Prenatal Substance Abuse: Short- and Long-term Effects on the Exposed Fetus
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FROM THE AMERICAN ACADEMY OF PEDIATRICS
TECHNICAL REPORT
Prenatal Substance Abuse: Short- and Long-term
Effects on the Exposed Fetus
Marylou Behnke, MD, Vincent C. Smith, MD, COMMITTEE ON
SUBSTANCE ABUSE, and COMMITTEE ON FETUS AND abstract
NEWBORN
Prenatal substance abuse continues to be a significant problem in this
KEY WORDS
country and poses important health risks for the developing fetus. The
prenatal drug exposure, alcohol, nicotine, marijuana, cocaine,
methamphetamine, growth and development primary care pediatrician’s role in addressing prenatal substance
ABBREVIATIONS exposure includes prevention, identification of exposure, recognition
AAP—American Academy of Pediatrics of medical issues for the exposed newborn infant, protection of the
THC—tetrahydrocannabinol infant, and follow-up of the exposed infant. This report will provide
This document is copyrighted and is property of the American information for the most common drugs involved in prenatal expo-
Academy of Pediatrics and its Board of Directors. All authors sure: nicotine, alcohol, marijuana, opiates, cocaine, and methamphet-
have filed conflict of interest statements with the American
Academy of Pediatrics. Any conflicts have been resolved through amine. Pediatrics 2013;131:e1009–e1024
a process approved by the Board of Directors. The American
Academy of Pediatrics has neither solicited nor accepted any
commercial involvement in the development of the content of
this publication. Substance abuse has been a worldwide problem at all levels of society
The guidance in this report does not indicate an exclusive since ancient times. Attention has been directed toward the use of legal
course of treatment or serve as a standard of medical care. and illegal substances by pregnant women over the past several
Variations, taking into account individual circumstances, may be decades. Almost all drugs are known to cross the placenta and have
appropriate.
some effect on the fetus. The effects on the human fetus of prenatal
All technical reports from the American Academy of Pediatrics
automatically expire 5 years after publication unless reaffirmed,
cigarette use have been identified and studied since the 1960s,1 the
revised, or retired at or before that time. effects of alcohol and opiate use have been studied since the 1970s,2–4
and the effects a variety of other illicit drugs have been studied since
the 1980s.5–7 This report reviews data regarding the prevalence of
exposure and available technologies for identifying exposure as well
as current information regarding short- and long-term outcomes of
exposed infants, with the aim of facilitating pediatricians in fulfilling
their role in the promotion and maintenance of infant and child
health.
PREVALENCE
www.pediatrics.org/cgi/doi/10.1542/peds.2012-3931
Prevalence estimates for prenatal substance use vary widely and have
doi:10.1542/peds.2012-3931
been difficult to establish. Differences are likely attributable to such
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). things as the use of different sampling methods and drug-detection
Copyright © 2013 by the American Academy of Pediatrics methods, screening women in different settings, and obtaining data
at different points in time. For example, prevalence will vary depending
on whether history or testing of biological specimens is used; whether
the biological specimen is hair, urine, or meconium; and whether the
specimens are merely screened for drugs or screened and confirmed
with additional testing. There also will be differences depending on
whether the sample being investigated is a community sample or
a targeted sample, such as women who are in drug treatment or are
incarcerated. Lastly, prevalence must be interpreted in light of the fact
PEDIATRICS Volume 131, Number 3, March 2013 e1009
Downloaded from pediatrics.aappublications.org by guest on October 27, 2015that the use of specific drugs waxes and cigarette use by pregnant and used for identification, methods of
and wanes over time nationwide as nonpregnant women. An additional adulteration of the sample, and ana-
the popularity of certain substances important finding from this survey lytical techniques, thus altering the
changes. was that the rate of cigarette smoking sensitivity and specificity for each drug
Although a variety of prevalence for those 15 to 17 years of age actually of interest. The most common analyt-
studies have been conducted over was higher for pregnant women than ical method used for screening bi-
the past 2 decades, there is 1 national for nonpregnant women (22.7% vs ological specimens is an immunoassay
survey that regularly provides in- 13.4%, respectively). This report details designed to screen out drug-free
formation on trends in substance many sociodemographic variables re- samples. Threshold values generally
abuse among pregnant women. The lated to drug use in the American are set high to minimize false-positive
National Survey on Drug Use and population, and the reader is referred test results but may be too high to
Health (formerly called the National to the Substance Abuse and Mental detect low-dose or remote exposure.
