Improving breastfeeding 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 pregnancy 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

Date of download: 1/27/2015 Copyright © 2015 American Medical

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

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.

Figure Legend:

Date of download: 1/27/2015 Copyright © 2015 American Medical

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

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.

Figure Legend:

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

• Long-Acting Opioids – Fentanyl Transdermal Patch

– Oxymorphone or Oxycodone

hydrochloride extended-release

– Morphine sulfate extended-release

• Short-Acting Opioids – Hydrocodone

– Oxycodone

– Tramadol

– Fentanyl (IV) or Morphine (IV)

– Codeine

– Hydromorphone

• Frequency of NAS

depends on amount

and duration of

maternal use

• Onset and duration of

withdrawal depends on

half-life of the drug

• Approx 5-20%

experience NAS

Treatment for opioid addiction

Methadone

• -opioid receptor agonist

• Half Life 23-48 hours

• Typical dose is 20 to 120

mg per day

• Mean hospital stay for NAS

– 17.5 days

• Later onset and longer

withdrawal

Buprenorphine

• partial -opioid agonist

• Half-life 26-34 hours

• Mean hospital stay for NAS

– 10 days

• 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, alcohol, other respiratory

depressants

• Shorter duration of NAS

Onset, Duration, and Frequency of NAS

Opioids Onset

(hours)

Frequency

(%)

Duration

(days)

Heroin 24-48 40-80 8-10

Prescription

Opioids

36-72 5-20 10-30

Buprenorphine 36-60 22-67 Up to 28 or

more

Methadone 48-72 13-94 Up to 30 or

more

Infants Admitted for Observation for Neonatal Abstinence Syndrome

Admit to NICU:

NAS (Finnegan score) q 4 hr.

Implement non-pharmacologic

therapies

Observation and Monitoring:

NAS < 8 continue to monitor until safe for

discharge

NAS >8 times 2 implement therapy

Observation Period:

• Short acting prescription narcotics: 4 days

• Benzo + opiates: 4-7 days

• Heroin/methadone: 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

Admit to NICU:

NAS (Finnegan score) q 4 hr.

Implement non-pharmacologic therapies

Observation and Monitoring:

NAS < 8 continue to monitor until

safe for discharge

NAS >8 times 2 implement therapy

Observation Period:

• Short acting prescription narcotics: 4 days

• Benzo + opiates: 4-7 days

• Heroin/methadone: 5-7 days

• Suboxone: 5-6 days

CNS Signs and Symptoms

Excessive High Pitched Cry

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.

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 stools

Score if loose (curds/seedy

appearance) or watery stools

(water ring on nappy around

stool) are observed.

Score if at least one episode

of regurgitation is observed.

Vomiting

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

Score if more than three

sneezes are noted within

the scoring interval

Sneezing

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

(hours)

Advantages Disadvantages

Morphine 9 Shorter weaning

course

Frequent doses

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 Abstinence Syndrome

Exposure to long-acting

narcotics (see list below)

Admit to NICU

Exposure to multiple agents such as short-acting

narcotics in addition to benzodiazepines,

antipsychotics, nicotine, etc.

Admit to NICU

Not at risk/low risk for Neonatal Abstinence Syndrome

Exposure to methamphetamines

or THC

Admit to couplet care*

Exposure to short-acting narcotics without

multiple exposures

Admit to couplet care and observe for 4 days.

(No NAS Scoring by nursing) Call MD to assess if concern

for opioid withdrawal.

Exposure to antipsychotics, antidepressants (ie SSRIs), and

other medications.

Admit to couplet

care

*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.

Breastfeeding

Permitted for almost all mothers/infants at admission to FMCC or NICU.

Continued breastfeeding will be determined by medical team.

Contraindications to breastfeeding are positive HIV status, medications that are

Category L5, or confirmed on-going illegal drug use.

Long-Acting Opioids Fentanyl Transdermal Patch

Methadone Buprenorphine (Butrans, Subutex)

Oxymorphone hydrochloride extended-release (Opana) Oxycodone hydrochloride controlled-release (Oxycontin) Morphine sulfate extended-release (Oramorph, Kadian)

Short-Acting Opiods

Hydrocodone and Hydrocodone+APAP (Vicodin, Norco) Oxycodone+APAP (Percocet) or oyycodone IR

Tramadol Fentanyl (IV) or Morphine (IV)

Codeine Hydromorphone (Dilaudid)

Infants Admitted for Observation for Neonatal Abstinence Syndrome

Admit to NICU:

NAS (Finnegan score) q 4 hr.

Implement non-pharmacologic therapies

Observation and Monitoring:

NAS < 8 continue to monitor until safe for

discharge

NAS >8 times 2 implement therapy

Observation Period:

• Short acting prescription narcotics: 4 days

• Benzo + opiates: 4-7 days

• Heroin/methadone: 5-7 days

• Suboxone: 5-6 days

NAS Patient Characteristics and Outcomes

NAS Patient

Characteristics and Outcomes

2012 (May-July) n=4

2013 (Sept-Nov) n=6

2014 (June-Sept) n=6

Length of Stay(days) Median

94.5 31.5 32

DC on Meds 100% 67% 40%

Any BM 50% 67% 67%

BM at discharge 0% 17% 50%

Reason no BM at dc In treatment,

counseled to stop(3)

HIV positive (1)

Incarcerated (3)

In treatment,

relapse (2)

