1. Difficult conversations in the Neonatal Period Opiate Use and Breastfeeding

2. A Common Scenario….. You are called to do a prenatal consult with a pregnant mom Mom is on methadone maintenance for a previous heroin addiction You meet a well dressed young woman who is obviously nervous about this discussion Her main question: Can I breastfeed? 2

3. Objectives Provide an update on the prevalence and patterns of opiate use in breastfeeding women Describe the passage of opiate medications into breast milk and the effects on the newborn Discuss indications and contraindications to breastfeeding in women using opiates

4. Illicit Substance Use 9.4% of Americans older than 18 are current illicit drug users Non-medical use of prescription drugs is second only to Marijuana use –Primarily opioid class pain relievers Use of Heroin has more than doubled since 2007 4 SAMSHA NSDUH 2013

5. Scope of the Problem: Among pregnant women: –5.9% report use of illicit drugs (Samsa-NSHUD 2013) –28% were prescribed at least one opioid pain reliever during pregnancy (Patrick 2015) 96% were non-maintenance prescription opioids –20% of women experience mood or anxiety disorders during pregnancy (Flynn 2006)

6. Substance Use Patterns 6 Prepared 3/3/2015 by Karina Atwell, MD UW ‐ Madison Preventive Medicine Resident

7. Opioids in Pregnancy Opioids easily pass the placental and blood-brain barrier. Fetus can develop physical addiction –Opioids inhibit release of norepinephrine from nerves in the brain –Tolerance develops and more norepinephrine is produced by the brain to overcome the inhibition –If opioids are suddenly taken away large amounts of norepinephrine are released and produce the physical signs of withdrawal If the mother stops using opioids her fetus will experience withdrawal and will be at increased risk for distress and fetal loss

8. Neonatal Abstinence Syndrome (NAS) 8

9. Incidence of neonatal abstinence syndrome per 1000 hospital births in the United States, 2009 to 2012. 9 Patrick, J Perinatol 2015

10. NAS in Wisconsin 10 Prepared 3/3/2015 by Karina Atwell, MD UW ‐ Madison Preventive Medicine Resident

11. Treatment of NAS Pharmacologic treatment with opiates –Restart the infant on morphine –Slowly wean Non-pharmacologic treatment –Tight swaddling –Holding and rocking –Quiet dark room –Limit number of visitors –Feeding on demand Small frequent feeds –Have pacifier available

12. Length of Stay 12 Prepared 3/3/2015 by Karina Atwell, MD UW ‐ Madison Preventive Medicine Resident

13. Breastfeeding and opiates 13

14. How do opiates work? 14

15. Passage of opiates into milk 15

16. What is baby getting? Depends on –Size of molecule –Degree of protein binding –Lipid solubility –Ionization –Maternal factors –Infant factors 16

17. Estimating Infant Dose Milk to Plasma Ratio –Ratio between the concentration of medication in the maternal plasma and milk at steady state –Estimate of the relative amount of drug in milk Of limited value unless you know the maternal serum concentration – even if a medication has a milk to plasma ratio of greater than 1, the concentration in the breast milk may still be low if maternal plasma levels are low 17

18. Methadone Full opioid agonist –Will interact with the brain in the same way that morphine does. Very long half life (mean half life is 22 hours) Mothers must go to the methadone clinic every day to get their dose

19. Transfer of Methadone into Breastmilk Variable but minimal transfer of methadone into breastmilk –Average amount transferred to infant 0.05- 0.19 mg/day 1-3% of maternal weight adjusted dose Less than dosage used to treat NAS 19

20. Buprenorphine Subutex/Suboxone Semi-synthetic partial agonist –Binds opioid receptors in the brain but is not very active. Can be prescribed to women who can pick up weeks worth of doses at one time Popular choice for women in rural or remote areas.