Household Survey on Drug Abuse), Health Services Administration Web Because immunoassay is a relatively
sponsored by the Substance Abuse site for the full report (http://www.oas. nonspecific test, positive results re-
and Mental Health Services Adminis- samhsa.gov/nhsda.htm). quire confirmation by using gas
tration (http://www.oas.samhsa.gov/ chromatography/mass spectrometry.
nhsda.htm), is an annual survey pro- IDENTIFICATION OF PRENATAL In addition, confirmation of the presence
viding national and state level in- EXPOSURE of a drug is not always associated with
formation on the use of alcohol, Two basic methods are used to identify drug abuse. Alternative explanations in-
tobacco, and illicit drugs in a sample drug users: self-report or biological clude passive exposure to the drug, in-
of more than 67 000 noninstitu- specimens. Although no single ap- gestion of other products contaminated
tionalized people older than 12 years. proach can accurately determine the with the drug, or use of prescription
Data are combined into 2-year epochs presence or amount of drug used medications that either contain the drug
and include reported drug use for during pregnancy, it is more likely that or are metabolized to the drug.14 Thus,
pregnant women between the ages of fetal exposure will be identified if careful patient histories remain essen-
15 and 44 years. Current illegal drug a biological specimen is collected tial to the process of identification.
use among pregnant women re- along with a structured interview.8 The 3 most commonly used specimens
mained relatively stable from 2007– to establish drug exposure during the
Self-reported history is an inexpensive
2008 (5.1%) to 2009–2010 (4.4%). prenatal and perinatal period are
and practical method for identifying
These average prevalence rates are urine, meconium, and hair; however,
prenatal drug exposure and is the only
significantly lower than reported none is accepted as a “gold standard.”
method available in which information
current illicit drug use rates for non- Urine has been the most frequently
can be obtained regarding the timing
pregnant women (10.9%). Importantly, tested biological specimen because of
of the drug use during pregnancy and
the rate of current drug use among its ease of collection. Urine testing
the amount used. Unfortunately, self-
the youngest and possibly the most identifies only recent drug use, be-
report suffers from problems with
vulnerable pregnant women was cause threshold levels of drug
the veracity of the informant and recall
highest (16.2% for 15- to 17-year-olds,
accuracy.9,10 Histories obtained by metabolites generally can be detected
compared with 7.4% among 18- to 25-
trusted, nonjudgmental individuals or in urine only for several days. A no-
year-olds and 1.9% among 26- to 44-
via computerized survey forms; ques- table exception to this is marijuana,
year-olds). Table 1 summarizes these
tions referring back to the previous the metabolites of which can be ex-
data along with information regarding
trimester or prepregnancy usage, not creted for as long as 10 days in the
current alcohol use, binge drinking,
current use; and pregnancy calendars urine of regular users15 or up to 30
TABLE 1 Comparison of Drug Use Among used to assist recollection each im- days in chronic, heavy users. Urine is
Women 15 to 44 Years of Age by prove the accuracy of the information a good medium as well for the de-
Pregnancy Status: 2009–2010 obtained.11–13 tection of nicotine, opiate, cocaine,
Pregnant Nonpregnant and amphetamine exposure.16,17
Women, % Women, %
Several biological specimens can be
used to screen for drug exposure. Each Meconium is also easy to collect
Illicit drug use 4.4 10.9
Alcohol use 10.8 54.7 specimen has its own individual var- noninvasively. It is hypothesized that
Binge drinking 3.7 24.6 iations with regard to the window of drugs accumulate in meconium through-
Cigarette use 16.3 26.7 detection, the specific drug metabolites out pregnancy, and thus, meconium is
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thought to reflect exposure during the laws required the reporting of women major structural development is
second and third trimester of preg- who used drugs during pregnancy to complete, drugs have more subtle
nancy when meconium forms. How- the legal system through states’ child effects, including abnormal growth
ever, use of meconium to determine the abuse statutes. In 2003, the Keeping and/or maturation, alterations in
timing or extent of exposure during Children and Families Safe Act (Public neurotransmitters and their recep-
pregnancy is controversial18 because of Law 108-36) was passed by Congress, tors, and brain organization. These are
a lack of studies regarding the effects requiring physicians to notify their considered to be the direct effects of
of the timing and quantity of the post- state child protective services agency drugs. However, drugs also can exert
partum specimen collection as well of any infant identified as affected by a pharmacologic effect on the mother
as the effects of urine or transitional illegal substances at birth or experi- and, thus, indirectly affect the fetus.
