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CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 00, Number 00, 000–000
r 2013, Lippincott Williams & Wilkins
The Use of Narcotics
and Street Drugs
During Pregnancy
MICHAEL K. LINDSAY, MD, MPH and ERIN BURNETT, MD
Department of Gynecology and Obstetrics, Emory University,
Atlanta, GA
Abstract: All prenatal care providers should offer
routine voluntary substance use screening to all patients. Parturients who screen positive for illicit substances require a multidisciplinary team approach to
drug rehabilitation and prenatal care. This review will
examine the pharmacological properties and the neonatal consequences of the use of opioids and amphetamines. Substance-abusing parturients typically abuse
multiple substances simultaneously and have other
comorbidities including psychosocial instability and
mental illness. These comorbidities must be effectively
addressed to achieve optimal health outcomes for
both mother and infant.
Key words: illicit substances, prenatal care, and
neonatal consequences
identifying, and treating substance-abusing pregnant women can improve their
pregnancy outcomes and lead to more
beneficial long-term health outcomes in
this high-risk population.
The use of street drugs and other illicit
substances in pregnancy is an expensive
public health problem. In 2008, drug
abuse costs in the United States were
estimated to be >$180 billion a year,
including $605 million associated with
health care costs for drug-exposed newborns.1 In addition, illicit drug use among
women of reproductive age has major
physical and mental health consequences
and is associated with increased rates of
sexually transmitted infections, including
hepatitis B, human immunodeficiency
virus (HIV), as well as depression, domestic
violence, poverty, and significant prenatal
and neonatal complications.2 The magnitude of substance abuse in pregnancy is
well characterized from 2010 data from
the Substance Abuse and Mental Health
Service Administration that performs an
annual survey on drug use the National
Survey on Drug Use and Health. The
2010 survey estimated that 22.6 million
(8.9%) of Americans, age 12 years and
Introduction
The use of illicit substances of abuse and
street drugs is an emerging public health
problem. The pharmacologic properties
of many of these substances cause physical dependence in the user and leads to
behaviors that cause adverse consequences for both mother and infant. Screening,
Correspondence: Michael K. Lindsay, MD, MPH,
Department of Gynecology and Obstetrics, 69 Jesse
Hill Jr. Drive, SE, Atlanta, GA. E-mail: mlindsa@
emory.edu
The authors declare that they have nothing to disclose.
CLINICAL OBSTETRICS AND GYNECOLOGY
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VOLUME 00
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Lindsay and Burnett
above, were ‘‘current’’ (past month) drug
abusers.3 The most commonly abused
substances were marijuana, psychotherapeutic drugs, and cocaine. Data from this
survey also revealed that 4.4% of pregnant women were current (past month)
substance abusers. The highest prevalence
of use was observed in 15 to 17 year olds
(16.2%), followed by 18 to 25 year olds
(7.4%), whereas the lowest prevalence of
use was observed in 26 to 44 year olds
(1.9%).3 Survey data, however, may
grossly underestimate drug use in pregnancy. A study of inner city parturients
who underwent universal drug screening
revealed that 19% screened positive for
Z1 substance at presentation to labor and
delivery. However, only one third of those
who screened positive actually gave a
history of drug use.4 The underreporting
of drug use by pregnant women is complex and may be attributable in part to the
stigma of drug use in pregnancy and/or
the fear of legal consequences and memory failure.4
All prenatal care providers should offer
routine voluntary substance use screening
to all patients. The goal of drug screening is
to identify women for counseling and referral to drug rehabilitation. The American
Congress of Obstetrician Gynecologist declares that Obstetrician Gynecologist have
the moral obligation to provide routine
alcohol and drug abuse screening to all
prenatal patients.1 Prenatal care providers
should provide prenatal substance use
screening in a culturally sensitive nonjudgmental matter and should clearly convey to
parturients the public health rationale for
screening that is, to protect both maternal
and fetal health. In addition to voluntary
substance use screening, several chemical
tests can be employed to detect illicit substances. Specimen used for testing exposure to illicit substances includes maternal
blood and urine, and fetal cord blood,
meconium, hair, and urine. However, the
most commonly used test because of ease
of availability for both mother and infant
involves urinalysis.5 It is important to realize that false-negative test results can occur
if too much or too little time has passed
since drug ingestion, or if the urine is too
dilute. Parturients who screen positive for
illicit substances either by self-report and/
or urine drug screens require a multidisciplinary team approach to drug rehabilitation
and prenatal care. This multidisciplinary
team should include an obstetrician, addiction specialist or a trained addiction counselor, mental health professional, newborn
specialist, and social worker. The diverse
expertise of the team should allow it to
effectively address the myriad of medical
and psychosocial issues encountered in
managing these high-risk pregnancies.
