SUBSTANCE ABUSE & NEWBORNS

Why is this important:

5.5% of pregnant women in the United States reported using at least one illicit drug during pregnancy.

21.2% of pregnant women aged 12-44 reported use of alcohol and 21.5% use of cigarettes during the past month.

Drug Abuse in Pregnancy

National Survey on Drug Use and Health (2002-2003): 4.3% of pregnant women ages 15-44 self-reported illicit drug use in past month, and may actually be as high as 15-30%.16

Opiate use in pregnant women ranges anywhere from 1% to 21%.1

Tobacco use in pregnancy: 20.3% 20

Alcohol use in pregnancy: 14.8% 20

Impact on Mom’s Prenatal Care/ Newborn

Outcome Poor Nutrition Late Prenatal Care Greater risk for: infectious diseases &

Sexually transmitted diseases Limited financial resources Increased risk: premature

birth, abruptio placenta,

and fetal demise.

Pathophysiology of Fetal Alcohol Syndrome: Symptoms of a baby with

fetal alcohol syndrome Poor growth while the baby is in the womb and after birth Decreased muscle tone and poor coordination Delayed development and significant functional problems in

three or more major areas: thinking, speech, movement, or social skills (as expected for the baby's age)

Heart defects such as ventricular septal defect (VSD) or atrial septal defect (ASD)

Structural problems with the face, including: Narrow, small eyes with large epicanthal fold Small head Small upper jaw Smooth groove in upper lip Smooth and thin upper lip

Alcohol

Associated with16: Teratogen IUGR Fetal alcohol spectrum disorder

Postnatal growth deficiency Cranial dysmorphology Mental retardation

Acute neonatal withdrawal20

Fetal Alcohol Syndrome

Fetal Alcohol Syndrome

Fetal Alcohol Syndrome: Tests

Blood alcohol level in pregnant women who show signs of being drunk (intoxicated)

Brain imaging studies (CT or MRI) shows abnormal brain development

Pregnancy ultrasound shows slowed growth of the fetus

Toxicology screen

Cocaine Abusing Pregnant Women

Increase the risk of miscarriage When the drug is used late in pregnancy, it may trigger

premature labor It also may cause an unborn baby to die or to have a

stroke, which can result in irreversible brain damage More likely to have a low birth-weight baby More likely to have babies born with smaller heads and

smaller brains proportionate to body size Twice as likely to have a premature baby Placental abruption Baby with a malformation of the urinary tract Feeding difficulties and sleep disturbances in newborn

Smoking while Pregnant Lower the amount of oxygen available to you and your

growing baby Increase your baby's heart rate Increase the chances of miscarriage and stillbirth Increase the risk that your baby is born prematurely

and/or born with low birth weight Increase your baby's risk of developing

respiratory (lung) problems Elevates the risk of having a child with

excess, webbed or missing fingers and toes

Drug Abuse in Pregnancy

No consistent pattern of congenital anomalies has been found with illicit substances (excluding EtOH, barbiturates, and maybe tobacco) in large-scale epidemiologic studies.

Tobacco

Associated with16: IUGR Behavioral problems via nicotine disruption of

CNS development May affect NAS Placental abruption20

PROM20

Placenta previa20

PTB20

Up to 20-30% of all LBW infants20

Tobacco

No increased RATE of congenital anomalies in smokers, but may contribute to RISK of anomalies associated with vascular disruption20: Cleft lip with/without cleft palate Gastroschisis Anal atresia Digital anomalies

Tobacco

Two to four fold increased risk of SIDS20

Smoking also increases risk of PTB & LBW, which are independent risk factors for SIDS

Four fold increased risk of DM II with maternal smoking >10 cig/d20

Inconsistent results from studies on cognitive ability

Tobacco

Smoking cessation Meta-analysis of RCT showed increased

BW and decreased LBW and PTB16.

But if that’s not good enough evidence to stop smoking…

Tobacco

“Effects of cocaine use were

NO DIFFERENT

than those observed from cigarette smoking”

on gestational age-adjusted BW, HC, and length16

Marijuana

Mechanism unknown as to how it may effect neonatal outcomes16

Proposed theory: reduced fetal oxygenation causing diminished fetal growth.16

Marijuana

Inconclusive data on birth weight (BW)16 or gestational age20

Full gamut: associated with LBW, no difference in BW among controls, & increased BW (up to 142 gm over controls).

