Opioid Dependence During Pregnancy

Michelle Lofwall, M.D. 

University of Kentucky

(slide 1)

©AMSP 2009


I.            Introduction

A.     Opioid dependence during pregnancy (preg) challenging to treat (slide 2)

1.      Doctors (medical student & resident) inadequately trained 1

2.      Medical & legal system prejudice

a.       ~25% OB/peds/family practice docs drug use in preg warrants incarceration 2

b.      Survey of new mothers report that nurses:

i.         Treat them negatively when find out test + for illicit drugs 3

ii.       Attention to them when find out test + for illicit drugs 3

c.       Legal charges brought against preg who use illicit drugs

i.         Charges include fetal murder/manslaughter, illegal drug delivery & trafficking (via umbilical cord), & child abuse 4

ii.       Fear of prosecution can deter ♀ from seeking treatment (rx) 2

iii.      Often highly publicized & may scare doctors from offering rx 4

3.      Doctors may need to report drug use in preg to various state agencies 5 

4.      Overall, problems establishing therapeutic doctor-patient alliance 5

B.     What you need to know about opioid dependence during preg (slide 3)

1.      Understand punishing preg ♀ for using illicits ≠ effective deterrent 

a.       Criminal prosecution hasn’t opioid use in preg  6, 7

b.      Comprehensive medical & psychosocial rx helps mom & baby 8, 9

i.         3-fold ↓ in mothers’ opiate use 10

ii.       Initiates & improves attendance to prenatal care 9, 11

iii.      3-fold ↓ risk of low birth weight baby (LBW: <2500 grams) 12

iv.     If mother HIV +, ↓ perinatal transmission to < 2% (vs. 25% if no rx)8

v.       Mom 2x likely retain custody/parenting role in 1st yr of child’s life 13

2.      This lecture addresses 4 areas: (slide 4)

a.       Definitions of opioids, abuse, dependence & withdrawal

b.      Causes, course, prevalence & comorbidities among opioid dependent mothers

c.       Medical complications of opioid dependence on mom, fetus & newborn

d.      Treatment of opioid dependence during pregnancy                                                       

e.       2 stars in figure indicates opportunity to help two people – mom & baby

II.            Definitions of opioids, abuse, dependence & withdrawal

A.     Opioids: all compounds related to opium 14 (slide 5)

1.      Natural alkaloid derivatives from opium = “opiates”

a.   Ex: morphine (MS Contin®) & heroin

b.      Detected on opiate urine drug test

2.      Semi-synthetics also called opiates

a.       Ex: hydrocodone (Lortab®, Vicodin®), oxycodone (Oxycontin®, Percocet®)

b.      Not always detected as opiate on urine drug screen

c.   May need test specifically for each (call lab if not sure)

3.   Fully synthetic are NOT called opiates – refer to as “opioids”

a.  Ex: methadone (Methadose®), fentanyl (Duragesic®), & buprenorphine (Suboxone®)

b.  Not detected on opiate urine drug tests

c.  Test specifically for each one

B.     Opioid abuse (DSM-IV) - repeated probs in same 12 months (mo) with ≥ 1 of: (slide 6)

            1.   Inability to fulfill role obligations

            2.   Use in physically hazardous situations 

            3.   Legal problems

            4.   Social or interpersonal problems

            Note: not meeting criteria for dependence

C.      Opioid dependence (DSM-IV) - repeated probs in same 12 months with ≥ 3 of: (slide 6)

1.      Use larger amts/longer time than intended

2.      Desire or unsuccessful efforts to cut down

3.      ↑ Time spent to get, use & recover

4.      Give up important activities

5.      Ongoing use despite problems

6.      Tolerance: ↑ use for same effect; ↓ effect with same amount used

7.      Withdrawal (discussed below)

8.      Most preg opioid studies focus on dependence (not abuse) – same with lecture

D.     Opioid withdrawal (DSM-IV) (slide 7)

1.      Occurs in 1 of 2 situations:

a.       Stop or ↓opioid use after regular/heavy use

b.      Opioid antagonist [naloxone (Narcan®)] given & displaces opioid from receptor

