Improving rates in Neonatal Abstinence Syndrome infants in the NICU

Donna Garey MD MPH Lisa Stellwagen MD UC San Diego Medical Center Division of Neonatology January 2015

FACULTY DISCLOSURE INFORMATION

Lisa Stellwagen MD I have a relevant financial relationship to disclose: Medela, Inc: speaker

Donna Garey MD MPH I have a relevant financial relationship to disclose: none Objectives • Identify current evidence based reasons to encourage breastfeeding of the Neonatal Abstinence Syndrome (NAS) infant • Identify what concrete steps can be implemented to improve breastfeeding rates at discharge in the NAS infant • Learn the what is currently known about the effects of Marijuana during and lactation, and then be able to accurately counsel mothers on this issue

Neonatal Abstinence Syndrome (NAS) • Due to abrupt discontinuation of chronic exposure to opioids in utero • Generalized multi-system disorder • Incidence of NAS increasing around the US

From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009

JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951

Figure Legend: Error bars indicate 95% CI. P for trend < .001 over the study period. The unweighted sample sizes for mothers diagnosed with and without antepartum opiate use are 987 and 833 494 in 2000; 1058 and 849 133 in 2003; 2160 and 879 910 in 2006; and 4563 and 816 554 in 2009; respectively.

Copyright © 2015 American Medical Date of download: 1/27/2015 Association. All rights reserved. From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009

JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951

Figure Legend: NAS indicates neonatal abstinence syndrome. Error bars indicate 95% CI. P for trend < .001 over the study period. The unweighted sample sizes for rates of NAS and for all other US hospital births are 2920 and 784 191 in 2000; 3761 and 890 582 in 2003; 5200 and 1 000 203 in 2006; and 9674 and 1 113 123 in 2009; respectively.

Copyright © 2015 American Medical Date of download: 1/27/2015 Association. All rights reserved. NAS Timeline

NAS. Pediatrics. Kocherlakota. 2014 Opiates • Mimic natural endogenous endorphins at  and  receptors on the neuronal cell membrane • Block transmission of noxious stimuli from the periphery to the spinal cord • Develop tolerance to analgesia, sedation, and euphoria • Cross the placenta – Lipophilic, low molecular weight compounds

Heroin • -opioid receptor agonist • Approx 40-80% of infants have NAS

• Earlier onset and shorter withdrawal – Onset of withdrawal symptoms at 24 to 48 hours – Duration of withdrawal is 8-10 days

Prescription Narcotics

• Frequency of NAS • Long-Acting Opioids depends on amount – Fentanyl Transdermal Patch and duration of – Oxymorphone or Oxycodone hydrochloride extended-release maternal use – Morphine sulfate extended-release • Onset and duration of • Short-Acting Opioids withdrawal depends on – Hydrocodone – Oxycodone half-life of the drug – Tramadol • Approx 5-20% – Fentanyl (IV) or Morphine (IV) – Codeine experience NAS – Hydromorphone

Treatment for opioid addiction

Methadone • -opioid receptor agonist • partial -opioid agonist • Half Life 23-48 hours • Half-life 26-34 hours • Typical dose is 20 to 120 • Mean hospital stay for NAS mg per day – 10 days • Mean hospital stay for NAS • Later onset and longer – 17.5 days withdrawal • Later onset and longer withdrawal Minimal relationship between maternal opioid dose and NAS.

Buprenorphine +/- Naloxone • Synthetic opioid receptor agonist • Prescribed in a doctor’s office by qualified MD • Available formulations: – Tablets - 2 and 8 mg tablets – Sublingual film - 2-4-8-12 mg – Patch form for chronic pain • Less respiratory depression than other narcotics – Can cause coma/death if combined with benzos, , other respiratory depressants • Shorter duration of NAS Onset, Duration, and Frequency of NAS

Opioids Onset Frequency Duration (hours) (%) (days)

Heroin 24-48 40-80 8-10

Prescription 36-72 5-20 10-30 Opioids Buprenorphine 36-60 22-67 Up to 28 or more 48-72 13-94 Up to 30 or more Infants Admitted for Observation for Neonatal Abstinence Syndrome

Observation Period: • Short acting Observation and Admit to NICU: Monitoring: prescription narcotics: 4 days NAS (Finnegan NAS < 8 continue to score) q 4 hr. monitor until safe for • Benzo + opiates: Implement non- discharge pharmacologic 4-7 days therapies NAS >8 times 2 • Heroin/methadone: implement therapy 5-7 days • Suboxone: 5-6 days Why treat maternal drug abuse and neonatal withdrawal?

• Decreases illicit drug use • When combined with good obstetrical care improves fetal outcomes • Avoids complications of NAS such as seizures and dehydration due to poor feeding, vomiting, and diarrhea. • Allows infant to have normal feeding and infant interactions.