1997 meta-analysis of 10 studies:

inadequate evidence that marijuana is associated with LBW in the amount typically consumed by pregnant women, but associated with 131 gm decrease in BW if used >4 times/wk.*

Opioids

Few studies have controlled for concomitant drug use, social, or psychosocial factors.

Among most studies, illicit opiate use is associated with LBW, PTB, and reduced fetal growth parameters.16

Opiates are not teratogens in humans3

Opioids Obstetric complications increase up to six fold1,11:

SAB LBW IUGR Preeclampsia Placental abruption PROM PTB Fetal distress Fetal demise Malpresentation, Low APGAR scores, PPH, septic

thrombophlebitis, Meconium aspiration, Chorioamnionitis

Opioids

Proposed Mechanisms: Anorexic effect on maternal nutrition16

Placental insufficiency11

Opioids

Neonatal complications3,1: Prematurity Low birth weight Postnatal growth deficiency Microcephaly Neurobehavioral problems* Increased neonatal mortality 74-fold increase in sudden infant death

syndrome (SIDS) Neonatal abstinence syndrome (NAS)

Opioids

Heroin8

Passage through placenta to fetus within 1 hour of administration

Accumulates in amniotic fluid Limited fetal detoxification due to immature

tissues Fluctuation in drug levels causes placental

changes* placental insufficiency and IUGR More significant placental change and LBW than

methadone or buprenorphine.8

CLINICAL SIGNS associated with Opiate Withdrawal in Newborns

Central Nervous System Dysfunction

Autonomic Dysfunction

Respiratory Dysfunction

Gastrointestinal Dysfunction

Risk Factors for Newborns of Substance Abusers

FEEDING PROBLEMS Suck-swallow incoordination Tongue thrust during feedings Poor formula intake Failure to thrive

SLEEP Sleep-wake cycles disorder

ATTENTION Difficulty with reactivity to stimuli

Risk Factors for Newborn of Substance Abusers

HYPERTONIC BABIES Also known as “stiff babies” Brief deep tendon reflexes Persistence of primitive infant reflexes

IRRITABILITY Neurological fragility Difficulty managing day-to-day stimuli Jerky movements

Screening

Every infant born to a substance abuser should be evaluated for HIV infection.

Signs of neonatal abstinence syndrome Small head size (brain size) Newborns who are underweight Stroke in the newborn Intestinal blood flow compromise (NEC) Positive drug screen in mother

Opioid Maintenance

Methadone Subutex (Buprenorphine) Suboxone (Buprenorphine/Naloxone) Oral slow release morphine

1 g heroin ~ 8 mg buprenorphine ~ 80 mg methadone

Methadone

Pregnancy Category C Full mu opioid agonist First-line treatment of opioid addiction

in pregnancy in the US2,5,6, UK, and Australia1.

Requires daily visits to methadone clinic.*

Methadone

Higher infant BW and less IUGR than seen in heroin-addicted moms.1,8

NAS in 60-100% of neonates Longer duration of NAS treatment vs.

buprenorphine & heroin 30 days vs. 11-12 days tx8

Likely due to long t1/2

Methadone

However, some experts believe that, when compared to buprenorphine, methadone is the preferred medication: They report buprenorphine has a “ceiling” dose,

which is surpassed by some woman…thus they require higher levels of opioid maintenance that can only be reached with methadone.10

Less structured regimen of buprenorphine tx vs. daily methadone dosing may lead to gaps in prenatal care, in addition to diversion or IVDA of buprenorphine.8

Subutex

Buprenorphine (Category C) Long-acting partial mu opioid agonist & kappa

antagonist While approved in the US for opioid detox &

maintenance, is not FDA-approved for use during pregnancy.7 *

However, is considered safe in pregnancy.9,15,11

First choice for opioid maintenance programs &

in pregnant women in Finland3 since 1996.14

Subutex

May have less placenta exposure than methadone1

Partial agonist profile may lower liability for NAS6

Cochrane Review6 favored buprenorphine over methadone in regards to: Higher infant BW* Shorter hospital stay

Subutex Low rates of prematurity2 (ave 39.2

wks3) NAS occurs in 62%, but only half

require treatment2

Less severe NAS than methadone2,3,5,6,8,11 (though no RCTs yet*) with ↓ incidence3,6 and ↓ need for pharmacologic treatment vs. methadone.6 *

