CLINICAL OBSTETRICS AND GYNECOLOGY

Volume 56, Number 1, 124–132

r 2013, Lippincott Williams & Wilkins

The Maternal, Fetal,

and Neonatal Effects
of Cocaine Exposure
in Pregnancy
MARY A. CAIN, MD, PATRICIA BORNICK, RNC, MSN and
VALERIE WHITEMAN, MD
Department of Obstetrics and Gynecology, Division of Maternal
Fetal Medicine, University of South Florida Morsani College of
Medicine, Tampa, Florida

Abstract: Despite multiple efforts to reduce the use of

illicit drugs, the epidemic of addiction continues to be
a significant public health issue. Through its easy
availability, the number of people afflicted with this
addiction continues to rise, including women of child-
bearing age. Secondarily, any health care crisis that
occurs in this age group of women will have potential
implications in pregnancy, infancy, and childhood.
The use of cocaine alone or in conjunction with other
illicit drugs, combined with the normal physiological
cardiovascular changes in pregnancy, leads to a
myriad of pathophysiological changes, thereby plac-
ing the life of the pregnant cocaine user, as well as the
health status of their unborn fetus and neonate at risk
for adverse outcomes. As more data are available, the
long-term physical, mental, and developmental seque-
lae for children exposed to cocaine in utero prove that
this public health crisis has serious implications. The
pregnancy-specific maternal, fetal, and neonatal risks
of cocaine use during the antepartum period are
reviewed.
Key words: maternal cocaine use, fetal cocaine expo-
sure, neonatal cocaine withdrawal
Correspondence: Valerie Whiteman, MD, Department
of Obstetrics and Gynecology, University of South
Florida, 2 Tampa General Circle 6th floor, Tampa,
FL 33606. E-mail: vwhiteman@health.usf.edu
The authors declare that they have nothing to disclose.
Introduction
Your teenager returns from school upset.
A high school senior experimented with
cocaine at a party over the weekend. The
student became incredibly sick; an ambu-
lance and the authorities were called.
They rushed her to the university hospital
in your city where, despite the medical
team’s best efforts, she died from cocaine-
related complications. Your 13 years old
has heard about cocaine in the locker
room but is now looking up some of the
medical complications of cocaine online.
She is scared. What is she reading about?
Cocaine (chemically known as ben-
zoylmethylecognine C17H21NO4) is de-
rived from the erythroxylon coca plant
of South America.1 The leaves of the coca
plant were consumed to increase energy,
reduce fatigue and hunger as long ago as
3000 BC.2 Medically, cocaine was used as a
local anesthetic, as a vasoconstrictor in an
effort to reduce surgical blood loss in the
late 1800s.3 Its use as a ‘‘recreational
drug’’ skyrocketed in the last century,

CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 56 / NUMBER 1 / MARCH 2013