This review will examine the pharmacological properties and the maternal and
neonatal consequences of the use of opioids,
and amphetamines in pregnancy. In many
instances substance-abusing parturients
abuse multiple substances simultaneously;
therefore it is difficult to determine the effect
of a particular substance of abuse in isolation. In addition, many substance abusers
have other comorbidities including psychosocial instability and mental illness. These
comorbidities must be considered and effectively addressed to achieve optimal health
outcomes for both mother and infant.
Opioids: Pharmacology and
Epidemiology
An opioid is a psychoactive chemical that
works by binding to opioid receptors
found principally in the central nervous
system and the gastrointestinal tract.6 The
receptors in these organs mediate both
the beneficial and side effects of this class
of drugs. There are 4 broad classes of
opioids; endogenous opioid peptides produced in the central nervous system such
as endorphin, and enkephelins; natural
opioids which are alkaloids contained
in the resin of opium poppy such as
morphine, and codeine; semisynthetic
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Illicit Substances of Abuse and Street Drugs
opioids created from natural opioids such
as oxycodone, heroin, and buprenorphine; and fully synthetic opioids such
as fentanyl, and methadone.7 The pharmacological effects of opioids analgesics are
derived from the interaction of 3 opioid
receptor types (m, d, k). The major pharmacological effects of opioids are decreased
perception and reaction to pain as well as
increased pain tolerance and feeling of euphoria, which is the major motivation for
recreational use of these drugs. Their major
side effects include sedation, respiratory
depression, and constipation.7 These drugs
can be administered by multiple routes including orally, by injection, absorbed by
skin, sniffing, or smoking. Opioid addiction
is characterized by physical dependence and
tolerance that leads to the need for higher
doses of the drug to achieve the same physiological effects.7 Once a parturient is opioid
dependent, withdrawal symptoms in both
the mother and infant will occur unless
additional drug is obtained. With short-acting opioids, such as heroin, withdrawal
symptoms can occur within 6 to 12 hours,
whereas for long-acting opioids, such as
methadone withdrawal symptoms can be
experienced between 72 to 96 hours.7
It is difficult because of its illicit nature
and transient use to obtain exact information on the prevalence of opioid use in
pregnancy. Over the past decade, prevalence data have primarily originated from
chemical analysis of meconium and maternal self-report. A 2004 observational
study that relied on meconium analysis
estimated that 7000 opiate-exposed birth
occurred annually in the United States,
whereas data from the 2010 National
Survey on Drug Use and Health estimated 1 in 1000 pregnant women admitted to heroin use in the past 30 days.3,8
The most commonly abused opioids in
pregnancy include heroin, and prescribed
opioids including codeine, morphine,
oxycodone, meperidine, hydromorphone,
hydrocodone, fentanyl, methadone, propoxyphene, and buprenorphine.9
3
Heroin: Pharmacology and
Epidemiology
Heroin or diacetylmorphine is a synthetic
opioid derived from the sap of the poppy
seed (Papaver somniferum). It is lipid soluble and rapidly crosses the blood brain
barrier where it is converted to morphine
and binds to natural opioid receptors.10 Its
primary route of use is intravenously but it
is also occasionally snorted or smoked.
