CARING FOR INFANTS WITH SHORT- AND LONG-TERM EFFECTS OF IN-UTERO OPIOID EXPOSURE

Bonny Whalen, MDMedical Director / Newborn Pediatrician

CHaD/DHMC Newborn Nursery

June 5, 2013

OBJECTIVES

Demonstrate an understanding of short- and long-term effects of in-utero opioid exposure on the developing fetus / neonate

Discuss the importance of multi-disciplinary, family-centered care for these infants in the newborn period

Help families best prepare for the birth of their at-risk infant including how to provide calm, nurturing environments, limiting visitors, etc.

ILLICIT DRUG USE IN U.S. WOMEN

~ 11% illicit drug use in past month in women 15-44 yr 15-17 yr: 13% 18-25 yr: 16.8% 26-44 yr: 7.6%

4.4% illicit drug use in past month in known pregnancy 15-17 yr: 16.2% 18-25 yr: 7.4% 26-44 yr: 1.9%

Most commonly reported illicit drugs used by women:1. Marijuana2. Psychotherapeutics (e.g., opioids)

2009 & 2010 National Surveys on Drug Use and Health

https://nsduhweb.rti.org/

Growth restriction Prematurity

Developmental abnormalities / long-term effects? Opioid system mediates developmental events

Farid WO, et al. Curr Neuropharmacol. 2008. Motor delays? Cognitive delays? ADHD? Review of available studies reveals no adverse effects on development

for opiate-exposed infants Jones HE, et al. Early Hum Dev. 2009.

Characteristic Heroin MTD BUP MTD vs BUP

Delivery < 37 wk (%) 29.8% 26.3% 21.8%* NS

Birthweight 2601 g 3050 g* 2900 g* NS

IUGR 27.7% 10.5%* 9.3%* NS

* P < 0.05 for heroin vs. substitution agentBinder T and Vavrinkova B. Neuroendocrinol Lett. 2008.

IN-UTERO OPIATE EXPOSURE AND ITS EFFECTS

NEONATAL ABSTINENCE SYNDROME (NAS)

CNS hyperirritabilityAutonomic hyperfunctionGI dysfunction

CNS HYPERIRRITABILITY

High-pitched crying Sleeplessness Hyperactive moro reflex Tremors Increased muscle tone Myoclonic jerks Seizures

http://newborns.stanford.edu/PhotoGallery/Jittery3.html

AUTONOMIC HYPERFUNCTION

Metabolic / Vasomotor / Respiratory Disturbances

Fever Sweating Yawning Mottling Nasal stuffiness Sneezing Nasal flaring Tachypnea Retractions

GI DYSFUNCTION

Excessive sucking Poor feeding Regurgitation Projectile vomiting Loose stools Watery stools

NAS: WHAT TO EXPECT

Lejeune et al. Drug Alcohol Depend. 2006.Sigman et al. J Peds. 2010

2/3 - 3/4 infants develop some degree of NAS Symptoms from long-acting opioids start on DOL 2

May see symptoms earlier if: Mom missed dose the day prior Baby has early rapid withdrawal phase of buprenorphine Mom using other substances / meds / nicotine

Symptoms usually peak DOL 3-4 May depend on med, mom’s other meds, baby’s metabolism ...

≥ 1/2 infants require Rx for NAS

No relationship b/w dose of substitution agent and NAS severity or duration of Rx

MINIMUM RECOMMEND MONITORING TIMES FOR OPIOID-EXPOSED INFANTS

2 days Short-acting opioids

e.g., morphine, oxycodone, Percocet

4 days Heroin Long-acting opioids

e.g., buprenorphine, methadone

Study Outcomes MTD(N = 73)

BUP(N = 58)

P

% infants treated for NAS 57% 47% 0.26

Peak NAS score 12.8±0.6 11.0±0.6 0.04

Total amount of morphine needed for Rx 10.4 mg 1.1 mg <0.0091

Duration of Rx for NAS 9.9 d 4.1 d <0.0031

Length of stay 17.5 d 10 d <0.0091

METHADONE VS. BUPRENORPHINEJones et al. N Engl J Med. 2010; 363:2320-2331.

