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Impact of intrauterine exposure to phencyclidine (PCP) and cocaine on neonates

Authors:

Abstract

A total of 505 newborns who were exposed to illicit drugs during intrauterine life were studied to investigate the prevalence, growth parameters, newborn manifestations, and other effects of intrauterine exposure to cocaine and phencyclidine (PCP). The results support the hypotheses that both drugs have serious effects on growth parameters, but this effect was much more pronounced in the cocaine group than in the PCP group. Furthermore, the incidence of borderline microcephalic infants (head circumferences less than the 10th percentile) was much higher in the cocaine group. It also appears that the signs and symptoms observed in both groups are not withdrawal manifestations typically seen in narcotic-exposed infants; rather, these symptoms are true drug effects and should not be considered manifestations of drug withdrawal symptoms.
IMPACT
OF
INTRAUTERINE
EXPOSURE
TO
PHENCYCLIDINE
(PCP)
AND
COCAINE
ON
NEONATES
Fariborz
Rahbar,
MD,
Antoine
Fomufod,
MD,
Davene
White,
RN,
NNP,
and
Lennox
S.
Westney,
MD
Washington,
DC
A
total
of
505
newborns
who
were
exposed
to
illicit
drugs
during
intrauterine
life
were
studied
to
investigate
the
prevalence,
growth
parame-
ters,
newborn
manifestations,
and
other
effects
of
intrauterine
exposure
to
cocaine
and
phen-
cyclidine
(PCP).
The
results
support
the
hy-
potheses
that
both
drugs
have
serious
effects
on
growth
parameters,
but
this
effect
was
much
more
pronounced
in
the
cocaine
group
than
in
the
PCP
group.
Furthermore,
the
incidence
of
borderline
microcephalic
infants
(head
circum-
ferences
less
than
the
10th
percentile)
was
much
higher
in
the
cocaine
group.
It
also
appears
that
the
signs
and
symptoms
ob-
served
in
both
groups
are
not
withdrawal
manifestations
typically
seen
in
narcotic-
exposed
infants;
rather,
these
symptoms
are
true
drug
effects
and
should
not
be
considered
manifestations
of
drug
withdrawal
symptoms.
(J
Nati
Med
Assoc.
1993;85:349-352.)
Key
words
*
fetus
*
neonates
*
cocaine
*
phencyclidine
(PCP)
The
use
of
cocaine
and
phencyclidine
(PCP)
over
the
last
5
years
has
increased
dramatically.
In
the
Washing-
ton
metropolitan
area,
a
sharp
rise
in
the
use
of
PCP
and
cocaine
has
occurred
among
young
black
females
of
childbearing
age.
Consequently,
a
large
number
of
black
infants
are
born
to
drug-addicted
mothers.
An
From
the
Departments
of
Pediatrics,
and
Obstetrics
and
Gynecology,
Howard
University
Hospital
College
of
Medicine,
Washington,
DC.
Requests
for
reprints
should
be
addressed
to
Dr
Fariborz
Rahbar,
Dept
of
Pediatrics,
Howard
University
Hospital,
2041
Georgia
Ave,
NW,
Washington,
DC
20060.
earlier
studyl
reported
on
31
infants
born
to
drug-
addicted
mothers;
none
of
these
infants
had
intrauterine
exposure
to
cocaine
or
PCP.
This
study
was
undertaken
to
investigate
the
preva-
lence,
growth
parameters,
neonatal
manifestations,
and
other
effects
of
intrauterine
exposure
to
cocaine
and
PCP
on
neonates.
Furthermore,
in
view
of
the
limited
information
available
in
the
literature
on
intrauterine
exposure
to
phencyclidine,2-4
a
special
effort
was
made
to
examine
and
compare
its
effects
with
those
of
cocaine.
METHODS
All
babies
born
between
January
1,
1988
and
December
31,
1989
to
actively
addicted
mothers
who
used
drugs
"regularly"
during
pregnancy
and
whose
urine
toxicology
was
positive
in
both
mother
and
baby
were
included
in
the
study
population.
Infants
whose
mothers
admitted
using
drugs
"regularly"
throughout
their
pregnancy,
but
whose
urine
toxicology
either
was
not
done
or
negative
also
were
included
in
the
study
population.
Mothers
who
admitted
using
one
drug
exclusively
throughout
pregnancy,
which
was
subsequently
con-
firmed
by
urine
toxicology,
were
classified
as
single-
drug
abusers.