stool contamination of the meconium encing drug withdrawal. Currently, For example, nicotine acts on nicotinic
samples.19 Meconium has been used issues of whether to use biological cholinergic receptors within the mes-
for the detection of nicotine, alcohol, specimens to screen for drug abuse; olimbic pathway, and neuropathways
marijuana, opiate, cocaine, and am- whether to screen the mother, her activated by alcohol enhance inhibitory
phetamine exposure.16,20 infant, or both; and which women and γ-aminobutyric acid (GABA) receptors
Hair is easy to collect, although some infants to screen are issues compli- and reduce glutamate receptor activ-
people decline this sampling method cated by legal, ethical, social, and ity. Drugs of abuse mimic naturally
because of cosmetic concerns and scientific concerns. Each of these occurring neurotransmitters, such
societal taboos. Drugs become trapped concerns must be taken into account that marijuana acts as anandamides,
within the hair and, thus, can reflect as obstetricians, neonatologists, and opiates act as endorphins, and co-
drug use over a long period of time. pediatricians work to develop proto- caine and stimulants act within the
Unfortunately, using hair to determine cols for identifying prenatal drug mesolimbic dopaminergic pathways
timing and quantity of exposure also exposure. For example, there is no to increase dopamine and serotonin
is controversial. In addition, envi- biological specimen that, when ob- within the synapses.32 Other indirect
ronmental contamination, natural hair tained randomly, identifies prenatal effects of drugs of abuse on the fetus
colors and textures, cosmetic hair drug use with 100% accuracy; hence,
include altered delivery of substrate
processing, and volume of the a negative drug screening result does
to the fetus for nutritional purposes,
not ensure that the pregnancy was
hair sample available all affect the either because of placental insuf-
drug free. Targeted screening of high-
rational interpretation of the results.21–24 ficiency or altered maternal health
risk women is problematic, because
Hair is useful for the detection of nic- behaviors attributable to the mother’s
it can be biased toward women of
otine, opiate, cocaine, and amphetamine addiction. These altered behaviors,
racial or ethnic minorities and those
exposure.16,25 which include poor nutrition, decreased
who are economically disadvantaged
Other biological specimens have been access/compliance with health care,
or socially disenfranchised. Universal
studied for use in the detection of in increased exposure to violence, and
screening of pregnant women is im-
utero drug exposure but are not increased risk of mental illness and
practical and not cost-effective.28–30
commonly used in the clinical setting. infection, may place the fetus at
Finally, testing of biological specimens
These include such specimens as cord risk.33
when the maternal history is positive
blood, human milk, amniotic fluid, and for drug use increases medical costs Nicotine concentrations are higher in
umbilical cord tissue.8,19,26 In the case and does not necessarily provide in- the fetal compartment (placenta, am-
of umbilical cord tissue, drug class- formation that guides the medical niotic fluid, fetal serum) compared with
specific immunoassays for amphet- care of the infant.31 maternal serum concentrations.34–36
amines, opiates, cocaine, and canna- Nicotine is only 1 of more than 4000
binoids appear to be as reliable as compounds to which the fetus is ex-
meconium testing, with the additional MECHANISMS OF ACTION OF posed through maternal smoking. Of
benefit of availability of the tissue at DRUGS ON THE FETUS these, ∼30 compounds have been as-
the time of birth.27 Drugs can affect the fetus in multi- sociated with adverse health out-
Beginning in the early 1980s, states ple ways. Early in gestation, during comes. Although the exact mechanisms
began to enact legislation in response the embryonic stage, drugs can have by which nicotine produces adverse
to the increasingly popular use of significant teratogenic effects. How- fetal effects are unknown, it is likely
“crack” cocaine in our society. Such ever, during the fetal period, after that hypoxia, undernourishment of
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effects on the placental and umbilical decreased protein, nucleic acid, and structure and function, which can
vessels all play a role.37,38 Nicotine also lipid synthesis.74,76–79 Marijuana can produce altered responsiveness to
has been shown to have significant remain in the body for up to 30 days, environmental or pharmacologic chal-
deleterious effects on brain devel- thus prolonging fetal exposure. In lenges later in life.98
opment, including alterations in brain addition, smoking marijuana pro- Methamphetamine is a member of
metabolism and neurotransmitter sys- duces as much as 5 times the amount a group of sympathomimetic drugs
tems and abnormal brain devel- of carbon monoxide as does cigarette that stimulate the central nervous
opment.39–43 Additional toxicity from smoking, perhaps altering fetal oxy- system. It readily passes through the
compounds in smoke, such as cyanide genation.80 placenta and the blood-brain barrier
and cadmium, contribute to toxicity.44–48 In humans, opiates rapidly cross the and can have significant effects on
Ethanol easily crosses the placenta placenta, with drug equilibration be- the fetus.99–101 After a single dose of
into the fetus, with a significant con- tween the mother and the fetus.81 methamphetamine to pregnant mice,
centration of the drug identified in the Opiates have been shown to decrease levels of substance in the fetal brain
amniotic fluid as well as in maternal brain growth and cell development in were found to be similar to those
and fetal blood.49,50 A variety of animals, but studies of their effects found in human infants after pre-
mechanisms explaining the effects of on neurotransmitter levels and opi- natal methamphetamine exposure,
alcohol on the fetus have been hy- oid receptors have produced mixed with accumulation and distribution
pothesized. These include direct tera- results.82–89 of the drug most likely dependent on
togenic effects during the embryonic the monoaminergic transport sys-
