1. M ANAGEMENT OF THE O PIATE -E XPOSED N EWBORN AND I MPLICATIONS FOR B REASTFEEDING 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

2. 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

3. DHMC EXPERIENCE: 2006-2009 - A DMIT D X : “ 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%)

4. OPIATE REPLACEMENT THERAPY Methadone: T 1/2 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.

5. CharacteristicHeroinMTDBUPMTD vs BUP Prematurity < 37 wk 29.8%26.3%21.8%*NS Growth Restriction (IUGR) 27.7%10.5%*9.3%*NS Birthweight (grams)26013050*2900*NS Weight loss, 3 rd day (grams)196248*269*NS * Denotes P < 0.05 for heroin vs. substitution agent Binder T and Vavrinkova B. Neuroendocrinol Lett. 2008;29:80-86. I N - 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.

6. N EONATAL A BSTINENCE S YNDROME (NAS) CharacteristicTotalMTDBUPP Mean age of NAS onset (hr)404537.5NS Mean age at maximum score (hr)728066NS % NAS treated514952NS Mean duration of Rx (days)171816NS 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

7. N EONATAL A BSTINENCE S YNDROME (NAS) CNS hyperirritability Autonomic hyperfunction GI dysfunction

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

9. AUTONOMIC HYPERFUNCTION Yawning Sneezing Fever Sweating Mottling Nasal stuffiness Respiratory distress Tachypnea Nasal flaring

10. GI DYSFUNCTION Excessive sucking Poor feeding Regurgitation Projectile vomiting Loose stools Watery stools

11. 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

12. 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

13. 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

14. SUPPORTIVE CARE FOR NEWBORNS Cluster care Undisturbed periods of sleep/rest Decrease environmental stimuli Low lights, quiet room, limit visitors Avoid “excessive handling” of baby Teach family calming techniques Rooming-in Skin-to-skin Feed at early feeding cues Swaddling Gentle rocking/swaying Shooshing noises Non-nutritive sucking

15. 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

16. 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

17. C OMORBIDITIES Infectious diseases (STDs, IVDU) Hepatitis C – 63% Lejeune et al. Drug Alcohol Depend. 2006;82:250-257. Cigarette smoking 86% 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

18. 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/day Relative Infant Dose: 2.8% Hale T. Medications and Mother’s Milk. 2008.

19. 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.

20. BREASTFEEDING AND OPIATE REPLACEMENT Rx Methadone and buprenorphine considered safe Ensure no active illicit drug use* Breastfed infants may experience decreased NAS severity Farid 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

21. 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

22. 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.