Risk Factors for Increased Severity/Intensity of NAS • Term • Polydrug abuse • Combination with benzodiazepines • Specific gene polymorphisms of the -opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) • Smoking • Methadone • Combination with SSRIs

Withdrawal in Preterm Infants

• Decreased intensity and severity – Decreased cumulative exposure – Decreased transmission across placenta in early gestation – Decreased receptor development and sensitivity – Decreased fatty tissues • Methadone accumulates in fatty tissues Modified Finnegan

Zimmerman-Baer U, et al. Addiction. 2010. Infants Admitted for Observation for Neonatal Abstinence Syndrome

Observation and Observation Period: Monitoring: • Short acting Admit to NICU: NAS < 8 continue prescription NAS (Finnegan score) q narcotics: 4 days 4 hr. to monitor until • Benzo + opiates: Implement non- safe for discharge 4-7 days pharmacologic therapies • Heroin/methadone: NAS >8 times 2 5-7 days implement therapy • Suboxone: 5-6 days CNS Signs and Symptoms Scored infants 30 – 60 minutes after a feed.

If the infant requires rocking to quiet during this time. Their cry is considered prolonged.

If infant’s cry is high pitched at its peak even though it is not prolonged – score 2.

If cry is high pitched throughout, or if crying is prolonged, even if not high pitched – score 3.

Excessive High Pitched Cry Increased muscle tone

Score if excessive or above-normal muscle tone.

For instance: no head lag when being pulled to a sitting position or tight flexion of the infant’s arms and legs. Moro Reflex

If the infant exhibits pronounced jitteriness (rhythmic tremors that are symmetrical and involuntary) of the hands during or at the end of a Moro reflex – score 2.

If jitteriness and clonus (repetitive involuntary jerks) of the hands and/or arms are present during or after a Moro – score 3. Myoclonic jerks

Score if involuntary muscular contractions which are irregular and exceedingly abrupt (usually involving a single muscle group) are observed. Tremors

Mild, Moderate, and Severe

Disturbed or Undisturbed

Undisturbed means that the baby is either sleeping or at rest in its bed.

Seizures

Most commonly seen as tonic extensions of all limbs.

Unusual limb movements may accompany a seizure. In the upper limbs these often resemble swimming or rowing in the lower limbs, they resemble pedaling or bicycling.

Other subtle signs may include staring, rapid involuntary eye movement, chewing, back arching, and fist clenching.

Occurs in 2-11% of infants with NAS Gastrointestinal Signs and Symptoms Excessive Sucking

Score if hyperactive or disorganized sucking, increased rooting reflex. Loose/watery Vomiting stools Score if at least one episode

of regurgitation is observed. Score if loose (curds/seedy appearance) or watery stools (water ring on nappy around stool) are observed. Poor Feeding

Score if the infant demonstrates excessive sucking prior to feeding, yet sucks infrequently during a feeding, taking a small amount; and/or demonstrates an uncoordinated sucking reflex. Respiratory and Vasomotor Signs and Symptoms Respiratory Rate

Score 1 only if respirations are >60/min in the absence of lung or airway disease.

Score 2 only if respirations are >60/min and retractions are present in the absence of lung or airway disease

Nasal Stuffiness

Score if the infant sounds congested; mucous may be visible

Sneezing

Score if more than three sneezes are noted within the scoring interval Yawning

Score if more than 3 yawns are observed within the scoring interval. Sweating

Score if sweating is spontaneous and not due to excessive clothing or high room temperature. Hyperthermia

Temperature should be taken per axilla.

Mild pyrexia is an early indication of heat produced by increased muscle tone and tremors.

Usually less than 102 Frequent low grade temp Mottling

Score if mottling is present on the infant’s chest, trunk, arms, or legs. Non-pharmacologic Adjunct Therapy • Swaddling • Settling • Rocking • Decrease outside stimulation/white noise • Massage • Relaxation Baths • Pacifiers Pharmacologic Treatment Half-life Advantages Disadvantages (hours) Morphine 9 Shorter weaning Frequent doses course Constipation Methadone 26 Long half-life Longer weaning course Phenobarbital 45-100 Long half-life Sedation Possible apoptosis Clonidine 44-72 No sedation Hypotension, Rebound hypertension Adjunct Pharmacotherapy • Phenobarbital – Binds to the GABA receptor, improving the effect of GABA by extending GABA-mediated chloride channel openings which permits an increasing flow of chloride ions across the membrane, causing neuronal hyperpolarization (e.g., membrane inhibition to depolarization). – Does not treat gastrointestinal symptoms • Clonidine – Central acting alpha-adrenergic receptor agonist – Stimulates presynaptic adrenergic receptor thus inhibiting CNS sympathetic outflow and reducing norepinephrine – Treats autonomic over activity - tachycardia, hypertension, restlessness, and diarrhea, sweating

Previous Pharmacologic Therapies • Tincture of opium – Very concentrated - small error in dosing leads to significant overdose – Contains 19% ethanol – Does not control diarrhea – No longer recommended • Paregoric – Contains anhydrous morphine – Also contains camphor, 44% ethanol, anise oil, benzoic acid, and glycerin – No longer recommended due to other toxic ingredients

Neonatal Abstinence Syndrome (NAS): Standardizing Management, Promoting Breastfeeding, and Improving Communication

University of California San Diego NICU Quality Improvement Team Donna Garey, MD, MPH Lisa Stellwagen, MD Mary Ekno, BSN, RNC-NIC Alicia Somers, PharmD Poster Session and Podium Presentation Specific Aims