Pharmacologic studies of cocaine in
and fetal stage of development as well tem. It is possible that the mecha-
animal models using a variety of
as toxic effects of alcohol on the pla- nism of action of methamphetamine
species have demonstrated that co-
centa, altered prostaglandin and pro- is an interaction with and alteration
caine easily crosses both the placenta
tein synthesis, hormonal alterations, of these neurotransmitter systems
and the blood-brain barrier and can
nutritional effects, altered neuro- in the developing fetal brain100
have significant teratogenic effects on
transmitter levels in the brain, altered as well as alterations in brain
the developing fetus, directly and in-
brain morphology and neuronal de- morphogenesis.102
directly.90 Cocaine’s teratogenic effects
velopment, and hypoxia (thought to be most likely result from interference
attributable to decreased placental with the neurotrophic roles of mono- MEDICAL ISSUES IN THE NEWBORN
blood flow and alterations in vascular aminergic transmitters during brain
PERIOD
tone in the umbilical vessels).51–69 development,91–94 which can signifi- Fetal Growth
Although the main chemical compound cantly affect cortical neuronal devel- Fetal tobacco exposure has been a
in marijuana, δ-9-tetrahydrocannabinol opment and may lead to morphologic known risk factor for low birth weight
(THC), crosses the placenta rapidly, its abnormalities in several brain struc- and intrauterine growth restriction
major metabolite, 11-nor-9-carboxy- tures, including the frontal cingulate for more than 50 years,103 with de-
THC, does not.70 Unlike other drugs, cortex.94 It also appears that the creasing birth weight shown to be
the placenta appears to limit fetal ex- development of areas of the brain related to the number of cigarettes
posure to marijuana, as fetal THC that regulate attention and executive smoked.104–107 Importantly, by 24 months
concentrations have been docu- functioning are particularly vulnera- of age, most studies no longer dem-
mented to be lower than maternal ble to cocaine. Thus, functions such as onstrate an effect of fetal tobacco ex-
concentrations in studies of various arousal, attention, and memory may posure on somatic growth parameters
animal species.15,70–72 The deleterious be adversely affected by prenatal co- of prenatally exposed infants.108-114
effects of marijuana on the fetus are caine exposure.89,91,95–97 Furthermore, Growth restriction is 1 of the hall-
thought to be attributable to complex insults to the nervous system dur- marks of prenatal alcohol exposure
pharmacologic actions on developing ing neurogenesis, before homeostatic and must be present to establish a di-
biological systems, altered uterine regulatory mechanisms are fully agnosis of fetal alcohol syndrome.3,115
blood flow, and altered maternal developed, differ from those on ma- However, even moderate amounts of
health behaviors.73–75 Similar to other ture systems. Thus, cocaine exposure alcohol use during pregnancy is asso-
drugs, marijuana has been shown to occurring during development of the ciated with a decrease in size at
alter brain neurotransmitters as well nervous system might be expected to birth.116–119 In general, marijuana has
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not been associated with fetal growth limited. However, Little et al131 reported neonates. A large multicenter trial
restriction, particularly after control- no increase in the frequency of major evaluating buprenorphine’s effect on
ling for other prenatal drug expo- anomalies in a small sample of exposed exposed infants documented de-
sures.109,120-122 Fetal growth effects are infants when compared with non- creased morphine dose, hospital
reported in studies of prenatal opiate exposed infants. length of stay, and length of treat-
exposure; however, confounding vari- ment.150–152 There has been no sub-
ables known to be associated with Withdrawal stantiation of early reports regarding
poor growth, such as multiple drug No convincing studies are available cocaine withdrawal.153 Currently, no
use and low socioeconomic status, that document a neonatal withdrawal prospective studies of withdrawal in
were not well controlled in many of the syndrome for prenatal nicotine expo- methamphetamine-exposed infants
studies.123 Using data from the Mater- sure. Although several authors de- are available. A retrospective study
nal Lifestyle Study, Bada et al124 scribe abnormal newborn behavior of by Smith et al154 reported with-
reported lower birth weight in opiate- exposed infants immediately after drawal symptoms in 49% of their
exposed newborn infants born at ≥33 delivery, the findings are more con- sample of 294 methamphetamine-
weeks’ gestation, independent of use sistent with drug toxicity, which exposed newborn infants. However,
of other drugs, prenatal care, or steadily improves over time,144,145 as only 4% required pharmacologic in-
other medical risk factors. An in- opposed to an abstinence syndrome, tervention. The AAP clinical report
dependent effect of prenatal cocaine in which clinical signs would escalate on neonatal drug withdrawal contains
exposure on intrauterine growth has over time as the drug is metabolized in-depth information on neonatal
been the most consistent finding and eliminated from the body. There is drug withdrawal, including treatment
across studies of prenatally exposed 1 report of withdrawal from prenatal options.155
infants.122,125-130 Early studies on pre- alcohol exposure in infants with fetal
natal methamphetamine exposure131 as alcohol syndrome born to mothers Neurobehavior
well as recent studies132 reveal in- who drank heavily during preg- Abnormalities of newborn neuro-
dependent effects of the drug on fetal nancy,146 but withdrawal symptoms behavior, including impaired orienta-
growth. However, the literature avail- have not been reported in longitudinal tion and autonomic regulation156 and
able is limited at this time. Several studies available in the extant litera- abnormalities of muscle tone,144,147,157
reviews on the effects of prenatal drug ture. Neonatal abstinence symptoms have been identified in a number of
exposure on growth contain additional have not been observed in marijuana- prenatal nicotine exposure studies.