Sniffing or smoking heroin has recently
gained popularity because of the availability of high-purity drug coupled with the
fear by users of sharing needles and contracting HIV or hepatitis B or C.11 Many
current heroin users mistakenly believe
that sniffing or smoking heroin will not
lead to addiction. Intravenous use produces effects within seconds,10,11 whereas
snorting or smoking produces effects in
minutes.10,11 The duration of heroin euphoric effect is 3 to 5 hours which leads to
repeated uses of this drug to maintain a
high.10 The adverse maternal consequences of heroin addiction are both short and
long term. The short-term adverse effects
include somnolence, altered mentation,
constipation, diarrhea, urinary retention,
and cardiorespiratory depression. Longterm adverse effects include physiological
withdrawal, liver disease, pulmonary complications, kidney disease, infectious morbidity from hepatitis B and C, sexually
transmitted diseases, HIV, endocarditis,
abscesses, pneumonia, and tuberculosis.10
Effects on Pregnancy
Heroin passes rapidly through the placenta with limited fetal detoxification and
within 1 hour accumulates in the amniotic
fluid.12 The lack of in utero metabolism of
heroin explains the high risk of the onset
of in utero withdrawal symptoms when
this opioid is not available to the mother.
Chronic untreated heroin use in pregnancy has been associated with increased
risk of adverse pregnancy outcomes
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Lindsay and Burnett
including poor fetal growth, preterm premature rupture of membranes, preterm
birth, neonatal abstinence syndrome
(NAS), antepartum hemorrhage, low birth
weight, maternal infections, use of other
illicit drugs, poor prenatal care, and social
adversity.13,14 Many of these adverse effects are felt to be secondary to poor health
behaviors of the mother combined with
repeated episodes of in utero opioid
withdrawal.
Prescribed Opioids; Effects on
Pregnancy
Three prescribed opioids codeine, meperidine, and oxycontin are also commonly
abused in pregnancy. Codeine or (3 methylmorphine) is a synthetic opiate used for
its analgesic, antitussive, and antidiarrheal
properties.6 Small case series and casecontrol studies have revealed an association between codeine use in pregnancy and
both congenital anomalies and NAS.15,16
However, a large prospective cohort study
of 2666 women who used codeine during
pregnancy compared with 65,316 women
who used no opioids during pregnancy
after adjusting for potential confounders
found no association with maternal codeine intake during pregnancy and the risk
of congenital anomalies or infant survival.17
Meperidine (ethyl 1-methyl-4-phenylpiperidine-4-carboxylate) is an opioid agonist of
the morphine type that is used to relieve
moderate to severe pain. This drug is administered by crushing, chewing, snorting,
or injecting dissolved products. Meperidine
abuse in pregnancy often results in uncontrolled delivery of this drug which poses
a significant risk of high drug levels, which
can lead to maternal overdose and death.
In addition, meperidine used within hours
of delivery can create drowsiness and potential serious breathing problem in the
newborn, whereas chronic use can cause
NAS.18 Oxycontin or oxycodone hydrochloride, (5a-epoxy-14-hydroxy-3-methoxy
methylmorphinan-6-one) is a synthetic
opioid with agonist activity on m, d, k
receptors.7 Oxycontin is similar in structure
to codeine and morphine. This drug is
among the most widely sold pain killers in
the United States with $2.9 billion in sales in
2009.19 This drug is highly addictive and can
be administered orally, by snorting or by
injections. Oxycontin is replacing heroin as
the opiate of choice in some rural regions of
the country and is very popular among
adolescents.20 There are little data about
oxycotin use in pregnancy, however, there
has been a case report linking oxycontin
abuse in pregnancy with neonatal withdrawal syndrome.21
Antepartum/Intrapartum/
Considerations
Screening for opioid use in pregnancy
should be part of a comprehensive approach to screening for alcohol and illicit
substances in pregnancy. Parturients
identified as heroin and or prescription
opioid users should be counseled about
the potential adverse maternal and infant/
newborn impact of continued use and be
referred for drug rehabilitation. There are
3 major options for the antepartum management of opioid abuse in pregnancy,
methadone maintenance, buprenorphine
maintenance, and detoxification.