• Decrease median LOS for infants with NAS  from 95 days to 30 days by September 2014

• Increase any human milk exposure in infants (with no contraindications)  from 50% to 75% by December 2014

• Increase human milk at discharge  from 0% to 25% by December 2014 Settings and Methods • Level III regional NICU – 2,500 deliveries and 700 admissions per year – Infants requiring NAS treatment are admitted to the NICU

• Chart review of infants treated for NAS – May to July 2012 (before internal QI project) – Sept to Nov 2013 (VON Day Quality Audit 1) – June to Sept 2014 (VON Day Quality Audit 2)

• Data collected – Based on the VON Day Quality Audits – Additional data on Breastfeeding (BF)

Interventions/PDSA Cycles • Optimizing Care Team – Hospitalist Service • Coordination with maternal outpatient providers – 2:1 Nursing ratios – Finnegan nursing superusers

• Provider education – VON iNICQ Core Webinars

• Revised policy/algorithm on Initial Management at risk for NAS – Included initial breastfeeding management

• Monthly QI Task Force meetings – Multidisciplinary involvement

In Utero Exposures

Risk for Neonatal Not at risk/low risk for Neonatal Abstinence Syndrome Abstinence Syndrome

Exposure to Exposure to Exposure to multiple agents Exposure to Exposure to short-acting antipsychotics, long-acting such as short-acting antidepressants narcotics in addition to methamphetamines narcotics without (ie SSRIs), and narcotics (see benzodiazepines, or THC multiple exposures list below) antipsychotics, , etc. other medications.

Admit to couplet care and Admit to couplet observe for 4 days. Admit to couplet Admit to NICU Admit to NICU (No NAS Scoring by nursing) care* Call MD to assess if concern care for opioid withdrawal.

*A positive maternal toxicology screen for THC and/or amphetamines can’t be used as an indication to legally separate a mother from her well newborn. These infants can only be separated from mother after a CPS hold has been placed. Long-Acting Opioids Fentanyl Transdermal Patch Breastfeeding Methadone Permitted for almost all mothers/infants at Buprenorphine (Butrans, Subutex) Oxymorphone hydrochloride extended-release (Opana) admission to FMCC or NICU. Oxycodone hydrochloride controlled-release (Oxycontin) Morphine sulfate extended-release (Oramorph, Kadian) Continued breastfeeding will be determined by medical team. Short-Acting Opiods Contraindications to breastfeeding are Hydrocodone and Hydrocodone+APAP (Vicodin, Norco) Oxycodone+APAP (Percocet) or oyycodone IR positive HIV status, medications that are Tramadol Category L5, or confirmed on-going illegal Fentanyl (IV) or Morphine (IV) drug use. Codeine Hydromorphone (Dilaudid) Infants Admitted for Observation for Neonatal Abstinence Syndrome

Observation and Observation Period: • Short acting prescription Admit to NICU: Monitoring: narcotics: 4 days NAS (Finnegan score) q 4 NAS < 8 continue to • Benzo + opiates: 4-7 hr. monitor until safe for days Implement non- discharge • Heroin/methadone: 5-7 pharmacologic therapies NAS >8 times 2 days implement therapy • Suboxone: 5-6 days NAS Patient Characteristics and Outcomes

NAS Patient 2012 (May-July) 2013 (Sept-Nov) 2014 (June-Sept) Characteristics and n=4 n=6 n=6 Outcomes Length of Stay(days) 94.5 31.5 32 Median DC on Meds 100% 67% 40% Any BM 50% 67% 67% BM at discharge 0% 17% 50% Reason no BM at dc In treatment, Incarcerated (3) Incarcerated (2) counseled to stop(3) In treatment, Not provided (1) HIV positive (1) relapse (2) % 100

90

80 Goal 70 Median 60 Any Breastmilk(%) 50 by Month Admitted 40

30

20

10

0

May- Jul-12 Sep- Nov- May- Aug-

13 13 14

12 14

Breastmilk at Discharge (%) by Month Admitted Summary/Key to Success • Multidisciplinary involvement – Nursing and SW champions – Updating policy to standardize initial management in L&D, couplet care, and NICU

• Continuity of care – Hospitalist service – Coordination with outpatient maternal treatment providers

• Monthly QI task force meetings – Kept leadership informed and involved

Breastfeeding in the NAS infant • BF benefits of specific interest to NAS infant • Review narcotic transfer in MBM • What had we tried? • What worked this time?

Benefits of breastmilk for the newborn that may be of specific significance to the NAS infant

• Reduction in SIDS • Significant reduction in infections in childhood • Improved maternal-child bonding • Decreased risk of neglect • Modified NAS symptoms/ length of hospital stay

Dose response for beneficial effects of breastfeeding

Condition Lower risk Otitis Media 50% Pneumonia 77% Asthma 27% RSV bronchiolitis 74% NEC 77% Eczema 27% Gastroenteritis 64% Inflammatory bowel 31% disease Obesity 24% Celiac disease 52% Type 1 diabetes 30% Type 2 diabetes 40% SIDS 73%