details.133–135 exposed infants, although abnormal Poor habituation and low levels of
newborn behavior has been reported arousal along with motor abnormali-
Congenital Anomalies with some similarities to that associ- ties have been identified in women
Nicotine has been associated with oral ated with narcotic exposure.147 An who drank alcohol heavily during
facial clefts in exposed newborn opiate withdrawal syndrome was first their pregnancy.80,158 Prenatal mari-
infants,136–140 although the data are described by Finnegan et al148 in juana exposure is associated with in-
relatively weak. There is a vast liter- 1975. Neonatal abstinence syndrome creased startles and tremors in the
ature on the teratogenic effects of includes a combination of physiologic newborn.120 Abnormal neurobehavior
prenatal alcohol exposure after the and neurobehavioral signs that in- in opiate-exposed newborn infants is
first description of fetal alcohol syn- clude such things as sweating, irrita- related to neonatal abstinence (see
drome in 1973.3 The American Acad- bility, increased muscle tone and earlier section on Withdrawal). Using
emy of Pediatrics (AAP) policy activity, feeding problems, diarrhea, the Brazelton Newborn Behavioral As-
statement “Fetal Alcohol Syndrome and seizures. Infants with neonatal sessment Scale,159 reported effects of
and Alcohol-Related Neurodevelopmental abstinence syndrome often require prenatal cocaine exposure on infants
Disorders” contains more informa- prolonged hospitalization and treat- have included irritability and lability
tion.141 No clear teratogenic effect of ment with medication. Methadone ex- of state, decreased behavioral and au-
marijuana or opiates is documented posure has been associated with tonomic regulation, and poor alertness
in exposed newborn infants.142 Origi- more severe withdrawal than has ex- and orientation.160 Recent data from
nal reports regarding cocaine terato- posure to heroin.149 Early reports re- the Infant Development, Environment,
genicity have not been further garding buprenorphine, a more recent and Lifestyle multicenter study on
documented.133,143 Studies of fetal meth- alternative to methadone, suggest min- the effects of prenatal methamphet-
amphetamine exposure in humans are imal to mild withdrawal in exposed amine exposure documented abnormal
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Downloaded from pediatrics.aappublications.org by guest on October 27, 2015neurobehavioral patterns in exposed supply and neurobehavioral effects on syndrome, it is the least sensitive
newborn infants consisting of poor the infant.172–174 However, for nicotine of the diagnostic criteria.185 No in-
movement quality, decreased arousal, and alcohol, the benefits of breast- dependent effect of prenatal mari-
and increased stress.161 feeding in the face of limited use of juana exposure on growth has been
these drugs outweigh the potential documented throughout early child-
risks. Marijuana has an affinity for hood and adolescence.109,182,184 Long-
Breastfeeding
lipids and accumulates in human term effects on growth have not
Few sources are available document- milk,175 as can cocaine26 and amphet- been documented in the opiate-
ing the prevalence of drug use during amines.101,165 Although the AAP consid- exposed child.186 The available litera-
breastfeeding. Lacking recent data, ers the use of marijuana, opiates, ture on the effect of prenatal cocaine
the 1988 National Maternal and In- cocaine, and methamphetamine to be exposure on growth throughout child-
fant Health Survey (http://www.cdc.gov/ a contraindication to breastfeeding, hood is not conclusive. Although sev-
nchs/about/major/nmihs/abnmihs.htm) supervised methadone use not only eral studies document the negative
revealed that the prevalence of drug is considered to be compatible with effects of prenatal cocaine exposure
use during pregnancy was compara- breastfeeding, with no effect on the on postnatal growth,187–189 others do
ble to the prevalence of use among infant or on lactation, but also is not.126,190,191 No studies are available
women who breastfed their infants. a potential benefit in reducing the linking prenatal methamphetamine
Women who used various amounts of symptoms associated with neonatal exposure to postnatal growth prob-
alcohol or marijuana and moderate abstinence syndrome. Several available lems. However, 1 study of unspecified
amounts of cocaine during their reviews provide more detailed in- amphetamine use suggests that in
pregnancy were not deterred from formation with regard to breastfeeding utero exposure may be associated