Multi-center RCT (n = 7) comparing MTD vs. BUP Rx in 175 pregnant women with opioid dependency (89 MTD, 86 BUP) Double-blind, double-dummy, flexible-dosing Comparison of 131 neonates whose mothers were followed to end of pregnancy

33% BUP vs. 18% MTD discontinued Rx (P > 0.02) - Most commonly due to maternal dissatisfaction with Rx

Unclear if pts with more severe dependence more likely to leave BUP group, therefore skewing towards better outcomes in BUP neonates; however post-hoc analyses remained significant when excluded moms on ≥ 100 mg methadone

SIGNIFICANT PREDICTORS RELATED TO NAS

Need for Rx for NAS Maternal cigarette

smoking Higher birthweight

Higher peak NAS score prior to Rx Lower maternal weight Maternal SSRI use Higher birthweight Lower gestational age Vaginal delivery

Longer duration of Rx Maternal use of SSRIs,

antidepressants, or antipsychotics

Higher dose of morphine required for Rx Maternal use of SSRIs,

antidepressants, or antipsychotics SSRIs independently

Lower # days of maternal receipt of study medication

Greater # of cigarettes smoked 24 hr prior to delivery

Kaltenbach, et al. Addiction. 2012;107:45-52.

SIGNIFICANT DIFFERENCES IN NAS PROFILES

Methadone-exposed

Higher incidence of: Undisturbed tremors Hyperactive Moro

Greater mean severity score: Total NAS score Disturbed tremors Undisturbed tremors Hyperactive Moro Excessive irritability Failure to thrive

Shorter time to Rx initiation 36 hr (compared with 59 hr for

buprenorphine)

Buprenoropine-exposed

Higher incidence of: Nasal stuffiness Sneezing Loose stools

Greater mean severity score: Sneezing

Gaalema, et al. Addiction. 2012;107:53-62.

Limitation = Data from neonates requiring Rx were excluded from analyses once Rx was initiated → may underestimate measures of incidence / severity

HOW TO ASSESS FOR NAS: FINNEGAN SCORING TOOL

Signs / symptoms Percentage

Tremors 90

Restlessness 85

Hyperactive reflexes 51

Regurgitation 45

Increased muscle tone 45

High pitched cry 33

Sneezing 31

Frantic sucking of fists 25

Inability to sleep 24

Stretching 22

Nasal stuffiness 18

Respiratory distress 12

Vomiting 9

Frequent yawning 9

Sweating 8

Excoriation of knees, toes and nose 7

Mottling 5

Diarrhea 3

Fever 3

Pallor 3

Lacrimation 2

Generalized convulsion 2

• Developed to: 1.monitor full spectrum of abstinence

sx due to narcotic withdrawal2.monitor response to Rx

• Determined prevalence of 20 most common sx seen in infants with narcotic withdrawal

• Ranked sx based on potential for greatest harm to infant

Finnegan LP, at al. Int J Clin Pharmacol Biopharm. 1975.

DEVELOPMENT OF THE FINNEGAN SCORING

TOOL

• Assigned score of “5” to sx with greatest potential to harm infant and “1” to sx with least pathological significance

Scored q 1 hr in 1st 24 hr, q 2 hr x 24 hr, then q 4 hr corresponding to “Nursery feedings”

Good inter-rater reliabilityFinnegan LP, et al. Int J Clin Pharmacol Biopharm. 1975

Modified in 1986- Score q 4 hr- Allow to feed q 2-3 hr

LIMITATIONS OF FINNEGAN TOOL

Designed for term infants

At times, difficult to interpret sx of ‘normal newborn’ vs NAS

Study of 102 non-addicted infants DOL 1-3: Median score = 2 Variability increased on DOL 1-2

DOL 1: 95th percentile = 5.5 DOL 2: 95th percentile = 7

Zimmermann-Baer et al. Addiction. 2010.