AAP Breastfeeding and the use of human milk. Pediatrics 2012 Does breastfeeding protect against substantiated child abuse and neglect? A 15-year cohort study. • 5890 Australian mother-infant pairs followed for 15 yrs • 512 children with maltreatment reports • 4.3% had >1 episode of maternal maltreatment • Assessed no BF (21%), < 4 mos (39%), > 4mos (40%) • No association with BF and non-maternal maltreatment • 2.6 times higher risk of maternal maltreatment for non-BF children • Maternal neglect was the only type of maltreatment associated with BF duration • Their conclusions: ‘among other factors, breastfeeding may help to protect agains maternally perpetrated child maltreatment, particularly child neglect’

Strathearn et al. Pediatrics 2009 Breastfeeding reduces the need for withdrawal treatment in opioid-exposed infants • 124 women in narcotic treatment (methadone and buprenorphine) and their infants (in Norway) • High rates of BF 77%, but also high rates of early weaning • Breastfed infants exposed to methadone prenatally had less need for opioid treatment (53% vs 80%) • This effect was not significant for buprenorphine (64% vs 44%) • For those that were treated, length of treatment was shorter for those who were breastfeed (27 d vs 47 d)

Welle-Strand et al. Acta Paediatrica 2013 What national metrics are there to support BF in the NAS population?

• ABM • AAP • VON network • LactMed • MotherRisk • Thomas Hale

RID: relative infant dose =

Dose: infant mg/kg/day ______

Dose: mother mg/kg/day

If RID <10% considered safe for baby

Thomas Hale, Medications and Mother’s Milk 2014 PEDIATRICS Vol. 132 2013 pp. e796 -e809

U.S. National Library of Medicine TOXNET Data Network: LactMed 2015 Methadone • Mother on methadone maintenance has about 1-3 % of her weight adjusted methadone in her milk (safe level < 10%) • Highest levels are about 1/3 baby treatment dose • Peak levels occur 4-6 hours after maternal dose • BF may reduce NAS symptoms and LOS in baby • Abrupt weaning may lead to symptom increase in baby • ‘Women who received methadone maintenance during pregnancy and are stable should be encouraged to breastfeed their infants postpartum’ U.S. National Library of Medicine TOXNET Data Network: LactMed 2015 Buprenorphine • Achieves low levels in breastmilk about 1.4-2.4% maternal weight adjusted dose • Poor oral absorption by infant • Low infant blood levels • Infant dose unlikely to aide in NAS symptoms • However infants have developed NAS with rapid BF cessation • ‘women who received buprenorphine for opiate abuse during pregnancy and are stable should be encouraged to breastfeed their infants postpartum’ Breastfeeding and the use of human milk AAP Policy Statement 2012 Maternal substance abuse is not a categorical contraindication to breastfeeding. Adequately nourished narcotic-dependent mothers can be encouraged to breastfeed if they are enrolled in a supervised methadone maintenance program and have negative screening for HIV and illicit drugs.96

PEDIATRICS Vol. 129 2012 pp. e827 -e841 From the American Academy of Pediatrics Clinical Report The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics

• Potential adverse effects on breastfeeding infants from methadone (according to product labeling) and buprenorphine include lethargy, respiratory difficulty, and poor weight gain.52 The long-term effects of methadone in humans are unknown. Nonetheless, methadone levels in human milk are low, with calculated infant exposures less than 3% of the maternal weight-adjusted dose.53,54 Plasma concentrations in infants are also low (less than 3% of maternal trough concentrations) during the neonatal period and up to 6 months postpartum.55,56 For these reasons, guidelines from the Academy of Breastfeeding Medicine encourage breastfeeding for women treated with methadone who are enrolled in methadone-maintenance programs.48 • Transferred amounts of methadone or buprenorphine are insufficient to prevent symptoms of neonatal abstinence syndrome.49,60 Neonatal abstinence syndrome can occur after abrupt discontinuation of methadone.51,61 Thus, breastfeeding should not be stopped abruptly, and gradual weaning is advised if a decision is made to discontinue breastfeeding.

PEDIATRICS Vol. 132 2013 pp. e796 -e809 Academy of Breastfeeding Medicine 2009 ABM Clinical Protocol #21: Guidelines for breastfeeding and the drug-dependent woman

• Women engaged in substance abuse treatment who have provided their consent to discuss progress in treatment and plans for postpartum treatment with substance abuse treatment counselor • Women whose counselors endorse that she has been able to achieve and maintain sobriety prenatally; counselor approves of client’s plan for breastfeeding • Women who plan to continue in substance abuse treatment in the postpartum period • Women who have been abstinent from illicit drug use or licit drug abuse for 90 days prior to delivery and have demonstrated the ability to maintain sobriety in an outpatient setting • Women who have a negative maternal urine toxicology testing at delivery except for prescribed medications • Women who received consistent prenatal care • Stable methadone-maintained women wishing to breastfeed should be encouraged to do so regardless of maternal methadone dose. MotherRisk website (Dr Gideon Koren) • Heroin toxicity has been observed in infants breastfed by mothers abusing heroin, but at therapeutic doses, most opioids, such as morphine, meperidine, methadone, and codeine, are excreted into milk in only minimal amounts18,19 and are compatible with breastfeeding.