2.      ≥3 of following signs/symptoms that resemble flu:

                                     a.      Dysphoric (unhappy) mood

                                    b.      Nausea or vomiting

                                     c.      Muscle aches

                                    d.      Lacrimation (eyes tearing) or rhinorrhea (runny nose)

                                     e.      Mydriasis (big pupils), piloerection (goose bumps), or sweating

                                      f.      Diarrhea

                                     g.      Yawning

                                     h.      Fever

                                       i.      Insomnia

3.      Miserable, but not deadly in otherwise healthy adults

4.      Possible death for fetus/neonate if untreated (why depend dx > attn than abuse) 8, 15

E.  Have now completed Defns section. Now discuss causes, course, prevelance & comorbities section. (slide 8)

III.            Causes, course, prevalence & comorbidities among opioid dependent mothers

A.     Etiology of opioid abuse/dependence = 50% genes & 50% environment 16 (slide 9)

1.       Role of genes vs. environmental factors determined by twin studies

2.       Female twins evaluated to determine: 16

a.       Genetic similarity: identical twins =100% same vs. fraternal = 50% same

b.      Environment:  shared and non-shared

3.      Environmental factors that contribute to etiology include: 17

a.       Availability & peer use

b.      Drug-using sexual partner

c.       History of victimization (e.g., childhood physical/sexual abuse)

B.     Course of opioid abuse/dependence = chronic, relapsing with mortality 18 (slide 10)

1.      >50%  preg opioid dependent relapse 19-21

2.      Opioid use starts before pregnancy for >90% of preg opioid dep in rx 19, 20, 22

3.      Mortality: 20x vs. age-matched non-sub abuse/dependent (note: mostly studied) 23, 24

C.     Prevalence of opioid abuse/dependence during preg unknown

1.      Epidemiologic data rely 1° on self-report of opioid use

2.      U.S. National Survey on Drug Use and Health: annual cross-sectional survey 7

a.       Preg ♀ age 15-44 yrs evaluated

b.      All are community dwelling (ř hospital, prison, homeless without shelter)

c.       1% of preg ♀ self-report current opioid use during preg vs. ~3% of non-preg

d.      1° opioids used = prescription pain pills (not heroin)

e.       Overall, low prevalence of opioid use in preg

3.      How accurate are self-reports? (slide 11)

a.       Study tested meconium (newborn stool) vs. maternal self-report of drug use 6

i.         Meconium opiate + : 8.7% vs. maternal self-report opiate use: 1%

ii.       Self-report underestimates opioid use

b.      Stigma/shame/fear ↓ self-report 5

c.       Message=cannot rely only on self-report to detect illicit opioid use

D.     Preg opioid dependent ♀ use other drugs (slide 12)

1.      2 most commonly used other substances = cigarettes & cocaine

a.       90% smoke cigarettes, 25, 26 which are independently associated with :

i.         ↑ Spontaneous abortion & stillbirths 27

ii.       ↑ Pre-term birth (<37 weeks gestation) 27

iii.      ↑ LBW 27

iv.     ↑ Sudden infant death syndrome (SIDS) 27

b.      >10% use cocaine, 28-30 which is independently associated with:

i.         ↑ Placental abruption 31

ii.       ↑ Pre-term birth 31

2.   Makes difficult determine what effects 2° to maternal opioid use

E.  Preg opioid dependent ♀ have non-substance psychiatric dx (slide 12)

1.   Psychiatric dxs in non-preg opioid dep ♀ in treatment (Note: limited data in preg ♀)

a.       >10% current non-substance Axis I DSM-IV dx (mood & anxiety do=#1) 32, 33