21. Buprenorphine and breastfeeding Buprenorphine has low oral bioavailability (31%) Very low levels in breastmilk –0.38% of maternal buprenorphine dose –0.18% of maternal norbuprenorphine dose Assumed to be safe – more studies needed 21 Ilett et al. Breastfeed Med 2012

22. Other Opiates Hydrocodone, oxycodone and fentanyl –Usual doses for pain relief have minimal to no effect on infant –When used as a drug of abuse mothers should be transitioned to maintenance opiate –Caution with codeine 22

23. Polydrug Exposure NAS complicated by the interplay between opioid withdrawal and withdrawal from other substances –SSRIs (7-8%) and Tobacco (85%) are common co-exposures –Symptoms are similar to NAS and may exacerbate NAS –Benzodiazepines, barbiturates and alcohol are also known to cause withdrawal signs in infants.

24. Polydrug Exposure Fetuses exposed to methadone + polysubstances in utero had: –Decreased fetal heart rate –Decreased fetal movement –Delivered 1 week earlier than fetuses exposed to methadone only or no methadone –Required treatment for NAS twice as often 24 Jannson, Drug and Alcohol Dependence 2012

25. Breastfeeding and NAS Challenges –Polydrug use –Infectious disease risk –Poor nutrition –Comorbid psychiatric disorders Lack of evidence based guidelines 25 Jansson. Breastfeeding Medicine 2009

26. Advantages of breastfeeding Breastfeeding is recommended for women compliant with treatment and on maintenance medications regardless of dose –Shorter length of hospital stay –Lower Finnegan scores –Less likely to require pharmacologic treatment –If treatment is needed: lower doses of medication and shorter duration of treatment 26 Abdel-Letiff, Pediatrics 2006

27. Breastfeeding and Incidence of NAS Requiring Pharmacologic Treatment 27 BreastfedFormula Fed Welle-Strand57% (n=58)69% (n=20) Wachman50% (n=38)77% (n=48) Abdel-Latif52.9% (n=85)79% (n=105) Dryden O’Connor23.1%30%

28. Breastfeeding and Length of Treatment BreastfeedingFormula Feeding Abdel Latif85 days (n=85)108 days (n=105) Welle-Strand31 days (n=58)49 days (n=20) Wachman15.8 days (n=38)27.4 days (n=48) 28

29. Why? Dosage of opioids in breastmilk low Known benefits of breastfeeding: –Skin to skin –Holding and soothing –Bonding –Enhanced confidence –Increased maternal participation in care of the infant 29

30. Breastfeeding and SIDS Protective effect of Breastfeeding against SIDS (AAP 2005) Infants exposed to opiates at higher risk for SIDS (Burns et al 2010) 30

31. Encourage breastfeeding Women in treatment Consent for communication No illicit substance use in last 90 days Negative urine tox screens Consistent prenatal care No medical contraindications 31 Reece-Stremtan Breastfeeding Medicine 2015

32. Consider breastfeeding Relapse in 90-30 days before delivery but not within 30 days of delivery Other prescription medications Prenatal care or substance abuse treatment after the second trimester Custody or sobriety as motivators Lack of family and community support systems 32 Reece-Stremtan Breastfeeding Medicine 2015

33. Counsel women not to breastfeed: Not in substance abuse treatment No prenatal care Relapse into illicit substance use within 30 days of delivery Unwillingness to seek treatment or allow communication Positive urine tox screen at delivery Women with active drug use Chronic alcohol use Other contraindication for breastfeeding 33 Reece-Stremtan Breastfeeding Medicine 2015

34. Screening for opiate use Based on risk? Universal screening? –Universal Drug Testing in a High-Prevalence Region for Opiate Abuse 2995 pregnant women, 96 + for opiates 77/96 had risk factors that would have triggered screening 19/96 had no risk factors that would have triggered screen 34 Wexelblatt et al. Journal of Pediatrics 2015

35. Breastfeeding Initiation Rates UK – 14% in women using opiates vs 50% in general population (Goel 2011) Norway – 77% in women using opiates vs 98% in general population (Welle-Strand 2013) US - 187 women using opiate with no contraindications to breastfeeding –66% did not initiate BF –24% did initiate BF: 40% still BF at time of discharge (Wachman 2010) 35

