Fetal, Neonatal and Early Childhood Effects of Prenatal Methamphetamine Exposure
Mary F Holley MD
See our new brochure Prenatal Drug Exposure Click Here
Drugs of abuse have a long legacy of causing significant impairment in the development of the human
brain. Alcohol abuse during pregnancy results in significant changes that include facial dysmorphisms, neurobehavioral
problems such as ADHD, and mental retardation. The full complex of alcohol related dysfunction is
known as fetal alcohol spectrum. Methamphetamine exposure has not been identified with a syndrome or an identifiable
pattern of malformation or dysfunction, but clusters of symptoms have been associated with neurologic deficits
identified on sophisticated brain scanning of children exposed to methamphetamine (Chang 2004). These findings
require our attention and reasonable changes in our patterns of practice in the prenatal clinic and the nursery.
There are a number of developmental risk factors that are common to all drugs of abuse and that may
overlap with the effects of lower socioeconomic status. These include genetic influences, nutritional status of the
mother, poverty and associated stressors, mental illness either as a predisposing factor to addiction, or as a consequence
of drug use, infectious diseases and lack of prenatal care. Each of these factors contributes to the environmental
stressors impacting the development of the child born into a family affected by drug abuse. We will also
consider the risk factors specific to methamphetamine use including placental insufficiency, preterm labor, congenital
malformations, and the neurotoxic effects of methamphetamine on the developing brain.
Early identification of drug exposed infants and children is crucial to our efforts to intervene in the lives
of these children. Early childhood development is strongly affected by the drug use of parents, particularly mothers.
Proactive intervention however demands that we know at the infancy or preschool stage that a child is at risk
for drug or alcohol related developmental challenges. In order to effectively intervene in these children’s lives we
have to know who they are, and be willing to take action to protect them. The consequences of our failure to do so
will be made manifest in the juvenile detention centers of the next decade.
Methamphetamine use among pregnant US women doubled over the six year span from 1998 to 2004 (Cox 2008)
as methamphetamine has gradually replaced cocaine as the drug of choice in many areas of the nation among
Americans in general and women of childbearing age in particular. Unlike cocaine, methamphetamine is used by
women at rates equal to men (Cohen 2007), primarily for weight loss and increased energy. Methamphetamine is a
much more toxic drug than cocaine, causing more rapid and intense addiction (Gonzalez 2000), more symptoms of
mental illness (McKetin 2006), and more rapid personal and family disintegration. For all these reasons, methamphetamine
has exacted a higher toll on the family, higher even than cocaine, which has already destroyed countless
families across this nation.
Both cocaine and methamphetamine produce sexual arousal and promote promiscuous sexual behavior,
but methamphetamine produces this effect for far longer than cocaine, and is commonly used by addicts to enhance
their sexual experience. As the people using methamphetamine are predominantly of childbearing age, this
drug poses greater risks to their unborn children than other comparable drugs of abuse. Increased risk of disease
transmission including Sexually Transmitted Diseases, Hepatitis C and HIV, and higher risks of obstetric complications,
prematurity and growth restriction are of particular concern as methamphetamine use increases in the
mothers of our children (Smith 2006).
Of major concern are the numerous anecdotal reports of significant neurologic dysfunction in children
exposed to methamphetamine in utero. Caretakers of these children have reported cases of severe ADHD, conduct
disorders, learning disabilities and developmental delays in the children of methamphetamine users. These
reports have been of great concern to the family members, adoptive and foster parents who are taking responsibility
for these children. Scientifically valid information regarding their prognosis and effective interventions is
Education professionals are concerned about the impact of methamphetamine abuse on the special education
demands placed on their schools as large numbers of children with learning disabilities and attention deficits
are enrolled in the nation’s public school system. And since children with learning disabilities and academic
failure have higher rates of delinquency (Aseltine 2000), methamphetamine exposed children are more likely to
grow up to be wards of the juvenile justice system, further straining our criminal justice system. Early identification
of the drug affected child would permit intervention and training opportunities before entry into the school
system, at a time when such interventions are most likely to be effective. But early identification requires drug
testing of neonates at or shortly after birth.
