Perinatal Addiction Opiate Maintenance During Pregnancy: What are the Options

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Perinatal AddictionOpiate Maintenance During
Pregnancy What are the Options?

• Gary D. Helmbrecht, M.D., F.A.C.O.G.
• Prenatal Diagnosis Center
• Charlottesville, Virginia

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Anatomy of Addiction
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Release signal
Dopamine
Dopamine receptor
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The drug dominates control of the reward center.

• Continued use of opiates makes the body
• rely on the presence of the drug to maintain
• rewarding feelings and other normal behaviors.
• The person is no longer able to
• feel the benefits of natural rewards (food,
  water, sex)
• can't function normally without the drug present.

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Learning Objectives

• Review the specific problems of women with
  addiction
• Review strategies to identify the pregnant
  addict/alcoholic
• Review the effects of opiates on the developing
  fetus
• Review the potential uses of Methadone and
  Buprenorphine as maintenance agents during
  pregnancy

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How prevalent is drug and alcohol use in
pregnancy?

• 12-24 of women use drugs and alcohol during
  pregnancy
• 1 of every 3-4 women expose fetus to alcohol
• Alcohol and tobacco illicit drugs and
  prescription drugs
• Prevalence in public clinicprivate practice
• CaucasiansAfrican AmericansHispanic
• No significant variation by socioeconomic status

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How prevalent is opiate abuse in pregnancy?

• Unknown
• 400,000 women admitted to treatment programs in
  1999
• 4 (16,000) were pregnant
• 19 (3,040) used opiates as primary DOC

Office of applied studies, 2002
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Review the specific problems of women with
addiction
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Women and Addiction

• In the general population, women are not as
  likely as men to be substance abusers
• yet these addicted women have a specific profile
  of
• confounding diagnoses
• family history
• current social situation
• pattern of substance use

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Addiction Males Women

• Monthly prevalence Epidemiology studies
• Males 5X greater rates of alcoholism, 3X greater
  rates for drugs
• If given the opportunity, women may progress from
  abuse to addiction at the same rate
• Exception prevalence of addiction is similar
  for males and females during the teen years
• Alcohol, marijuana, cocaine, tobacco

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Confounding Diagnoses

• Most women in treatment for addiction have at
  least one coexisting mental disorder
• Anxiety
• Depression
• Personality Disorders
• More likely than men to have had a suicide
  attempt or ideation prior to treatment
• More likely than men to have a history of
  previous treatment

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Family History and Social Situation

• Often have a family history of addiction
• Exposed to parental violence as children
• Experienced emotional, physical, sexual abuse as
  children
• More likely to have a family history of mental
  illness, particularly in their mothers
• More likely to live with a violent, addicted
  partner

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Family History and Social Situation
Effect of childhood sexual abuse on addiction
and mental disorders in adult women
Relative Risk
Drug Addiction
Alcohol Addiction
Major Depression
General Anxioty
Kendler KS, et.al. Arch Gen Psych. 57953,2000
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Pattern of Substance Use

• Both women and men primarily abuse alcohol and
  illicit drugs
• Women are more likely to abuse prescription drugs
• Women are more likely to abuse sedative-hypnotics,
  specifically benzodiazepines
• Women are more likely to be poly substance abusers

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Identification of the pregnant addicted woman
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Risk factors social history

• Positive family history of addiction
• Living with a partner who abuses drugs and
  alcohol
• Positive legal history
• History of domestic violence in current living
  situation
• If FOB is abusing drugs and alcohol, look here
  first

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Risk factors medical and psychiatric history

• Previous mental health diagnosis depression,
  personality disorder
• Previous problem pregnancies (unexplained IUGR)
• Infections Hepatitis, HIV, STDs are secondary
  to
• Mode of use ( IV, snorting)
• Method of procurement (prostitution)

The use of opiate antagonists to diagnose
dependence in pregnancy is ABSOLUTELY
CONTRAINDICATED
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Issues specific to opiate abuse

• Chronic opiate abuse frequently causes amenorrhea
  and infertility
• Methadone normalizes endocrine function
• Symptoms of early pregnancy are often mistaken
  for withdrawal symptoms
• Results in increased opiate use
• Unintended pregnancy early in MAT is common

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Screening

• All pregnant women should be screened for drug
  and alcohol use
• T-ACE
• TWEAK
• A positive screen indicates the need for a
  further evaluation
• Elements of the history and physical may indicate
  need for a urine drug screen

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T-ACE
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TWEAK
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T-ACE Score