http://www.motherisk.org Medications and Mother’s Milk 2014 Thomas W Hale, PhD & Hilary E Rowe PharmD • Buprenorphine: L2 ‘no evidence that the use of this drug will have an adverse effect in the breastfed infant’ • Buprenorphine + Naloxone: L3 ‘probably compatible with breastfeeding’ • Methadone: L2 ‘averages 2.8% of the maternal dose…the amount in milk is insufficient to prevent neonatal withdrawal syndrome’

UCSD breastmilk and maternal medication policy 2011 • Despite being Baby Friendly since 2006 with BF rates of 95%... • We were not consistent about who could and could not BF • Different rules for NICU and well baby unit • OB and Peds not on the same page • Policy written and maternal handouts made • Party line was to be: anything taken in pregnancy is safe for early breastfeeding • All mothers encouraged to BF (except HIV+, very few contraindicated medications/combinations) • Pediatric medical team would sort out feeding plan after birth • But policy not adhered to • Methadone mothers in particular were told not to BF

POLICY/PROCEDURE TITLE: UCSD Medical Center: BREASTMILK: DRUGS OF ABUSE, WOMEN & INFANT SERVICES NARCOTICS AND USE OF HUMAN MILK

RELATED TO: ADMINISTRATIVE CLINICAL PAGE 1 OF _

Medical Center Policy (MCP) Nursing Practice Stds. Effective date: 1/11 Revision date: Review date: JCAHO Patient Care Stds. Unit/Department of Origin: ISCC, FMCC QA Other Other Approval: Newborn Management, ISCC Core Group & Title 22 Perinatal Practices 1/11

KEY ELEMENTS:

1. Drugs of abuse are known to have potential for risk to the young or premature infant 2. Infants gain benefit from early exposure to their mother’s milk 3. Most medications used by mothers result in very low levels of drug exposure in human milk 4. Straightforward unit policy will help to extend human milk benefits to all infants and clarify to mothers their role in the health of their infant 5. Support of the mother/infant couplet at risk for substance abuse is a priority in our unit

POLICY STATEMENT:

1. All mothers will be asked about medication use in pregnancy 2. Mothers that use narcotics under a physicians order for chronic pain are, in general, allowed to breastfeed 3. Mothers with known or suspected street drug or alcohol use will be given the benefit of the doubt, educated about providing safe milk for their infant, and followed closely 4. There is no need to discard milk, test the milk, or have the mother refrain from breastfeeding

PROVIDER: RN, NP, MD

EQUIPMENT:

PROCEDURE: 1. The pediatric medical team will review mother’s history, consult with pharmacy and standard tertiary references (e.g. LactMed, Medications and Mother's Milk), to make an assessment of the breastfeeding safety of a mother’s medications 2. Maternal chart will be reviewed for history of drug use, recent toxicology screening, and time of last positive toxicology test 3. NICU/FMCC social worker will evaluate mothers with a drug or alcohol history re: willingness to abstain from substance abuse and to provide expressed breastmilk or breastfeed the infant 4. Mothers with known or suspected drug or alcohol history will be given handout on ‘Providing safe milk for your baby’

1

Why were we non-compliant with our own policy?

• Policy in place, but not followed • Consultant for NAS infants told mothers not to BF • Staff believed – methadone in milk made baby hard to wean – most mothers were not staying clean – that rapid discontinuation of breastfeeding could precipitate significant risk for baby – that maternal dose over 90 mg of methadone made breastfeeding dangerous • Mothers are tested weekly during pregnancy, but not routinely after delivery • We had no information about mother’s compliance with her methadone clinic • We did not weight the benefits to baby of human milk against the risks of not breastfeeding

As we worked to improve our NAS policy, we incorporated new BF guidelines • Neonatologists all agreed on new guidelines • Reaffirmed our policy • Clarified the tiny amount of methadone in mother’s milk • Additional rules to address concerns • Arranged MD-to-MD contact with mother’s methadone clinic • Clinic asked to test mother every week and call us if tox+ • Encouraged staff to consider the great benefit to the baby of breastmilk • Presented BF as part of our treatment of baby. • Encouraged parents to stay with baby, do skin to skin and breastfeed as part of non-pharmacologic management of NAS

Complicating factors:

• A high number of these mothers smoke cigarettes which can make withdrawal more difficult and add risk to infant (of SIDS, otitis media) • Mothers who are incarcerated have much difficulty in pumping and getting their milk to baby • Mothers with narcotic addiction may relapse • Mothers who are not clean often will not provide breastmilk- this was the first sign of relapse.