b.      ~25% with current personality disorder (Axis II) DSM-IV dx 32

2.      Non-substance psychiatric dxs associated with adverse preg outcomes

a.       E.g.,: mood disorders ↑ incidence of low birth weight, fetal growth 34

b.      Makes difficult determine what effects 2° to maternal opioid use

F.  Preg opioid dependent ♀ have complex social problems (slide 13)

1.   Poor psychosocial supports (e.g., >50% are single moms) 35-37

2.   Low socioeconomic status (e.g., receiving public health care) 9

3.      > 50% unemployed 35, 36

4.   > 25% history of physical/sexual abuse 8, 36, 38

5.   These social problems adversely affect pregnancy 8

a.       ↓ Access to prenatal care

b.      ↓ Adherence with prenatal appt

c.       Direct physical harm to mom/fetus (e.g., due to physical abuse)

6.      Makes difficult determine what effects 2° to maternal opioid use

G. Preg opioid dependent ♀ engage in risky behaviors (slide 14)

1.      Sharing needles/drug paraphernalia, dealing drugs, unprotected sex, prostitution

2.      ↑ risk for infectious diseases, cellulitis (infection of skin), physical trauma, homicide

3.      Infections in mom can be harmful to fetus: 39

                                     a.      Infxn can spread to placenta/amniotic fluid causing chorioamnionitis

                                    b.      Mom’s immune response (ex: IL-6, TNF, prostaglandines) exacerbate situation

                                     c.      These can then induce:

i.         Premature uterine contractions, labor & delivery

ii.       Breakdown of fetal membranes & spontanteous abortion

H.     Now completed Causes, course, prevalence & comorbities. Major points are: (slide 15)

1.      Etiology of opioid abuse/dependence = genes & environment

2.      Serious psychosocial & medical problem, often chronic in nature

3.      Many comorbidities associated with opioid abuse/depend in preg

4.      These comorbidities independently ↑ risk for harm to mother & baby

I.  Medical complications will be discussed next

IV. Medical complications of opioid dependence on mom, fetus & newborn

A.  Medical problems in mother and fetus 40, 41 (slide 16)

1.  Multifactorial etiology (as discussed above because of all comorbidities)

2. Infectious diseases include (but not limited to):

a.       HIV: Major concern given risk of IV drug use (IVDU) & unprotected sex

                                                   i.       ~If mom HIV + 25%  transmit to baby if untreated 8

                                                 ii.      If mom receives HIV rx <2% transmission to baby 8

                                                iii.      Mom cannot breastfeed if she is HIV+

b.      Hepatitic C: present in >2/3 of IVDU 42

                                                   i.      ~5% transmit to fetus (higher if mom also HIV +) 43, 44

                                                 ii.      No way yet to decrease transmission rate (e.g., C-section does not help) 43, 44

                                                iii.      Mom can breastfeed if she is Hep C +

                                               iv.      Hepatitis C most common reason for liver transplant request in U.S.

c.       Endocarditis (infection of heart valve) among IVDU

i. Often right-sided involving tricuspid valve 42

ii. Can lead to heart failure inadequate oxygenated blood supply to fetus

iii. 10% mortality in adults 42

3.  Nutritional deficiencies 40, 41

      a. Cause often poor diet & not taking prenatal iron-fortified vitamins

b. Iron-deficiency anemia in preg (prevalence ~25%) independently associated with:45

      i. Preterm birth

      ii. Low birth weight

      iii. Small for gestational age

B. Fetal hypoxia (low oxygen) = major concern for fetus in opioid depend moms (slide 17)

1.      Many causes (ex: cocaine, smoking) & fluctuating maternal intake of opioids

2.      Opioids cross placenta 8

3.      Maternal opioid use pattern: use a lot, stop, withdrawal, use again causes:

a.       Changing opioid concentrations (conc) for fetus = unstable environment

b.       Repeated cycles of fetal opioid intoxication & withdrawal 39

c.       Constant conc. mitigate problem (why methadone rx helps – discuss more later)

4.  Hypoxia can lead to: 39

                                     a.            Spontaneous abortion

                                    b.            Placental insufficiency

                                     c.            Hypertensive emergencies

                                    d.            Pre-term labor

                                     e.            Poor fetal growth

C.     Medical problems in newborn 32, 40, 41, 46 (slide 18)

1.      ~50% low birth weight (vs. < 20% in methadone maintenance rx)