124 | www.clinicalobgyn.com

and as of 2004, in the United States alone
there are an estimated 1 million first-time
users each day. Porter and Porter4 esti-
mated at least 4.6 million female cocaine
users accounting for 750,000 exposed
pregnancies and births each year. The
commonly used form, crack, is almost
pure cocaine formed through ‘‘cooking’’
the cocaine rocks with water and sodium
bicarbonate, chemically producing the al-
kalinized form of cocaine. Once ‘‘cooked’’
the cocaine separates from the solution.
This form, known as crack from the char-
acteristic noise made during the cooking
process, is the most addictive form and is
smoked.5 The hydrochloride salt of cocaine
decomposes while heated and is taken by
mouth, intranasally, or intravenously.
Regardless of the form, cocaine is ab-
sorbed quickly. Smoked cocaine has the
most rapid onset of action, within 3 to 5
seconds with a peak effect within 3 mi-
nutes yet a relatively short duration of
action lasting up to 15 minutes. The intra-
venous route also has rapid pharmacoki-
netics, with up to 60 seconds for the onset
of action, 5 minutes for the peak effect,
and duration of action up to 60 minutes.
The intranasal (snorted) route is slower
with onset within 5 minutes, peak effect of
20 minutes, and duration of action of 1½
hours. Orally administered cocaine is the
slowest route, with on onset of action by
20 minutes, peak effect by 1½ hours, and
total duration of action up to 3 hours.
Once absorbed, the physiological
hallmark of cocaine is profound vaso-
constriction, through its sympathomimetic
properties. Cocaine blocks the presynap-
tic reuptake of the sympathomimetic neu-
rotransmitter norepinephrine, serotonin,
and dopamine. The norepinephrine ef-
fects lead to hypertension, tachycardia,
and possible cardiac arrhythmias. The
dopaminergic effects on the limbic system
and cerebral cortex lead to the ‘‘high’’ or
euphoria experienced with cocaine use.6–8
Cocaine is metabolized through hepatic
and plasma cholinesterase to form the
Efficacy of Cocaine in Pregnanacy 125
water-soluble inactive forms benzoylecgo-
nine and ecgonine methylester. Any patient
with altered liver function, including preg-
nant women and their fetus, neonates and
people with preexisting liver disease are at
risk for a potentiation of the effect of
cocaine due to decreased metabolism. Un-
fortunately, cocaine users often have con-
comitant habits, and the combination of
cocaine and alcohol increases the vascular
risk. The combined use of cocaine and
alcohol leads to the formation of cocathey-
lene, which has been demonstrated to in-
crease the risk for cardiac events 40-fold
with a 25-fold increase in sudden death.9
Cocaine may also have delayed activity
remote from acute use, as the noncocaine
metabolite is also active.10 The water-solu-
ble cocaine metabolites are present in the
urine for 72 hours afterward.11,12 Cocaine
metabolites can also be detected by hair
analysis and detects 4 times as many co-
caine users than identified through self-
reporting.13
To better understand the maternal
consequences of cocaine use, the effects in
the nonpregnant abuser must be realized.
Jenkins et al14 studied the cardiovascular
and emotional effects of smoked cocaine
on human subjects. Within 2 minutes of
use, systolic blood pressures (BPs) rose by
a mean of 25 mm Hg, whereas diastolic
BPs rose by a mean of 6 mm Hg. The
mean increase in the heart rate was 20
beats/min. Interestingly, the cardiovascu-
lar parameters did not have a smooth
decline, and all were below the initial
baseline within 2 hours of administration.
Aside from these changes, cocaine induces
other physiological responses that could
theoretically place a pregnant woman at
an increased risk for adverse outcomes.
Other effects of acute cocaine use include
coronary vasospasm, possible ischemia
after reduced cardiac oxygen delivery, pla-
telet activation, increased platelet aggreg-