New version of NAS policy regarding breastmilk The role of breastfeeding in the setting of neonatal abstinence syndrome is controversial. For mothers on a stable maintenance methadone regimen, breastfeeding may reduce length of stay, though care must be taken in weaning from mother’s own milk. Recommendation regarding which women should be allowed to breastfeed in this scenario from the Academy of Breastfeeding Medicine (2009): •Women engaged in substance abuse treatment who have provided their consent to discuss progress in treatment and plans for postpartum treatment with substance abuse counselors •Women whose counselors endorse that she has been able to achieve and maintain sobriety prenatally; counselor approves of client’s plan for breastfeeding •Women who plan to continue in substance abuse treatment in the postpartum period •Women who have been abstinent from illicit drug use or licit drug abuse for 90 days prior to delivery and have demonstrated the ability to maintain sobriety in an outpatient setting •Women who have a negative maternal toxicology testing at delivery except for prescribed medications •Women who received consistent prenatal care •Women who do not have HIV or other contraindications to breastfeeding •Women who are not taking a psychiatric medication that is contraindicated in lactation •Stable methadone-maintained women wishing to breastfeed should be encouraged to do so regardless of maternal methadone dose •Women and their partners should be fully informed about the risk of rapid weaning from the breast or exposure to street drugs during lactation

In Utero Exposures

Risk for Neonatal Not at risk/low risk for Neonatal Abstinence Syndrome Abstinence Syndrome

Exposure to Exposure to multiple agents Exposure to Exposure to Exposure to short-acting antipsychotics, long-acting such as short-acting narcotics in addition to methamphetamine narcotics without multiple antidepressants narcotics (see benzodiazepines, s or THC exposures (ie SSRIs), and list below) antipsychotics, nicotine, etc. other medications.

Admit to couplet care and Admit to couplet observe for 4 days. Admit to couplet Admit to NICU Admit to NICU (No NAS Scoring by nursing) care* Call MD to assess if concern care for opiod withdrawal.

*A positive maternal toxicology screen for THC and/or amphetamines can’t be used as an indication to legally separate a mother from her well newborn. These infants can only be separated from mother after a CPS hold has been placed. Long-Acting Opioids Breastfeeding Fentanyl Transdermal Patch Methadone Permitted for almost all mothers/infants at Buprenorphine (Butrans, Subutex) admission to FMCC or NICU. Oxymorphone hydrochloride extended-release (Opana) Oxycodone hydrochloride controlled-release (Oxycontin) Morphine sulfate extended-release (Oramorph, Kadian) Continued breastfeeding will be determined by medical team. Short-Acting Opiods Hydrocodone and Hydrocodone+APAP (Vicodin, Norco) Oxycodone+APAP (Percocet) or oyycodone IR Contraindications to breastfeeding are Tramadol positive HIV status, medications that are Fentanyl (IV) or Morphine (IV) Codeine Category L5, or confirmed on-going illegal Hydromorphone (Dilaudid) drug use. Benefits we have seen since our policy change • We have a clear message- less frustration • Mothers feel needed- and welcome • Less adversarial relationship • Mother has a role no one else can fill • Fathers or family empowered to help her visit and breastfeed, or ferry milk • For the compliant NAS mother, it can be a success and an early positive experience as a mother Thank you! Questions?

Marijuana and Milk… what to do?

Donna Garey MD MPH Lisa Stellwagen MD UC San Diego Medical Center Division of Neonatology

http://ideatransfuser.wordpress.com/2013/11/12/marijuana-legalization-is-not-a-free-for-all-good-times-smoke-fest-bonanza/ Emerging Public Health Problem • Legalization of marijuana in Washington and Colorado • Decriminalized in many states – Including California, Oregon, Nevada, Nebraska… • Medical Marijuana – 19 states (Oregon, Nevada, Arizona, New Mexico, Montana…) • Increasing Potency (data from seized samples) – 1985 – THC content 2.8% – 1993 – THC content 3.4% – 2008 –THC content 5.8 to 9.3%

Emerging Public Health Problem • States responding to new concerns – Focusing on education regarding the negative effects on the fetus and infants • Colorado formed health advisory committee Marijuana and THC • Marijuana: leaves and flowers of sativa • ∆-90-tetrahydrocannabinol is the psychoactive ingredient – Highly lipophilic – Half life of 20-36 hours (slow excretion) – Excreted well into breastmilk (because it is fat soluble) – Crosses the placenta • Like smoking it can increased carboxyhemoglobin levels – May impair fetal oxygenation and growth

Djulus J et al. Marijuana and breastfeeding. Can Fam Physician 2005 What do we know about the effects of THC on the baby via the placenta/breastmilk?

Pregnancy Lactation • Complicated by other exposures • THC does pass into milk • Baby may have mild withdrawal • Infant effects unclear due to • There may be long term neuro- prenatal exposure as well in behavioral deficits for the child almost all cases • No increased risk of SIDS for • Theoretical risk milk supply in maternal use (+ for paternal use) mother-but no decrease in duration of lactation • Concern about maternal intoxication and infant care • No data on infant effects

Jaques SC et al. J of Perinatology 2014 LactMed 2014 Marijuana Use in Pregnancy • Most commonly used illicit drug in women of reproductive age • Self-reported use of 2.9% during pregnancy THC in pregnancy • No known “safe” threshold for use in pregnancy • Endogenous cannabinoids involved in development of the nervous system – Role is progenitor cell commitment and survival – Five receptors identified • CB1 –predominant CNS – Involved in neuronal proliferation, migration, and synaptogenesis

• Estimated dose to fetus unclear – Human studies THC level 3 to 6 times lower in cord blood than maternal blood

Early Neurologic Disturbances

Withdrawal symptoms • No reports of withdrawal • Tremors requiring treatment • Exaggerated startle • Described as “mild narcotic response withdrawal” • Increased hand to mouth behavior • High pitched cry • Sleep cycle disturbance Neurodevelopment and Growth Effects