Those
admitting
multiple
drug
use
and
confirmed
by
urine
toxicology
were
classified
as
polydrug
abusers.
The
single-drug
abusers
were
divided
into
two
groups:
cocaine
abusers
and
PCP
abusers.
The
follow-
ing
parameters
were
studied
on
both
groups:
*
status
of
prenatal
care:
classified
as
regular,
irregular,
and
no
prenatal
care,
*
urine
toxicology,
*
fetal
growth
parameters,
birthweight,
height,
and
occipitofrontal
circumferences,
JOURNAL
OF
THE
NATIONAL
MEDICAL
ASSOCIATION,
VOL.
85,
NO.
5
349
IMPACT
OF
PCP
&
COCAINE
ON
THE
FETUS
Day
Day
Day
Day
Day
No.___
No.
No.
No.
__
No.
Symptomni
Mild
|1sv
IDE
DEN
D
E
N
D
E
N
E
D
E
E|
Excessive
movement
1/2
1
2
Persistent
crying
or
high-pitched
cry
1/2
1
2
Skin
abrasions
1/2
1
2
Coarse
tremors
1/2
1
2
Diarrhea
1
1
1
Vomiting
1
1
1
Excessive
lip
smacking
or
sucking
on
hands
and
fingers
1
1
1
Frank
convulsions
5
5
5
f
|
~~~~~~~Total
n|Inlals
and
TIe
Indicate
with
a
+
or
-
whether
or
not
Sleep
pattern
the
infant
is
sleeping
.2
hours
at
a
time
Indicate
with
a
+
or
-
whether
or
not
the
TLC
response
infant
is
calmed
with
tender
loving
care
(TLC)
InItIal
Figure.
Score
sheet
for
recording
neonatal
drug
withdrawal
symptoms.
(Howard
University
Hospital
Department
of
Pediatrics
and
Child
Health,
Washington,
DC.)
*
complete
physical
examination
with
emphasis
on
dysmorphic
features,
and
*
drug
withdrawal
and
drug
effects.
A
special
scoring
sheet
(Figure)
was
used
to
examine
the
status
of
withdrawal
and
drug
effects
of
cocaine
and
PCP.
The
drug
withdrawal
symptoms
were
divided
into
three
groups:
mild,
moderate,
and
severe.
The
scores
were
recorded
as
0.5
for
mild,
1
for
moderate,
2
for
severe
symptoms,
and
5
for
frank
convulsions.
Infants
were
evaluated
every
8
hours,
and
scores
were
documented
on
the
"Drug
Withdrawal
Score
Sheet"
(Figure).
RESULTS
Incidence
During
the
study
period,
2710
infants
were
born.
In
1988,
211
out
of
1213
(17.3%)
and
in
1989,
294
out
of
1497
(19.6%)
were
exposed
to
illicit
drugs
during
intrauterine
life.
350
JOURNAL
OF
THE
NATIONAL
MEDICAL
ASSOCIATION,
VOL.
85,
NO.
5
IMPACT
OF
PCP
&
COCAINE
ON
THE
FETUS
Status
of
Prenatal
Care
Thirty-five
percent
of
mothers
had
no
prenatal
care,
53%
had
irregular
care,
and
only
12%
had
regular
prenatal
care.
Urine
Toxicology
Urine
samples
were
not
obtained
on
60
infants
(12%).
Of
the
remaining
445
infants,
22%
had
negative
urine
toxicology
tests
and
78%
had
positive
tests.
Cocaine,
PCP,
methadone,
heroin,
and
marijuana
were
the
most
commonly
used
drugs.
Intrauterine
exposure
to
polydrug
abuse
comprised
21%,
while
single-drug
exposure
was
79%.
Among
single-drug
abusers,
83
(21%)
were
in
the
PCP
group,
and
287
(73%)
were
in
the
cocaine
group.
Dysmorphic
Features
No
special
physical
characteristics
(ie,
slanted
eyes,
small
mandibular
angle,
and
triangular
face)
were
noted
in
either
group.
Drug
Withdrawal
and
Drug
Effects
The
mean
withdrawal
score
for
the
cocaine
group
was
2.5
and
3
for
the
PCP
group.
In
the
cocaine
group,
neurological
dysfunctions,
ie,
tremors,
hypertonia,
increased
reflexes,
and
abnormal
sucking
and
rooting
reflexes,
were
noted
most
frequently.
