1. Priya Jegatheesan, MD Balaji Govindaswami, MBBS, MPH Division of Neonatology, Santa Clara Valley Medical Center, San Jose. August 12 th, 2014

2. Objective Scope of the problem of substance abuse Biology of addiction in adult vs. newborns Challenges in the care of newborns exposed to substances in utero

3. Substance Abuse – Global Problem Alcohol – causes 6% of global death Drugs 3.4-6.6% adults use drugs 1 % of deaths attributable to drugs Annual Prevalence and number of illicit drug users at the global level, 2010 Prevalence (%)Number (thousands) LowHighLowHigh Cannabis2.65.0119,420224,490 Opioids0.60.826,38036,120 Opiates0.30.512,98020,990 Cocaine0.30.413,20019,510 Ampheta mine– type 0.31.214,34052,540 Ecstasy0.20.610,48028,120 Any illicit3.46.6153,000300,000 http://www.unodc.org/documents/data-and-analysis/WDR2012/WDR_2012_web_small.pdf

4. Substance Abuse – National Problem: SAMHSA 2012 24 m (9%) used illicit substance in the last month Most common is Marijuana – 7% Methamphetamine 0.2-0.3% Non-medically used prescription drugs 2.6% Dependence – 8.5% Pregnant women – 5.6% used illicit drugs (lower than in non-pregnant (10.7%) population; 15-17 y – 18% http://www.samhsa.gov/data/NSDUH/2012SummNatFindDetTables/NationalFindings/NS DUHresults2012.pdf

6. Maternal co-morbidities Psychiatric illness Depression, Anxiety disorders 45% Axis 1 diagnosis, 75% Axis 2 diagnosis Psychosocial Lower socio-economic status & educational level Adverse Childhood Experiences: Abuse – emotional, physical, sexual Dysfunctional household Substance abuse Mental illness Domestic violence Incarceration separation

7. Maternal co-morbidities Infections – HIV, Hep B, Hep C Transmission IV, blood products, sexual transmission Risk Factors IV drug use Risky sexual related behavior Risky drug related behavior Immunocompromised

8. Biology of Addiction – Reward Pathway

9. Biology of Addiction VTA – dopaminergic neurons tell the individual if the stimuli is rewarding or aversive NA – GABAergic neurons mediate the rewarding effect Amygdala – establishes conditioned learning, learns associations to environmental cues and the rewarding experience. Hippocampus – establishes memory associated with reward experiences Pre-frontal cortex – glutamatergic neurons controls the executive function that mediates drug seeking behavior.

10. Biology of Withdrawal in Newborns Physical signs of withdrawal from opiates is mediated by Neuro Epinephrine Neurons in Locus Ceruleus in Mid Brain. LC – Neurons have Mu receptors, Alpha 2 Adrenergic receptors that decrease NE via adenyl cyclase – cAMP - PKA

11. Biology of Withdrawal in Newborns

12. Challenges in Care Universal Screening vs. Risk Based Scoring; Toxicology: Urine vs. Meconium vs. Cord vs. Hair Score for Withdrawal - which score, when to score, how to score, when to treat Treatment options only for opiate withdrawal: opiates vs. phenobarb vs. clonidine Breastfeed or not Discharge planning difficulties: home with mom or foster care

13. Screening for Substance Exposure Universal Standardized questionnaire Non-judgemental Trauma informed care 5Ps, … etc. Toxicology Urine Meconium Hair / Umbilical cord Legal Implications Consent CPS referral

14. Withdrawal Scores Only for opiate withdrawal Finnegan Score vs. Modified Standardized, inter rater reliability – staff education When to score – before or after feeds Polysubstance abuse may impact the scores (nicotine withdrawal etc.) however it is used specifically to treat opiate withdrawal Encourage Parental involvement Optimize non-pharmacological measures

15. Medical treatment for NAS Opiate agonist – Morphine / methadone acts on Mu receptors Clonidine – Alpha 2 adrenergic agonist – suppresses noradrenergic mediated sympathomimetic symptoms of withdrawal Phenobarbital - GABAergic agonist, but also blocks AMPA (excitatory) receptor, also non-specific to other receptors in brain Ondansetron – 5HT antagonist – decreases the withdrawal symptoms in animals / adults

16. Breastfeeding Uncertain pharmacokinetics of illicit drugs in mothers and newborns Adulterants in the drugs Variable excretion into breastmilk Co-morbid psychiatric illness Psychiatric medications Viral infections that are contraindications (HIV, HSV with active lesions on the breast)

17. Recommendations from ABM and AAP

21. Challenges with breastfeeding Complicated recommendations Medical team often ineffective in making social assessments Medical drugs vs. Illicit drugs Marijuana – medical / non-medical When in hospital, do you initiate breastfeeding and then evaluate, pump and dump, discourage ……..

22. Discharge Planning Difficult social situation, lack of a support system Unstable / unsafe home environment Lack of adequate residential treatment programs for mother and babies Outpatient Perinatal Substance Abuse Programs Foster care vs. discharge with biological mother with CPS supervision Breastfeeding but at still at risk of relapse

23. Acknowledgement Substance exposed mothers and newborns at SCMVC SCVMC MCH Staff Perinatal Substance Abuse Program at SC County Santa Clara First Five VMC Foundation VON iNICQ Collaborative NIH Funding for Prevention of NAS study SAMHSA Advisory group – MAT NAS