True primary prevention would require antenatal identification of the drug using mother in the first trimester
of pregnancy, a time when many mothers are amenable to interventions to help their children. Drug testing
in the prenatal clinic however is generally not done because of fears such testing would deter women from
seeking prenatal care. Lacking reliable prenatal information we are left with secondary prevention, limiting the
effects of a disease by controlling its complications – damage control. This we seek to do by neonatal drug testing
to detect exposure early and offer remedial assistance to the child and rehabilitation to the mother after prenatal
exposure has already occurred.
There is a great deal of controversy over the utility and validity of drug testing of neonates. There are
concerns over the accuracy of the tests, false positive results, interactions with prescribed medications, and possible
lawsuits by mothers alleging breaches of their privacy rights. There are also concerns over possible legal
prosecution against the mothers of these children, actions taken by child protective services workers including
termination of parental rights, custody battles, and the lack of rehabilitation facilities accepting mothers with
their young children.
An accurate understanding of and response to the epidemic of drug use in this nation is essential to prevent
a public health disaster of epic proportions as today’s children become tomorrow’s parents. In view of the
significant neurotoxicty of methamphetamine, the anecdotal reports of neurologic dysfunction and learning disability
in methamphetamine affected children cannot be dismissed altogether as unreliable. These reports instead
must be investigated and fully understood in order to institute preventative measures and offer meaningful intervention
to affected children and their families.
3. Non Specific risk factors
Nutrition is a strong variable associated with poor outcomes in drug using pregnancies (Knight 1994).
Some drugs of abuse, such as alcohol, replace normal food intake and compete with nutrients for entry into the
mother. Other drugs are potent anorectics, among them cocaine and methamphetamine. These drugs can cause
profound nutritional deficiencies in chronic users, to the point of starvation. Vitamin deficiencies, anemia and
protein calorie malnutrition are significant risks to a pregnancy already complicated by substance abuse.
Poverty is also strongly associated with drug abuse, as addicts are unable to hold down a job or manage
their finances appropriately. Some methamphetamine addicts are employed and hold middle income jobs, but all
of their resources go to procure drugs and alcohol, and adequate housing and nutrition are not priorities for these
people. Uninsured mothers living in poverty are less likely to attend prenatal clinics and more likely to have untreated
infections and poor nutrition regardless of their drug abuse status.
Chronic stress is often a characteristic of the lifestyle of drug abusing mothers (Derauf 2007). Homelessness
is common, and many addicts move from place to place with no permanent address. Addicts sometimes live in
cars or abandoned buildings without utilities or a stable food supply, conditions not conducive to a healthy pregnancy.
Legal problems are common with multiple arrests, bonds, and fines. Criminal activity and domestic violence
are especially common in methamphetamine affected households. Methamphetamine addicts are irritable and
impatient, and with the onset of psychotic symptoms sometimes become violent. This violence is often directed at
Mental illness is very common in substance abusers, especially methamphetamine abusers. Addicts sometimes
have pre-existing major illnesses such as bipolar or schizophrenia, but more often they develop methamphetamine
induced symptoms of mental illness, which may or may not clear after a period of detoxification
(Mahoney 2008). Addicts may become paranoid, suspicious and hyper-vigilant. Real and apparent threats are ubiquitous.
Addicts feel threatened by other addicts, aggressive dealers, ‘snitches,’ and the authorities and often develop
delusions surrounding these and other threats. Their mental problems lead directly to severe distress, and
indirectly to occupational failure, economic distress, non-compliance with prenatal care, and poor parental adjustment.
Long term methamphetamine use can cause a form of dementia with memory loss and frontal lobe dysfunction
leading to severe impairment in some users (McCann 2007).
