What's New in Obstetric Medicine

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What's New in Obstetric Medicine?

• 9 Key Questions (and Answers) about Substance Use
  and Psychiatric Disorders in Pregnancy

SOAP 40th Annual Meeting
Ellen D. Mason, M.D. May 2008
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And, now for something completely different.
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Substance Use in Pregnancy Science versus
Popular Myths
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What's New in Obstetric Medicine? 9 Key
Questions (and Answers) about Substance Use and
Psychiatric Disorders in Pregnancy

• Learning Objectives
• Review the epidemiology of behavioral and mental
  disorders in pregnancy and their impact on
  perinatal outcomes
• Become familiar with recommendations for
  screening, intervention and treatment of
  substance use and psychiatric disease

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What's New in Obstetric Medicine? 9 Key
Questions (and Answers) about Substance Use and
Psychiatric Disorders in Pregnancy

• Learning Objectives, continued
• Understand risk/benefit of some medications used
  to treat SUDS and psychiatric disease.
• Review how patient and physician attitudes and
  beliefs might impact management of substance use
  and mental disease in pregnant patients

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1. Why is this important?

• Ubiquitous common and in all groups
• Effects on pregnancy outcomes
• Effects on womens health short term and long
  term
• Effects on offspring
• Clinicians are often relatively unfamiliar with
  behavioral issues in pregnancy compared to other
  disease entities

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Prevalence of Medical/Obstetric Complications

• Gestational Diabetes 3-14
• Chronic hypertension 3-5
• Asthma 3-8
• Thromboembolic disease 3-12
• Preeclampsia 5
• Substance use disorders 4-20
• Psychiatric disorders 0.4-7.0

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2. How many pregnant women use alcohol, tobacco
or drugs?

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Substance Use in PregnancySurveys of Prevalence
in Prenatal Patients

• State surveys
• -California 11 used alcohol, illicit drugs or
  abused prescription drugs (urine)
• -Rhode Island 10.7 used illicit drugs
  (meconium and self-report)
• -Utah 5.5 illicit drugs (urine tox only)
• -South Carolina 25.8 alcohol or drugs
  (meconium )
• Local surveys Pinellas County Fla
• Hollingshead, MMWR1990, Vega, NEJM 1993, Buchi
  Obstet/Gynecol 1993
• Chasnoff, NEJM, 1990, Nalty Alcohol Drug
  Abuse 1991

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Substance Use in PregnancyPrevalence

• National Pregnancy and Health Survey
• -First and only pregnancy specific national
  survey, done in 1992
• -Self report anonymous toxicology data from 52
  urban and rural hospitals
• Results 221,000 women used illicit drugs in
  1992 (5.5), 820,000 (20.4) smoked tobacco,
  757,000 drank alcohol ((18.8)
• NCADI 1996
• ,

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Substance Use in PregnancyTobacco
DUHS/SAMHSA 2007
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Substance Use in PregnancyTobacco/Ethnicity

• Percentages of Past Month Cigarette Use
• Women 15-44 by Pregnancy Status, Age, and
• Race/Ethnicity

NSDUH SAMHSA 2005
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Alcohol Use in PregnancyNSDUH
NSDUH Report SAMHSA 2007
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Pregnancy and Alcohol Use Binge and Heavy
Drinking by Groups
USDHHS, HRSA, 2005
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Illicit Substance Use by Women
NSDUH Report SAMHSA 2007
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Illicit Drug Use in PregnancyNSDUH
Percentage Past Month Illicit Drug Use, Women
15-44, 2002, 2003
NSDUH Report, SAMHSA, 2005
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3. How does ATD use affect maternal health and
pregnancy outcomes?
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Adverse OutcomesLimitations of the Data

• Single, intermittent, chronic use (abuse vs.
  dependence)
• Timing, dose
• Polysubstance exposure
• Confounders SES, environment, nutrition,
  education
• Animal data, secondary endpoints
• Publication bias

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Limitations of the LiteraturePublication Bias
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Substance Use in PregnancyAdverse Maternal
Outcomes

• Obstetric emergencies
• Abruption
• Previa
• Catastrophic medical events
• Infection
• HIV/AIDS
• Hepatitis
• Pneumonia
• UTI/Pyelonephritis
• Death

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Substance UseAdverse Maternal/Obstetric Outcomes

