Caring for Infants with Neonatal Abstinence Syndrome and their Families 4-year experience from a -year experience from a Primary Service Area in MainePrimary Service Area in Maine

Acadia Hospital Grand RoundsApril 13, 2012

Mark S Brown MD MSPHEastern Maine Medical Center

Pediatrics and Neonatology

Roadmap Where are we going today? Looking at the scope by the numbers Looking at the development of the infrastructure of a

comprehensive NAS Program Prenatal counseling Who gets screened Confounders of withdrawal Assessment of withdrawal – Scoring system Treatment

Dropping routine phenobarbital use Methadone versus morphine Understanding variation in NAS treatment

Breast feeding Importance of transitions to the community – an aftercare safety

net The continued challenge: Can we change their Legacy

A Role for Infant Mental Health through enhancing attachment and individualized infant sensitivity?

I HAVE NO FINANCIAL DISCLOSURES

OR CONFLICTS OF INTEREST

TO DECLARE

The HeadwatersNarcotic Replacement Therapy during Pregnancy

• Methadone– Long acting – Prescribed daily

• Usually in liquid form• Earn take-homes for up to a

week

– No ceiling effect• Better for those coming into

treatment during pregnancy

– Agonist– Recommendation to

NOT wean during pregnancy

• Buprenorphine– Longer acting

• Subutex and Suboxone

– Prescribed for up to 30-day take-homes

• IV, strips, and sublingual forms

– Ceiling effects on euphoria and respiratory depression

• Better for those already on treatment before pregnancy

– Agonist – antagonist• Tight binding to μ receptor

– Recommendation to NOT wean during pregnancy

The Downstream Impactis on Healthcare Resources and Family

69%

51%

23%

55%

0%

20%

40%

60%

80%

Methadone Buprenorphine Prescribed Opiates Illicit

Treatment Rate by Prenatal Opioid Exposure for Newborns Admitted to EMMC

>36 weeks, Nov 2007 - Nov 2011, N = 494

26.3

20.8

15.1

19.4

0

10

20

30

Day

s

Methadone Buprenorphine PrescribedOpiates

Illicit

Length of Stay when Treated by Prenatal Opioid Exposure

>36 weeks, Nov 2007-Nov 2011, N = 263

Treatment of Neonatal Abstinence Syndrome• Non-pharmacologic:

– Higher calorie nutrition to maintain weight gain within tolerance

– Minimal stimulation environment– Swaddling/bundling– Rooming in

• Pharmacologic:– Phenobarbital – sedative not an opiate replacement

• Does not treat gastrointestinal symptoms (cramps, vomiting or diarrhea)

– Morphine– Methadone – Buprenorphine – not FDA approved– Clonidine – alpha agonist– NO Paregoric (contains many toxins)

US and UK Surveys about Treatment of NAS:US N=75/102 and UK N = 215/235

0%

25%

50%

75%

100%

Non-m

ethad

one o

piate

s

Met

hado

ne

Pheno

barbi

tal

Chlora

l hyd

rate

Benzo

Medications for First Line Treatment of NAS from Prenatal Opiate Exposure

US 2006 UK 2008

EMMCNICU Pediatrics

BackgroundLet’s Look at the

Numbers

What’s the Trickle-down of the Increase in Replacement Therapy for Mothers?

Metro Clinic Opens 10/2005

Discovery HouseOpens 9/2007

Acadia Clinic Opens 2001

24 26

50 55

75

94

139154 159

0

25

50

75

100

125

150

175

2003 2004 2005 2006 2007 2008 2009 2010 2011

Annual Admissions of Opioid-Exposed Newborns to Eastern Maine Medical Center

42%

32%

17%

9%

0%

10%

20%

30%

40%

50%

Methadone Buprenorphine Prescribed Opiates Illicit

Distribution of Opioid-Exposed Newborns Admitted to EMMC by Opioid Category

Nov 2007 - Nov 2011, N = 568

Buprenorphine released Oct 2002

Buprenorphine patient limits

go from 30 to 100

0

20

40

60

80

100

120

140

2005 2006 2007 2008 2009 2010 2011

Prenatal Methadone and Buprenorphine Exposures for Newborns Admitted to EMMC

2005-2011

Methadone Buprenorphine

MOTHERS Trial published

Dec 2010

21.6%

10.5%

19.1%

42.3%

10.3%

0%

10%

20%

30%

40%

50%

Methadone Buprenorphine PrescribedOpiates

Illicit Maine 2008

Prematurity Rate (<37 weeks) for Opioid-Exposed Newborns Admitted to EMMC

Nov 2007 - Nov 2011, N = 111/568

What Issues Have We Taken Care Of?• Who gets screened upon admission to

L&D?• What do we know about confounders

to opiate withdrawal?• Trying to achieve consistency with our

withdrawal scoring tool• Challenging “conventional treatment”

– a change from phenobarbital-first to methadone-first

• Should mothers be encouraged to breast feed and under what circumstances?

