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Opioid Use Disorder in Pregnancy

Hemant Satpathy, MD

Evening of Perinatology

November 5th, 2018

No Disclosures Objectives

• Identify the scope and prevalence of opioid use in pregnancy and the postpartum period

• Identify fetal and maternal risks associated with opioid use in pregnancy

• Review screening and testing for opioid use in pregnancy

• Discuss treatment options and review recommended pregnancy surveillance for those with opioid use disorder

Introduction

• What are Opioids?• Natural or synthetic chemicals that interact with mu receptors on nerve cells,

gastrointestinal tract, spinal cord, and brain.

• Powerful effect on brain—Positive and negative

-reduces feeling of pain

• Can lead to addiction

-Tolerance– escalate the dose to achieve same desired effect

-Dependence–withdrawal symptoms in the absence of the drug

Introduction

• Types• Codeine (only available in generic form)

• Oxycodone: (Oxycontin)

• Aspirin and oxycodone: (Percodan)

• Hydrocodone (Hysingla ER, Zohydro ER)

• Hydrocodone/acetaminophen (Vicodin)

• Hydromorphone (Dilaudid)

• Meperidine (Demerol)

• Methadone (Dolophine, Methadose)

Opioid Use Disorder Diagnosis

• Opioid use leading to clinically significant impairment or distress manifested by at least two of the following, occurring within a 12 month period:

• Taken in larger amounts or over a longer period than was intended• Persistent desire or unsuccessful efforts to cut down or control opioid use• A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects• Craving, or a strong desire or urge to use opioids• Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home• Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the

effects of opioids.• Important social, occupational, or recreational activities are given up or reduced because of opioid use• Recurrent opioid use in situations in which it is physically hazardous.• Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological• Problem that is likely to have been caused or exacerbated by the substance• Tolerance, as defined by either of the following:

• A need for markedly increased amounts of opioids to achieve intoxication or desired effect.• A markedly diminished effect with continued use of the same amount of an opioid. Withdrawal, as manifested by either of the following:

• The characteristic opioid withdrawal syndrome (refer to Criteria A and B of the criteria set foropioid withdrawal).

• Opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.

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Scope of Opioid Epidemic

• Fewer than 5% of world’s population live in US, but nearly 80% of world’s opioid are written for in US

• 2012, 259 million prescriptions were written in the US • more than enough to give every American adult their own bottle of pills

• 2015, 2 million people abuse opioids• 1,400,000 from prescription abuse

• 600,000 from heroin• 80% started with prescription opioids

Scope of Opioid Epidemic

• 2015, 52,404 drug overdose deaths

• 33,000 from Opioids• 12,990 deaths due to Heroin• 20,101 deaths due to prescription drugs• 90 people every day• Over 60% are from prescription Opioids

• Drug overdose is now the leading cause of accidental death in the US

• 1999-2015, the deaths from Opioid prescriptions• Female deaths increased by 471%• Male deaths increased by 218%

• Estimated cost of $78 Billion each year due to Opioid abuse

Scope of Opioid Epidemic

Scope of Opioid Epidemic Scope of Opioid Epidemic

Haight SC, Ko JY, Tong VT, Bohm MK, Callaghan WM. Opioid Use Disorder Documented at Delivery Hospitalization — United States, 1999–2014. MMWR Morb Mortal Wkly Rep 2018;67:845–849

Prevalence of opioid use disorder per 1,000 delivery hospitalizations

Scope of Opioid Epidemic

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Scope of Opioid Epidemic We are part of the problem

Free from friend/

relative (53%)

Bought or took from friend

(20%)Drug dealer/

stranger (4.3%)

Internet (0.1%)

Other1 (4.3%)

One doctor

(21%)

More than one

doctor (2.6%)

Desantis C Cancer J Clin. 2014;64:52-62

We are part of the problem

• Emphasis on post operative pain control

• National campaign to improve patients experience with pain

• Concurrently, marketing efforts by pharmaceutical industry to reassure medical community that patients would not become addicted

We are part of the problem

Historic Pain Questions During this hospital stay, did (you/your family member) need medicine for pain? (Yes/No) During this hospital stay, how often was (your/your family member's) pain well controlled? Would you say: (Never/Sometimes/Usually/Always) During this hospital stay, how often did the hospital staff do everything they could to help (you/your family member) with (your/his or her) pain? Would you say: (Never/Sometimes/Usually/Always) Current Pain Questions During this hospital stay, did (you/your family member) have any pain? (Screener question if yes next two asked) During this hospital stay, how often did hospital staff talk with (you/you or your family member) about how much pain (you/your family member) had? Would you say: During this hospital stay, how often did hospital staff talk with (you/you or your family member) about how to treat (your/your family member's) pain? Would you say:

Peripartum Opioid Use

• 1:300 opiate naïve women will become addicted after receiving opiates after cesarean

Opioid use duringpregnancy

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Anesthesiology. 2014 May;120(5):1216-24

Obstet Gynecol. 2014 May;123(5):997-1002

Eur J Clin Pharmacol. 2011 Sep;67(9):953-60

Clin Ther. 2012 Jan;34(1):239-249

Drug Saf. 2010 Jul 1;33(7):593-604

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Maternal and Fetal risks

• Lack of prenatal care

• Risk of infectious disease• HIV, Hep C, STI’s

• Criminal activity and arrests

• Maternal trauma

• Loss of child custody

• Depression

• Under nutrition

• Prematurity

• Growth restriction

• Abruption

• Stillbirth

• Congenital anomalies

• Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome (NAS/NOWS)

Maternal and Fetal risks

• Endogenous opioids are regulators of development

• Exogenous opioids may impact on development

• Animal studies: May be toxic to the developing CNS

Am J Obstet Gynecol. 2011 Apr;204(4):314.e1-11.

TeratogenicityaOR (95% CI)

Spina bifida 1.8 (1.1 – 3.0)

HLHS 2.5 (1.5 – 4.3)

Pulmonary stenosis 2.0 (1.3 – 3.1)

Gastroschisis 1.9 (1.2 – 3.1)

Teratology of Fallot 2.1 (1.2 – 3.5)

Perimembranous VSD 1.8 (1.1 – 3.0)

ASD/VSD 2.3 (1.2 – 4.1)

Cleft palate 2.9 (1.3 – 6.4)

Interrante et al, Ann Epidemiol 2017

Pregnancy Outcome

aOR (95% CI)Fetal growth restriction 2.7 (2.4–2.9)

Abruption 2.4 (2.1 – 2.6)

Preterm birth 2.1 (2.0 – 2.3)

Stillbirth 1.5 (1.3 – 1.8)

Transfusion 1.7 (1.5 – 1.9)

Cardiac arrest 3.6. (1.4–9.1)

Died during hospitalization 4.6 (1.8–12.1)

Maeda et al, Anesthesiol 2014

Screening for Opioid Use in Pregnancy

• American College of Obstetricians and Gynecologists (ACOG, 2015 and 2017)

• Screening should be:• “part of comprehensive obstetric care”• “done at first prenatal visit in partnership with the pregnant woman”• “applied equally to all people, regardless of age, sex, race, ethnicity, or

socioeconomic status”

• “rely on validated screening tools, such as quesIonnaires, including 4Ps, NIDA quick screen and CRAFFT (for women 26 years and younger).”

4P’s and NIDA Quick Screen

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Peripartum Opioid Use Bateman et al.

• What is the risk that women exposed to opioids after CD go on

to become persistent opioid users?• Over 80,000 opioid naïve women dispensed opioids following CD

• Trajectory models used to define distinct patterns of opioid use for 1

year following CD

Am J Obstet Gynecol. 2016 Sep;215(3):353.e1-353.e18

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Persistent users

Non-persistent users

1 in 300

Bateman et al.

Bateman et al.

• Risk Factors

• Younger age

• Smoking

• Cocaine abuse

• Pain Conditions:• Back pain

• Fibromyalgia

• Headache

• Benzodiazapine use

Pain in pregnancy

• Common in pregnancy• Low back pain

• Pelvic girdle pain

• Hip and knee pain

• Leg cramps

• Carpal Tunnel

• Acute and Chronic conditions unrelated to pregnancy

• Postpartum pain

Strategies to minimize opioid use in pregnancy

• Vaginal delivery• Are Opioids REALLY needed

• If so limit duration to 3 days or less

• Maximize Non-opioid treatment options• Pharmacologic

• NSAIDS, acetaminophen, adjuvant pain medicines

• Non pharmacologic • Exercise, PT, behavioral therapy, etc

• Shared decision making model

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Strategies to minimize opioid use in pregnancy-Cesarean Delivery

• Popcorn theory of opioid prescribing

Tiny Small Medium

Post Discharge Opioid Use After Cesarean

• ¾ Women did not use all prescribed opioids • median of 10 unused tablets of 5 mg oxycodone

• Majority of unused opioids are stored in unlocked locations, risking potential nonmedical use and diversion

• A small subset use all opioids prescribed

• Homogenous or “one-size-fits-all” opioid prescribing risks underprescribing to an important subset of the population.