Shorter duration of NAS treatment vs. methadone8

Subutex

Preliminary MDFMR stats show: None were low BW All had APGARS of 8 or greater at 1 and 5

minutes Possible dose-dependent relationship Unable to draw conclusions about when

babies may develop withdrawal symptoms High degree of variability in the frequency

of NAS scoring

Suboxone

Buprenorphine (Category C) + Naloxone (Category B)

Limited studies in pregnant women. US DHHS Center for Substance Abuse Tx:

cautious use of naloxone in opioid-addicted pregnant women may precipitate withdrawal in both mother & fetus.2

Recommends buprenorphine monotherapy, though admit it has great potential for abuse & diversion.2

Oral slow release morphine

Used in Austria since 1998 for treatment of opioid dependence.9

One study showed better success over methadone in helping pregnant women abstain from illicit substances.1

Opioid Maintenance – Monitoring in

pregnancy UDS, UDS, UDS

At increased risk for: anemia, malnutrition, HTN, hyperglycemia, STDs, TB, hepatitis, and preeclampsia.11

Regular Prenatal panel LFTs, Renal function, PPD, glucose intolerance,

anti-HCV antibody3,11

Consider repeat CBC, serology at 24-28 wks.11

Opioid Maintenance dosing in pregnancy

Varied opinion on monitored detoxification & abstinence during pregnancy.

If attempt to wean, suggested in 1st vs. 2nd Trimester 1st – theoretical risk of miscarriage11

3rd – risk of premature labor or fetal death11

Generally not recommended Higher methadone doses related to increased

BW, prolonged gestation11

Attempt to decrease incidence of NAS by weaning may cause continued substance abuse11

Opioid Maintenance dosing in pregnancy

In fact, increased dosage of maintenance therapy may be required in 2nd-3rd trimester:

Increased maternal fluid volume + altered opioid metabolism in placenta & fetus same dose produces lower blood level of particular drug11

Pain Management during Labor & Delivery

o Opioid-dependent patients may require higher and more frequent doses of opioid analgesics to maintain pain control.

Methadone & buprenorphine suppress opioid withdrawal for 24-48 hours, but only provide analgesia for 4-8 hours.4

Pain Management during Labor & Delivery

NO Stadol or Nubain! Opioid agonist-antagonists, thus can

displace the maintenance opioid from the mu receptor, precipitating acute withdrawal4

Epidural use reported in 73% of deliveries to opioid-dependent mothers.8

Impact on Baby

60-90% of opiate

exposed infants develop

neonatal abstinence

syndrome (NAS). Symptoms will manifest within 48 to 72 hours

after birth

S&S of Neonatal Abstinence Syndrome

Withdrawal Irritability Tremors High-pitched cry Diarrhea & Vomiting Respiratory Distress Abrasions Weight loss Aberrant temp control Lack of sucking Sneezing

Signs of Neonate Withdrawl Irritability

Tachypena Tremors Shrill Cry Mottling Hypertonicity of muscles Frantic Sucking of hands Temperature instability Loose diarrheal stools Seizures Nasal stuffiness

Sleep Disturbances

Which leads to:“Unlovable Infant…

Baby Outcomes

Guilt and Denial from the mother contribute to a poor communication/ connection between mom and baby

Leads to impaired language development, social-emotional problems, and/ or neglect and abuse.

Increased risk for medical, emotional/ behavior, and developmental difficulties.

Haven House and CAP

Most drug treatment programs cater to male clients

Those who accept women will often rescind treatment to women who become pregnant while in program

Provision of child-care for existing children is also vital to most women… high risk of relapse during immediate postpartum period.

So….

Placenta

Breastfeeding in Opioid Maintenance

In brief, it’s OK to breastfeed on Suboxone or methadone.

…so go ahead & encourage it!

Contraindications: illicit substance abuse HIV

Breastfeeding in Opioid Maintenance

Buprenorphine: breastfeeding infant will receive only 1/5 to

1/10 of the total available buprenorphine2,9.

No evidence to support theory that breastfeeding will help suppress NAS.2

Likewise, NAS does not occur after breastfeeding is discontinued.2

Postpartum Care in Opioid Maintenance

Continue maintenance opioid (or switch to Suboxone if on Subutex).

80% abstinence rate shown postpartum at Mercy’s Recovery Center in Westbrook, ME.

Opioid Maintenance

Improved outcomes when therapy includes3,11: prenatal care addiction treatment other social services, including

individual/group/family therapy to address the psychological and psychosocial factor of substance abuse.