• - Abruptio placenta
• Vasoconstrictors- nicotine, cocaine,
  amphetamines
• Animal models suggest dose-response for tobacco,
  ? cocaine Tobacco RR 1.4-2.4, cocaine OR
  3.92 (CI 2.77-5.46)- (? Confonders)
• -Placenta previa-most data from case control
  studies
• Tobacco OR2.3 (CI 1.5-3.5), dose response
• Cocaine AOR 2.5- 4.39 (CI 1.17-16.4)
• Hulse Addiction 1997, Ananth Obstet-Gyne, 1999
• Handler Am J. Obstet Gyncol 1994, Macones Am
  J. Obstet Gyencol 1997

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Substance Use Adverse OutcomesMortality

• California study- increased mortality for
  maternal death in polydrug, drug and alcohol,
  amphetamine and cocaine using parturients OR
  2.0, ( CI1.74, 2.5)
• Increased rates of abuse, violent trauma and
  murder noted
• Wolfe J. Perinatology. 2005
• Tardiff NEJM, 1994, Thompson Addictive
  Behaviors 1998,
• Berenson Am J. Ob-Gyn 1991

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4. What are the effects of ATD use on offspring?
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Substance Use in PregnancyAdverse Outcomes In
Offspring

• Congenital Anomalies
• PTL/PTD
• IUGR
• Neonatal abstinence syndrome
• SIDS/Infant Death
• Behavioral Abnormalities

Early
Later
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Substance UseAdverse Obstetric Outcomes

• Preterm labor/Preterm delivery
• - Uterine artery vasospasm
• - Increased catecholamines
• - Increased body temperature
• - Estrogen/progesterone potentiate contraction of
  cardiac and smooth muscle in vessels and
  myometrium

Increased BP
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Substance AbuseFetal Growth Restriction

• Seen with all substances illicit drugs, alcohol,
  tobacco
• Effects multifactorial direct vasoconstriction
  with hypo-perfusion altered oxygen delivery,
  placental disruption, poor maternal
  nutrition/micronutrient delivery, direct
  cytotoxic effects, binding carbon monoxide to
  fetal hemoglobin
• Cigarettes best evidence for effect,
• RR 1.5-2.9, dose response, positive response
  to cessation in early pregnancy

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Substance UseCongenital Anomalies

• Cocaine
• Nicotine ?
• Hallucinogens
• Opiates
• Amphetamines
• Marijuana
• Alcohol
• Sedative-hypnotics?

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Substance Use Anomalies Fetal Alcohol Spectrum
Disorder

• Alcohol/Acetaldehyde
• Dose dependent cumulative/binge
• Effects throughout gestation
• Systems affected
• Cardiac
• Genitourinary
• Oral/ocular/auditory
• CNS

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Fetal Alcohol Spectrum Disorder
Fetal Alcohol Syndrome/Effect
Persistent growth deficits, behavioral problems
and learning disorders
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Substance Use Neonatal Abstinence Syndrome

• Opiates
• Nicotine

Chirboga, J Devel Peds 1998, Neuspiel
Cocaine/Crack Res Newsletter 1991
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Perinatal Substance UseInfant Death

• Michigan study- increased perinatal mortality in
  drug positive infants. Increased mortality in LBW
  infants exposed to cocaine, opiates (OR 5.9, CI-
  1.4-24)
• Meta-analysis of opioid exposure and neonatal
  mortality from 1970s to 1997 RR compared to
  non-using controls 3.79 (95CI 0.95-9,60)
• SIDS-associated with tobacco, opiates and
  marijuana

Ostrea Pediatrics, 1997 Hulse Aus/New Zealand
J. Ob/Gyn, 1998 Klonoff-Cohen. Arch Ped Adol
Med 2001, Kahlert C. Arch Dis Children
92(11)2007 Kandall S. Neurotoxicity and
Teratology. 1991, Cnattinguis. Nicotine and Tob
Res 2004, Scragg RKR. Acta Ped, 200190
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Substance UseNeurodevelopmental Abnormalities

• Seen with all substances
• that affect the limbic
• system, both licit and illicit
• Vulnerable kids more
• affected
• Often very subtle include altered psychomotor,
  mental and behavioral functioning, poor emotional
  regulation and social interaction
• Amenable to post-natal
• intervention

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Perinatal Substance ExposureSelected Studies

• -Ottawa Prenatal Prospective Study
• Results in 9-12 and 13-16 year old- subtle
  deficits in executive functions, poorer
  self-regulation, mild attention deficit abnls.
  No change in IQ or language skills
• -Maternal Health Practices and Child Development
  Study
• Head circumference differences by age 3.
  Height deficits by age 6, severe hyperactivity,
  deliquincy and behavioral problems
• -NIDA Methamphetamine Study
• J. Clin Pharmacology 42, 2002
• Neurology Teratology 24, 2002,
  Neurotoxicology/Teratology 22, 2000