ability, and alteration of the thromboxane
production leading to an increased risk of
thrombosis.15–17 As a result, 25% of
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126 Cain et al
myocardial infarctions in young patients
below 45 years of age are related to co-
caine.18 These events, although dramatic,
are rarely fatal because these are due to
coronary artery vasospasm instead of
thrombosis. However, when these patients
present to the emergency room, b-blockade
is contraindicated, as the patient would
have the relatively unopposed a-adrenergic
stimulation.19,20 Large amounts of cocaine
may lead to hypotension, arrhythmia, and
cardiovascular collapse with sudden death
due to inhibiting the sodium channel
pumps.
Aside from the cardiovascular effects,
cocaine negatively impacts every organ
system in the body.21,22 Smoked cocaine
and the resultant crack vapors are asso-
ciated, with thermal pharyngeal injury
and interstitial pneumonitis. A separate
entity ‘‘crack lung’’ that has pulmonary
edema as its hallmark, presents with acute
dyspnea, hypoxia, and possible fever, he-
moptysis, and respiratory failure.23 Lung
biopsies of crack lung demonstrate alveo-
lar damage, alveolar hemorrhage with
interstitial and intra-aveolar infiltration
of eosinophilic inflammatory cells.
Central nervous system (CNS) mani-
festations of cocaine are also related to the
vasoconstriction effects. The vascular
fluctuations with cocaine use places the
abuser at risk for cerebrovascular acci-
dents. In a review of 42 patients with
cocaine use and stroke, only 15 had an
aneurysm. The remaining had confirmed
stroke with 9 deaths recorded in the
group.24 Other CNS manifestations in-
clude seizure, hallucinations, and the
emotional ‘‘high.’’
Maternal Consequences of
Cocaine Use in Pregnancy
Cocaine use during the pregnancy increases
the risk for a multitude of adverse out-
comes including hypertensive crises, unex-
plained intrauterine fetal loss, preterm
www.clinicalobgyn.com
labor, precipitous delivery, unexplained
cerebrovascular events, myocardial infarc-
tions, and placental abruption. Because of
other confounding factors including poor
nutrition, dire socioeconomic conditions,
and smoking, cocaine-abusing pregnant
women often seek little or no prenatal care.
The concomitant use of multiple substan-
ces can make assignment of the adverse
pregnancy outcome solely to cocaine chal-
lenging. Finally, lifestyle choices, including
the exchange of drugs for sexual favors,
result in many of these women acquiring
sexually transmitted diseases.25 In 1986,
Chasnoff et al26 documented that cocaine-
abusing pregnant women had a 24% in-
cidence of hepatitis and a 10.5% incidence
of venereal diseases.
As with any other substance, the most
dangerous periods is during ogranogene-
sis. Owing to the significant vascocon-
strictive effects, cocaine users experience
a significant increase in first trimester
spontaneous abortion.27 Presumably be-
cause of the cardiovascular fluctuations
affecting the uteroplacental unit, the over-
all risks of labor-related adverse events
are increased as follows: preterm labor
17.4%, precipitous labor 13.4%, placen-
tal abruption 17.3%, abnormal fetal mon-
itoring 15.3%, and meconium-stained
fluid 25%.28 Acute cocaine intoxication
can mimic severe preeclampsia and
eclampsia during pregnancy and/or in
the postpartum period.29,30 Therefore, a
high index of suspicion should be held
with unusual presentations especially if
the patient presents with the CNS and/
or emotional manifestations of cocaine.
The cocaine-induced coronary syndrome
has also been documented in the peripar-
tum period, with severe preeclampsia and
an acute myocardial infarction.31
It would be challenging to obtain con-
trolled evidence-based data demonstrat-
ing the cardiovascular response to cocaine
in pregnant humans, and therefore, we
have to rely upon the response in the
laboratory. Although this may not strictly