2.      Death (no good current data on rates)

3.      Meconium aspiration (no good current data on rates)

4.      ~ 10% microcephaly (small head): 0.8 cm smaller than nondrug-exposed neonates8, 13

5.      HIV/hep C infection passed from mom (discussed above)

6.      Neonatal abstinence syndrome

        D.      Neonatal abstinence syndrome (NAS) = opioid withdrawal in newborn (slide 19)

1.      Distressing for med stud/mom to see; why mom’s say baby born “addicted”

2.      Dx based on signs from 4 systems 8 (slide 20)

                                  a.         CNS excitability: seizure, tremors, hypertonia, poor sleep, high pitched cry

                                 b.         Autonomic nervous system ↑: sweating, sneezing, tearing, hyperthermia

                                  c.         GI system: uncoordinated suck/swallow → feed difficult, vomit, diarrhea

                                 d.         Respiratory distress: ↑ secretions, hyperpnea (↑ RR), cyanosis, apnea

                                  e.         Can be deadly if not recognized & treated

3.      Time course of NAS (slide 21)

                                  a.      Multiple factors affect onset & duration: 8

                                                i.         Half-life (T ˝) of opioid (the shorter the T1/2 the sooner NAS develops)

                                              ii.         Fetal opioid storage (if stored prolongs time to development of NAS)

                                             iii.         Rate of fetal metabolism & excretion (faster = more abrupt NAS)

b.         Heroin

                                             i.            Has short T ˝ (5 minutes) & not stored by fetus 8

                                           ii.            Typically see NAS develop 4-24 hrs after birth 8

c.       Methadone

                                                i.         Has longer T ˝ (27 hrs) & stored by fetal lung/liver/spleen 8

                                              ii.         Typically see NAS develop 24-72 hrs after birth 8

                                 d.         Duration of NAS: highly variable from 6 days to 8 weeks

4.      Risk factors: (slide 21)

                                  a.         Maternal opioid depend: ~70% of babies will have NAS 47

                                 b.         Smoking 1ppd vs. ˝ ppd: ↑ peak NAS severity x2 48

                                  c.         Prematurity ↓ severity of NAS 49, 50

5.      NAS treatment = medication if severe & supportive interventions always (slide 22)

                                  a.      Supportive: swaddle, quiet spaces, freq feeds, suction excretions 41

                                 b.      Med: tincture of opium (TOC) recommended by American Academy of Pediatrics51

                                               i.                      TOC has many ingredients (e.g., morphine, codeine)

                                              ii.                      TOC concentration =10mg/mL but is typically diluted 25-fold

                                            iii.                      25-fold dilution results in 0.4 mg/mL of morphine

                                            iv.                      Starting dose = 2 drops/kg or 1 mL/kg every 4 hrs

                                             v.                      Dose increased by 2 drops/kg every 4 hrs as needed to control withdrawal