Infectious disease is common in drug abusing populations regardless of the substance used. Sexually
transmitted diseases flourish in the climate of promiscuity, the sex-for-dope economy, and reduced precautions
characteristic of methamphetamine abuse. Methamphetamine increases sexual desire and drive much more than
other drugs of abuse, and so is associated with extremely high rates of infection with STD’s. Methamphetamine
users experience drying of mucous membranes due to the vaso-constrictive effects of the drug further increasing
attack rates of STD’s. Methamphetamine addicts engage in higher rates of unprotected sex and larger numbers of
anonymous partners. They are less likely to present for medical care and less compliant with treatment for STD’s.
Increased risks of Hepatitis B and C and HIV are well known, particularly in IV drug users and sexually
promiscuous users. Methamphetamine appears to act as an adjuvant, increasing the risk of infection when exposed
to either Hepatitis C (Ye 2008) or HIV (Nair 2006, Mahajan 2006, Talloczy 2008). These infections are transmitted
vertically to the neonate at birth. While measures can be taken to protect the developing fetus from HIV, there
are currently no prophylactic treatments available to prevent Hepatitis C from transmitting to the newborn.
Substance abusers are also less likely to present for prenatal care and so are less likely to have been tested
and treated for infectious diseases. Methamphetamine abusers often first present to the hospital in advanced labor
having no prior relationship with any healthcare provider. Fearing involvement with the legal system, they frequently
deny illegal drug exposure. Their drug use can only be detected by drug testing in the presence of high risk
4. Methamphetamine specific risk factors
Aside from the general risk factors associated with abuse of any drug, there are also a host of risk factors
specific to methamphetamine abuse. These include obstetric complications, poor prenatal growth, increased risk of
congenital malformations, and neurologic injury to the neonatal brain related to exposure to a potent neurotoxin.
The human fetus and placenta lack enzymes that could metabolize methamphetamine as it crosses the placental
barrier (Dixon 1989). Since methamphetamine crosses the placenta very efficiently, blood and tissue levels in the
fetus are comparable to maternal blood and tissue levels (Stek 1993, Won 2001). Methamphetamine has a much
longer half life than cocaine, particularly in the human fetus. These factors can result in the accumulation of active
drug in the fetus, and higher blood levels of the drug have been seen in the developing fetus than seen in the
mother under conditions of chronic administration (Stewart 1997).
The immature organ systems of the fetus are therefore exposed to ‘big people’ doses of a potent stimulant
drug with all of its vasoconstrictor and cellular toxic properties. The picture is further complicated by the fact that
more than 80% of methamphetamine using mothers also use one or more additional drugs of abuse, most commonly
alcohol (Brecht 2007). The impact on the developing fetus is thus increased exponentially in its clinical
Obstetric complications are significantly increased in methamphetamine abusing pregnant mothers. Because
of its prolonged half life in humans – twelve to twenty hours – chronic vascular disruption is seen leading to
long term complications. Placental insufficiency is often seen leading to intrauterine growth restriction in the fetus
(Smith 2006). Some congenital malformations may also be associated with the intense vasoconstriction associated
with methamphetamine use (Hoyme 1990). Maternal hypertension associated with methamphetamine is of much
longer duration than similar findings in cocaine abusers and can lead to obstetric catastrophe with abruption and
fetal distress or fetal demise (Stewart 1997).
Maternal hypertension associated with methamphetamine use is often mistaken for pre-eclampsia or cooccurs
with pre-eclampsia (Elliot 1990). Accurate diagnosis is essential since the treatment for hypertension differs
for methamphetamine abusers. Treatment with beta blockers such as Labetolol can have untoward results in
methamphetamine abusers as these drugs do not block the alpha adrenergic effect of methamphetamine and can
lead to rapidly progressive heart failure in methamphetamine abusing gravidas (Samuels 1979 and personal experience).
Older anti-hypertensive are preferred such as appressoline or nipride, which block alpha receptors and control
the hypertension seen in methamphetamine abuse. These drugs must be dosed carefully and slowly to prevent
overshoot hypotension and resulting fetal distress.