38%

46%

31%

0%

20%

40%

60%

Methadone Buprenorphine Prescribed Opiates

Breast Milk on Day 5 by Prenatal Opioid Exposure for Newborns Admitted to EMMC, >36 weeks

Nov 2007 - Nov 2011, N = 456

76%

56%

67%

31%

45%

20%

0%

20%

40%

60%

80%

Methadone Buprenorphine Prescribed Opiates

Treatment Rate by Prenatal Opioid Exposure and Feeding Choice on Day 5 for Newborns Admitted to EMMC

>36 weeks, Nov 2007-Nov 2011, N = 494

Formula day 5 & Treated Breast milk day 5 & Treated

27.3

23.9

22.1

17.515.8

11.2

0

10

20

30

Da

ys

Methadone Buprenorphine Prescribed Opiates

Length of Stay when Treated by Prenatal Opioid Exposure and Feeding Choice on Day 5 for Newborns Admitted to EMMC

> 36 weeks, Nov 2007-Nov 2011, N = 263

LOS with Formula day 5 & Treated LOS with Breast milk day 5 &Treated

*

±

What Issues are We Currently Taking Care of?• Prenatal Counseling• Challenging “conventional treatment” –

comparing methadone-first to morphine-first

• Why is there such a response variation to treatment?

• What are the determinants for longer term developmental outcome?

• What is the feedback from parents about their experience?

• Working on transitions and aftercare for the newborn and family – Linking

Prenatal Counseling• Preparing the parents for experience of the opiate-

exposed newborn– No one likes surprises – especially unanticipated ones with

your baby• Group meeting

– Acadia, Discovery House, Metro Clinic, Open Door Recovery Center

• Individual or small groups• Topics covered

– Don’t wean off opiate replacement medication during pregnancy

– Importance of supportive care and attachment for the baby– Length of stay – 5-day observation and criteria for treatment– Helpful hints in getting along with staff – e.g., don’t sleep

with baby or fall asleep with baby, do what you say you will do

– Breast feeding• Potential for judgment – family and staff

What Issues Are We Taking Care of?

• Prenatal Counseling• Challenging “conventional treatment”

comparing methadone-first to morphine-first– This is a double-blinded, randomized

protocol – 22 babies entered 1st year

• Response to treatment variation• Longer term developmental outcome• Feedback from parents• Transitions and aftercare of Newborn and

Family

What Issues Are We Taking Care of?

• Prenatal Counseling• Challenging “conventional

treatment” comparing methadone-first to morphine-first

• Response to treatment variation• Longer term developmental outcome• Feedback from parents• Transitions and aftercare of

Newborn and Family

Addiction• There are at least 3 different categories of

factors that contribute to the vulnerability to develop addiction:– Environmental factors – cues, external

stressors (e.g., ACEs)– Drug-induced factors that lead to

neurobiological changes - neuroadaptation– Genetic factors – these represent

approximately 40 to 60% of the risk to develop addiction

Opiate Genetics – A SNiP of Information about NAS Treatment

• Why do some newborns get treated for withdrawal and others don’t despite same prenatal exposure and dose?

• Why do some newborns get treated with a 2nd drug and others don’t?

• What is the source of this wide variation?• Domains of Opiate Neurobiology on which to

focus– μ-Opioid receptor– Membrane transport of opiates into the brain– Potentiating pleasure pathways such as dopaminergic

“Exploring the source of variation is fertile soil in which to sow our seeds of ignorance”

Opiate Genetics Single Nucleotide Polymorphisms A single-nucleotide

polymorphism (SNP) is a DNA point mutation for which alternative paring occurs

The sequence variation occurs when a single nucleotide — Adenosine, Thymine, Cytosine or Guanine — is replaced in the genome and can cause a functional change in the protein for which it codes

Opiate Genetics Single Nucleotide Polymorphisms

SNP of 118A→G in the opiate receptor (OPRM1) has been associated with reduced opiate effectiveness in the variant Correlated with increased rates of opioid

dependence SNP of 472G→A catechol-O-

methyltransferase (COMT) results in a 4-fold decrease in activity of metabolism of dopamine transmitter. Correlated with the ability to experience reward

Single Nucleotide Polymorphisms and Variability in Severity of Neonatal Abstinence Syndrome

EM Wachman1*, MS Brown2, BA Logan3, NA Heller3, H O Kasaroglu1, T Marino4, JM

Davis1, and MJ Hayes3

1Neonatology, Tufts Medical Center; 2Neonatology, Eastern Maine Medical Center; 3Psychology, Univ Maine; 4OB/Gyn, Tufts Medical CenterAbstract for Society for Pediatric ResearchAbstract for Society for Pediatric ResearchBoston May 2012Boston May 2012

Candidate Genes for NAS μ-Opioid Receptor (OPRM1) = Site of Action

A118G SNP Multi-Drug Resistance Gene (MDR1) = Transporter

G2677T SNP C1236T SNP C3435T SNP

Catechol-O-methyltransferase (COMT) = Modulator A158G SNP (Val158Met)

Lotsch J, et al. Clin Pharmacokinet, 2004; Yuferov V, et al. Ann NY Acad Sci, 2010; Reyes-Gibby CC, et al. Pain, 2007.