breastfeeding their infants. Thus, the and substance abuse.162,176 The reader with poor growth throughout early
pediatrician is faced with weighing is also referred to the AAP policy childhood.192
the risks of exposing an infant to statement “Breastfeeding and the Use
drugs during breastfeeding against of Human Milk.”177 Behavior
the many known benefits of breast- After controlling for a variety of po-
feeding.162 For women who are absti- tentially confounding socioeconomic,
nent at the time of delivery or who are
LONG-TERM EFFECTS RELATED TO
PRENATAL DRUG EXPOSURE psychosocial, family, and health vari-
participating in a supervised treat- ables, a number of studies have
ment program and choose to breast- Growth identified independent effects of pre-
feed, close postpartum follow-up of The effects of prenatal tobacco expo- natal tobacco exposure on long-term
the mother and infant are essential. sure on long-term growth are not behavioral outcomes extending from
For most street drugs, including mar- clear-cut. Reports in the literature of early childhood into adulthood. For
ijuana, opiates, cocaine, and meth- effects on height and weight178–181 example, impulsivity and attention
amphetamine, the risks to the infant of have not been substantiated by re- problems have been identified in
ongoing, active use by the mother search teams able to control for other children prenatally exposed to nico-
outweigh the benefits of breastfeeding, drug use in the sample.109,117,182,183 tine.193–195 In addition, prenatal to-
because most street drugs have been Recent studies, some of which include bacco exposure has been associated
shown to have some effect on the adolescents, have suggested that the with hyperactivity196 and negative197
breastfeeding infant.163–166 In addition, effect on growth might be attributable and externalizing behaviors in chil-
the dose of drug being used and the to a disproportionate weight for dren,198–200 which appear to continue
contaminants within the drug are un- height, such that prenatally exposed through adolescence and into adult-
known for most street drugs. Nicotine children were more likely to be obese hood in the form of higher rates of
is secreted into human milk167,168 and as evidenced by a higher BMI, in- delinquency, criminal behavior, and
has been associated with decreased creased Ponderal index, and in- substance abuse.201–206 Prenatal alco-
milk production, decreased weight gain creased skinfold thickness.113,183,184 A hol exposure is linked with significant
of the infant, and exposure of the infant robust and extensive literature is attention problems in offspring207–210
to environmental tobacco smoke.169–171 available documenting the effects of as well as adaptive behavior problems
Alcohol is concentrated in human milk. prenatal alcohol exposure on long- spanning early childhood to adult-
Heavy alcohol use has been shown to term growth. Although poor growth hood.211 Problems identified included
be associated with decreased milk is 1 of the hallmarks of fetal alcohol disrupted school experiences, delinquent
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and criminal behavior, and substance behavioral problems. However, studies alcohol exposure has been shown to
abuse. Kelly et al212 published an in- of both young and older children interfere with the development and use
depth review of the effects of prenatal prenatally exposed to nicotine have of language,259 possibly leading to long-
alcohol exposure on social behavior. revealed abnormalities in learning and term problems in social interaction.260
Inattention and impulsivity at 10 years memory227,228 and slightly lower IQ No effect of prenatal marijuana expo-
of age have been associated with scores.201,229–231 Prenatal alcohol ex- sure on language development has
prenatal marijuana exposure.213 Hy- posure frequently is cited as the most been identified in children through 12
peractivity and short attention span common, preventable cause of non- years of age.227,258 Subtle language
have been noted in toddlers prenatally genetic intellectual disability. Although delays have been associated with pre-
exposed to opiates,214 and older ex- IQ scores are lower in alcohol-exposed natal cocaine exposure.256,261,262 Cur-
posed children have demonstrated offspring,207,232 they can be variable. rently, no data are available relating the
memory and perceptual problems.215 Additionally, prenatal alcohol expo- prenatal use of opiates or metham-
Caregiver reports of child behavior sure has been associated with poorer phetamine to language development in
problems in preschool-aged216 and memory and executive functioning exposed offspring.