cross over to the response in humans, this
information is helpful in providing under-
standing of the human experience with
cocaine exposure. Animal data document
the BP fluctuations with cocaine are ex-
aggerated in comparison with the non-
pregnant animal. This may provide
insight into the etiologies of a preeclamp-
sia-like picture and placental abruption
with cocaine use. A dose-dependent in-
crease in BPs is observed after cocaine
administration in ewes, with pregnant
ewes demonstrating a significantly in-
creased response in comparison with non-
pregnant ewes.32 Woods and Plessinger33
documented maternal cocaine levels were
8 to 10 times higher in pregnant ewes
compared with nonpregnancy, with a
concomitant increase in the systemic vas-
cular resistance and other vascular pa-
rameters. Although the uterine blood
flow is unaffected in nonpregnant rabbits,
a dose-dependent reduction in blood flow
was demonstrated in the uterine and pla-
cental vasculature in pregnancy.34,35
Fetal and Neonatal
Consequences of In Utero
Cocaine Exposure
A 23-year-old G1P0 presents to your la-
bor and delivery suite with no prenatal
care and contractions, vaginal spotting,
and decreased fetal movement. BP was
170/100; urine has trace protein. A urine
drug screen is positive for cocaine. A bed-
side ultrasound confirms a 34-week intra-
uterine pregnancy with a fetal demise. She
rapidly delivers a stillborn with no mor-
phologic abnormalities. The aftercoming
placenta has a fresh clot adherent to it
consistent with a 70% placental abrupt-
ion. Her mother is wondering how this
happened and could the cocaine habit she
advised her daughter to quit have led to
this outcome?
The previously mentioned cardiovas-
cular effects of cocaine exposure directly
Efficacy of Cocaine in Pregnanacy 127
alter the uteroplacental blood flow with
resultant fetal and neonatal sequelae. Co-
caine crosses the placental barrier easily,
owing to its low molecular weight, lipid
solubility, and low ionization.36 Some
data suggest that aside from the exposure
through the maternal blood, cocaine, ben-
zoylecgonine, and noncocaine are stored
in the placental membranes and myome-
trium, leading to a potential continuous
source of exposure after the acute use.37
The amniotic fluid also acts as a reservoir
for fetal cocaine exposure. The fetal se-
rum levels of cocaine and its metabolites
are only 3% of the amniotic fluid levels in
ewes.38 Therefore, the fetus is exposed to 3
routes of exposure, transplacental pas-
sage, the placental membranes, and my-
ometrium and recycling through the
amniotic fluid. The presumed etiology
for the adverse fetal outcomes is reduced
uteroplacental blood flow secondary to
the vasoconstrictive effects of cocaine ex-
posure. As with any other substance, one
of the most dangerous periods is during the
first trimester. Owing to the significant
vascoconstrictive effects, cocaine users ex-
perience a significant increase in first tri-
mester spontaneous abortion.27,39 An
increased risk of congenital malformations
especially of the CNS and cardiac system
has been suggested.39–41 The overall mal-
formation rate in these pregnancies is 10%
versus 2% for cocaine-negative controls.39
Fetal brain growth is also adversely af-
fected presumably due to fetal intracranial
vasoconstriction, as Handler et al42 docu-
mented that cocaine use was associated
with a 16% incidence of microcephaly,
which occurred in only 6% of nonusing
controls. Other fetal vascular beds are at
risk, as the cocaine-mediated vasoconstric-
tion is the presumed etiology of various
disruption patterns including bowel infarc-
tion, atresia or perforations, porencephalic
cysts, and nonsyndromic limb defects.43
The effect of cocaine use on birth weight
has been studied extensively. However,
because of the multitude of confounding
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128 Cain et al
variables, the changes in birth weight and
