MANAGEMENT OF THE OPIATE-EXPOSED NEWBORN

AND IMPLICATIONS FOR BREASTFEEDING

Bonny Whalen, MD - Medical Director, Newborn Nursery at CHaD/Dartmouth-Hitchcock

Barbara Philipp, MD - Medical Director, The Birth Place at Boston Medical Center

Anne Johnston, MD - Neonatology, University of Vermont/Fletcher Allen Health Care

BACKGROUND

2007-2008:

14.2% U.S. women aged ≥ 12 yr used illicit drugs in past year (33.5% aged 18-25 yr) Marijuana/hashish 10.3% Non-therapeutic use of pain relievers 4.8% Cocaine 2.1% Heroin 0.2%

2008 National Survey on Drug Use and Health

http://www.oas.samhsa.gov/nsduh/2k8nsduh/2k8Results.pdf

DHMC EXPERIENCE: 2006-2009 - ADMIT DX: “SUBSTANCE-EXPOSED INFANT”

10/16/06 to 10/16/07 1333 deliveries 55 babies admitted (4.1%)

31 to ICN 24 to NNN, 12 with subsequent transfer to ICN (50%)

10/17/07 to 10/16/08 1314 deliveries 67 babies admitted (5.1%)

26 to ICN 41 to NNN, 18 with subsequent transfer to ICN (44%)

10/1/08 to 10/1/09 1356 deliveries 69 babies admitted (5.1%)

31 to ICN 38 to NNN, 16 with subsequent transfer to ICN (42%)

OPIATE REPLACEMENT THERAPY

Methadone: T1/2 in mom = 24 hr; in newborn = 32.5 hr

Farid WO et al. Curr Neuropharmacol. 2008;6:125-150.

Buprenorphine: Biphasic – initial rapid phase = 3-5 hr, slow phase > 24 hr,

Farid WO et al. Curr Neuropharmacol. 2008;6:125-150. Preterm infants (27 – 32 wk): 20 hr +/- 8 hr

Barrett DA, et al. Br J Clin Pharmacol. 1993;36:215–219.

Characteristic Heroin MTD BUP MTD vs BUP

Prematurity < 37 wk 29.8% 26.3% 21.8%* NS

Growth Restriction (IUGR) 27.7% 10.5%* 9.3%* NS

Birthweight (grams) 2601 3050* 2900* NS

Weight loss, 3rd day (grams) 196 248* 269* NS

* Denotes P < 0.05 for heroin vs. substitution agent

Binder T and Vavrinkova B. Neuroendocrinol Lett. 2008;29:80-86.

IN-UTERO OPIATE EXPOSURE AND THE NEONATE

Neurodevelopmental effects Methadone

• visual responsiveness• disorganized and avoidant behavior• contact-maintaining behavior• aggression and school disruptions•delayed cognitive development

Farid WO et al. Curr Neuropharmacol. 2008;6:125-150.

NEONATAL ABSTINENCE SYNDROME (NAS)

Characteristic Total MTD BUP P

Mean age of NAS onset (hr) 40 45 37.5 NS

Mean age at maximum score (hr) 72 80 66 NS

% NAS treated 51 49 52 NS

Mean duration of Rx (days) 17 18 16 NS

Lejeune et al. Drug Alcohol Depend. 2006;82:250-257.

France: 35-center prospective observational study 78% all infants developed NAS

No relationship b/w dose of agent and NAS severity

NEONATAL ABSTINENCE SYNDROME (NAS)

CNS hyperirritabilityAutonomic hyperfunctionGI dysfunction

CNS HYPERIRRITABILITY

Irritability High-pitched, excessive crying Sleeplessness Hyperactive reflexes Jitteriness Increased muscle tone Excessive suck Abrupt “state” changes

AUTONOMIC HYPERFUNCTION

Yawning Sneezing Fever Sweating Mottling Nasal stuffiness Respiratory distress

Tachypnea Nasal flaring

GI DYSFUNCTION

Excessive sucking Poor feeding Regurgitation Projectile vomiting Loose stools Watery stools