• Tolerance Two or more drinks to feel high is a
  positive screen
• OR
• Two positive answers to the other three questions
  is a positive screen
• TWEAK Score
• Three or more points indicate that a pregnant
  woman is a problem drinker

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Resources Available

• www.nida.gov

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Review the medical and obstetric complications
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Common Medical Problems Among Opiate Addicted
Gravidas
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Common Medical Problems Among Opiate Addicted
Gravidas

• HBV
• Vertical perinatal transmission 70 90
• If Hb ag , give neonate HBV Vaccine HBV immune
  globulin
• HCV
• Universal screening in opiate addiction
  recommended (Anti-HCV, HCV RNA)
• If positive, post natal GI referral, follow LFTs
• Medical therapy contraindicated during pregnancy
• Vertical transmission low (4-7) increased by
  coinfection with HIV (4-5 fold)
• NOT affected by breast feeding or vaginal
  delivery
• Infants should be tested for HCV RNA at 2 and 18
  months

Roberts and YeungMaternal-infant transmission of
hepatitis C virus infection. Hepatology (2002
Nov) 36(5 Suppl 1)S106-13
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Common Medical Problems Among Opiate Addicted
Gravidas

• HIV/AIDS
• Interaction between HIV, methadone and immune
  function is largely unknown
• Vertical transmission
• No treatment 25 30
• AZT monotherapy 5 6
• AZT cesarean delivery
• Combination antiretroviral therapy after the
  first trimester is standard of care
• HIV does not affect the course of pregnancy
• Pregnancy does not affect the progression of HIV

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Laboratory Testing for the Opiate Addicted Gravida
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Obstetric Complications in the Opiate Addicted
Gravida
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Obstetric Complications in the Opiate Addicted
Gravida
Abruption Preterm labor IUFD, IUGR Placental
insufficiency
Hypoxia

• Repeated withdrawal
• Concurrent stimulant abuse

Preterm labor and delivery Chorioamnionitis Post
partum hemorrhage Preterm rupture of
membranes Spontaneous abortion
Inflammatory
Infectious complications
Cytokines
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Placental Abruption and Infarction
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Intrauterine Growth Restriction
Umbilical Artery
Middle Cerebral Artery
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Premature Labor
Inflammatory response
Cytokines Prostaglandins Subclinical uterine
activity
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Cytokine Mediated Inflammatory Response
Infection
TNF/IL-1
IL-6 CRH
IL-8



Proteases, apoptosis
Uterotonins PG, Endothelin
Contraction
Cervical Change
Membrane Rupture
Adapted from Lockwood, 1999
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Methadone Dosage and Management
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Methadone Dosage and Management

• Pharmacology of methadone in pregnancy
• Volume of distribution is NOT limited by blood
  volume extensive tissue reservoirs
• Peak plasma levels in 2 6 hours following
  ingestion -
• Dose requirement increases as pregnancy
  progresses
• Blood volume expands by 50
• Tissue reservoir variably expands

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Methadone Dosage and Management

• Low v. High dose
• Low dose
• Traditional belief that lower methadone doses led
  to less NAS.
• Outcomes in low dose program (average dose 40mg)
• Prematurity 28
• IUGR 27
• Microcephaly 13
• Polydrug abuse 73
• NAS 62

Arlettaz R, Kashiwagi M, Das-Kundu S,
et.al. Acta Obstet Gynecol Scand (2005 Feb)
84(2)145-50       
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Methadone Dosage and Management
Data are given as mean SD.
Independent samples t-test.
Mann-Whitney test.
Data are given as mean SD.
Independent samples t-test.
Mann-Whitney test.

• Low v. High dose
• High dose
• Maternal methadone dose group
• All (n81) 100 mg/d (n45) (n36) P value
• dose (mg/d) 101 42.4 132 24.1 62
  24.3 .08
• GA (wk) 37.3 3.1 37.1 2.9 37.2 3.3 .47
• BW (g) 2792 694.6 2795 693 2787 687 .74
• NAS (n) 37 (46) 19 (51) 18 (49) .32
• UDC result(n)15 (18) 5 (11) 10 (27) .05

McCarthy JJ, Leamon MH, Parr MS, et.al. Am J
Obstet Gynecol(2005)193606-10
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Methadone Dosage and Management

• Low v. High dose

McCarthy JJ, Leamon MH, Parr MS, et.al. Am J
Obstet Gynecol(2005)193606-10
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Methadone Dosage and Management

