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

And, now for something completely different…….

Substance Use in Pregnancy Science versus Popular Myths

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

What's New in Obstetric Medicine? 9 Key Questions (and Answers) about

Substance Use and Psychiatric Disorders in Pregnancy

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

1. Why is this important?

• Ubiquitous – common and in all groups

• Effects on pregnancy outcomes

• Effects on women’s health: short term and long term

• Effects on offspring

• Clinicians are often relatively unfamiliar with behavioral issues in pregnancy compared to other disease entities

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%

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

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, MMWR:1990, Vega, NEJM: 1993, Buchi Obstet/Gynecol 1993

** Chasnoff, NEJM, 1990, Nalty Alcohol & Drug Abuse: 1991

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,

Substance Use in PregnancyTobacco

DUHS/SAMHSA 2007

Substance Use in PregnancyTobacco/Ethnicity

• Percentages of Past Month Cigarette Use

• Women 15-44; by Pregnancy Status, Age, and

• Race/Ethnicity

NSDUH SAMHSA 2005

Alcohol Use in PregnancyNSDUH

NSDUH Report SAMHSA 2007

Pregnancy and Alcohol Use: Binge and Heavy Drinking by Groups

USDHHS, HRSA, 2005

Illicit Substance Use by Women

NSDUH Report SAMHSA 2007

Illicit Drug Use in PregnancyNSDUH

Percentage Past Month Illicit DrugUse, Women 15-44, 2002, 2003

NSDUH Report, SAMHSA, 2005

3. How does ATD use affect maternal health and pregnancy

outcomes?

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

Limitations of the LiteraturePublication Bias

Substance Use in PregnancyAdverse Maternal Outcomes

• Obstetric emergencies– Abruption– Previa

• Catastrophic medical events

• Infection– HIV/AIDS– Hepatitis– Pneumonia– UTI/Pyelonephritis

• Death

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: OR=2.3 (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

Substance Use Adverse OutcomesMortality

• California study- increased mortality for maternal death in polydrug, drug and alcohol, amphetamine and cocaine using parturients OR= 2.0, ( CI=1.74, 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

4. What are the effects of ATD use on offspring?

Substance Use in PregnancyAdverse Outcomes In Offspring

•Congenital Anomalies•PTL/PTD•IUGR•Neonatal abstinence syndrome

•SIDS/Infant Death•Behavioral Abnormalities

Early

Later

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

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

Substance UseCongenital Anomalies

• Cocaine

• Nicotine ?

• Hallucinogens

• Opiates

• Amphetamines

• Marijuana

• Alcohol

• Sedative-hypnotics?

Substance Use: Anomalies Fetal Alcohol Spectrum Disorder

• Alcohol/Acetaldehyde

• Dose dependent – cumulative/binge

• Effects throughout gestation

• Systems affected– Cardiac

– Genitourinary

– Oral/ocular/auditory

– CNS

Fetal Alcohol Spectrum Disorder

Persistent growth deficits, behavioralproblems and learning disorders

Fetal Alcohol Syndrome/Effect

Substance Use Neonatal Abstinence Syndrome

• OpiatesOpiates

• Nicotine

Chirboga, J Devel Peds 1998, Neuspiel Cocaine/Crack Res Newsletter 1991

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 (95%CI 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, 2001:90

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

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

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

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

5. How should we screen for ATD use?

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

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

Screening for Illicit Drug UseIn Pregnancy

• Universal questioning – part of routine history

(avoid-”You don’t 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

Screening for Illicit Drug UseIn Pregnancy

Toxicology 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

Toxicology Testing for Substance Abuse in Pregnancy

Medical-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

Screening: Brief Intervention

5% Dependent Use

At-Risk + Problem UseIntervene

Screen

US Preventive Services Task Force recommends screening & behavioral counseling in primary care and prenatal settings to

reduce substance misuse by adults

20%

Evidence Level B

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

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

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: 105Hankin JR. Alcohol Research and Health 2002: 26,

6. Does treatment work?

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): 1689 1695NIDA, Principles of Drug Addiction Treatment: A Research-Based Guide, NIH Bethesda, MD, July 2000

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

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; 2001Ashley, Am J. Drug and Alcohol Abuse; 2003Brouekhuizen, Am J. Obstet/Gynecol; 1992

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

Substance Abuse in PregnancyOpiate Stabilization/Detoxification

• Methadone- prevents fetal withdrawal, PTL, promotes rehab and compliance with prenatal care. Better BW, decreased m&m

• Pregnancy affects pharmacokinetics of methadone: drug metabolism, plasma volume, volume distribution, clearance

Methadone in PregnancyPrinciples of Use

• Individualize dose, use SOWS or COWS

• Maintain pre-pregnancy dose if conceives on therapy- (confirm dose with pt’s 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

• Physiologic changes- hormonal, neuro-endocrine, immunologic, body mechanics

• Altered self image

• Role changes

7. Does pregnancy improve/worsen psychiatric

disorders?

Prevalence of Mental Disorders in Women

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

Prevalence Depression by Trimester

Bennett H. A. Obstet/Gynecol 2004, 103

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

Untreated Depression and Pregnancy

• Poor nutrition

• Poor prenatal care attendance

• Substance use

• Suicide

• PTD/LBW/SGA

• Cognitive abnormalities offspring

• Postpartum depressionHalbreich U. Am J. Obstet Gynecol, 2005: 193Henry AL. Clin Obstet Gynecol 2004: 47Bonari L Can J Psych, 2004: 49

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),

Effects SSRIs on Pregnancy Outcomes

Kulin NA. JAMA, 1998:279

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

Moses-Kolko EL, JAMA 2005;293Nordeng H, Drug Safety, 2005: 28Chambers DC, N. Engl J. Med 2006: 354Gentile S. CNS Drugs, 2005: 19

?Long term effects on child development?

Psychotherapeutic AgentsBipolar Agents

• Carbamezepine (Tegretol)

• Gabapentin (Neurontin)

• Lamotrigine (Lamictal)

• Lithium

• Topiramate (Topamax)

• Valproic acid (Depakote)

Valproic Acid: Effects on Pregnancy

Relative risk of congenitalmalformations in patients receiving monotherapy was 3.77 (CI 2.18-6.52).

Overall rate of anomalies was 2.5X higher than baseline (p<.oo1)

9. Attitudes and Ethics…Patients and Providers- what should we remind ourselves of…always ?

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

-Provider’s personal issues of substance use, of addiction and recovery affect treatment of SUDS patients

• Patients

-Denial

-Guilt

-Fear of stigmatization and loss control

Substance Abuse in PregnancyAttitudes-Providers

• “If she cared about her baby, she’d stop using drugs”

• “These women are a pain in the neck, they take time from ‘real patients’ ”

• “She’s just trying to get pain meds, she’s manipulative”

March of Dimes Substance Abuse Curriculum for OB/Gyn 1995

Corse et al . J Sub Abuse Treatment 12: 1995

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

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

• “Transference”So when you come to me, don’t assume

That you know me so well as that

Don’t 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 MOM’S Project