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Perinatal Substance ExposureSelected Studies

• Maternal Lifestyles Study
• Interagency- NICHHD, NIDA, PPB
• 11,800 mother-infant dyads, 3 groups O, C, N
• SES matched controls, both cases and controls had
  alcohol, tobacco /or marijuana

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Maternal Lifestyles Study

• Phase I - Obstetric outcomes- Increased UTIs,
  STDs, hepatitis and HIV in opiate and cocaine
  using mothers. 19 fold higher hospitalization for
  violence-related injury. Low prevalence of
  medical complications or acute events.
• Phase II Evaluation infants 1- 36 months of age
• Assessed q 4 to 20w. No significant differences
  in mental, psychomotor or behavioral functioning.
  Subtle differences in psychomotor and
  neuro-developmental parameters noted
• Phase III and IV- Focus on evaluation child
  outcome, school performance
• Bauer, Am J. Obstet Gynecology 2002,
  Messinger, Pediatrics 2004

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5. How should we screen for ATD use?
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Screening

• Universal and also risk-based
• Logical inclusion in behavioral history
• Instruments designed and validated for different
  substances-choice of instrument based on patient
  and provider characteristics
• Recommendation for screening is based on the
  level of evidence that intervention makes a
  difference

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Screening in PregnancyAlcohol

• CAGE and AUDIT validated in many populations.
  Poor pick-up low level drinking. Excellent
  negative predictive performance in women (0.94,
  0.97)
• TWEAK , T-ACE higher sensitivity for detection
  drinking in pregnancy-(90 and 79)
• TWEAK (Tolerance, Worry by spouse, Eye-Opener,
  Amnesia, Cut down)
• T-ACE (Tolerance, Annoyed, Cut down, Eye-opener)
• USPHS Evidence Level B

Bradley. JAMA. 1998
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Screening for Illicit Drug UseIn Pregnancy

• Universal questioning part of routine history
• (avoid-You dont use drugs, do you?)
• versus
• Risk based screening repeat as needed
• - Medical clues infections, trauma, GI dz, pain
  syndromes, dental dz, blackouts,
  depression/anxiety, tobacco
• - Obstetric clues PTL, PPROM, abruptio, IUGR,
  IUFD, Sabs, neonatal abstinence
• -Social/behavioral clues noncompliance,
  family/spouse abuse, ER visits, employment,
  unstable family/housing situation, relationship
  difficulties

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Screening for Illicit Drug UseIn
PregnancyToxicology Testing

• Not used to establish chronic use
• Short half life drugs metabolites
• False positives and false negatives common
• Meconium, hair analysis remain investigational
• Legal issues

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Toxicology Testing for Substance Abuse in
PregnancyMedical-Legal Issues

• Informed consent US Supreme Court Ferguson v.
  City of Charleston, 2001- states that pregnant
  women cannot be non-consensually tox tested under
  the 4th Amendment for non-medical purposes.
  Rights of women both statutory and constitutional
  are not forfeited because of pregnancy
• Non-discriminatory testing Testing only per
  hospital protocol and policy for medical cause
• Confidentiality- Follow Federal and State
  guidelines for information transfer

Annas NEJM, 2001, USDHHS, IDASA-1991
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Screening Brief Intervention
US Preventive Services Task Force recommends
screening behavioral counseling in primary care
and prenatal settings to reduce substance misuse
by adults
Dependent Use
At-Risk Problem Use
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Intervene Screen
Evidence Level B
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Screening/Brief Intervention The 5 As and FRAMES

• ASK- 1 minute Use multiple choice questions
• a. I have never smoked, b. I stopped before I
  was pregnant,
• c. I stopped after pregnancy diagnosed, d. I
  smoke but cut down,
• e. I smoke regularly, same as before pregnancy
• ADVISE -1 minute
• ASSESS- 1minute willingness to quit
• ASSIST- 3 minutes skills, social support,
  pregnancy specific materials
• ARRANGE- 1minute reassess smoking at follow-up
  visits.
• FRAMES (Feedback, Reinforce, Advice, Menu,
  Empathy, Support)
• Melvin, Recommended smoking cessation counseling
  for pregnant women who smoke. Tobacco Control
  2000
• Miller Rollnick, Motivational Interviewing 1991
• Evidence level B

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Evidence for BI with many substances