Preterm labor, premature rupture of membranes and chorioamnionitis are all increased in methamphetamine
affected pregnancies (Eriksson 1981). The result is often a low birth weight newborn with signs of drug withdrawal
including tremors, lethargy, poor feeding, excess irritability, and other neurobehavioral abnormalities
(Smith 2003). Physical signs of intoxication in the neonate include tachycardia, hypertension, hyper-reflexia, often
mixed with symptoms related to the concurrent use of narcotics such as heroin. The Neonatal Abstinence Scoring
system is validated for neonates exposed to all drugs of abuse although the findings can be widely different for
infants withdrawing from heroin vs. those exposed to stimulants (Oro 1987). Many of these children are exposed to
multiple drugs with conflicting effects leading to confusing findings and missed detection of exposed children.
The incidence of congenital malformations has been studied in chart review studies (Forester 2007a and
b), or retrospective studies of affected children (Torfs 1994), but these studies did not include a routine neonatal
drug testing protocol and instead relied on patient report and sporadic drug testing in response to risk factors over
the course of normal obstetric care. Both methods of detection are fraught with difficulty as only 25% of drug
abusing mothers admit to drug use when questioned (Ostrea 1992), and drug testing is often done based on stereotype,
missing many drug using mothers who do not fit the profile of the ‘drug addict.’ As a result we do not know
the true incidence of congenital malformations in the infants of methamphetamine abusing mothers. Anecdotal
reports have linked methamphetamine abuse with gastroschisis, eye and ear malformations, cardiac defects, renal
anomalies, and limb reduction defects, all of which are exceedingly rare (Bays1990).
Effects of methamphetamine exposure on the developing brain have been extensively studied particularly
in light of the overwhelming evidence that methamphetamine is a neurotoxin in the adult brain (for a review Yamamoto
2005). Most of these studies have been done on rodent species. Very few human studies have been done
to assess human brain development in methamphetamine exposed children, but those that have been done suggest a
significant effect. And a long lasting effect, with behavioral changes and increased social problems extending into
5. Methamphetamine effect on brain development
Theoretically, methamphetamine should have a significant impact on brain development. It is a potent
vasoconstrictor, reducing blood supply to the placenta and thus delivery of oxygen and nutrients to the developing
fetus. It is also a potent neurotoxin, releasing free radical compounds that cause neural cell death (Yamamoto
2005). And indeed stimulants do impact embryogenesis of the developing central nervous system. Cell proliferation
and migration are impacted and synaptogenesis is impaired (Weissman 1995). There is reduction in neural
growth factor and a marked increase in reactive oxygen species and free radicals (Jeng 2005, Wells 2005). These
toxic chemicals are known neurotoxins and have been implicated in the progression of cellular damage to the brain
in adult methamphetamine users (AÃ§ikgÃ¶z 2000).
Animal models, rats, mice and gerbils, have been used to study the fetal effects of many drugs including
methamphetamine. Rodents metabolize methamphetamine differently from humans; the half life of methamphetamine
in rodents is only around one hour, compared with twelve hours in humans (Cho 2001). Rodents also mature
their central nervous system in the first month post-natally while humans do so in the third trimester of pregnancy
(Gomez- DeSilva 1998). This explains the significant differences in dosing of animals compared to typical human
use patterns. Rodents are born at an earlier gestational maturity than humans, and so are usually dosed ten – twenty
days after birth to simulate third trimester human exposure. Neonatal rodents have been found to be relatively resistant
to the effects of methamphetamine compared to adults. These differences often cloud interpretation of animal
data by clinicians who accuse animal researchers of vastly overdosing the animals. Because of the markedly
reduced half life of methamphetamine in rodents, these studies more likely underestimate the impact of fetal
methamphetamine exposure, rather than overestimating it. Overall, methamphetamine appears to be a much more
neurotoxic drug than cocaine, as might be expected based on its metabolic profile.
