Transcript to view Dr. O'Connor's slides

Alane B. O’Connor DNP, FNP
Faculty, Maine Dartmouth Family Medicine Residency
Adjunct Instructor, Dartmouth Medical School
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I do not have any real or apparent conflict(s)
of interest that may have a direct bearing on
the subject matter of this education program.
Use of buprenorphine while breastfeeding is
off label.
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Brief introduction to buprenorphine, scope of
opioid addiction problem, particularly during
pregnancy.
Latest data on use of buprenorphine during
pregnancy.
Breastfeeding rates at MDFMR; potential impact
of breastfeeding on neonatal abstinence
syndrome.
Challenges of monitoring/caring for infants born
to mothers taking more than one substance that
can cause a withdrawal syndrome.
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FDA approved (2002) medication for the treatment of
opioid dependence.
◦ Partial agonist for mu opioid receptor; high affinity, low
activity.
◦ Monotherapy during pregnancy; dissolved sublingually.
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MAT recommended for opioid dependence during
pregnancy, fetal risk of intoxication/withdrawal.
◦ Methadone is standard of care during pregnancy.
◦ If methadone is refused or unavailable, buprenorphine is an
alternative (US SAMHSA).
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Infants exposed to opioids during pregnancy are at
risk for neonatal abstinence syndrome (NAS).
◦ Finnegan scoring system.
◦ Irritability, tremors, poor feeding/sleeping, GI distress,
respiratory complications.
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11% of women of childbearing age used illicit
drugs in the past month.
◦ 4.5% of all pregnant women.
◦ Pregnant teens at greatest risk (16% ).
◦ May be as high as 25%.
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Maine leads the US (8x national average) in
per capita rate of residents seeking treatment
for addiction to painkillers.
Maine: 165 DABs in 2005, 667 DABs in 2011.
More Mainers die of drug overdose than in
automobile accidents.
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First delivery December 2007; more than 70
deliveries since.
Prenatal, intrapartum, postpartum care for
mom; care for infants in hospital and after
birth.
Integrated care model.
◦ Offer medical care, MAT with buprenorphine and
psychological care in one setting.
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Research approved by MaineGeneral IRB.
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Ethical considerations of studying drug
dependent pregnant women.
Limited data available about buprenorphine
during pregnancy.
Measuring opioid use:
◦ urine toxicology;
◦ self-report.
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Polysubstance use.
◦ Paying for negative urine drug screens.
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Impact of poverty, poor nutrition, lack of
access to prenatal care on outcomes.
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Few randomly controlled trials.
◦ 3 randomized controlled studies (2 of 3 had fewer than 10
women).
◦ MOTHER :
 175 opioid dependent pregnant women in 8 sites (58 delivered
on buprenorphine).
 Double-blind, double-dummy, flexible-dosing, randomized,
controlled study comparing buprenorphine to methadone.
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Prospective studies (US, Europe).
 Only 1 with more than 100 women delivering on buprenorphine.
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Case reports and retrospective chart reviews.
 O’Connor A, Alto W, Musgrave K, et al. Observational study of
buprenorphine treatment of opioid-dependent pregnant women in a family
medicine residency: Reports on maternal and infant outcomes. Journal of
the American Board of Family Medicine. 2011;24(2):194-201.
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MOTHER:
◦ No significant differences in 6 maternal outcomes :
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Weight gain.
Number of OB visits.
Incidence of cesarean section.
Abnormal presentation of fetus.
Use of analgesia during delivery.
Positive urine drug screen at delivery.
◦ Maternal methadone exposure associated with:
 Increased incidence of non-serious medical events
(variations HR, BP).
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MOTHER:
◦ Fetuses (32-35 wks): methadone condition showed
more motor activity suppression, shorter duration
movements than buprenorphine condition.
◦ Fetuses (31-33 wks): higher incidence of nonreactive non-stress tests for methadone group vs.
buprenorphine group.
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Long term implications unknown.
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MOTHER:
◦ When compared to buprenorphine, infants exposed
to methadone had:
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More severe NAS: Peak NAS score 12.8 vs. 11.0;
Longer duration NAS treatment: 9.9 days vs. 4.1 days;
Longer overall hospitalization: 17.5 days vs. 10.0 days;
Required more morphine for NAS treatment:10.4 mg
vs. 1.1 mg.
◦ No significant difference in number of infants
treated for NAS (57% methadone vs. 47%
buprenorphine).
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Treatment of opioid dependent pregnant women
must be individualized.
◦ Comprehensive: medical (OB, pediatric), psychological
care, social services, public health nursing, etc.
◦ Risk-benefits of methadone, buprenorphine.
◦ Previous recovery attempts, successes.
◦ Patient preference (informed consent).
◦ Polysubstance use.
◦ Inpatient vs. outpatient buprenorphine initiation.
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Pregnancy, substance abuse outcomes improved
when care provided in same setting.
Buprenorphine first line therapy?
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Very limited previous literature.
Appears safe.
◦ US DHHS “not contraindicated,” “use professional
judgment.”
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Likely minimal infant exposure.
◦ Concentration breast milk similar to maternal
serum levels but poor bioavailability.
◦ Relative ingestion per kg of infant body weight less
than 1% of dose per kg weight mother.
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Lack of professional recommendations leads
to inconsistencies across institutions:
◦ Negative urine toxicology at admission?
◦ No evidence of illicit drug use in third trimester?
◦ Maternal intoxication at birth (pump and dump first
feed only)?