The first option and the standard of care
for over 4 decades is methadone (6-[dimethylamino]-4, 4-diphenyl-3-hepatonone)
maintenance. Observational studies report
improved pregnancy outcomes in women
maintained on methadone compared with
those on no therapy. These studies report
improvement in prenatal clinic attendance,
better nutrition, better obstetrical outcomes including lower risk of spontaneous
abortion, intrauterine growth restriction,
and neonatal morbidity and mortality.22 A
2002 systematic review further confirmed
the benefits of methadone maintenance
in pregnancy. The review of randomized
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controlled trials reported a 3-fold reduction in heroin use and a 3-fold increase in
retention in treatment relative to nonpharmacologic therapy.23 However, a common
side effect from methadone maintenance
was neonatal withdrawal.24 The second
antepartum management option for opiate
abuse is the use of recently approved buprenorphine (subutex). Buprenorphine is a
partial opioid agonist as opposed to heroin
or methadone which are full agonists. As a
partial agonist it has a lower likelihood of
causing overdose or respiratory depression. This drug has the ability to suppress
opioid cravings and withdrawal, blocks the
effect of self-administered opioids, and
decreases illicit opioid use.25 A recent
randomized controlled trial found that using buprenorphine for opioid dependence
during pregnancy resulted in fewer episodes
of NAS than use of methadone. Both drugs
were associated with similar reduction in
illicit opioid use.26 However, more largescale use of buprenorphine is contingent
on easier availability and currently access
is limited to providers that are board certified in Addiction Medicine, Addiction Psychiatry, or licensed physicians who complete
8 hours of training. The final antepartum
management option is inpatient opioid detoxification. Opioid detoxification can
safely be accomplished in an inpatient setting, and it is recommended that detoxification be conducted under the supervision of
physicians experienced in prenatal addiction
in a perinatal unit equipped with fetal monitoring to detect signs of fetal stress or
preterm labor.27,28
There are no clear guidelines for the
initiation of antenatal testing in opioidabusing parturients who are not on maintenance therapy. A reasonable approach
is to offer antenatal testing beginning
at 32-week gestation, unless the clinical
situation warrants earlier testing. Parturients who are in labor and maintained on
methadone should receive standard obstetrical pain relief as maintenance doses
do not provide adequate relief. These
5
parturients are candidates for both epidural and spinal anesthesia the same as nonopioid–using mothers. Opioid agonist and
antagonist such as nubain, talwin, stadol,
and narcan should be avoided as they can
precipitate acute withdrawal symptoms.29
Postpartum Considerations
Neonatal withdrawal is a well-recognized
risk of maternal opioid use in pregnancy
and is seen in the majority of infants
exposed in utero to heroin, methadone,
morphine, oxycotin, codeine, and buprenorphine. NAS is characterized by hyperactivity of the central and autonomic
nervous systems. Newborn symptoms
may present anytime in the first 2 weeks
of life with peak in symptoms at 3 to 4
days.24 All infants born to opioid addicted
mothers must be monitored closely in the
nursery and treated if needed. The American Academy of Pediatrics recommends
that breastfeeding should be avoided in
heroin users, as breastfeeding may cause
tremors, restlessness, vomiting, and poor
feeding in the infants. However, methadone users are encouraged to breastfeed
and breastfeeding has been found to lead
to improved NAS scores.30
Amphetamines/
Methamphetamine/Ecstasy/
Bath Salts
PHARMACOLOGY, EPIDEMIOLOGY,
PATHOPHYSIOLOGY
Amphetamines are noncatecholamine
sympathomimetic drugs that stimulate
the central nervous system. They are not
naturally occurring but are synthetic and
are structurally similar to ephedrine—a
natural stimulant. Amphetamines release
stores of neurotransmitters (norepinephrine, dopamine, and serotonin) from
nerve endings and inhibit recycling of
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Lindsay and Burnett
these products. These actions increase the
concentrations of these neurotransmitters
in nerve spaces, promoting nerve impulse
transmission.31 Physiologically, amphetamines increase alertness, euphoria, exhilaration, and decrease tiredness, and
inhibition. They are highly addictive,
and often only 1 use is needed for dependence to occur. Amphetamines may be
smoked, injected, or taken orally. Shortterm systemic effects include tremors,