Can be prone to subjectivity

Not to be used for a “one point in time” quick assessment

Lacks specificity DDx: hunger, nicotine or benzo withdrawal,

SSRI toxicity vs withdrawal, hypoglycemia, infection, CNS injury, hypocalcemia, hyperthyroidism

CO-MORBIDITIES

Nicotine withdrawalTobacco use in pregnancy ~85%

Lejeune et al. Drug Alcohol Depend. 2006. Zimmermann-Baer et al. Addiction. 2010.

SSRI withdrawal / toxicity13% maternal SSRI use in pregnancy

Zimmermann-Baer et al. Addiction. 2010.

Other substance / med toxicity12% benzodiazepine Rx in pregnancy

Zimmermann-Baer et al. Addiction. 2010.

Difficulties feeding

Increased weight loss

NAS SCORING TIPS

Teach parents how NAS scoring is performed

Teach parents how to help monitor infant e.g., watch for decreased sleep, yawning, sneezing, excessive sucking

Score within 2 hr of birth, then q 3 - 4 hr

Score baby when awake to elicit reflexes & behaviors

Do not awaken unless asleep for > 3 hr

Allow infant to calm first e.g., allow infant to feed before scoring, place skin-to-skin with mother especially important for muscle tone & RR

Score all symptoms that occur within interval

If score ≥ 8, score NAS q 2 hr until < 8 x 24 hr

SUPPORTIVE CARE FOR NEWBORNS

Rooming-inAllows family to respond to infant at early feeding / stress cues, empowers family to care for their infant independently, and provides opportunity for calmer environment for infant

Decreased need for NAS RxShorter length of stayMore likely to be discharged into custody of mother

Abrahams R et al. Can Fam Physician. 2007.

SUPPORTIVE CARE FOR NEWBORNS

Feed baby at early feeding cues, till content

Frequent skin-to-skin contact

Use calming techniquesC-positionSwaddlingGentle jigglingSlow, rhythmic up & down movements*

Clap baby’s bottom with cupped hand*

Shooshing Non-nutritive sucking

*May not work for some babies

SUPPORTIVE CARE FOR NEWBORNS

Provide undisturbed periods of sleep / restCluster care

Decrease environmental stimuliLow lightsQuiet roomLimit visitors / # caregiversAvoid “excessive handling” of baby

Introduce stimuli as baby able to tolerate Infant touch / massage

BREASTFEEDING AND OPIATE REPLACEMENT Rx

Methadone and buprenorphine considered safe

Breastfed infants may experience decreased NAS severityFarid et al. Curr Neuropharmacol. 2008.

Ensure no active illicit drug use - see ABM guidelines

Provide lactation support Promote calm, organized environment Frequent, ad lib feedings Provide emotional support Teach ways to help baby if NAS present

Skin-to-skin Hand expression / breast massage during feeding Organize baby’s suck on finger first if suck disorganized

Feed small amount of colostrum first C-hold in cross cradle / football positions May require caloric supplementation for increased

metabolic needs

ABM’S BREASTFEEDING GUIDELINES

Consistent prenatal care Abstinent from illicit drug use or licit drug abuse for 90 days

prior to delivery & able to maintain sobriety in outpt setting Women engaged in substance abuse Rx who have provided

consent to discuss progress with Rx & postpartum plans with substance abuse Rx counselor

Negative urine toxicology testing at delivery No medical contraindications

e.g., HIV, contraindicated antipscyh med

The Academy of Breastfeeding Medicine Protocol Committee. ABM Clinical Protocol #21: Guidelines for breastfeeding and the drug-dependent woman. Breastfeeding Medicine. 2009;4:225-228.

DRUG OF ABUSE SCREENING

Obtain specimens within 24 - 48 hr of delivery to help: Anticipate timing and type of withdrawal symptoms Inform DCF / DCYF of exposure, when clinically indicated Make recommendations re: safety of breastfeeding

Urine drug of abuse screen Urine confirmatory testing Meconium drug of abuse screen

WHEN TO CONSIDER RX / ICN TRANSFER

Apnea Seizures 3 consecutive scores (or average of) ≥ 8 2 consecutive scores (or average of) ≥ 12 Inability to feed orally due to NAS sx