In
the
PCP
group,
symptoms
were,
for
the
most
part,
neurobehavioral
in
nature
(ie,
high-pitched
cry,
poor
tracking,
and
de-
creased
attention).
Intrauterine
Growth
Parameters
The
incidence
of
intrauterine
growth
retardation
was
increased
in
both
groups
as
determined
by
a
chart
developed
at
the
University
of
Colorado
Medical
Center,
classification
of
newborns
by
birthweight
and
gestational
age.5
In
the
cocaine
group,
158
of
287
infants
(55%)
had
birthweight
for
gestational
age
below
the
25th
percentile,
and
in
the
PCP
group,
35
of
83
infants
(42%)
had
birthweight
for
gestational
age
below
the
25th
percentile.
In
the
cocaine
group,
140
of
287
infants
(48.7%)
had
birth
heights
for
gestational
age
below
the
25th
percentile,
and
in
the
PCP
group,
31
of
83
(37.3%)
had
birth
heights
for
gestational
age
below
the
25th
percentile.
The
findings
on
occipitofrontal
head
circumferences
were
more
striking.
In
the
cocaine
group,
195
of
287
(67.9%)
had
head
circumference
below
the
25th
percentile.
Of
these,
114
infants
(30.7%)
had
borderline
microcephaly
below
the
10th
percentile.
In
the
PCP
group,
38
of
83
infants
(45.7%)
had
head
circumfer-
ences
below
the
25th
percentile,
10
of
whom
(12%)
had
head
circumferences
below
the
10th
percentile.
DISCUSSION
Drug
use
during
pregnancy
is
increasing
at
an
alarming
rate.
Among
the
study
population,
the
incidence
was
17.3%
in
1988
and
19.6%
in
1989.
A
large
number
(88%)
of
these
mothers
did
not
seek
any
prenatal
care
or
had
limited
prenatal
care.
Conse-
quently,
the
incidence
of
perinatal
mortality
and
morbidity
is
much
higher.6
Both
cocaine
and
PCP
cross
the
placenta
and
enter
fetal
circulation.
Cocaine
is
rapidly
metabolized
by
plasma
and
hepatic
cholinesterases
after
absorption.
Cocaine
is
highly
water
and
lipid
soluble
and
has
low
molecular
weight.
Therefore,
it
enters
the
placenta
by
simple
diffusion.
Concentration
of
plasma
and
liver
cholinesterases
is
lower
in
the
fetus.
This
makes
the
fetus
much
more
sensitive
to
smaller
doses
of
cocaine.7
The
results
of
this
study
indicate
that
while
symmet-
rical
intrauterine
growth
retardation
occurs
in
both
the
cocaine
and
the
PCP
groups,
this
effect
was
more
pronounced
in
the
cocaine
group.
Placental
transport
in
animals
has
shown
that
concentration
of
PCP
is
almost
10
times
higher
in
the
fetus
than
that
of
the
mother
indicating
greater
vulnerability
to
the
fetus.8
Cocaine
also
has
been
shown
to
affect
the
growth
and
development
of
the
fetus.9
However,
the
most
important
finding
in
this
study
was
a
threefold
increase
in
the
incidence
of
borderline
microcephaly
in
the
cocaine
group
compared
with
the
PCP
group.
Maternal
cigarette
smoking
and
alcohol
abuse
also
affect
fetal
growth.
There
were
no
significant
differ-
ences
in
the
amount
of
smoking
in
both
groups.
Heavy
alcohol
consumption
during
pregnancy
has
been
shown
to
produce
symmetrical
growth
retardation.10
Thirty-
eight
percent
of
the
patients
in
this
study
gave
a
positive
history
of
"occasional"
alcohol
use
during
pregnancy;
however,
the
amount
of
consumption
in
both
groups
was
not
determined,
and
the
remainder
denied
alcohol
use.
Specific
physical
characteristics
have
been
re-
ported
following
intrauterine
exposure
to
alcohol.
I
'
These
features
(ie,
fetal
alcohol
syndrome)
were
not
observed
in
our
affected
infants.
Infants
born
to
drug-dependent
mothers
were
evalu-
ated
every
8
hours
by
nurses
and
doctors
for
evidence
of
neurological,
neurobehavioral,
or
physiological
dys-
function
(ie,
vomiting,
diarrhea,
temperature
irregulari-
ties,
and
sweating).
There
was
no
evidence
of
signifi-
cant
physiological
dysfunction
in
either
group.
However,
the
cocaine
group
demonstrated
mostly
JOURNAL
OF
THE
NATIONAL
MEDICAL
ASSOCIATION,
VOL.