Future ResearchNational Institute on Drug Abuse16:

“little information is available as to whether the detrimental effects seen in drug-

exposed offspring are the direct result of perturbations in the development of

placenta & its functions OR

caused by ‘host’ factors such as poor prenatal care, stress, infection, and poor

maternal nutrition, which are common comorbid factors in drug abusing women.”

Future research

Chronic stress has consistently been related to LBW and PTB16

Hypothesis = neuroendocrine, immune, and vascular roles that may influence uteroplacental transfer & delivery.

No studies of drug abuse in pregnancy have controlled for chronic stress.

Future treatment

Biggest influence of prenatal substance abuse may in fact be the increased postnatal risks16 rather than any direct drug-effect: Diminished bonding Neglect Foster care placement Disruptions in home environment

Summary Prematurity and IUGR are associated with tobacco, alcohol,

opioids, cocaine, and maybe amphetamines.

Teratogens: alcohol and barbiturates

Adverse effects of prenatal drug exposure are usually self-limited and confined to infancy. Exceptions include: Alcohol lifelong impairments Cigarettes may have long term behavioral effects

Psychosocial factors and concomitant maternal illnesses may play an even larger role in long term development of these infants.

Summary

Thus, when caring for a drug-addicted pregnant woman, understanding the complex roles that illicit drugs, inner stressors, and her surrounding external environment will not only help us better provide interventions to improve pregnancy outcomes, but also to give both her and her child a stepping stone toward a healthier lifestyle in the future.

REFERENCESAlbersheim, S. (1991). Newborn Patients of Mothers with Substance AbuseProviding proper

health care for mothers and their babies. Can Fam Physician.(37):1739–1746.

Bertrand J, Floyd LL, Weber MK. Guidelines for identifying and referring persons with fetal alcohol syndrome. MMWR Recomm Rep. 2005 Oct 28;54(RR-11):1-14.

Gorski, Terence T. (2001). Cocaine use during pregnancy. Gorski-Cenaps Web Publications. Retrieved on November 10, 2009. http://www.tgorski.com/Prevention/cocaine_use_during_pregnancy.htm

Nazario, Brunilda MD. Smoking During Pregnancy, Retrieved November 10, 2009. http://www.nlm.nih.gov/medlineplus/ency/article/000911.htm

Perinatal Substance Abuse. UCSF Children’s Hospital: http://www.ucsfchildrenshospital.org/pdf/manuals/59_SubAbuse.pdf

Stoll BJ. Metabolic disturbances. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 106. 

References1. Minozzi S, Amato L, Vecchi S, Davoli M. Maintenance agonist treatments for opiate dependent pregnant

women (Review). The Cochrane Library, Issue 2, 2008: 1-20.2. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment

of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS publication no. (SMA) 07-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration. 2007:67-71.

3. Kahila H, Saisto T, Kivitie-Kallio S, et. al. A prospective study on buprenorphine use during pregnancy: effects on maternal and neonatal outcome. Acta Obstetricia et Gynecologica. 2007; 86: 185-190.

4. Alford D, Compton P, Samet J. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Annals of Internal Medicine. 2006; 144:127-135.

5. Jones HE, Johnson RE, Jasinski DR, Milio L. Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. Drug and Alcohol Dependence. 2005; 78: 33-38.

6. Kakko J, Heilig M, Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: Comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug and Alcohol Dependence. 2008; 96: 69-78.

7. Jones HE, Suess P, Jasinski DR, Johnson, RE. Transferring methadone-stabilized pregnant patients to buprenorphine using an immediate-release morphine transition: An open-label exploratory study. The American Journal on Addictions. 2006; 15: 61-70.

8. Binder T, Vavřinková B. Prospective randomised comparative study of the effect of buprenorphine, methadone and heroin on the course of pregnancy, birthweight of newborns, early postpartum adaptation and course of the neonatal abstinence syndrome in women followed up in the outpatient department. Neuroendocrinology Letters. 2008; 29: 80-86.

9. Schindler SD, Eder H, Ortner R, et al. Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction. 2003; 98: 103-110.

10. Personal communication. Gary Kaufman, MD, Director of Maternal Fetal Medicine at Dartmouth-Hitchcock/Nashua and Director of its methadone program for pregnant patients.

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Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. DHHS publication no. (SMA) 06-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration. 2006: 211-224.

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