Understanding the scope of the opioid epidemic as it relates to

1. Opioid Dependency During
Pregnancy
David E. Abel, MD
UCSF-Fresno Resident Didactics
November 10, 2017

6. Opiate vs. Opioid
 Opiates derived from the opium poppy
 Opioids
– Used to be called “synthetic opiates”
– Active ingredients are chemically synthesized
 Opioid is used for the entire family
of opiates including natural, synthetic and
semi-synthetic

7. OPIATES OPIOIDS
Opium oxycodone
heroin hydrocodone
morphine hydromorphone
codeine fentanyl
All the above may be swallowed, injected,
nasally inhaled, smoked, chewed, or used
as suppositories.

8. Opioid Use Disorder
Definition1
 Repeated occurrence within a 12-month period
of 2 or more of 11 problems, including
withdrawal, giving up important life events in
order to use opioids, and excessive time spent
using opioids
 Mild (2-3 symptoms)
 Moderate (4-5 symptoms)
 Severe (≥ 6 symptoms)
1
DSM, 2013

9. Schuckit, NEJM.

10. Opioid Pharmacology
 Opioids activate specific transmembrane
neurotransmitter receptors
– Mu, kappa, delta (mu most studied)
– Located in CNS and PNS
 Once activated, these receptors couple G proteins
– this is why they are called G coupled-protein
receptors (GCPR’s)
 Once the G proteins are coupled, signal transduction
begins (intracellular communication) which affects
cAMP
 Opioid receptor SNP’s can reduce analgesia and
increase likelihood of dependence

11. Scope of the Problem
 Four people in the U.S. die every hour due
to an opioid overdose (2015)1
 More people die from overdoses than from
auto accidents
 Almost one-third of women of reproductive
age were prescribed an opioid in the
previous year2
1
Rudd et al.
2
Ailes et al.

12. Scope of the Problem
 In the U.S. over the past decade, opioid
use has quadrupled with 259 million
prescriptions in 20121
 80% of heroin users began with misusing
prescription opioids
1
CDC
2
Jones

13. Scope of the Problem
 In the past decade, fivefold increase in
neonatal opioid withdrawal syndrome
(NOWS)1
 Each year, since 2012,~22,000 neonates
born with NOWS in the U.S.2
– Translates to one neonate with NAS born
every 30 minutes
– Costs (hospital charges) approach $1.5
billion1
Patrick et al., J
Perinatol

14. Origin of the Problem
 In 1990’s, concerns about neglecting
patient’s pain, leading to overprescribing of
narcotics
 93% of those who undergo cesarean section
have leftover narcotics
– many unfamiliar with disposal techniques
 1 in 300 who undergo cesarean section
become a persistent user of opioids

15. Obstacles
 As of 2016, only 19 states have drug
treatment programs specifically targeted
to pregnancy1
 Only 12 states provide pregnant women
with priority access to state-funded drug
treatment programs
 Limited number of providers for
buprenorphine
1
Guttmacher

16. Risks of Untreated Heroin Addiction
During Pregnancy
 lack of prenatal care
 increased risk IUGR
 increased risk placental
abruption
 PTL
 IUFD
 meconium passage in-
utero
 STI’s
 prostitution
 loss of child custody
 incarceration

17. Symptoms of Opioid Withdrawal
 generalized pain
 muscle pain
 nausea
 diarrhea
 sweating
 rhinorrhea
 tearing
 dilated pupils
 tremor
 gooseflesh
 restlessness
 anxiety

18. Timing of Opioid Withdrawal
Symptoms
 Short-acting opioids (heroin)
– begin within 4–6 hours of use
– peak at 1–3 days
– gradually subside over 5–7 days
 Long-acting opioids (methadone)
– begin within 24–36 hours of use
– decrease by day 10
– may last for several weeks
 Opioid withdrawal rarely associated with
severe morbidity

19. Screening For Substance Abuse
During Pregnancy
 Clinical utility of standardized questionnaires
unclear
 Disagreement among professional societies
 Per USPSTF, insufficient evidence to evaluate
benefits and harms of screening
 ACOG recommends screening all women for
substance use before and during early
pregnancy and providing intervention when
needed

20. ACOG Comm
Opinion, 2017

21. Drug Screening
 Urine testing has high specificity and PPV
depending on the assay and opioid being tested
 Urine testing may not be able to distinguish
between occasional and regular use
 Short half-life of most substances and related
metabolites limits urine detection to recent use
only
 Negative test does not rule out substance use
(especially if sporadic)
 False-positive tests can occur