Question Are SNPs in the OPRM1, MDR1, and COMT

genes associated with treatment and length of stay in opiate-exposed newborns?

N = 26 newborns GA >36 weeks Methadone 70%, buprenorphine 30% Blood or saliva samples for DNA 54% Treated for NAS

OPRM1 – Treatment for NAS

68% vs 18% χ² = 4.34; p<0.05 *

0%

20%

40%

60%

80%

100%

AA AG/GG

GENOTYPE

* n=20 n=6

OPRM1 – Length of Hospital Stay

Mean 24.5 vs 8.8 days p=0.006 *

0

5

10

15

20

25

30

35

AA AG / GGGENOTYPE

DA

YS

*

n=20n=6

COMT – Length of Hospital Stay

Mean 34.3 vs 16.9 days p<0.05 *

0

10

20

30

40

50

60

AA AG/GG

GENOTYPE

DA

YS

* n=6 n=20

Conclusions SNPs in the OPRM1 and COMT

genes affect the incidence and severity of NAS

Infants with the minor allele present in the OPRM1 A118G and COMT A158G demonstrated a milder phenotype vs. homozygotes for the major allele

What Issues are we Taking Care of?

• Prenatal Counseling• Challenging “conventional

treatment” comparing methadone-first to morphine-first

• Response to treatment variation• Longer term developmental

outcome• Feedback from parents• Transitions and aftercare of

Newborn and Family

What do parents tell us that they are worried about?• That they will be judged – “methadone mother”

– By Providers– By their own family

• Lack of understanding by those in charge of services they need– WIC– Shelters– Transportation often based on NTP and are not available to EMMC– Barriers to frequent hospital visitations

• Babies will be stigmatized – “methadone baby”• Birth defects during pregnancy• Is my baby going to be normal?• Terrified of losing baby to DHHS even though they have done

the “right things”• Knowing how to do the NAS scoring ‘right’• Feeling that they can never do enough according to some

nursing staff

What works well for them?

• Prenatal groups at narcotic treatment programs• Participation in research about infant

development• Public Health Nursing in the home• Advanced notice of CAPE involvement• Maine Families• Gas cards, taxi vouchers, housing• Some providers that are very respectful – being

listened to and validated concerns

What Issues are we Taking Care of?• Prenatal Counseling• Challenging “conventional treatment”

comparing methadone-first to morphine-first

• Response to treatment variation• Longer term developmental outcome• Feedback from parents• Transitions and aftercare of

Newborn and Family – Penquis District Linking Group

Penquis District Linking Project

• Began community-based meetings in November 2010• Goal has been:

– “To link families of substance-exposed newborns – aged from prenatal to preschool age in Penobscot and Piscataquis counties – to a well coordinated system of care to optimize their social developmental and medical well being.”  

• Conference planned in the Fall 2012• Seeking funding for Coordinator and focus groups

What Issues do we Need to Take of?

• Formalize the transitions work with parents– Synchronizing mother and infant to each other allow

the mother to appropriately respond to the infant’s needs within the context of the mother’s own sphere of limitations.

• Continue to expand Linking Project for aftercare of Newborn and Family – funding, coordinator

• Update NAS scoring• Move the inpatient treatment to an outpatient

setting• Extend long-term developmental assessments to

learn more about permutations that impact the newborn’s developmental plasticity

Lessons Learned• Support the mother’s recovery • Build trust of the parent(s) and their support

– The health care setting is often a black hole of judgment and criticism for those in recovery

– Consistency, consistency• Caregivers, treatment

– Predictability – plan of care, length of treatment, endpoints

– Accountability – do what you say you will do– Informal networks

• Variation in parental and newborn opiate genetics account for half of the variation in addiction and newborn response to treatment

• Ultimate focal point is to enhance attachment to improve family outcomes

Roadmap Where have we been? Looking at the scope by the numbers Looking at the development of the infrastructure

of a comprehensive NAS Program Prenatal counseling Who gets screened Confounders of withdrawal Assessment of withdrawal – Scoring system Treatment

Dropping routine phenobarbital use Methadone versus morphine Understanding variation in NAS treatment

Breast feeding Importance of transitions to the community – an aftercare safety

net The continued challenge: Can we change their Legacy

A Role for Infant Mental Health through enhancing attachment and individualized infant sensitivity?

The Window of the “Learning Moment” for the Mother is the Cornerstone for Attachment

Key Resources• Maine Office of Substance Abuse

2010 data– http://www.maine.gov/dhhs/osa/– http://www.maine.gov/dhhs/osa/data/p

ubrpts.htm

• CDC Website with Information about ACEs– http://www.cdc.gov/ace/index.htm