of infants with opioidexposure.

The Child Welfare System and Plansof Safe Care

The opioid crisis resulted in greaterdemands on the US child welfaresystem.12,13 Although evidencesuggests that keeping the familyintact improves outcomes for parentsand infants, child safety must still beparamount.12 A report to childprotective services should beconsidered when the mother has notreceived or been adherent totreatment of OUD, when there isconcern or evidence of polysubstanceuse during pregnancy, or when thereis a concern for infant safety. In casesin which a child cannot be safelycared for by his or her parents,appropriately trained kinship orfoster care placement may benecessary. Referral to child protectiveservices is not a substitute for referralto treatment of the pregnant orparenting woman.

Recently, there have been numerouschanges to the child welfare system toprovide parental supports andconnection to treatment. In 2016, theComprehensive Addiction andRecovery Act amended the ChildAbuse Prevention and Treatment Actto ensure that “plans of safe care” arecreated for infants “being affected bysubstance abuse or withdrawalsymptoms, or a fetal alcohol spectrumdisorder.” Importantly, these plansshould address the “health andsubstance use disorder treatmentneeds of the infant and affectedfamily or caregiver.”101 Ideally, plansof safe care are well coordinatedwithin state child welfare agencies,and planning begins before birth.States may interpret and implementlegislation related to plans of safecare differently; therefore, it isimportant for pediatricians to beaware of their local requirements.The creation of plans of safe care are

actively being developed, and there isevidence that many states arestruggling with implementation.13

Pediatricians should considerinvolvement in the development ofplans of safe care in theircommunities. Because of theirexpansive nature of supporting themother-infant dyad, some states haveelected to call their plans of safe care“plans of supportive care.” Suchpartnerships between pediatriciansand child welfare professionals canhelp fill education gaps, fosterpositive partnerships, and promoteunderstanding, with the ultimate goalof improving outcomes for themother-infant dyad.102

Public Health Considerations

NOWS reflects the downstreamimplications of a complex publichealth crisis. To prevent NOWS,pregnant women, women and men ofreproductive age, and thecommunities they live in needeffective access to prevention,treatment, and services (eg, accessto comprehensive treatment ofsubstance use disorder, access tohighly effective contraception)(Fig 3).103,104 As public health andsurveillance efforts continue toevolve, involvement of pediatriciansat the local, state, and national levelwill continue to be important toensure that the unique needs ofchildren are addressed.

A federal prevention strategy outlinedin the 2015 Protecting our InfantsAct105 provides several mandates forthe US Department of Health andHuman Services (HHS) to addressproblems related to prenatal opioidexposure. The strategy requiresHHS agencies to plan, review, andcoordinate activities related toprenatal opioid exposure and NOWSto (1) develop recommendations forprevention; (2) treat OUD in pregnantwomen and infants with NOWS; (3)identify pregnant women and infantsin need of services to treat OUD inpregnancy and NOWS, including any

long-term consequences; and (4)develop a coordinated strategy toaddress gaps in research. In fall2018, the HHS held a summit toimprove coordination of nationalsurveillance, research, andprevention efforts.106

Currently, there is considerablevariation in reporting of NOWS bystate or jurisdiction. Improvement inreporting of NOWS to public healthofficials can help to identifycommunities in critical need ofintervention. Currently, only a handfulof states have mandatory reporting ofNOWS,107 and states vary in casedefinitions for state reporting. Ina study of 6 states with case reportingfor NOWS during 2013–2017,considerable variability was found inhow states defined and usedsurveillance.107 Nevertheless, forstates and other jurisdictions toimprove reporting, a consistentdefinition is needed. In an attempt toprovide a more universal definitionfor public health surveillance, theCouncil on State and TerritorialEpidemiologists, in collaboration withthe Centers for Disease Control andPrevention, met with state healthofficials to improve reporting inall states on the basis of maternalopioid use reported in prenatal anddelivery records as well as newbornhospitalization records.108 With moreconsistent reporting, states may beable to better and more rapidlyidentify needs among and betweenlocalities.

State and regional collaborations aredeveloping strategies to improveaccess to maternal medications forOUD, improve the quality of carefor newborn infants with NOWS,and reduce hospital length of stayand associated costs. Ohio’sPerinatal Quality Collaborativeinitiated a statewide approach tothe care of infants with NOWSthat included standardizedassessment and treatment, includingboth pharmacologic andnonpharmacologic interventions.