22. Drug Screening
 Urine should be performed with patient’s
consent in compliance with existing state
laws
 Before screening, patients should be
informed of potential consequences of a
positive test, including any mandatory
reporting requirements

23. Neonatal Opioid Withdrawal
Syndrome (NOWS)
 Also referred to as neonatal abstinence syndrome
(NAS)
 Hyperactivity of the CNS and ANS
 Incidence highly variable
– Up to 80% of opioid-exposed neonates require
pharmacologic intervention
 Optimal assessment of the neonate with NOWS not
been definitively established
 Current tools subjective in nature and designed to
assess term neonates
– Don’t apply well preterm or polysubstance-exposed

24. Neonatal Opioid Withdrawal
Syndrome (NOWS)
 All neonates born to women who use opioids
during pregnancy should be monitored for
NOWS for at least 5 days1
 Other substances such as nicotine, selective
serotonin reuptake inhibitors, and
benzodiazepines may increase incidence and
severity of NOWS
 Promote breastfeeding
1
American Academy of Pediatrics

25. Neonatal Opioid Withdrawal
Syndrome (NOWS)
 With methadone exposure:
– signs appear within 3–5 days of birth
– may appear as late as a week of age
– may last days to weeks and rarely months
 With buprenorphine exposure:
– signs appear within 12-48 hours of life
– peak at 72–96 hours
– resolve by 7 days of life

26. Signs of NOWS
 irritability
 high-pitched cry
 tremors
 hypertonia
 hyperreflexia
 sleep disturbances
 regurgitation, loose
stools,
 dysrhythmic
sucking/swallowing
 nasal stuffiness
 hyperthermia
 poor feeding
 weight loss
 tachypnea
 sweating
 sneezing
 yawning

27. Opioid Dependent Patients
Breastfeeding
 Decreased severity of NOWS
 Increased maternal confidence, stress reduction
 Enhanced maternal-child bonding
 Breastfed infants less likely to need pharmacologic
treatment for NOWS
 If infant treated for NOWS, breastfed infants require
lower doses of morphine, shorter LOS
 May enhance compliance with MAT
 AAP recommends breastfeeding for women
taking methadone or buprenorphine regardless
of the dose

28. Opioid agonist pharmacotherapy (medication-
assisted treatment) is the standard of care for
women with
opioid use disorder in pregnancy.
Both the World Health Organization and
the American Society of Addiction Medicine
support
methadone and buprenorphine as medication
treatment
options for pregnant women.

29. Opioid Agonist Therapy
During Pregnancy
 Lower risk of maternal relapse to street drugs
 Improved compliance with prenatal care
 Improves adherence to prenatal care and addiction
treatment programs
 No increased risk of congenital anomalies
 In combination with prenatal care, appears to
reduce the risk of adverse outcomes
 Risk of NOWS 30-80%
The potential benefits outweigh the risk of NOWS

30. Methadone
 Complete mu agonist
 Better option for women with longstanding multi-
substance abuse and previous failed attempts at
detoxification
 No established relationship between dose
and NOWS
– Increase as necessary to prevent relapse and
withdrawal
 Usually need increased dosing during pregnancy

31. Methadone
 Dose usually started at 10-20 mg/d
 Almost 50% require a low dose (<60 mg/d)
 High dose considered >90 mg/d
 Often need bid dosing

32. Buprenorphine
 Partial mu agonist, kappa receptor antagonist
– Higher affinity but lower activity than complete
agonists (i.e. methadone, heroin)
– Longer duration of action than methadone
 Reduced risk of overdose
 Ceiling effect for respiratory depression-32 mg
 As with methadone, may require dose increases
as pregnancy progresses
 Administered sublingually

33. Buprenorphine Advantages
 Reduced risk of overdose compared to methadone
 Lower NOWS risk
 Less morphine required to treat NOWS
 Allows for outpatient treatment
 Less stigma
 Buprenorphine-exposed neonates had higher mean
gestational age, weight, length, and head
circumference at birth1
 Fewer women treated with buprenorphine used illicit
opioids near delivery1
1
Brogly et al.

34. Buprenorphine Disadvantages
 Lack of long-term data on infant and child outcomes
 Nonsignificant yet clinically important dropout rate
resulting from dissatisfaction with the drug
 More difficult induction
 Potential risk of precipitated withdrawal
 Reports of hepatic dysfunction
– Recent data refutes this

Significant pharmacokinetic interactions (i.e. ART)
 Inappropriate for some who require more intensive
counseling and supervision

35. Buprenorphine/Naloxone
 Administered sublingually or as a film
(sublingual or buccal) in 4:1 ratio
 Naloxone added to prevent diversion and
IV administration
– Limited availability bioavailability SL
– Active when IV-can precipitate withdrawal
 Usually not administered during pregnancy
• Some data suggests less NAS compared to
methadone1
1
Wiegand et al.