                                  c.         ~60% of babies with NAS require medication 47

                                 d.         Treatment of severe NAS is life-saving

E.  Have now completed Medical Complications section. Major points are: (slide 23)

      1. Many serious medical problems in mom/fetus/neonate

      2.  Repeated opioid withdrawal & intox causes unstable fetal environment & hypoxia

      3. Opioid withdrawal can be deadly in neonate, but it’s treatable & rx = life-saving

F. Treatment of opioid dependence during pregnancy discussed next

V.  Treatment of opioid dependence during pregnancy

A.     4 treatments will be reviewed (slide 24)

1.      Psychosocial interventions/counseling

2.      Methadone maintenance (MM) rx

3.      Methadone withdrawal

4.      Buprenorphine maintenance

B.     Psychosocial interventions/counseling (slide 25)

1.      Essential component/cornerstone of rx for all substance use disorders

2.      Counseling: individual, group, 12-step oriented (ex: Narcotics Anonymous)

3.      Build therapeutic alliance 9

a.       Recognize ♀’s courage in ask for help

b.      Facilitate rx entry: remove barriers   

                                                   i.      Flexible scheduling

                                                 ii.      Timely – no long waiting lists

                                                iii.      Emphathic treatment providers 

                                               iv.      Allow children to come

4.      What to do when pt is demanding & resistant? 9

a.       View as expected & normal behavior

b.      Think of as challenge & discuss with other rx team members

c.       Don’t give up, be positive & encouraging

d.      Behavior & attitudes change over time

5.       Make complete assessment of all rx needs 9, 40

a.       Assess for psychiatric problems & treat

b.      Assess for medical problems & treat

c.       Assess social situation & assist

                                                   i.      Living situation – homeless, domestic violence, partner using drugs?

                                                 ii.      Employment status – job skills training need?

                                                iii.      Need to apply for public health care?

C.     Methadone maintenance (MM): standard of care for opioid depend in preg 40 (slide 26)

1.      Methadone = synthetic opioid agonist with long T ˝ (27 hrs)14

2.      1972 FDA-approved for opioid dependence rx

3.      Methadone & the law 52

a.       Only federally licensed MM clinics can prescribe

b.      Must be at least 18 yr old

c.       If < 18 yrs old need:

                                                i.         Parental consent &

                                              ii.         Failed 2 detoxification or drug-free treatments

d.      Must >1 yr opioid dependent & evidence of depend (preg is exception)

e.       Must come daily to get medicated for 1st 90 days

                                                   i.      Supervised dosing helps to ensure medication taken as prescribed

                                                 ii.      risk of diversion/misuse of medication by injection

                                                iii.      Opportunity deliver on-site psychosocial/med services

4.      Goals of MM:

a.       Mother 40 (slide 27)

                                                i.         Prevent opioid withdrawal

                                              ii.         Stop illicit opioid & all illicit drug, alcohol & nicotine use

                                             iii.         Assist with psychosocial problems

                                            iv.         Treat comorbid medical & psychiatric problems

                                              v.         Form supportive abstinent network

                                            vi.         Engage in prenatal care & other medical/psychiatric care

                                           vii.         Develop parenting skills

                                         viii.         Notice: goals = more than drug abstinence b/c probs > drug use

                                 b.         Fetus/neonate 40  (slide 28)

                                                   i.      Stabilize intrauterine environment

                                                 ii.      Stop fetal cycles of opioid withdrawal/intoxication

                                                iii.      Deliver term, healthy neonate

                                               iv.      Promote + maternal bonding

5.      Achieved by following components of rx: 40 (slide 29)

a.       Multidisciplinary team working together

                                                   i.      Social workers & counselors

                                                 ii.      Physician at methadone clinic

                                                iii.      OB

                                               iv.      Anesthesiologist for pain management during delivery/post-partum

                                                 v.      Other specialities as needed (Infectious diseases, internist, psychiatrist)

b.      Individual & group counseling

                                                i.         Identify & prioritize rx needs

                                              ii.         Similar as in psychosocial rx discussed already

                                             iii.         Non-confrontational approach

                                            iv.         Amount of counseling + affects drug use 53

c.       Parenting classes

d.      Daily oral methadone administration     

                                                         i.            Only legal if through licensed methadone clinic

                                                       ii.            Initial doses 30 mg usually, 40 mg maximum on 1st day 52

                                                      iii.            Typical maintenance doses: at least 50 mg daily 52

                                                     iv.            Dose must be individualized – no single “right” dose for everyone

                                                       v.            Dose may change with trimesters as gain more total body water

                                                     vi.            Effective dose = suppress withdrawal & block + illicit opioid effects if use

e.       Notice: methadone only 1 part of MM rx

6.      Benefits of MM rx vs. no rx 8, 9 (slide 30)

a.       3-fold ↓ in mothers’ opiate use 10

b.      Initiates & improves attendance to prenatal care 9, 11

c.       3-fold ↓ risk of low birth weight baby 12

d.      If mother HIV + & accepts rx, ↓ perinatal transmission to < 2% 8

e.       Mother ~2x more likely retain custody/parenting role in childs’ 1st year of life 13