PHARMACOLOGIC RX FOR NAS

Capture Phase Oral morphine*§ q 4 hr, dose increased until NAS sx controlled Phenobarbital added if difficult to capture or wean

Maintenance Phase Find smallest dose that adequately controls baby’s sx Goal of Rx = NAS scores < 8

Weaning Phase Begin wean when scores < 8 x 48 hr & baby clinically stable Wean by 10% daily when following present:

NAS scores < 8Baby clinically stable

*Agent of choice at DHMC, alternative agents sometimes preferred at other institutions (e.g., methadone)

§2010 Cochrane Systematic Review on Opiate Rx for opiate withdrawal in newborn infants: “There is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate.”

CARE COORDINATION

Clinical Resource Coordinator Assist in identifying and arranging postnatal supports

VNA, Good Beginnings, breast pump rental, etc. Identify Primary Care Physician (PCP)

Social Worker Perform initial assessment of mother and newborn Assist in identifying and arranging postnatal supports Review risk for postpartum depression / stress & identify coping

mechanisms / supports Mandated report to DCF/DCYF, when clinically indicated

Consider offering that mother make report herself Review how report will help engage parenting/family supports

KEEPING CHILDREN AND FAMILY SAFE ACT

As a condition of federal funds under Child Abuse Prevention and Treatment Act, each state must develop policies & procedures to address needs of infants born and identified as being affected by illegal substance abuse or withdrawal symptoms resulting from prenatal drug exposure Notify CPS of substance-exposed newborns Develop plan of safe care for infant

Law specifies that reports of prenatal substance exposure shall not be construed to be child abuse or require prosecution for any illegal action

DHMC MANDATED REPORTING GUIDELINES

Mother continuing to use any of following substances during pregnancy, subsequent to documented teaching on potential dangers of substance(s) and resources offered for cessation: Alcohol Controlled medication not prescribed to the mother Illicit substance

Mother who admits to prenatal use of illicit substance and use not previously disclosed

Baby tests positive for any of above substances Baby with Fetal Alcohol Syndrome or Adverse Effects

DISCHARGE READINESS

No apnea or respiratory compromise Stable vital signs Baby has completed appropriate observation period

No active concerns for significant sx of NAS Feeding well with appropriate weight pattern Parents demonstrate appropriate response to / care of baby Home environment assessed as safe Referrals to community resources in place

COMMUNITY RESOURCES

Information and Referral NH Resource 211 802-652-4636 VT Resource 211 866-444-4211

Support/Home-based programs (e.g., VNA, Good Beginnings, Parenting Programs)

Health and Mental Health / Treatment Programs Child Protective Services Domestic/Family Violence Housing Emergency Financial Assistance Legal Assistance Transportation Long-term follow-up programs /

interventions (e.g., Early Intervention)

GOING HOME …

Communication with community supports Identify known family challenges (domestic violence, mental

health issues, homelessness) Identify known family strengths and informal supports

Update state CPS agency, as clinically indicated Known family challenges and strengths Issues in the home which may pose risk for baby Results of drug of abuse screening Community supports recommended / accepted

Communication with baby’s PCP & 1st visit made Update on medical course, social issues,

community resources offered / accepted

PRENATAL PREPARATION

Maintain abstinence Engage social supports Encourage breastfeeding (with abstinence) Decrease / stop smoking Educate families regarding what to anticipate

Likelihood of NAS symptoms / what sx look like Need to stay in hospital for at least 4 days for monitoring Possibility of needing Rx / duration of Rx if needed Providing calm environments for baby / calming techniques

Limiting visitors, rooming-in, skin-to-skin, swaddling, etc. Drug of abuse screening Need for mandated reporting / referral to DCF/DCYF

RESOURCES FOR PROVIDERS

“Parenting and Substance Abuse: Developmental Approaches to Intervention” - Book that explores issues of the substance exposed dyad pre- and post-partum Edited by Nancy Suchman, Marjukka Pajulo and Linda

Mayes (Oxford University Press, 2013). “Highs and Lows” - Book about women and addiction.

http://www.camh.ca/en/education/about/camh_publications/Pages/highs_lows.aspx

QUESTIONS?