Among 52 of the state’s 54 neonatalcare facilities, standardizedpharmacologic treatment andincreased use of nonpharmacologictreatment reduced both the length oftreatment and the length of hospitalstay from 13.4 to 12 days and from18.3 to 17 days, respectively.109

Among a multistate, multicenterquality improvement collaborative,participating hospitals were able toreduce the median length ofpharmacologic treatment from 16 to15 days and the infant length ofhospital stay from 21 to 19 daysthrough a standardized scoringprocess for NOWS. Albeit noteworthy,these reductions in length of stay andcosts are modest. Additional qualityimprovement approaches andmeasures are needed to improve careto the mother-infant dyad.

CONCLUSIONS

The opioid crisis has had a profoundeffect on pregnant women and theirinfants. Despite improvements in theidentification, assessment, andtreatment of NOWS, substantialknowledge gaps remain. Pediatriciansare well positioned to improveoutcomes for the mother-infant dyadthrough evidence-based practice andconnection of families to publicresources.

RECOMMENDATIONS

NOWS is a major consequence of theopioid crisis, with dramatic increasesover the last decade. Pediatric careclinicians can help reduce newbornmorbidity, hospitalization, and costsand help improve maternal screening,referral, and follow-up for the

mother-infant dyad. We present thefollowing recommendations for care.

Access to Treatment

1. All pregnant women should haveaccess to medications for OUDbecause they have been shown toreduce risk of overdose death andimprove pregnancy outcomes.

2. Pediatricians should partner withstate and local child welfareagencies to advocate for funding toimprove access to qualitytreatment of OUD.

Antenatal Counseling and Screening

1. Pregnant women with OUD shouldreceive antenatal counseling toprovide education on the clinicalsigns of withdrawal and enhancematernal understanding ofpostnatal treatment (eg,

FIGURE 3Public health approaches to opioid use in pregnancy and in infants with opioid exposure. (Reprinted with permission from Patrick SW. Improving publichealth systems for substance-affected pregnancies. Am J Public Health. 2019;109(1):22–23.)


nonpharmacologic treatment,including breastfeeding andpharmacotherapy). When possible,maternal antenatal counselingshould be provided by a pediatricprovider.

2. Multiple modalities of testingshould be considered for theinfant, including, infant urine,meconium, and umbilical cordtissue testing.

3. For women in treatment of OUDwho receive frequent toxicologytesting, infant meconium and/orumbilical cord tissue testing maynot be necessary.

4. For many substances, urinetoxicology only captures a shortwindow of substance use for somesystems.

5. Pediatricians should assessadditional social risks, including,but not limited to, food andhousing insecurity, and connect tocommunity resources.

Observation

1. All infants with chronic opioidexposure should be observed forat least 72 hours to monitor forthe development of withdrawal.Although there is increasingevidence that multiple factors mayincrease an opioid-exposedinfant’s risk of withdrawal (eg,gestational age, specific genotypes,tobacco use, benzodiazepine, andgabapentin), there remainsinsufficient evidence of how to usethese exposures to tailor aninfant’s postnatal observationperiod. Institutions may use thefollowing approach forobservation of infants with opioidexposure:

2. immediate-release opioids: 3 days;

3. buprenorphine and sustained-release opioids: 4 to 7 days; and

4. methadone: 5 to 7 days.

Diagnosis

1. For all infants at risk for NOWS,a standardized assessment

approach by using a commonlyused tool (eg, modified Finneganscore) should be employed tomeasure the presence and severityof withdrawal symptoms as well asthe response to treatment (Fig 1).

2. Comorbidities should also beconsidered, including infectiousand neurologic conditions. If noclear in utero exposure isidentified through maternalhistory, screening, or testing,NOWS is a diagnosis that shouldbe used only if other potentialcauses of an infant’s symptomshave been evaluated fully andno other cause has been identified.

Treatment

1. Hospitals should prioritizekeeping the mother-infant dyadintact throughout observationand treatment of an infantwith opioid exposure.Rooming-in is the preferredmodel of care.

2. Hospitals should have a writtenprotocol for thenonpharmacologic andpharmacologic treatment of aninfant with opioid exposure.

3. Admission to a NICU only for opioidexposure or NOWS is not required.

4. All hospitals should havea written protocol for initiatingnonpharmacologic andpharmacologic treatment of aninfant with opioid exposure.

5. Nonpharmacologic interventionsshould be used for all infants withopioid exposure and should beconsidered the foundation of care.

6. Nonpharmacologic treatmentshould be tailored to the clinicalsigns of the infant.

7. All hospitals should havea protocol for breastfeeding aninfant with substance exposure.

8. For infants of mothers intreatment of OUD withbuprenorphine or methadonewho have not had relapse for$90 days, breastfeeding should

be supported if there are no

other contraindications.

9. For infants of women with activesubstance use or with relapseswithin the last 30 days,breastfeeding should bediscouraged.