◦ “Abuse of narcotics” not contraindication to
breastfeeding?
◦ Decision should be on case by case basis after
weighing benefits and risks if mother is not able to
remain abstinent?
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Breastfeeding okay if:
◦ Engaged in substance abuse treatment;
◦ Received consistent prenatal care;
◦ Abstained from illicit substance use in 90 days prior to
delivery.
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Breastfeeding NOT okay if:
◦ Not engaged (or planning to engage) in substance abuse
treatment;
◦ Relapsed in the 30 days prior to delivery.
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???:
◦ Relapsed in the 30 to 90 days prior to delivery;
◦ Recently entered treatment;
◦ Maintained sobriety only in an inpatient setting.
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Historically, opioid dependent pregnant
women have low rates of breastfeeding.
3 previous studies with breastfeeding rates:
◦ 50% (Fischer et al., 2006);
◦ 45% (Wachman et al., 2010);
◦ 21% (Lejeune et al., 2006).
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At MDFMR, 78% breastfed at delivery, 65%
still breastfeeding at 2 months.
Significantly more likely to breastfeed at
delivery (p<.001) than those previously
studied.
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Born at Baby Friendly Hospital?
◦ Only 45% at BMC, also Baby Friendly.
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Women in Maine more likely to breastfeed?
◦ 73.5% compared to US rate 74.6%.
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Unique integrated medical behavioral health
model?
◦ Maybe. Reduces barriers to breastfeeding
hypothesized by other authors.
◦ Superb support of nurses/lactation consultants.
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Less restrictive policy than other institutions.
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52 maternal-infant pairs:
◦ 41 breastfeeding, 11 non-breastfeeding.
◦ Method by choice, except 1 maternal-infant pair.
◦ No differences in exposure to other substances that may
cause withdrawal syndrome: illicit substances, tobacco,
antidepressants.
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Breastfeeding infants:
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But not significant (small number of non-breastfed
infants = larger standard error than expected).
◦ Less likely to require NAS treatment (27% vs. 45%, p=.204).
◦ Less severe NAS (9.5 vs. 10.4, p=.390).
◦ Experienced NAS resolution earlier (68.6 hrs vs. 82.0 hrs,
p=.359).
◦ No difference in infant length of hospitalization.
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No previous literature to compare to:
◦ One poster (Brown et al., 2011):
 49% (36/73) of women on buprenorphine breastfeeding.
 36% of breastfeeding infants required NAS treatment vs. 68%
of non-breastfed infants, (p=.007).
 No information about polysubstance use.
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Breastfeeding can be abruptly discontinued.
Difficult to distinguish potential breastfeeding
effects from non-pharmacologic NAS
interventions that accompany breastfeeding (e.g.,
swaddling, enhanced skin-to-skin contact).
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Finnegan scoring system only validated for use in
opioid withdrawal.
Many substances can cause a withdrawal
syndrome in infants.
◦ High rates of polysubstance use (75%) including illicit
opioids, amphetamines, cocaine, marijuana, bath salts.
 Challenges properly assessing this use.
◦ Majority of women in treatment for opioid dependence
(64%) have one or more psychiatric diagnosis beyond
opioid dependence.
◦ Majority of women (81%) use tobacco during pregnancy.
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Complications of selecting NAS treatment
medication.
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High rate of concurrent substance abuse and
mental health diagnoses.
Depressed pregnant women who are not treated
at risk for poor outcomes.
◦ Decision is based on risk-benefit assessment.
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No randomized, controlled trials assessing
efficacy and safety of antidepressant drugs
during pregnancy.
30% of infants exposed to SSRIs in 3rd trimester
experience withdrawal syndrome:
◦ Irritability, tremor, constant crying, shivering, GI
disturbances, increased tonus, eating/sleeping
difficulties, and convulsions.
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52 maternal-infant pairs:
◦ 6 exposed to antidepressants third trimester, 46
not exposed.
 3 sertraline, 1 each on bupropion, trazodone,
amitriptyline.
◦ No differences in exposure to other substances that
may cause withdrawal syndrome: illicit substances,
tobacco, maternal dose**.
◦ Infants exposed to antidepressants in utero more
likely to be preterm (3/6 vs. 4/46, p=0.026).
 Impact of concurrent use?
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52 maternal-infant pairs (cont’d):
◦ No difference in NAS severity (p=.737).
◦ No difference in NAS treatment rate (p=.608)
◦ No significant difference in length of hospitalization
(p=.218) though longer in those exposed to both (9
days vs. 6.9 days).
◦ Time to NAS resolution significantly longer in
infants exposed to both buprenorphine and
antidepressants (101 hrs vs. 68 hrs) (p=.034).
 Why? Shared metabolic pathway in the liver? Variations
in placental transfer of substances?
◦ Longer NAS resolution not related to being preterm.
15
Peak NAS Score
10
Antidepressant
exposure only
Buprenorphine
exposure only
Buprenorphine and
antidepressant
exposure
5
0
0
24
48
72
Time to Last Peak NAS Score (hours)
96
120
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Ideally more RCTs.
Larger samples to investigate relationship
between breastfeeding and NAS as well as
concurrent use of buprenorphine and
antidepressants.
Integrated assessment tool that can reliably
differentiate between prenatal exposure to
opioids vs. variety of other substances that cause
withdrawal syndromes.
Standardized, evidenced based treatment
protocol for NAS including pharmacologic
approaches.