hypertension, wakefulness, decreased appetite, and dilated pupils. Long-term effects
include toxic psychosis, hallucination, and
change in brain structure. If consumed at
high enough doses they may cause retinal
damage, cardiac arrhythmias, hyperthermia, toxic hepatitis, seizures, shock, stroke,
or death.31 Methamphetamines (N-methyl1-phenyl-propan-2-amine) can easily be
made from over-the-counter-cold medication or decongestants. Studies have shown
that chronic use is associated with cerebral
deterioration, most commonly in the medial temporal lobe and basal ganglia. The
effects in the basal ganglia are due to
increased iron concentration which exacerbates the toxicity of free radicals created
from catecholamine break down. Decreased catecholamine stores in the body
leads to anxiety, somnolence hallucinations,
and can precipitate psychotic breaks.32
Ecstasy 3,4 methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine that is chemically similar to
methamphetamine and mescaline. MDMA
is taken orally as a capsule but can also be
smoked, injected, or absorbed as a suppository. MDMA may exert its effects centrally
via serotonin. It may cause serontonin
vesicles in the neurons to release quantities
of serontonin into the synapses.33 MDMA
can produce confusion, depression, and
drug craving. It is commonly used in night
clubs settings and produces feeling of euphoria, intimacy, and decreased anxiety and
warmth. Common side effects include tachycardia, and hyperthermia, rare side effects include psychosis and death. This drug
was initially popular among adolescents
and young adults but recently its use is
becoming more widespread.34 A potential
side effect from ecstasy use is a decrease in
frontal gray matter, secondary to sustained
local vasoconstriction.35 Bath salts are a
new class of synthetic drugs with effects
similar to cocaine and lyseric acid diethylamide. These chemical mixtures of principally mephedrone, methylenedioxyprova
lezone, and methylone are central nervous
system stimulants. Their route of administration include ingestion, sublingual, intravenous, insufflations, inhalation, and
rectally. Use of these drugs can cause euphoria, alertness, and agitation. Users of
these drugs may become hypertensive and
experience acute neurological, cardiovascular, and psychopathologic symptoms that
are felt to be mediated by the action of
methylenedioxyprovalezone on monoamine inhibitor uptake.36 Bath salts are
marketed and labeled not for human consumption to skirt the law and to avoid being
labeled as illegal. They are sold as plant food
and water cleaner in smoke shops, convenience stores, gasoline stations, on line, and
on the black market.37
There are limited data on the extent of
amphetamine use in pregnancy. National
prevalence estimates for methamphetamine
use in pregnancy vary from 0.7% to 5.2%.38
However, these figures may represent an
underestimate as more pregnant women in
drug treatment programs are there due to
methamphetamine use than any other drug
based on a review of data from the Treatment Episode Data Set. During the 12-yearstudy period (1994 to 2006), the number of
parturients seeking treatment for methamphetamines abuse tripled from 8% to
24%.39 There also has been a recent epidemic of emergency room visit because of
acute intoxication from bath salts. Data
from the American College of Emergency
Physicians clearly captures the scope of the
problem. In 2010, there were 300 calls to
poison control centers for bath salt ingestion
while, during the first 8 months of 2011 there
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were >4700 calls.37 The US Drug Enforcement Agency recently, because of the rise in
emergency room visits secondary to acute
intoxication from these drugs, made sales of
the 3 principal chemical used to make bath
salts illegal. The ban was issued on October
2011 and is in effect for 1 year, and will be
reassessed in November 2012 at which time
it may become permanent.40
EFFECTS ON PREGNANCY
Both amphetamines and methamphetamines cross the placenta and appear to
cause vasoconstriction leading to adverse
consequences for both the mother and the
baby.41 However, in 2005 an expert panel
concluded that there was insufficient evidence to conclude that prenatal exposure
to amphetamines caused adverse pregnancy
outcome because the studies failed to adjust
for poor prenatal care and nicotine use.42
Nevertheless observational studies have reported an association between amphetamine
use and adverse pregnancy outcome including increase risk of hypertension, postpartum hemorrhage, Ob intensive care unit
admission, social disruption, domestic violence, and placement of kids in foster care.