36. Barriers to Breastfeeding Low SES High prevalence of mental health issues Lack of knowledge about specific benefits of breastfeeding Prejudice Need for urine drug screening 36

37. No easy answers….. Trauma informed care Family centered care of the newborn Prenatal counseling and education 37

38. References CDC. Vital Signs: Overdoses of Prescription Opioid Pain Relievers and Other Drugs Among Women — United States, 1999–2010. Morbidity & Mortality Weekly Report. 2013, July 5:62(26);537-542 Chisholm MS et al. Relationship between cigarette use and mood/anxiety disorders among pregnant and methadone maintained patients. Am J of Addiction. 2009;18:422-429 Finnegan LP et al. Neonatal Abstinence Syndrome: Assessment and Management. Addictive Diseases. 1975;2(1):141- 158 Flynn HA, Blow FC, Marcus SM. Rates and predictors of depression treatment among pregnant women in hospital- affiliated obstetrics practices. General Hospital Psychiatry, Vol, 28, No. 4, July-August 2006, pp 289-29.Flynn HA, Blow FC, Marcus SM. Rates and predictors of depression treatment among pregnant women in hospital- affiliated obstetrics practices. General Hospital Psychiatry, Vol, 28, No. 4, July-August 2006, pp 289-29. Hudak ML et al. Neonatal Drug Withdrawal. Pediatrics. 2012;129(2):e540-e561 Jansson LM et al. The opioid exposed newborn: Assessment and pharmacologic management. Journal of Opioid Management. 2009;5(1):47-55 Johnston A. Neonatal Abstinence Syndrome Scoring: Guidelines for treatment with methadone. Scoring Tool Training MOTHER study 2006 Jones HE et al. Neonatal Abstinence Syndrome after methadone or buprenorphine exposure. NEJM. 2010;363(24):2320-2331 King JC. Substance Abuse in Pregnancy. A bigger problem than you think. Postgrad Medicine. 1997;102(3):149-150 Lambers DS and Clark KE. The maternal and fetal physiologic effects of nicotine. Semin Perinatol. 1996;20(2):115-26 Patrick SW et al. Prescription Opioid Epidemic and Infant Outcomes. Pediatrics 2015 135(5) Patrick SW et al. Incidence and Geographic distribution of NAS: United States 2009 to 2012. J Perinatol 2015 Substance Abuse and Mental Health Services Administration. Results from the 2009 National Survey on Drug Use and Health: Vol 1: Summary of National Findings 2010

39. References Reese-Stremtan S. ABM Clinical Protocol #21: Guidelines for Breastfeeding and Substance Abuse or Substance Use Disorder, Revised 2015 Breastfeeding Medicine 2015: 10(3) Welle-Strand GK, Skurtveit S, Jansson LM, et al. Breast- feeding reduces the need for withdrawal treatment in opioid- exposed infants. Acta Paediatr 2013;102:1060–1066. Abdel-Latif ME, Pinner J, Clews S, et al. Effects of breast milk on the severity and outcome of NAS among infants of drug-dependent mothers. Pediatrics 2006;117:1163–1169. Jansson LM, Choo R, Velez ML, et al. Methadone main- tenance and breastfeeding in the neonatal period. Pediatrics 2008;121:106–114. Jansson LM, Choo R, Velez ML, et al. Methadone main- tenance and long-term lactation. Breastfeed Med 2008;3: 34–37. Kocherlakota P. Neonatal abstinence syndrome. Pediatrics 2014;134:e547–e561. Wachman EM, Byun J, Philipp BL. Breastfeeding rates among mothers of infants with neonatal abstinence syn- drome. Breastfeed Med 2010;5:159–164. D’Apolito K. Breastfeeding and substance abuse. Obstet Clin Gynecol 2013;56:202–211. Jannson et al. Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: A comparison of fetal neurobehaviors and infant outcomes. Drug and Alcohol Dependence 2012 122(3): 213-219 39

40. Questions Elizabeth Goetz MD MPH Department of Pediatrics University of Wisconsin – Madison Meriter Hospital