elementary school-aged children217,218 skills.233 Marijuana has not been
have not been related to cocaine ex- shown to affect general IQ, but it
posure, except in combination with has been associated with deficits in Achievement
other risk factors.219–221 However, in problem-solving skills that require The literature available evaluating ac-
longitudinal modeling of caregiver sustained attention and visual memory, ademic achievement is limited. In
reports at 3, 5, and 7 years of age, the analysis, and integration230,231,234–236 nicotine-exposed children, Batstra
multisite Maternal Lifestyles Study and with subtle deficits in learning and et al200 identified poorer performance
revealed that prenatal cocaine expo- memory.237 Longitudinal studies of on arithmetic and spelling tasks that
sure had an independent negative ef- prenatal opiate exposure have not were part of standardized Dutch
fect on trajectories of behavior produced consistent findings with achievement tests. Howell et al232
problems.222 There have been teacher regard to developmental sequelae. Al- reported poorer performance in
reports of behavior problems in pre- though developmental scores tend to be mathematics on achievement tests in
natally exposed children,223 although lower in exposed infants, these differ- adolescents who had been exposed
again, findings have not been consis- ences no longer exist when appropriate prenatally to alcohol. Streissguth
tent across studies,190 and some have medical and environmental controls are et al263 describe a variety of signifi-
been moderated by other risks.224 included in the analyses.238–240 With little cant academic and school problems
There also have been reports in this exception,241 prenatal cocaine exposure related to prenatal alcohol exposure,
age group of deficits in attention pro- has not predicted overall development, primarily associated with deficits in
cessing190 and an increase in symp- IQ, or school readiness among toddlers, reading and math skills throughout
toms of attention-deficit/hyperactivity elementary school-aged children, or the school years.263–266 Prenatal mar-
disorder and oppositional defiant middle school-aged children.190,242–250 ijuana exposure has been associated
disorder self-reported by the ex- However, several studies have revealed with academic underachievement,
posed children.217,218 To date, no alterations in various aspects of ex- particularly in the areas of reading
studies are available that link pre- ecutive functioning,221,241 including and spelling.267 School achievement is
natal methamphetamine exposure visual-motor ability,244 attention,251–253 not an area that has been studied
with long-term behavioral problems. and working memory.254 To date, lim- adequately with regard to prenatal
However, 1 study of unspecified am- ited data are available revealing an opiate exposure. Reported effects of
phetamine use during pregnancy association between prenatal meth- cocaine exposure on school achieve-
suggests a possible association with amphetamine exposure and IQ.255 ment are variable. In the longitudinal
externalizing behaviors and peer Maternal Lifestyle Study, 7-year-old
problems.225,226 children with prenatal cocaine expo-
Language sure had a 79% increased odds of
Poor language development in early having an individualized educational
Cognition/Executive Functioning childhood after prenatal nicotine ex- plan (adjusted for IQ),268 and Morrow
The link between prenatal nicotine posure has been reported,227,256,257 et al249 found 2.8 times the risk of
exposure and impaired cognition is as have poor language and reading learning disabilities among children
not nearly as strong as the link with abilities in 9- to 12-year-olds.258 Prenatal with prenatal cocaine exposure
PEDIATRICS Volume 131, Number 3, March 2013 e1015
Downloaded from pediatrics.aappublications.org by guest on October 27, 2015compared with their peers who were Mounting clinical data support an in- Alcohol remains the most widely
not exposed to drugs prenatally. creased risk of ethanol abuse later in studied prenatal drug of abuse, and
However, other studies do not support life after prenatal exposure.275,277 the evidence is strong for fetal growth
significant cocaine effects on school Prenatal marijuana exposure has problems, congenital anomalies, and
achievement.190,269 No data are available been associated with an increased abnormal infant neurobehavior. There
for the effects of methamphetamine on risk for marijuana and cigarette use has been no convincing evidence of
school achievement. Cernerud et al270 in exposed offspring.273 Insufficient a neonatal withdrawal syndrome.
reported on 65 children prenatally ex- data are available to draw any con- Ongoing longitudinal studies con-
posed to amphetamines. At 14 to 15 clusions relative to the affects of tinue to document long-term effects
years of age, the children in their co- prenatal opiate, cocaine, or metham-
on growth, behavior, cognition, lan-
hort scored significantly lower on phetamine exposure on the risk for
guage, and achievement, and alcohol
mathematics tests than did their tobacco, problem alcohol, or illicit
is the most common identifiable te-
classmates who were not exposed to drug use later in life.
ratogen associated with intellectual
amphetamines prenatally and had
a higher rate of grade retention than disability.