10. For infants of women intreatment between 30 and90 days without relapse,breastfeeding should beconsidered.

11. HIV is a contraindication tobreastfeeding in high-incomecountries, such as the UnitedStates. HCV-positive motherswith cracked or bleeding nipplesshould consider abstaining frombreastfeeding.

12. Lactation support should beprovided in the inpatient settingand after discharge.

13. Pharmacologic therapy should beconsidered for severe opioidwithdrawal (eg, MOTHER score.8 3 2 or .12 3 1) in additionto nonpharmacologicinterventions. Vomiting and loosestools are associated withdehydration and poor weightgain and are relative indicationsfor treatment.

14. Opioids should be used as a first-line therapy for severe NOWS.

15. Infants who requirepharmacologic treatment shouldbe monitored (eg, pulseoximetry).

16. Recent data suggest thatopioids with a longer half-life,such as buprenorphine andmethadone, may reduce lengthof treatment. However, cautionshould be considered if thepreparation has a high alcoholcontent.

17. Paregoric and deodorized tinctureof opium should not be used.

18. If a second agent is needed forsevere opioid withdrawal, the use

of clonidine should be considered

over phenobarbital.


19. Naloxone should never be usedin the treatment of an infantwith chronic opioid exposurebecause it may precipitaterapid withdrawal andseizure.

Discharge

1. Discharge of infants from thehospital on pharmacotherapyshould be avoided and shouldonly occur if there isa structured, close outpatientfollow-up plan for the mother-infant dyad.

2. A discharge checklist should becompleted (Table 3):

3. no significant clinical signs ofwithdrawal for 24 to 48 hoursafter treatment;

4. parent education about NOWSand routine newborn care,emphasizing safe sleep;

5. pediatrician or primary careprovider follow-up visitwith 48 hours ofdischarge;

6. early intervention servicesreferral;

7. consideration of home-nursevisitation and Early HeadStart;

8. hepatitis C and HIV testingreferral, including referral topediatric infectious disease whenappropriate;

9. plan of safe care, coordinatingwith child welfare;

10. developmental-behavioralpediatrician referral, asappropriate; and

11. consideration of behavioral and/or mental health system referralsto address dyadic relationalhealth.

LEAD AUTHORS

Stephen W. Patrick, MD, MPH, MS, FAAPWanda D. Barfield, MD, MPH, FAAPBrenda B. Poindexter, MD, MS, FAAP

COMMITTEE ON FETUS AND NEWBORN,2019–2020

James Cummings, MD, FAAP, ChairpersonIvan Hand, MD, FAAPIra Adams-Chapman, MD, MPH, FAAPSusan W. Aucott, MD, FAAPKaren M. Puopolo, MD, FAAPJay P. Goldsmith, MD, FAAPDavid Kaufman, MD, FAAPCamilia Martin, MD, FAAPMeredith Mowitz, MD, FAAP

LIAISONS

Timothy Jancelewicz, MD, FAAP – AmericanAcademy of Pediatrics Section on SurgeryMichael Narvey, MD – Canadian PaediatricSocietyRussell Miller, MD – American College ofObstetricians and GynecologistsRADM Wanda Barfield, MD, MPH, FAAP –Centers for Disease Control and PreventionLisa Grisham, APRN, NNP-BC – NationalAssociation of Neonatal Nurses

STAFF

Jim Couto, MA

COMMITTEE ON SUBSTANCE USE ANDPREVENTION, 2019–2020

Lucien Gonzalez, MD, MS, FAAP, ChairpersonDeepa R. Camenga, MD, MHS, FAAPStephen W. Patrick, MD, MPH, MS, FAAPJoanna Quigley, MD, FAAPSheryl A. Ryan, MD, FAAPLeslie Walker-Harding, MD, FAAP

LIAISON

Rebecca Ba’Gah, MD – American Academy ofChild and Adolescent Psychiatry

STAFF

Renee Jarrett, MPH

ABBREVIATIONS

AAP: American Academy ofPediatrics

ACOG: American College ofObstetricians andGynecologists

CI: confidence intervalESC: Eat, Sleep, ConsoleHCV: hepatitis C virusHHS: US Department of Health and

Human ServicesMOTHER: Maternal Opioid

Treatment: HumanExperimental Research

NOWS: neonatal opioidwithdrawal syndrome

OUD: opioid use disorder

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2020 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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PREVENTIONFETUS AND NEWBORN, COMMITTEE ON SUBSTANCE USE AND

Stephen W. Patrick, Wanda D. Barfield, Brenda B. Poindexter and COMMITTEE ONNeonatal Opioid Withdrawal Syndrome

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