• Higher doses of methadone are associated with
• Fewer relapses to polydrug abuse
• ?Improved neonatal and maternal outcomes?
• No change in incidence or severity of NAS

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Induction and Stablization

• Outpatient or inpatient
• Start with 10 to 20mg in the morning reassess
  in the evening
• Add another 5 to 10mg
• Completed in 48 to 72 hours
• Split dosing
• Popular with little evidence for efficacy
• Some evidence of less relapse to cocaine

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Management of Overdose

• Naloxone is treatment of choice
• Use with great caution in pregnancy
• Procedure
• Establish an airway (ABCs)
• Naloxone 0.01mg/kg IV
• Repeat every 5 minutes until conscious
• Duration of action is 30 minutes to 2 hours
• May need to repeat if opioid used was longer
  acting

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Medically Supervised Withdrawal

• Never during the 1st or 3rd trimester
• In consultation with an addictionist
• High relapse rates to opioids
• Indications
• Live in area where MAT not available
• Have been stable and refuse to be maintained
• Agrees to use a structured program
• Close fetal monitoring
• 1.0 to 2.5mg/day (inpatient) 2.5 to 10mg/wk
  (outpatient)

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Fetal/Neonatal Opioid Withdrawal

• Abrupt cessation of opioid use during 1st and 3rd
  trimester may be lethal for fetus
• 20-70 of infants born to pregnant women abusing
  or prescribed opioids may have symptoms and signs
  of withdrawal
• Life threatening if untreated
• Seizures
• Dehydration
• Pneumonia
• Autonomic instability

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Neonatal Opioid Withdrawal

• CNS Disturbed sleep, irritable, feed/suck
  poorly, seizures
• GI Vomiting, diarrhea, abdominal discomfort
• Autonomic sweating, yawning, temperature
  instability, mottling, respiratory difficulties,
  increased or decreased tone, myoclonic jerks

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Neonatal Opioid Withdrawal

• Assessment Neonatal Abstinence Scale
• Assigns points according to babies signs or
  withdrawal every 4-6 hours
• Treatment
• Symptom triggered according to NAS
• Opioid agonists
• Paregoric, Tincture of Opium, Oral Morphine,
  methadone (0.4mg/kg MsO4 equivalent)
• Infants may have chronic withdrawal symptoms for
  up to 6 months after birth

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Finnegan Neonatal Abstinence Scoring for Opioid
Withdrawal in Newborns
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Breast Feeding

• Mothers on methadone should be encouraged to
  breastfeed
• Exception is HIV infected women
• HCV infection is NOT a contraindication
• AAP recommends only if maternal dose
• Excretion into breast milk is minimal up to
  180mg/day

Geraghty, et.al.J Human Lactation,
1997,13227 McCarthy and PoseyJ Human Lactation
2000,132000
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Use of Buprenorphine During Pregnancy
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How Does Buprenorphine Work?

• High Affinity for Mu Opioid Receptor
• Competes with other opioids and blocks their
  effects
• Displaces heroin or other opiates from
  receptors(This can produce withdrawal if patient
  has opiates in system)
• Slow Dissociation from Mu Opioid Receptor
• Prolonged therapeutic effect 24 hours
• Ceiling Effect on Opiate Effects
• Poor drug for intoxication purposes
• Safer in an overdose
• Formulated with Naloxone
• Naloxone is poorly absorbed if taken orally
• Naloxone blocks opiate effects if injected

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Buprenorphine and Pregnancy

• Not approved by FDA for use in pregnancy
• Preliminary data from Europe very positive
• No prospective, randomized trials
• Limited indications for use
• Potential benefits must outweigh risks
• Conceive already on Buprenorphine
• Opioid addicted but cannot tolerate methadone
• Poor program compliance or MAT not available
• Documented informed consent
• Limit use to monotherapy (Subutex)

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Buprenorphine and Pregnancy
Jones HE, Johnson RE, Jasinske DR, et.al. Drug
Alcohol Depend(2005)791-10

• Effects on NAS

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Buprenorphine and Pregnancy

• Compared to Methadone, Buprenorphine is
• As safe
• Easier to administer
• Less potential for abuse/overdose
• The observed NAS is
• Of shorter duration and severity
• Lower prevelence

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Perinatal Addiction
No matter what, these patients deserve our
compassion and respect.

• If you learn nothing else today, remember this

Addiction is a genetic disease. Like diabetes,
the addict did not choose to become addicted.
Good people can do some very bad things while in
the active phase of their disease.
The disease drives the behavior the behavior
does NOT drive the disease.
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