Osmundson et al. Obstet Gynecol 2017;130:36-41

Post Discharge Opioid Use After Cesarean

Bateman B, Obstet Gynecol 2017;130:29-35

All Things ConsideredNational Public Radio January 23,2017

All Things ConsideredNational Public Radio January 23, 2017 Postpartum pain management

• Contributes to opioid epidemic

• Opioid exposure as a precipitant for persistent use

• Excessive prescribing leading to leftover medication• Over 50% of opioids used non-medically were obtained from a friend or family member

JAMA Intern Med. 2014 May;174(5):802-3

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Patterns of Opioid Prescription and Use after Cesarean• Survey at 6 academic medical centers in the U.S. from 9/2014 to 1/2016.

• MGH

• BWH

• Michigan

• Columbia

• Wake Forest

• Stanford

Obstet Gynecol. 2017 Jul;130(1):29-35.

Normative opioid consumption after cesarean

Number of pills Median (IQR)

Dispensed 40 (30-40)

Consumed 20 (8-30)

Leftover 15 (3-26)

Obstet Gynecol. 2017 Jul;130(1):29-35.

Normative opioid consumption after cesarean

Number of pills Median (IQR)

Dispensed 40 (30-40)

Consumed 20 (8-30)

Leftover 15 (3-26)

95% had not disposed of leftover at time of the interview

Obstet Gynecol. 2017 Jul;130(1):29-35.

Patterns of Opioid Use after Cesarean

Bateman B, Obstet Gynecol 2017;130:29-35

Opioid Use Disorder in Pregnancy

• Ethical Considerations

• Prenatal Care

• Medical Assisted Therapy (MAT)

Ethical Considerations

• Key principles

– Respect of autonomy---Nothing without disclosure and

permission

– Justice---policies, approaches, benefits and burdens are

equally shared

– Truth---honest in disclosing plans and consequences

– Beneficence---screening/testing should be directed toward

improving health and outcomes: treatment not punishment

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Ethical Considerations

• Disease and illness should not be treated as a moral failing

– Care, not prosecution, will result in best and healthiest

outcomes for women with OUD in pregnancy

• If consequence/purpose is separation of child from mother

– What evidence that this benefits the mother?

– What evidence that this benefits the child?

Ethical Considerations

• ACOG: “Ob/Gyn’s have an ethical responsibility…to

discourage separation of parents from children solely

based on substance use disorder either suspected or

confirmed.”

• However….

Physician attitudes concerning legal coercion of pregnant alcohol and drug abusersAbel et al. AJOG 2002

• 95% indicate that pregnant women have a moral responsibility to act for the health of a pregnancy

• 58% indicate that pregnant women have a legal responsibility to act for the health of a pregnancy

• 61-75% favor mandatory [testing] for alcohol abuse

• 43-55% favor mandatory [testing] for illicit drugs

• 61% fear that prosecution deter patients seeking prenatal care

• 52% believe that drug abuse in pregnancy should be defined as child abuse and neglect (for the purposes of removing from custody)

• 23-34% supported incarceration for drug abuse in pregnancy

Physician attitudes concerning legal coercion of pregnant alcohol and drug abusersAbel et al. AJOG 2002

• 95% indicate that pregnant women have a moral responsibility to act for the health of a pregnancy

• 58% indicate that pregnant women have a legal responsibility to act for the health of a pregnancy

• 61-75% favor mandatory [testing] for alcohol abuse

• 43-55% favor mandatory [testing] for illicit drugs

• 61% fear that prosecution deter patients seeking prenatal care

• 52% believe that drug abuse in pregnancy should be defined as child abuse and neglect (for the purposes of removing from custody)