Fetal Development Neonatal Development • Mixed BW effects – • Increased tremors and depends on exposure and startles population • Differences in sleep – Decreased growth and BW recordings after 2nd trimester exposure – Decreased length after first trimester exposure • Decreased gestational age • No definitive link to congenital anomalies Neurodevelopment and Behavior

Infant/Toddler Child • Mixed results – some show • 6 years: increased no difference impulsivity and • 18 months: more hyperactivity inattention and aggression • 10 years: decreased • 36 months: decreased abstract and visual short-term memory reasoning, decreased function and verbal attention reasoning • 9-12 years: impaired visuo- perceptual functioning

More effects with heavy use

What is known about THC levels in MBM? • Review past & current statements • Many references are based on opinion and not study • THC is confounded with other illicit drugs and cigarette smoking • THC use only during BF has not been well studied • Legal issues are rapidly changing • Child Welfare Services in SD does not act on THC issues • We should balance what is really known with risks of not BF

Committee on Nutritional Status during Pregnancy and Lactation, Institute of Medicine 1990 • “despite the relatively high prevalence of marijuana use during pregnancy, no conclusive data are available on the effect of marijuana on the developing fetus. There is, however, suggestive evidence that marijuana use during pregnancy may impair fetal growth” Breastfeeding and the use of human milk AAP Policy Statement 2012 “Street drugs such as PCP (phencyclidine), , and cannabis can be detected in human milk, and their use by breastfeeding mothers is of concern, particularly with regard to the infant’s long-term neurobehavioral development and thus are contraindicated.97

Section on breastfeeding vol 129 PP e827 2012 Reference 97: cannabis and breastfeeding Garry et al. Journal of toxicology 2009

• “There are a few studies about the effects of cannabis consumption during lactation on infant health and development. More attention has been directed towards adverse effects of prenatal cannabis exposure.” • “Cannabis consumption during breastfeeding is contraindicated according to Hale and the American Academy of Pediatrics in Breastfeeding Mothers. If the mother regularly uses cannabis, breastfeeding is contraindicated” • “In conclusion, clinical and pharmacokinetic data indicate that cannabis use is dangerous during breastfeeding for the child. Observed effects in breastfed infant like sedation or reduced muscular tonus could be due to, not only cannabis, but also other drugs or medicines (psychotropic, antiepileptic, etc.) that mothers are likely to take.” Medications and Mother’s Milk 2014 Thomas W Hale, PhD & Hilary E Rowe PharmD • Marijuana: L5 ‘studies concerning the use of cannabis in pregnant women appear to be inconsistent in their results. Cannabis should not be used during pregnancy or breastfeeding’ • ‘this drug should not be used by nursing mothers’ • ‘while the data on neurobehavioral effects of cannabis on infants from breastfeeding mothers is limited, cannabis use in breastfeeding mothers should be strongly discouraged. For daily continued use, mothers should be advised not to breastfeed’

MotherRisk

• Despite abundant recreational use of cannabinoids by women of reproductive age, very little is known about marijuana use and lactation. • The passage of THC into breast milk has not been extensively studied. A study by Perez-Reyes and Wall in 1982 suggested that THC is excreted into human breast milk in moderate amounts.8 Based on their findings, 0.8% of the weight-adjusted maternal intake of one joint would be ingested by an infant in one feeding7. In heavy users, the milk-to-plasma ratio (ie, levels in milk vs levels in maternal blood) was as high as 8:1.8 Animal studies suggest that marijuana can decrease the amount of milk produced by suppressing prolactin production and possibly through a direct effect on the mammary glands. There are no human data to corroborate these observations. • In 1990, a study by Astley and Little suggested that exposure to THC through breast milk in the first month of life could result in decreased motor development at 1 year old.9 No studies have adequately addressed the effects on long-term neurodevelopment. Lethargy, less frequent feeding, and shorter feeding times are other observations reported after babies’ exposure to THC through breast milk.10 A mother’s ability to nurse and care for her child might be compromised because marijuana can affect mood and judgment. • With chronic use, THC can accumulate in human breast milk to high concentrations.8 Because a baby’s brain is still forming, THC could theoretically affect brain development. It is also important to avoid environmental exposure to maternal marijuana smoke. Nursing mothers should be referred to appropriate services for counseling.

http://www.motherisk.org/prof/updatesDetail.jsp?content_id=724 Academy of Breastfeeding Medicine 2009 ABM Clinical Protocol #21: Guidelines for breastfeeding and the drug-dependent woman • D9-Tetrahydrocannabinol (THC) is present in human milk, and metabolites not found in human milk are found in infant feces, indicating that THC is absorbed and metabolized by the infant. There may or may not be long-term effects on infant development from perinatal THC exposure.