Incarcerated (2) Not provided (1)

Any Breastmilk(%) by Month Admitted

Breastmilk at Discharge (%) by Month Admitted

Median

Goal

0

10

20

30

40

50

60

70

80

90

100

Ma

y-

12

Jul-1

2

Se

p-

13

Nov-

13

Ma

y-

14

Au

g-

14

%

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

AAP Breastfeeding and the use of human milk. Pediatrics 2012

Condition Lower risk

Otitis Media 50%

Pneumonia 77%

Asthma 27%

RSV bronchiolitis 74%

NEC 77%

Eczema 27%

Gastroenteritis 64%

Inflammatory bowel

disease

31%

Obesity 24%

Celiac disease 52%

Type 1 diabetes 30%

Type 2 diabetes 40%

SIDS 73%

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

Thomas Hale, Medications and Mother’s Milk 2014

PEDIATRICS Vol. 132 2013 pp. e796 -e809

RID: relative infant dose =

Dose: infant mg/kg/day

____________________

Dose: mother mg/kg/day

If RID <10% considered safe for baby

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

1

UCSD Medical Center: WOMEN & INFANT SERVICES

POLICY/PROCEDURE TITLE:

BREASTMILK: DRUGS OF ABUSE, NARCOTICS AND USE OF HUMAN MILK

RELATED TO:

Medical Center Policy (MCP) Nursing Practice Stds.

JCAHO Patient Care Stds.

QA Other

Title 22

ADMINISTRATIVE CLINICAL PAGE 1 OF _

Effective date: 1/11 Revision date:

Review date:

Unit/Department of Origin: ISCC, FMCC Other Approval: Newborn Management, ISCC Core Group &

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’

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 Abstinence Syndrome

Exposure to long-acting

narcotics (see list below)

Admit to NICU

Exposure to multiple agents such as short-acting

narcotics in addition to benzodiazepines,

antipsychotics, nicotine, etc.

Admit to NICU

Not at risk/low risk for Neonatal Abstinence Syndrome

Exposure to methamphetamine

s or THC

Admit to couplet care*

Exposure to short-acting narcotics without multiple

exposures

Admit to couplet care and observe for 4 days.

(No NAS Scoring by nursing) Call MD to assess if concern

for opiod withdrawal.

Exposure to antipsychotics, antidepressants (ie SSRIs), and

other medications.

Admit to couplet

care

*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.

Breastfeeding

Permitted for almost all mothers/infants at admission to FMCC or NICU.

Continued breastfeeding will be determined by medical team.

Contraindications to breastfeeding are positive HIV status, medications that are

Category L5, or confirmed on-going illegal drug use.

Long-Acting Opioids Fentanyl Transdermal Patch

Methadone Buprenorphine (Butrans, Subutex)

Oxymorphone hydrochloride extended-release (Opana) Oxycodone hydrochloride controlled-release (Oxycontin) Morphine sulfate extended-release (Oramorph, Kadian)

Short-Acting Opiods

Hydrocodone and Hydrocodone+APAP (Vicodin, Norco) Oxycodone+APAP (Percocet) or oyycodone IR

Tramadol Fentanyl (IV) or Morphine (IV)

Codeine Hydromorphone (Dilaudid)

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 Cannabis 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 • Complicated by other exposures

• Baby may have mild withdrawal

• There may be long term neuro-

behavioral deficits for the child

• No increased risk of SIDS for

maternal use (+ for paternal use)

Lactation • THC does pass into milk

• Infant effects unclear due to

prenatal exposure as well in

almost all cases

• Theoretical risk milk supply in

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

• Tremors

• Exaggerated startle

response

• Increased hand to mouth

behavior

• High pitched cry

• Sleep cycle disturbance

• No reports of withdrawal

requiring treatment

• Described as “mild narcotic

withdrawal”

Neurodevelopment and Growth Effects

Fetal Development

• Mixed BW effects –

depends on exposure and

population

– Decreased growth and BW

after 2nd trimester exposure

– Decreased length after first

trimester exposure

• Decreased gestational age

• No definitive link to

congenital anomalies

Neonatal Development

• Increased tremors and

startles

• Differences in sleep

recordings

Neurodevelopment and Behavior

Infant/Toddler

• Mixed results – some show

no difference

• 18 months: more

inattention and aggression

• 36 months: decreased

short-term memory

function and verbal

reasoning

Child

• 6 years: increased

impulsivity and

hyperactivity

• 10 years: decreased

abstract and visual

reasoning, decreased

attention

• 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), cocaine, 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

Altered maternal caregiver

Socio-economic factors

Other toxin exposures

Prenatal THC exposure

Prematurity

Breastfed vs formula fed

Growth restriction

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

Altered maternal caregiver

Socio-economic factors

Other toxin exposures

Prenatal THC exposure

Prematurity

Breastfed vs formula fed

Growth restriction

Risk of obesity

Altered maternal child bonding

Lack of developmental benefits of mother’s milk

Increased risk of infections Increased risk of SIDS

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

– Heroin, morphine, codeine

• 1-2 days

– Hydromorphone,

oxycodone

• 2- 4 days

– Methadone

• 2-3 days

– Methadone metabolites

• up to 6 days

– Buprenorphine

• 2-3 days

• Marijuana

– Single Use

• 1- 3 days

– Moderate Use

• 5-7 days

– Heavy Use

• up to 10 days

– Chronic Heavy Use

• up to 30 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?