7.      Limitations of MM (slide 31)

a.       Limited MM availability - some states 0 or 1 clinic 40

b.      Limited patient acceptance: stigma, daily visits, fear baby born “addicted”

c.       Does not reduce risk for NAS

8.      Developmental effects for children prenatally exposed to MM 8, 13, 54-57

a.       Multiple factors influence - environment, parenting (not just the drug)

b.      Mental & motor fxn within normal range

c.       Possible fine motor skill probs (but not different from untreated drug-exposed)

D.     Methadone-assisted opioid withdrawal (slide 32)

1.   Recommended rx  early 1970’s until case-reports of fetal deaths appeared 58

2.      Now utilized when MM is unavailable or refused 11

3.      Goals of rx:

a.       Prevent & ↓ severity of op withdrawal to mom/fetus

b.      Achieve opioid-free state in mother/fetus

c.       No NAS

4.      Achieved by following components: (slide 33)

a.       Inpatient hospital admission with multi-disciplinary team

b.      Stabilize on methadone to alleviate withdrawal

c.       Taper methadone dose while OB monitors fetus for evidence of distress

                                                   i.      No specified amount of time

                                                 ii.      If fetal distress emerges – prolong taper/adjust dose to relieve withdrawal

                                                iii.      Tapers completed safely within 3 and 7 days at specialty inpatient rx units 11

d.      Discharge patient from hospital

e.       Cont’d treatment aimed at maintaining opioid abstinence

5.      Outcomes (slide 34)

a.       40-100% preg relapse 19-21 – why such high relapse rate?

                                                   i.      Problem not only about physical dependence & withdrawal

                                                 ii.      Complicated psychosocial problem – remember the comorbidity discussed

b. MM vs methadone detox study - detox resulted in: 11

                                                   i.      2x drug + urine at time of delivery

                                                 ii.      5x days retained in substance abuse treatment

                                                iii.      6 fewer OB appts attended

                                               iv.      No diff in NAS or other fetal/neonatal outcomes

E.   Buprenorphine -  potential future rx for opioid depend in pregnancy (slide 35)

1.      2002 FDA-approved for trx of opioid dependence, but not approved in preg

2.      Pharmacology 59

                                  a.         Partial opioid agonist = not as strong as full op agonist

                                 b.         Enhanced safety profile (Schedule III) - ceiling effect on respiratory depression

                                  c.         Sublingual tablet b/c poor gut absorption

                                 d.         T ˝ = 37 hrs – allows for daily or alternate day dosing

3.      Buprenorphine & the law 59 (slide 36)

                                  a.  Drug Abuse Treatment Act of 2000 allows it to be prescribed in a doctor’s office

                                 b.  Doctor must be qualified to prescribe:

                                             i.      Most commonly done by completing a 8 hr CME about bup

                                           ii.   Must get special DEA X # before prescribing

4.      Potential office-based treatment advantages over MM clinic 59, 60

a.       ↑ patient acceptability

b.      ↑ patient anonymity

c.       ↓ stigma

d.      ↑ availability of rx

5.      Research shows as good as methadone on several outcomes 9, 28, 30, 61-65

                                     a.      Maternal illicit opioid use

                                    b.      Maternal attendance at prenatal OB visits

                                     c.      Maternal treatment retention

                                    d.      Neonatal birth weight

                                     e.      Rate of NAS

                                      f.      Severity of NAS

                                     g.      Neonatal days in ICU

6.      Large NIH multi-site clinical trial of bup vs. methadone in preg underway

         F.         Now completed rx review. Summary:  (slide 37)

1.   MM is current standard of care

2.   Improves maternal & fetal outcomes

3.   MM = more than just methadone administration

4.   Must treat all psychosocial aspects, too

5.   Overall, golden opportunity to make + impact




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