Pertinent THC references all from 1980’s Presence of Δ9-tetrahydrocannabinol in human milk Perez-Reyes M and Wall ME. NEJM 1982 • This was a correspondence; not peer reviewed • 2 mothers who self reported smoking marijuana brought in milk samples and infant urine samples • Mother 1 milk: 105 ng/ml • Mother 2 milk: 340 ng/ml • Neither urine was positive for THC • Mother 2 declined to stop using THC and agreed to have her blood and milk and baby’s stool tested again – Milk was tested at 1 hour after smoking (peak level) (estimated 0.8% of weight adjusted dose now frequently quoted) – Infant 1 stool had THC metabolites

U.S. National Library of Medicine TOXNET Data Network: LactMed 2015

• Although published data are limited, it appears that active components of marijuana are excreted into breastmilk in small quantities. Data are from random breastmilk screening rather than controlled studies because of ethical considerations in administering marijuana to nursing mothers. Concern has been expressed regarding marijuana's possible effects on neurotransmitters, nervous system development and endocannabinoid-related functions.[1][2] One long-term study found that daily or near daily use might retard the breastfed infant's motor development, but not growth or intellectual development.[3] This and another study[4] found that occasional maternal marijuana use during breastfeeding did not have any discernable effects on breastfed infants, but the studies were inadequate to rule out all long- term harm. • Marijuana use should be minimized or avoided by nursing mothers because it may impair their judgment and child care abilities. Some evidence indicates that paternal marijuana use increases the risk of sudden infant death syndrome in breastfed infants. Marijuana should not be smoked by anyone in the vicinity of infants because the infants may be exposed by inhaling the smoke. Because breastfeeding can mitigate some of the effects of smoking and little evidence of serious infant harm has been seen, it appears preferable to encourage mothers who use marijuana to continue breastfeeding while minimizing infant exposure to marijuana smoke and reducing marijuana use.[5] Does THC exposure increase risk of SIDS? • 239 SIDS cases and matched controls (SoCal) • Parents interviewed • THC, Methamphetamine, cocaine, LSD (mostly during pregnancy not BF) • After adjusting for risk factors no association with SIDS for maternal recreational drug use • Paternal use of marijuana was associated with SIDS (x2)

Klonoff-Cohen et al. Arch Pediatr Adolesc Med 2001 How to separate all the effects of THC use in lactating mothers?

Low milk supply Prenatal THC exposure

Other toxin exposures Prematurity

Socio-economic factors

Breastfed vs formula fed Growth restriction Altered maternal caregiver

Paternal use of THC How to separate all the effects of THC use in lactating mothers? And balance that with the risk of not receiving breastmilk?

Low milk supply Prenatal THC exposure Increased risk of infections Increased risk of SIDS Other toxin exposures Prematurity Altered maternal child bonding

Socio-economic factors

Breastfed vs formula fed Growth restriction Altered maternal caregiver

Lack of developmental benefits of mother’s milk Risk of obesity Paternal use of THC So what should we tell mothers? • THC gets transmitted to fetus and breastfed infant • Placenta and fetal brain are full of THC receptors • Long term effects of THC use in pregnancy are not clear; but may include abnormalities in development and school performance • Long term effects of THC use while breastfeeding are not clear • Breastfeeding however, is protective for baby whether or not mother uses THC • Is there a safe way to pump and dump with THC for occasional use?

Next steps at UCSD… • For select compliant mothers in treatment: – Improve pre-delivery counseling – Parent handout about our policies – Mom and baby stay together in couplet care for 5 days – Baby to NICU if starts to withdraw • MJ + BF handout to be given out prenatally and after delivery for women known to use THC Urinary Drug Screening and Duration of Detection in Neonate • Opioids • Marijuana – Heroin, morphine, codeine – Single Use • 1-2 days • 1- 3 days – Hydromorphone, – Moderate Use oxycodone • 5-7 days • 2- 4 days – Heavy Use – Methadone • up to 10 days • 2-3 days – Chronic Heavy Use – Methadone metabolites • up to 30 days • up to 6 days – Buprenorphine • 2-3 days

Meconium Drug Screening in Neonate • More sensitive than urine screening • Longer window of detection – From 20 weeks gestation

References

• Brown MS, Hayes MJ et al. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial. J Perinatol. 2014 (epub ahead of print) • Hall ES et al. A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome. Pediatrics. 2014;134(2):e527-34 • Hudak ML et al, committee on drugs: committee on fetus and newborn, American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics. 2012;129(2):e540-60 • Huizink AC, et al. Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. Neuroscience and Behavioral Reviews. 2006; 30: 24-41. • Huizink AC. Prenatal cannabis exposure and infant outcomes: Overview of studies. Progress in Neuro-Psychopharmacology and Bilogical Psychiatry. 2014; 52: 45-52. • Jaques SC et al. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol. 2014;34:417-24 • Jones H, et al. Neonatal Abstinence Syndrome after Methadone and Buprenorphine Exposure. NEJM. 2010; 363(24): 2320-2331. • Kocherlakota P. Neonatal Abstinence Syndrome. Pediatrics 2014;134:e547–e561 • Hill M, Reed K. Pregnancy, breastfeeding, and marijuana: a review article. Ob and Gyn survey. 2013:69(10):710-8 • Stratherarn L, et al. Does breastfeeding protect against substantiated child abuse and neglect? A 15- year cohort study. Pediatrics. 2009:123(2):483-93 • Klonoff-Cohen H, Lam-Kruglick P. Maternal and paternal recreational drug use and sudden infant death syndrome. Arch Pediatr Adolesc Med. 2001;155:765-770

Thank you! Questions?