85,
NO.
5
351
IMPACT
OF
PCP
&
COCAINE
ON
THE
FETUS
neurological
dysfunctions,
while
the
PCP
group
dem-
onstrated
neurobehavioral
dysfunctions.
CONCLUSION
The
signs
and
symptoms
observed
in
both
groups
(cocaine
and
PCP)
are
not
the
withdrawal
manifestations
typically
seen
in
narcotic-exposed
infants.
Rather,
these
symptoms
are
true
drug
effects
and
should
not
be
considered
manifestations
of
drug
withdrawal
syndrome.
Acknowledgments
The
authors
thank
Ms
Diedra
L.
Mitchell,
ACSW,
for
research
assistance,
Ms
Vendetta
M.
Mitchell,
BSW,
for
data
gathering,
and
Ms
Michele
Boykin
for
secretarial
assistance.
Literature
Cited
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Rahbar
F.
Observation
on
methadone
withdrawal
in
16
neonates.
Clin
Pediatr
(Phila).
1975;
14:369-37
1.
2.
Strauss
A,
Madaxilous
HD,
Bosu
SK.
Neonatal
manifes-
tation
of
phencyclidine
(PCP)
abuse.
Pediatrics.
1981;68:550-
555.
3.
Golden
NL,
Kuhnert
BR,
Sokol
RJ,
Martier
S,
Bagby
BS.
Phencyclidine
use
during
pregnancy.
Am
J
Obstet
Gynecol.
1984;
1
48:254-258.
4.
Golden
NL,
Kuhnert
BR,
Sokol
RJ,
Martier
S,
William
T.
Neonatal
manifestation
of
maternal
phencyclidine
exposure.
J
PerinatMed.
1987;15:185-191.
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FC,
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LO.
Classification
of
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by
birthweight
and
gestational
age
and
by
neonatal
mortality
risk.
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1967;71:161-166.
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Rahbar
F,
Momehi
J,
Fomufod
A,
Westney
LS.
Prenatal
care
and
perinatal
mortality
in
a
black
population.
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Dyke
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PC,
Jatlon
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after
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application
of
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in
man.
Science.
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8.
Cooper
JE,
Cumming
AJ,
Jones
H.
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transferof
phencyclidine
in
the
pig.
JPhysiol.
1977;16:267-270.
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Hadeed
A,
Siegel
SR.
Maternal
cocaine
use
during
pregnancy:
effect
on
the
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infant.
Pediatr
1989;84:205-
209.
10.
Jones
KL,
Smith
DW,
Ulleland
CN,
Streissguth
AP.
Patterns
of
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in
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alcoholic
mothers.
Lancet.
1973;1:1267-1269.
11.
Jones
KL.
Recognizable
Patterns
of
Human
Malforma-
tion.
4th
ed.
Philadelphia,
Pa:
WB
Saunders
Co;
1988.
12.
Golden
N,
Sokol
RJ,
Rubin
IL.
Angel
dust:
possible
effects
on
the
fetus.
Pediatr
1980;65:18-20.
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.M................EDICAL
A
VO
.
85,
NO.
352
JOURNAL
OF
THE
NATIONAL
MEDICAL
ASSOCIATION,
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... Interestingly, these PPI deficits last even after withdrawal, which is not the case when PCP is administered in adulthood, suggesting that this aspect of the disease is better modeled by neonatal administration of PCP. Finally, PCP abuse during pregnancy has been associated with neurobehavioral defects (11) and with long-term consequences on social behavior and motor control in children (12), further highlighting the need to understand the consequences of PCP exposure on the development of neuronal networks. ...
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Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates “dual-hit” neurodevelopmental insults like neonatal phencyclidine plus isolation rearing (PCP-Iso). Glutamatergic dysfunction contributes to schizophrenia pathophysiology and may represent a treatment target, so we used enzyme-based microsensors to evaluate basal- and drug-evoked glutamate release in hippocampal slices from rats that received neonatal PCP and/or isolation rearing. 5-HT6 antagonist-evoked glutamate release (thought to be mediated indirectly via GABAergic disinhibition) was reduced in PCP-Iso, as were cognitive effects of a 5-HT6 antagonist in a hippocampal glutamate-dependent novel object discrimination task. Yet mGlu7 antagonist-evoked glutamatergic and cognitive responses were spared. Immunohistochemical analyses suggest these findings (which mirror the apparent lack of clinical response to 5-HT6 antagonists in schizophrenia) are not due to reduced hippocampal 5-HT input in PCP-Iso, but may be explained by reduced calbindin expression. This calcium-binding protein is present in a subset of GABAergic interneurons receiving preferential 5-HT innervation and expressing 5-HT6 receptors. Its loss (in schizophrenia and PCP-Iso) would be expected to reduce interneuron firing and potentially prevent further 5-HT6 antagonist-mediated disinhibition, without impacting on responses of VIP-expressing interneurons to mGlu7 antagonism. This research highlights the importance of improved understanding for selection of appropriate preclinical models, especially where disease neurobiology impacts on cells mediating the effects of potential therapeutics.