36. NIH Executive Summary, 2017

37. Medically Assisted Withdrawal
(Detoxification)
 Currently not recommended
 No good data supporting link to IUFD and PTB
 No good long-term data
 Higher relapse rate (59-90%)1
 No reported decrease in NOWS2
 Limited resources
1
Saia et al., Curr Obstet Gynecol
Rep

38. Intrapartum Pain Management
General Principles
 Regional anesthesia preferred
– May have reduced effectiveness if short-acting
opioids also used
– May need higher doses of local anesthetic
– Non-opioids (i.e. clonidine) may be helpful
 Can use short-acting opioids
– Especially if cannot tolerate regional anesthesia
 Avoid mixed agonists/antagonists (butorphanol,
nalbuphine, pentazocine)-can precipitate
withdrawal

39. Patient on Methadone Maintenance
Intrapartum Pain Management
 Continue maintenance dosing while in
hospital
 May require higher doses of local
anesthetic for regional anesthesia

40. Patient on Buprenorphine
Maintenance
Intrapartum Pain Management
 Two options
– Discontinue when arrives on L&D
• substitute with long-acting opioid (MS contin,
fentanyl patch) or short-acting opioid
(immediate release hydrocodone or
oxycodone)
• good option for planned cesarean section
 Administer buprenorphine in divided doses
(every 6 hours at 25% of maintenance dose to
maximize analgesic effects
NIH Executive Summary

41. Postpartum Pain Management
General Principles
 Women maintained on methadone or
buprenorphine often experience more pain after
vaginal and cesarean delivery
 Require more opioid analgesia after cesarean
delivery than women in a control group
– Especially true for buprenorphine (partial mu
agonist)
 Treatment of acute postsurgical pain for patients
on methadone is not a risk factor for relapse (non-
pregnant data)

42. Opioid Dependent Patients
Postpartum Pain Management
 Vaginal delivery
– NSAID’s, ice packs, analgesic creams
– Acetaminophen (avoid if hepatitis C positive)
 Cesarean section
– Consider PCA
– Choose hydrocodone over oxycodone
 Watch for oversedation
 Avoid sedating drugs that may cause respiratory
depression (benzodiazepines, zolpidem)
 Prescribe limited quantities, taper when possible,
adding in NSAID’s

43. Opioid Dependency in Pregnancy
Summary
 Still a lack of evidence on long-term effects of prenatal
opioid exposure
 Many gaps in knowledge
 Many other needs/issues to address
– increased rates of co-occuring mental health disorders
– history of sexual abuse
– history or polydrug use
– limited social supports
– chronic illnesses
– poor nutrition

44. Opioid Dependency in Pregnancy
Summary
 Screen as indicated for STI’s
 Screen for hepatitis C/HIV, low threshold to repeat
in third-trimester
 Know your state laws re: drug testing/mandatory
reporting
 Help create a standardized plan re: monitoring of
both mom and baby (peds/NICU, nurses, social
workers, CNM’s, ob/gyn, MFM)
 Try not to be “punitive”

45. Opioid Dependency in Pregnancy
Summary
 Antepartum testing not indicated
– If done, perform if possible 4-6 hours after methadone
dose
 NICU/peds and anesthesia consults
 Early epidural
 Continue MAT in hospital
 Encourage breastfeeding
 Prescribe less after cesarean section
 Consider prescribing naloxone kit for a
relative/caregiver

46. https://www.justthinktwice.gov/video-chasing-
dragon-life-opiate-addict

47. Opioid Treatment Program
Directory
http://dpt2.samhsa.gov/treatment/dire
ctory.aspx

48. Final Thoughts………
“It is important to advocate for this often
marginalized group
of patients, particularly in terms of working to
improve
availability of treatment and to ensure that pregnant
women with opioid use disorder who seek prenatal
care are not criminalized.”
ACOG Comm Opinion
“Obstetric care providers have an ethical
responsibility to their pregnant and parenting
patients with substance use disorder to discourage
the separation of parents from their children solely
based on substance use disorder, either suspected or
confirmed.”

49. Thank you for your attention!
Dabel@fresno.ucsf.edu