Fetal and newborn risk include abruption,
preterm birth, intrauterine growth restriction, low birth weight, small head circumference, congenital anomalies, learning
disabilities, low 5-minute Apgars, and increased neonatal death.43,44 Infants exposed
in utero to methamphetamines are at high
risk of suffering from amphetamine withdrawal syndrome characterized by tremors,
sleep problems, poor feeding, excessive crying, muscle spasms, and irritability.45
Parturients with first trimester ecstasy
exposure are at increased risk of delivering
infants with congenital anomalies. The
United Kingdom Teratology Information
Service using prospective data from 136
pregnancies with exposure to ecstasy
found a 15.4% rate of congenital anomalies with cardiovascular and muscular
skeleton anomalies being predominant.46
7
There is a paucity of information on the
use of bath salts in pregnancy. There have
been recent reports of bath salt use in pregnant women in Michigan and Florida. The
Michigan Health Department reported
use among pregnant women and a Florida
Department of Law Enforcement reported 61 calls to poison centers a number
of which involved pregnant women.47,48
There is no test to detect bath salts therefore health care providers must inquire
during their screening for alcohol and
other substances about bath salt use.
ANTENATAL/INTRAPARTUM/
POSTPARTUM CONSIDERATIONS
Identification of amphetamine, methamphetamine, ecstasy, and bath salt abuse
during pregnancy is challenging. As with
other illicit substances in pregnancy it is
important to systematically inquire during
prenatal registration about substance abuse.
Both rehabilitation and detoxification are
the gold standards for treating amphetamine
and methamphetamine addiction in pregnancy. However, prospects for successful
rehabilitation and detoxification are
guarded because of the physiological effects
of these drugs which induce an intense craving that is difficult to extinguish. Detoxification should only be attempted in
consultation with a trained addiction specialist because once the parturient stops
taking amphetamines she is at high risk of
experiencing withdrawal symptoms with
risk of depression, insomnia, and visual
hallucinations. These symptoms may be
managed with the use of psychotropic medications. Once the parturient is stabilized, the
providers can refer the patient to trained
mental health professionals for psychological healing. During the intrapartum period,
amphetamine abusers are at risk of experiencing obstetrical emergencies such as fetal
distress and placenta abruption. Regional
anesthesia places these patients at risk for
severe hypotension and response to treatment with vasopressors is unpredictable. If
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Lindsay and Burnett
general anesthesia is selected for cesarean
section, potent inhalation agents such as
halothane should be avoided as they may
sensitize the myocardium to endogenous
catecholamines.29 Finally, breastfeeding is
strongly discouraged in these mothers because of the high concentration of amphetamines in breast milk and the detrimental
effects on the fetus including poor sleep and
irritability.49
4.
5.
6.
7.
Conclusions
The impact of the use of street drugs and
illicit substances during pregnancy can have
devastating maternal and newborn consequences. An effective strategy to address this
important public health problem is for all
prenatal care providers to offer routine
voluntary substance use screening at the
time of the obstetrical intake interview.
Parturients who are identified as drug users
should receive a multistep management approach that includes comprehensive counseling concerning the adverse maternal and
fetal/newborn impact of continued use comprehensive prenatal care with referral to a
multidisciplinary team for drug rehabilitation and a high-risk pregnancy specialist for
ongoing fetal surveillance; and comprehensive postpartum follow up with referral to
family planning, a primary care provider
and referral to social service to insure that
the newborn has a safe home environment.
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