other parameters may be due to several
other factors including the gestational age
during which cocaine was used, overall
socioeconomic status, maternal nutrition-
al status, cigarette smoking, alcohol con-
sumption during the pregnancy and
concomitant polydrug abuse.44
Earlier documentation of fetal growth
aberrations were published by Zuckerman
et al in 1989.45 Women with positive urine
assays for cocaine had infants with a 93 g
lower in birth weight, a 0.7-cm reduction in
length, and a 0.43-cm reduction in head
circumference. Although the reduction in
birth weight did not reach statistical sig-
nificance, the change in length and head
circumference was significantly different
with a P = 0.01. The Maternal Lifestyle
Study of 717 cocaine-exposed infants and
7442 nonexposed controls evaluated the
physical and behavioral findings during
the neonatal period.46 This multicenter
prospective study demonstrated an earlier
gestational age at delivery by 1.2 weeks, a
536 g reduction in birth weight, 2.6-cm
reduction in birth length, and a 1.5-cm
reduction in head circumference in com-
parison with nonexposed controls. All of
these parameters attained statistical signifi-
cance with P<0.001.47 Therefore, the
growth restriction pattern associated with
cocaine use may be symmetric or asymmet-
ric. A meta-analysis of 31 studies evaluat-
ing the effects of cocaine use in pregnancy
included confirmed a significant increase in
low birth weight (<2500 g) with an odds
ratio (OR) of 3.66 and 95% confidence
interval (CI) of 2.90-4.63. Antenatal expo-
sure to cocaine was also associated with a
significant increase in small for gestational
age<10 percentile for the gestational age
with OR 3.23 (2.43-4.30). The risk for
preterm birth (<37 wk) was increased with
OR 3.38 (2.72-4.21). Overall maternal co-
caine use led to a mean reduction in birth
weight by 492 g.48
The etiology for preterm labor in
the general population is uncertain.
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However, whether the blood flow and
BP fluctuations with cocaine, the fetal
neuroendocrine environment, infection,
or other factors are the culprit, these
pregnancies are at risk for spontaneous
prematurity. Ischemic injuries not related
to other medical factors have been docu-
mented in premature infants of cocaine
abusers.49 The exposed infants also had
significant increases in CNS symptoms
including jitters/tremors (adjusted OR
2.17; 99% CI, 1.44-3.29), high pitched
cry (2.44:1.06-5.66) irritability (1.81; 1.1-
2.80), excessive suck (3.58; 1.63-7.88),
hyperalertness (7.78: 1.72-35.06), and
autonomic instability (2.64; 1.17-5.95). It
is uncertain whether these behavioral
manifestations are due to the cocaine ex-
posure or withdrawal. However, Chasn-
off and colleagues document that these
symptoms commonly occur within the
first 2 to 3 days of life, whereas the cocaine
metabolites remain in the neonatal urine
for as long as the first week of life.
A meta-analysis of 31 studies evaluat-
ing the effects of cocaine use in pregnancy
confirmed a significant increase in low
birth weight (<2500 g) with an OR of
3.66 and 95% CI of 2.90-4.63. Antenatal
exposure to cocaine was also associated
with a significant increase in small for
gestational age<10 percentile for the ges-
tational age with OR 3.23 (2.43-4.30).The
risk for preterm birth (<37 wk) was in-
creased with OR 3.38 (2.72-4.21). Overall
maternal cocaine use led to a mean reduc-
tion in birth weight by 492 g.48
In utero ‘‘stress’’ is thought to acceler-
ate fetal lung maturation. In 1996, Han-
lon-Lundberg and colleagues compared
the lung maturation profiles by surfac-
tant/albumin ratio in cocaine-exposed
pregnancies to negative controls. Cocaine
doubled the odds of a mature lung pro-
file.50 Cocaine users with preterm prema-
ture ruptured membranes are also more
likely to present with advanced cervical
dilatation and have a shorter latency peri-
od to delivery than noncocaine users.51