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The revised and updated second edition covers practical approaches to caring for healthy and high-risk infants. https://shop.aap.org/neonatalogy-for-primary-care-2nd-edition-paperback/
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Arylcyclohexamines (also known as arylcyclohexylamines) are a group of compounds that contain a cyclohexamine unit with an aryl moiety, typically a phenyl ring, attached to the same atom to which the amine group is linked (see Fig. 1). They all exhibit dissociative effects due to their antagonism of N-methyl-d-aspartate (NMDA) receptors, and many have been studied as alternatives to traditional anesthetic agents but subsequently abused recreationally in pursuit of these same effects. The most well-characterized arylcyclohexamines are phencyclidine ((1-(1-phencyclohexyl) piperidine; PCP)), ketamine, and, of the novel analogues, methoxetamine.
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Arylcyclohexamines (also known as arylcyclohexylamines) are a group of compounds that contain a cyclohexamine unit with an aryl moiety, typically a phenyl ring, attached to the same atom to which the amine group is linked (see Fig. 1). They all exhibit dissociative effects due to their antagonism of N-methyl-d-aspartate (NMDA) receptors, and many have been studied as alternatives to traditional anesthetic agents but subsequently abused recreationally in pursuit of these same effects. The most well-characterized arylcyclohexamines are phencyclidine ((1-(1-phencyclohexyl) piperidine; PCP)), ketamine, and, of the novel analogues, methoxetamine.
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Phencyclidine (PCP) is the most common member of the “dissociatives.” The dissociatives constitute an entirely synthetic class of drugs that act at multiple receptor sites. They act as agonists or antagonists at cholinergic, dopaminergic, noradrenergic, opioid, serotonergic, sigma, and NDMA (N-methyl-D-aspartate) -high-affinity and -low-affinity receptor sites. As a result, dissociatives can mimic atropinic, GABAminergic, opioid, psychedelic, and sympathomimetic drugs. Since the drugs in this class are active in powdered, crystalline, suspended, and volatile forms, they can be ingested, snorted, injected, smoked, or inhaled (Giannini, 1987b).
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Using three-year cumulative data relative to perinatal mortality, the present study examines the relationship of prenatal care and birth weight to pregnancy outcome. The results support the hypothesis that links prenatal care to pregnancy outcome and the relationship between birth weight and pregnancy outcome is found to be strong. The study indicates that the knowledge of birth weight would reduce the number of errors in predicting the chances of survival of the newborn by 37.0%. © 1985 by The American College of Obstetricians and Gynecologists.
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Phencyclidine, a frequently abused drug, has been shown to cross the placenta and may cause harmful effects in the fetus. Therefore, a prospective study was undertaken to determine the extent of phencyclidine use during pregnancy. Two thousand three hundred twenty-seven pregnant women were screened for phencyclidine use by questionnaire and enzyme-mediated immunoassay technique urine testing. Nineteen women were identified as using phencyclidine during pregnancy and 149 were past users. Women with a history of phencyclidine use were compared with a population sample of nonusers. Phencyclidine users were more likely to be white; they were also younger and of lesser parity than nonusers. The majority had a history of multiple drug abuse. Although 7.3% of the population gave a history of phencyclidine use and 0.8% were found to use the drug during pregnancy, these figures are believed to underestimate the problem.
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A case report of an infant whose mother used phencyclidine (PCP, "angel dust") during pregnancy is presented. As a neonate, the infant showed abnormal behavior and an unusual appearance, and later, spastic quadriparesis. Based on previous animal studies, it is likely that this infant had prolonged exposure to PCP as a fetus. His abnormal neonatal behavior was consistent with previously reported effects of this drug. The relationship between his exposure to PCP and his dysmorphology and spasticity remains speculative. It is suggested that clinicians be alert to further cases of these associations.