FINNEGAN NAS SCORING

Developed in1975, modified in 1986

Assess opiate-exposed newborns

Describe NAS symptoms Onset Severity Progression Response to Rx

Can be prone to subjectivity

Monitor ≥ 4 days for long-acting opiates

NAS SCORING TIPS

Score within 2 hr of birth, then q 3 - 4 hr Score all symptoms that occur within interval Instruct parents on how to perform NAS scoring Feed infant before scoring Calm infant prior to assessing muscle tone, RR Score baby when awake to elicit reflexes & behaviors

Do not awaken unless asleep for > 3 hr Assess while baby is asleep if needing to score more frequently

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

CONSIDER OTHER DIAGNOSES Hunger Nicotine withdrawal SSRI withdrawal or toxicity (e.g., cocaine) Substance toxicity Electrolyte abnL (e.g., low glucose, calcium, magnesium) Sepsis CNS abnL Metabolic abnL Hyperthyroidism

SUPPORTIVE CARE FOR NEWBORNS Cluster care

Undisturbed periods of sleep/rest

Decrease environmental stimuliLow lights, quiet room, limit visitorsAvoid “excessive handling” of baby

Teach family calming techniquesRooming-inSkin-to-skinFeed at early feeding cuesSwaddlingGentle rocking/swayingShooshing noises Non-nutritive sucking

WHEN TO CONSIDER RX / ICN TRANSFER

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

PHARMACOLOGIC RX FOR NAS

Capture Phase Morphine q 4 hr, dose increased until sx controlled

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

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

NAS scores consistently < 8 and Baby clinically stable

Phenobarbital added if difficult to capture or wean

COMORBIDITIES Infectious diseases (STDs, IVDU)

Hepatitis C – 63% Lejeune et al. Drug Alcohol Depend. 2006;82:250-257.

Cigarette smoking86% nicotine use

Lejeune et al. Drug Alcohol Depend. 2006;82:250-257.

NAS onset and severity greater in neonates with prenatal tobacco exposure > 20 cigs/day vs < 10 cigs/day

` Choo et al. Drug Alcohol Depend. 2004;75:253-260.

Psychiatric disease / antipsych medications

METHADONE AND BREASTFEEDING

Very long acting opiate analgesic Introduced into clinical use 1965 No RCTs in Pregnancy or Lactation

Case studies only Lactation Risk Category: L3

Small amounts transfer into breastmilk Theoretic Infant Dose: 38 mcg/kg/dayRelative Infant Dose: 2.8%

Hale T. Medications and Mother’s Milk. 2008.

BUPRENORPHINE AND BREASTFEEDING

Long acting narcotic agonist and antagonist No RCTs in Pregnancy or Lactation

Case studies only w/ limited #s Lactation Risk Category: L2

No documented increase in adverse effects for infants Oral bioavailability = 31% Theoretic Infant Dose: 2.2 mcg/kg/day Relative Infant dose: 1.93%

Hale T. Medications and Mother’s Milk. 2008.

BREASTFEEDING AND OPIATE REPLACEMENT Rx

Methadone and buprenorphine considered safe Ensure no active illicit drug use*

Breastfed infants may experience decreased NAS severityFarid WO et al. Curr Neuropharmacol. 2008;6:125-150.

Provide lactation support Frequent, ad lib feedings Promote calm, organized environment Perform infant oral-motor evaluation, if needed Emotional support for the mother

DHMC’S BREASTFEEDING GUIDELINES

Mother compliant with standard of care prenatal visits for at least the 3rd trimester

Mother with negative drug of abuse screening for at least the 3rd trimester

Mother compliant in drug addiction treatment program for at least the 3rd trimester

ABM’S BREASTFEEDING GUIDELINES

Women engaged in substance abuse Rx Provide consent to discuss Rx progress and postpartum plans

with substance abuse Rx counselor Abstinent from illicit drug use or licit drug abuse for

90 days prior to delivery Negative urine toxicology testing at delivery Consistent prenatal care No medical contraindications to BF

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.