• Ballesteros et al. 2004 -meta-analysis alcohol
• MTP Research Group et al. 2004. cannabis (USA)
• Copeland et al. 2001. cannabis (Australia)
• Heather et al. 2004. benzodiazepines (UK)
• McCambridge, Strang. 2004. tobacco and cannabis
  (UK)
• Berstein et al. 2005. cocaine and heroin (US)
• Significant literature for tobacco cessation

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Effectiveness BI in PregnancyRCTs

• AUDIT , BI- reduction Etoh, increased use
  contraception and reduction AEP
• T-ACE, support partner, BI recipients had
  highest level of reduction in drinking, partner
  participation enhanced effect
• Protecting the Next Pregnancy affected index
  pregnancy, 5 year f/u. Decreased drinking, better
  birth outcomes, less LBW, less PTD, better
  neurobehavioral scores on subsequent offspring

Floyd RL. Am J Preventive Med, 2006 32
Chang G. Obstet/Gynecol 2005 105 Hankin JR.
Alcohol Research and Health 2002 26,
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6. Does treatment work?
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Addiction treatment is effective

• Goal of addiction treatment is to return to
  productive functioning, reduce excess health risk
• reduces substance use by 40-60
• reduces crime by 40-60
• increases employment by 40
• Rates of adherence similar to treatment for other
  chronic diseases such as diabetes, asthma,
  hypertension
• Every 1 spent for treatment saves up to 12 in
  reduced health care and crime-related costs

McLellan AT, Lewis DC, O'Brien CP, Kleber HD,
JAMA, 284 (2000) 16891695 NIDA, Principles of
Drug Addiction Treatment A Research-Based Guide,
NIH Bethesda, MD, July 2000
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90 of people with substance use disorders are
untreated
23.2 million (9.5) of US pop. 12 years old
have a current substance use disorder. Less than
10 of these get treatment
National Survey on Drug Use and Health, SAMHSA
2005
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Substance Abuse Treatment Special Services for
Pregnant Women

• Parenting classes
• Family therapy
• On-site child care
• Case management services
• Coordination with medical/prenatal/pediatric care
• Improved outcomes in BW, addiction/prenatal
  program retention and perinatal mortality if
  women receive specialized services
• Daley, J. Psychoactive Drugs 2001
• Ashley, Am J. Drug and Alcohol Abuse 2003
• Brouekhuizen, Am J. Obstet/Gynecol 1992

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Substance Abuse in PregnancyAlcohol
Detoxification

• Cold turkey not safe in pregnancy at 8oz
  Etoh/day
• Hospital detoxification may be needed
• Evaluate using standardized tool-
• CIWA-Ar. Low score in pregnancy (8-14) should
  consider pharmacotherapy
• Avoid high dose benzodiazepines in early first
  and late third trimesters-barbiturates better
  choice in later gestation

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Substance Abuse in PregnancyOpiate
Stabilization/Detoxification

• Methadone- prevents fetal withdrawal, PTL,
  promotes rehab and compliance with prenatal care.
  Better BW, decreased mm
• Pregnancy affects pharmacokinetics of methadone
  ? drug metabolism, ?plasma volume, ?volume
  distribution, clearance

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Methadone in PregnancyPrinciples of Use

• Individualize dose, use SOWS or COWS
• Maintain pre-pregnancy dose if conceives on
  therapy- (confirm dose with pts program)
• May need hospitalization to initiate therapy
• Methadone trough levels may be useful for
  determining maternal dose (keep at 0.24-0.3mg/L)
• Drozdick, Obstet Gynecol 2002 Dashe Obstet
  Gynecol 2002
• Dyer, Addiction 1991

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7. Does pregnancy improve/worsen psychiatric
disorders?

• Physiologic changes- hormonal, neuro-endocrine,
  immunologic, body mechanics
• Altered self image
• Role changes

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Prevalence of Mental Disorders in Women
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Effect of Pregnancy on Psychiatric Disorders

• Anxiety disorders
• Schizophrenia and schizoaffective disorders
• Panic disorder
• Bipolar disease
• Pregnancy neither protective nor increases risk
  unless meds are withdrawn

Viguera Can J. Psych 2000 Gilbert Arch Gen
Psych 1995 Wisner J. Affect Dis 1996
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Prevalence Depression by Trimester
Bennett H. A. Obstet/Gynecol 2004, 103
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8. What about psychiatric medication in
pregnancy?(Prescribing Dilemmas)
Pregnant women do not like taking medications
and doctors do not like prescribing medications
for them Rosene-Montella K., Keely E.,
Medical Care Of the Pregnant Patient 2nd ed, 2008
58
Untreated Depression and Pregnancy

