EMMC NAS Program Database Summary
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Transcript EMMC NAS Program Database Summary
Caring for Infants with Neonatal
Abstinence Syndrome and their
Families
4-year experience from a
Primary Service Area in Maine
Acadia Hospital Grand Rounds
April 13, 2012
Mark S Brown MD MSPH
Eastern 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 Headwaters
Narcotic Replacement Therapy during Pregnancy
• Methadone
• Buprenorphine
– 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
– 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 Impact
is on Healthcare Resources and Family
Treatment Rate by Prenatal Opioid Exposure
for Newborns Admitted to EMMC
>36 weeks, Nov 2007 - Nov 2011, N = 494
80%
69%
55%
60%
51%
40%
23%
20%
0%
Methadone
Buprenorphine
Prescribed Opiates
Illicit
Length of Stay when Treated
by Prenatal Opioid Exposure
>36 weeks, Nov 2007-Nov 2011, N = 263
30
26.3
20.8
20
19.4
Days
15.1
10
0
Methadone
Buprenorphine
Prescribed
Opiates
Illicit
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
Medications for First Line Treatment of NAS from Prenatal Opiate Exposure
100%
75%
50%
25%
US 2006
UK 2008
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0%
EMMC
NICU
Pediatrics
Background
Let’s Look at the
Numbers
What’s the Trickle-down of the Increase in
Replacement Therapy for Mothers?
Annual Admissions of Opioid-Exposed Newborns
to Eastern Maine Medical Center
175
154
150
Discovery House
Opens 9/2007
125
Metro Clinic
Opens 10/2005
100
139
94
Acadia Clinic
75 Opens 2001
75
50
25
159
24
26
2003
2004
50
55
2005
2006
0
2007
2008
2009
2010
2011
Distribution of Opioid-Exposed Newborns Admitted to EMMC
by Opioid Category
Nov 2007 - Nov 2011, N = 568
50%
42%
40%
32%
30%
17%
20%
9%
10%
0%
Methadone
Buprenorphine
Prescribed Opiates
Illicit
Prenatal Methadone and Buprenorphine Exposures
for Newborns Admitted to EMMC
2005-2011
MOTHERS Trial published
Dec 2010
140
Buprenorphine patient limits
go from 30 to 100
120
100
80
Buprenorphine released
Oct 2002
60
40
20
0
2005
2006
2007
Methadone
2008
2009
Buprenorphine
2010
2011
Prematurity Rate (<37 weeks)
for Opioid-Exposed Newborns Admitted to EMMC
Nov 2007 - Nov 2011, N = 111/568
50%
42.3%
40%
30%
21.6%
19.1%
20%
10.5%
10.3%
10%
0%
Methadone
Buprenorphine
Prescribed
Opiates
Illicit
Maine 2008
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?
Breast Milk on Day 5 by Prenatal Opioid Exposure
for Newborns Admitted to EMMC, >36 weeks
Nov 2007 - Nov 2011, N = 456
60%
46%
38%
40%
31%
20%
0%
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
80%
76%
67%
60%
56%
45%
40%
31%
20%
20%
0%
Methadone
Buprenorphine
Formula day 5 & Treated
Prescribed Opiates
Breast milk day 5 & Treated
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
30
±
27.3
*
23.9
22.1
20
17.5
Days
15.8
11.2
10
0
Methadone
Buprenorphine
LOS with Formula day 5 & Treated
Prescribed Opiates
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-Omethyltransferase (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 Center
Abstract for Society for Pediatric Research
Boston 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
100%
80%
60%
40%
20%
n=6
n=20
*
0%
AA
AG/GG
GENOTYPE
68% vs 18% χ² = 4.34; p<0.05 *
OPRM1 – Length of Hospital Stay
35
30
DAYS
25
20
*
15
10
5
n=6
n=20
0
AA
GENOTYPE
AG / GG
Mean 24.5 vs 8.8 days p=0.006 *
COMT – Length of Hospital Stay
60
50
DAYS
40
30
20
10
*
n=6
n=20
AA
AG/GG
0
GENOTYPE
Mean 34.3 vs 16.9 days p<0.05 *
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