• 23-34% supported incarceration for drug abuse in pregnancy

Prenatal Care considerations

• Agree on things that promote healthy outcomes for mothers and fetuses/neonates

– This is generally not a dichotomy

– Focus on provision of treatment for OUD

• Focus less on presence and prevalence of NAS

– Which is an expected out come for MAT, a treatment that

promotes healthier outcomes in women with OUD

Prenatal Care of OUD Patient

• Universal screening—using validated method• Early ultrasound (8-12 weeks) if possible• Detailed anatomic survey ultrasound at 20 weeks• Fetal echocardiogram ultrasound at 22-24 weeks• Serial growth ultrasounds every 4 weeks• PTL assessments (cervical length only if indicated)• Antepartum testing in the third trimester• Medication Assisted Therapy (MAT) using Buprenorphine• Delivery at 39 weeks EGA • Behavioral health/counseling

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Postpartum Considerations of OUD Patient

• Women on MAT should have it continued intrapartum and postpartum

• Epidural/spinal anesthesia is appropriate

• Patients on Methadone should NOT receive partial agonists • (eg butorphanol, nalbuphine, pentazocine) due to precipitating withdrawal

• Post operative pain can be successfully treated with acetaminophen, NSAIDs, and FULL agonist (eg., oxycodone) when needed

• OUD patients may have hypersensitivity to pain and poor tolerance• most commonly in the first 24 hours post c/s• may require up to 50% more drug

Common Misconceptions Surrounding Pregnancy and Medication-Assisted Therapy (MAT)

Common Misconception• Medication-assisted therapy must be stopped in

order to achieve pain control with opioids (eg., after C/S)

• FALSE

• Patients with a history of opioid use disorder cannot be treated postoperatively with opioids for pain control because they will relapse

• FALSE

• Patients on medication-assisted therapy cannot breastfeed

• FALSE

Reasoning• Pain control can be achieved with full opioid agonists

despite taking medication-assisted therapy

• When prescribed for pain control, there is no evidence to suggest increased risk of relapse

• Breastfeeding has been shown to improve neonatal outcomes

Medication Assisted Treatment (MAT)

+ + ++ + +

+

+ + + + ++ + + +

+ + +

MethadoneAgonist

BuprenorphinePartial Agonist

NaltrexoneAntagonist

ACOG Committee Opinion 711:

• Gold Standard Treatment• Methadone

• Buprenorphine

• Decreased:• Opioid use

• Opioid related overdose

• Opioid related mortality

• Criminal Activity

• Infectious Disease transmission

• Increased:• Social functioning

• Employment

• Treatment retention

Opioid Agonist Treatments Decreased Heroin OD Deaths

Baltimore, Maryland, 1995-2009

Schwartz RP et al., Am J Public Health 2013.

Medication Assisted Treatment (MAT) Buprenorphine vs Methadone

• 8 site RCT

• 175 Perinatal OUD

• Comprehensive addiction and obstetric care

• Primary Outcomes• NAS, NAS treatment, length hospital stay

• Secondary Outcomes• Other neonatal outcomes (Wt., PTB, GA, Apgar) Maternal outcomes

(c/s, complications, UDS)

Jones et al., N Engl J; 363:2320-31, 2010

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Buprenorphine vs Methadone Buprenorphine vs Methadone Perinatal OUD Treatment

• Opioid Use Disorder [Heroin and/or IV Opioid Use]• Buprenorphine or Methadone

• Opioid Use Disorder [Prescription Opioids]• Buprenorphine or Methadone

• If considering taper

• Not to mitgate neonatal withdrawal, but for patient preference

• Individual assessment

• Long tapers, intensive follow-up care

Perinatal OUD Treatment

• MORE RESEARCH IS NEEDED!!

• Can we taper? Who can taper? Optimal treatments?

• Large, prospective studies, in depth maternal, fetal and newborn assessments

• Buprenorphine, Naltrexone

• Pharmacokinetics, Pharmacodynamics

• Naltrexone• Large, prospectve studies, in depth maternal, fetal and newborn assessments

In Summary..

• Perinatal Opioid Use Disorders are a major public health issue in US

• Evidence based guidance for prevention and management in pregnancy is lacking

• Universal Screening at the first prenatal visit is recommended

• Testing should be performed with informed consent

• Antepartum, Intrapartum and Postpartum pain is common and should be treated appropriately

• Medication Assisted Treatment reduces severity of neonatal withdrawal and decreases relapse

• MUCH WORK IS NEEDED

Questions?

Joshua D. Dahlke MD

Methodist Women’s Hospital and Perinatal Center

717 N 190th Plaza, Suite 2400

Omaha, Nebraska 68022

Office: 402-815-1970

joshuadahlke@gmail.com

Joshua.Dahlke@NMHS.org