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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.