However, this study was done before the
routine use of antenatal steroids and the
present-day group B strep coverage (pro-
tocols with antibiotics). This finding was
corroborated by Martinez et al in 1996,52
who also demonstrated a significant in-
creased risk of intrauterine fetal death in
these patients (18.2% vs. 0%). Bateman
et al53 demonstrated a doubled risk for
preterm labor and delivery in an inner city
cocaine-positive population. Over the
past decades, the successful efforts to
reduce the vertical transmission of human
immunodeficiency virus have been life-
saving. However, cocaine and other illicit
drugs are known to negatively impact
overall immunity. In 1997, Bulterys
et al54 demonstrated a risk ratio of 4.0
(95% CI, 2.0-8.1) for vertical human im-
munodeficiency virus transmission with
injected cocaine and heroin.
There are no evidence-based data dem-
onstrating an optimal medical manage-
ment for infants with in utero exposure,
and this is an area for potential future
research as the cocaine epidemic contin-
ues.55 The etiology for the different
neonatal neurological findings in co-
caine-exposed neonates is uncertain. In
adults, the association of cocaine expo-
sure with and resultant cerebrovascular
insults is well documented. Frank et al56
performed a longitudinal evaluation of
head ultrasounds in infants with in utero
exposure compared with nonexposed
controls. Although there was no differ-
ence in the scans with light exposure to
cocaine, those infants exposed to heavy
exposure had an increased incidence of
subependymal hemorrhage in the caudo-
thalamic groove (covariate adjusted OR:
3.88; 95% CI, 1.45-10.35).57
Postnatal Consequences of In
Utero Cocaine Exposure
It is a rewarding day in the nursery. Baby
boy Doe was born at 28 weeks to a
Efficacy of Cocaine in Pregnanacy 129
cocaine-abusing mother. She quickly real-
ized that she was not ready to handle the
responsibility of a child and put the baby
up for adoption. Your local adoption
agency has found a wonderful couple
who know of the child’s rough entry into
the world, but regardless they are pro-
ceeding with the adoption process. They
have a few questions on what to expect, so
they can prepare to handle the physical
and emotional needs of the baby as he
grows and develops. What information is
the nursery and adoption agency going to
share?
The concept of fetal origins of adult
disease was first described by Barker et al
in 198958 who documented that low birth
weight placed the offspring at significant
risk for heart disease. Although the exact
pathophysiological etiology for this is
uncertain, Hincliffe et al59 proposed that
low birth weight infants had a reduction
in nephrons, which would lead to a risk
for hypertension later in life. As the co-
caine/crack epidemic of the 1980s, data
are now emerging on the long-term effects
of in utero exposure and the implications
for these children, especially as they reach
school age. A literature review by Messiah
and colleagues highlights the issues of
long-term evaluation of these neonates.
For various reasons, including patients
lost to follow-up, sample size, varying
documentation regarding actual expo-
sure, and other confounding variables,
little is known regarding the long-term
cardiovascular and metabolic effects of
cocaine exposure.60
A continuation of the Maternal Life-
style Study evaluated the body mass index
and BPs of 9 year olds with in utero
cocaine exposure. The parameters were
compared in 277 cocaine-exposed chil-
dren and 603 nonexposed controls with
regression analysis performed to rule out
other lifestyle-related factors such as diet,
sedentary lifestyle as an etiology. Interest-
ingly, children who were exposed to heavy
cocaine use in utero had significantly
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130 Cain et al
higher body mass index and BPs. The
children delivered at the onset of the
cocaine epidemic are now becoming
adults. Little is known regarding the
long-term adult health effects associated
with their in utero exposures. As their
cardiovascular system is primed to react
differently than the rest of the population,
there is the possibility for increased hyper-
tension, heart disease, and other adverse
health conditions.61 Xiao and colleagues
evaluated the long-term risk of in utero
cocaine exposure on vascular reactivity
in rats. Cocaine exposure significantly
increased norepinephrine-induced vasocon-
striction while decreasing the phosphoryla-
tion of nitric oxide synthase with a
concomitant reduction in the baroreflex
sensitivity in the adult male rats.62 These
physiological changes would increase the
risk for hypertension. There is no evidence
that this is true in humans.
The emotional response to stress is
enhanced in children with in utero expo-
sure. Chaplin et al, using the Trier Social
Stress Test, evaluated emotional response
to stress in 49 adolescents with prenatal
cocaine exposure and 33 nonexposed ado-
lescents. They compared salivary cortisol,
BP, and heart rate. Exposed adolescents
demonstrated increased cortisol before
and after stress. Exposed girls also had
an increased anxiety and anger response
to stress in comparison with nonexposed
girls. Exposed boys had a reduced dia-
stolic BP response.63 The long-term
behavioral and social implications of
these results have yet to be determined.
Summary
The non–obstetric-related sequelae of the
cocaine epidemic are well documented in
the literature. Unfortunately, this epi-
demic also includes women of childbear-
ing age, with resultant risks for
pregnancy-related adverse outcomes.
Mothers using cocaine during pregnancy
place themselves and their fetus at risk for
www.clinicalobgyn.com
adverse outcomes. Maternal risks include
hypertensive disorders, cardiovascular
fluctuations, and placental abruption.
Prenatal exposure has a profound effect
on the unborn fetus, with known in-
creased incidence of growth aberrations
and fetal loss. The exposed neonate must
endure a multitude of CNS aberrations
and are at risk for intracranial events.
Unlike in utero exposure to opiates, there
is no evidence-based treatment plan de-
veloped for the management of the neo-
nate exposed to cocaine.
Each jurisdiction has their own ruling
regarding which patients can have urine
drug testing, and under which circumstan-
ces. A high index of suspicion for cocaine as
a possible factor for the patient scenario
must be held until confirmatory test results
are obtained. However, the conversation
regarding drug use should not be delayed
until the acute event. Upon presentation for
prenatal care, all pregnant women should
be questioned. Although the May 2012
ACOG Committee Opinion is directed to-
ward opiate exposure, the basic principal of
nonjudgmental questioning, and informing
the patient that this information is being
requested so the health care team can best
take care of her during the pregnancy and
afterward holds true for all illicit drugs.64
Each location has their own requirements
for consenting neonates for antenatal drug
exposure, and therefore, consultation with
the local authorities regarding this is
recommended.
As the initial group of children born
during the recent cocaine epidemic be-
come adults, the long-term medical effects
of their in utero exposure will become
evidenced. The controversies abound.
The potential long-term effects for the
upcoming generations are beyond com-
prehension. Certainly this would be asso-
ciated with a significant personal and
health care cost. All of these issues raise
the need for means to reduce the use of
illicit drugs in general, and specifically
during the antepartum period.

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