SUMMARY
the Swedish norm. Although there have been studies re-
Although methodologic differences vealing subtle abnormalities in infant
Predisposed to Own Drug Use between studies and limited data in neurobehavior related to prenatal
A limited number of studies are the extant literature make general- marijuana exposure, there have been
available that have investigated the ization of the results for several of the no significant effects documented for
association between prenatal sub- drugs difficult, some summary state- fetal growth, congenital anomalies, or
stance exposure and subsequent drug ments can be made by using the
withdrawal. Long-term studies reveal
abuse in exposed offspring. These current knowledge base (Table 2).
effects of prenatal exposure on be-
studies did not document cause and The negative effect of prenatal nicotine havior, cognition, and achievement but
effect, and it remains to be determined exposure on fetal growth has been not on language or growth.
how much of the association can be known for decades; however, longitu-
linked to prenatal exposure versus dinal studies do not reveal a consistent The most significant effect of prenatal
opiate exposure is neonatal absti-
socioeconomic, environmental, and effect on long-term growth. Clinical
genetic influences. Studies available studies have failed to reach a consen- nence syndrome. There have been
for prenatal nicotine exposure suggest sus regarding congenital anomalies, documented effects on fetal growth
an increased risk of early experi- and there is no evidence of a with- (but not on long-term growth) and
mentation271 and abuse of nicotine drawal syndrome in the newborn infant neurobehavior as well as long-
in exposed offspring.272,273 Brennan infant. Recent studies document term effects on behavior. There is
et al274 reported an association of a negative effect of prenatal exposure not a consensus as to the effects of
prenatal nicotine exposure with on infant neurobehavior as well as on prenatal opiate exposure on cognition,
higher rates of hospitalization for long-term behavior, cognition, lan- and few data are available regarding
substance abuse in adult offspring. guage, and achievement. language and achievement.
TABLE 2 Summary of Effects of Prenatal Drug Exposure
Nicotine Alcohol Marijuana Opiates Cocaine Methamphetamine
Short-term effects/birth outcome
Fetal growth Effect Strong effect No effect Effect Effect Effect
Anomalies No consensus on effect Strong effect No effect No effect No effect No effect
Withdrawal No effect No effect No effect Strong effect No effect *
Neurobehavior Effect Effect Effect Effect Effect Effect
Long-term effects
Growth No consensus on effect Strong effect No effect No effect No consensus on effect *
Behavior Effect Strong effect Effect Effect Effect *
Cognition Effect Strong effect Effect No consensus on effect Effect *
Language Effect Effect No effect * Effect *
Achievement Effect Strong effect Effect * No consensus on effect *
* Limited or no data available.
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Prenatal cocaine exposure has a neg- LEAD AUTHORS COMMITTEE ON FETUS AND
ative effect on fetal growth and subtle Marylou Behnke, MD NEWBORN, 2012–2013
Vincent C. Smith, MD Lu-Ann Papile, MD, Chairperson
effects on infant neurobehavior. How-
Jill E. Baley, MD
ever, there is little evidence to support William Benitz, MD
COMMITTEE ON SUBSTANCE ABUSE,
an association with congenital anom- 2012–2013 Waldemar A. Carlo, MD
alies or withdrawal. There is not Sharon Levy, MD, Chairperson
James J. Cummings, MD
a consensus regarding the effects of Eric Eichenwald, MD
Seth D. Ammerman, MD
Praveen Kumar, MD
prenatal cocaine exposure on either Pamela Kathern Gonzalez, MD
Richard A. Polin, MD
Sheryl Ann Ryan, MD
long-term growth or achievement; Rosemarie C. Tan, MD, PhD
Lorena M. Siqueira, MD, MSPH
however, there are documented long- Vincent C. Smith, MD
Kasper S. Wang, MD
term effects on behavior and subtle
effects on language. Although there is FORMER COMMITTEE MEMBER
PAST COMMITTEE MEMBERS Kristi L. Watterberg, MD
little evidence to support an effect on Marylou Behnke, MD
overall cognition, a number of studies Patricia K. Kokotailo, MD, MPH
Janet F. Williams, MD, Immediate Past Chair-
LIAISONS
have documented effects on specific CAPT Wanda D. Barfield, MD, MPH – Centers for
person
areas of executive function. Disease Control and Prevention
Ann L. Jefferies, MD – Canadian Pediatric Society
Studies on prenatal methamphet- LIAISON George A. Macones, MD – American College of
amine exposure are still in their in- Vivian B. Faden, PhD – National Institute on Obstetricians and Gynecologists
fancy. Early studies have documented Alcohol Abuse and Alcoholism Erin L. Keels APRN, MS, NNP-BC – National
Deborah Simkin, MD – American Academy of Association of Neonatal Nurses
an effect of prenatal exposure on fetal
Child and Adolescent Psychiatry Tonse N. K. Raju, MD, DCH – National Institutes of
growth and infant neurobehavior but Health
no association with congenital anom- STAFF
alies and no data regarding infant Renee Jarrett STAFF
withdrawal or any long-term effects. James Baumberger Jim Couto, MA
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