• Poor nutrition
• Poor prenatal care attendance
• Substance use
• Suicide
• PTD/LBW/SGA
• Cognitive abnormalities offspring
• Postpartum depression

Halbreich U. Am J. Obstet Gynecol, 2005
193 Henry AL. Clin Obstet Gynecol 2004 47 Bonari
L Can J Psych, 2004 49
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Psychotherapeutic Agents Antidepressants

• Monoamine Oxidase Inhibitors- seligline (Emsam),
  isocarboxizide (Marplan), tranlycypromine
  (Parnate) , tranylcypromine (Parnate)
• Selective Serotonin Reuptake Inhibitors-
  citalopram (Celexa), escitalopram (Lexapro),,
  paroxetine (Paxil), fluoxetine (Prozac),
  sertaline (Zoloft), fluvoxamine (Luvox)
• Heterocyclics- amitriptyline (Elavil),
  nortriptyline (Pamelor), amoxapine (Asendin),
  doxepin (Sinequan), imipramine (Tofranil),
  maprolitine (Ludiomil), clomipramine (Anafranil)
• Miscellaneous- bupropion (Wellbutrin),duloxetine
  (Cymbalta), mirtazapine (Remeron), trazadone
  (Desyrel), venlafaxine (Effexor),

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Effects SSRIs on Pregnancy Outcomes
Kulin NA. JAMA, 1998279
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Effect of SSRIs in PregnancyNeonatal Behavioral
Syndrome

• Respiratory Distress
• Cyanosis
• Apnea
• Weak or Absent Cry
• Seizures
• Temperature Flucts
• Feeding Problems

• Hypoglycemia
• Hypotonia
• Persistent crying
• Irritability
• Tremors

?Long term effects on child development?
Moses-Kolko EL, JAMA 2005293 Nordeng H, Drug
Safety, 2005 28 Chambers DC, N. Engl J. Med
2006 354 Gentile S. CNS Drugs, 2005 19
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Psychotherapeutic AgentsBipolar Agents

• Carbamezepine (Tegretol)
• Gabapentin (Neurontin)
• Lamotrigine (Lamictal)
• Lithium
• Topiramate (Topamax)
• Valproic acid (Depakote)

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Valproic Acid Effects on Pregnancy
Relative risk of congenital malformations in
patients receiving monotherapy was 3.77 (CI
2.18-6.52). Overall rate of anomalies was 2.5X
higher than baseline (p 64
9. Attitudes and EthicsPatients and Providers-
what should we remind ourselves ofalways ?
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Behavioral Disease in PregnancyProvider/Patient
Attitudes

• Providers
• -Addiction is a disease, not a moral failure
• -That treatment works and that patients can
  change their behaviors
• -Providers personal issues of substance use, of
  addiction and recovery affect treatment of SUDS
  patients
• Patients
• -Denial
• -Guilt
• -Fear of stigmatization and loss control

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Substance Abuse in PregnancyAttitudes-Providers

• If she cared about her baby, shed stop using
  drugs
• These women are a pain in the neck, they take
  time from real patients
• Shes just trying to get pain meds, shes
  manipulative

Corse et al . J Sub Abuse Treatment 12 1995
March of Dimes Substance Abuse Curriculum for
OB/Gyn 1995
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Substance Use/Psychiatric DiseaseEthics

• Patients
• Suffer from stigma, poverty,
• co-morbid illness, homelessness, violence,
  emotional loss
• Clinicians
• Need to translate fundamental ethical
  principles respect for persons,
• compassion,
• honesty,
• justice,
• into practices that serve the well being of
  patients

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Future Directions in Substance Use During
Pregnancy (challenges and unanswered questions)

• Refine knowledge of best practices. Obtain
  reimbursement for screening and interventions in
  health care settings
• Adapt and expand specialty addiction care to meet
  needs of a pregnant patients
• Change clinician perception of role compatibility
  (among generalists and specialists)
• Create organizational and professional common
  ground for collaboration between health care and
  addiction providers (patients clients)

Smith J. SBIRT of Illinois 2008
69

• Transference
• So when you come to me, dont assume
• That you know me so well as that
• Dont come with preconceptions
• Or expect me to fit the mold you have created
• Because we fit no molds
• We have no limitations
• And when you come, bring me your hopes
• Describe for me your visions, your dreams
• Bring me the best that you can
• Come in a dialogue of we
• you and me reacting, responding
• Being, something new
• Discovering.
• Sandra Maria Esteves The MOMS Project