A summary of the most recent research in the field of methamphetamine’s effect on brain development
reveals some disturbing trends. Acevedo (2006) studying mice found significant disruption of hippocampus dependent
cognitive function in adult animals exposed to methamphetamine in the neonatal stage. Cognitive functions
affected included spatial learning, memory and object recognition. Vorhese (2007) looked at rats and also
found spatial learning and memory deficits that persisted into adulthood, suggesting a permanent structural change
in brain development. In an older but well done study, Hildebrandte (1997) localized the site of methamphetamine
induced injury to the dentate gyrus of the hippocampus, specifically to impaired granule cell proliferation (a 34%
deficit). Even low dose methamphetamine exposure caused significant spatial learning deficits in rats suggesting
that there is no safe level of exposure during pregnancy (Williams 2004a).
Gomez-DeSilva (2004) demonstrated increased catecholamines in neonatal rat brains exposed to methamphetamine,
particularly in the substantia nigra, caudate putamen, and nucleus accumbens. Williams (2004b) demonstrated
injury to the hippocampus, nucleus accumbens and parietal lobes in rats exposed to methamphetamine.
These findings have been replicated repeatedly by numerous researchers demonstrating a significant neurotoxic
effect of methamphetamine in brain development with functional loss of memory and coordination.
The mechanism of this damage was elucidated by Jeng (2005) who investigated the metabolic pathways
by which methamphetamine damages developing neural tissue. He found that methamphetamine causes oxidative
cell injury in the brains of mice exposed to neonatal methamphetamine. Oxygen free radicals are produced by the
metabolism of both methamphetamine and the mono-amine neurotransmitters released in response to methamphetamine.
These free radicals are potent neurotoxins. The fetal brain lacks key enzymes needed to metabolize
mono-amines and methamphetamine, leading to the build up of high levels of oxygen free radicals and consequent
long term impairment of brain development (Wells 2005).
These neurotoxic changes persist into adulthood and sensitize the adult brain to the effects of adult exposure
to methamphetamine, particularly in males. Neurotoxicity to the dopaminergic projections in response to
methamphetamine challenge in adulthood was significantly increased in animals that had been exposed to methamphetamine
prenatally, suggesting a persistent sensitivity (Heller 2001). This finding has significant implications for
meth exposed children growing up in meth abusing homes who learn early in life how to solve their problems with
6. Human studies of methamphetamine impact
Clearly methamphetamine should not be given to neonatal rats, mice or gerbils. It damages their little
brains. But what about humans? Do the animal studies apply to the human infant? Most human methamphetamine
users are poly-drug users and have multiple other risk factors in addition to their drug use including poverty, stress,
nutritional deficiencies and infections to name a few. For these reasons the rodent studies more likely underestimate
the impact of the total prenatal environment on the human fetus and its development.
The earliest studies on human response to fetal methamphetamine exposure were grim indeed. Tests of
visual recognition in human infants exposed to methamphetamine showed significant decreases (Hansen 1993) and
corresponding differences in attention, distractibility and activity level (Struthers 1992). Changes in visual recognition
in the infant are strongly associated with cognitive function later in life. Dixon and Bejar at UCSD (1989)
found that 35% of neonates exposed to cocaine and /or methamphetamine in utero had abnormalities in brain structure
at birth, including intraventricular hemorrhage, necrotic echodensities, and cavitary lesions. These lesions
were thought to be due to the severe vaso-constrictive effects of stimulant drugs of abuse. A significant number of
stimulant exposed infants (10%) had ventricular dilation reflecting diffuse atrophy of cortical tissue.
But the human brain is not quite the same as a rodent brain. Cortical areas are much more richly developed
in humans, and the human cortex continues postnatal development over the first 21 years of life, especially in
the first three years of life. The developmental window that extends from birth to age three is a time of explosive
growth in cognitive, emotional, verbal and social development. Given adequate interaction, stimulation and nutrition,
the human cortex increases in size significantly, though subcortical structures do so to a much lesser degree.
If the meth exposed child is sent home with responsible parents, much (though perhaps not all) of the brain injury
sustained before birth could be compensated for and its impact diminished. Early intervention in methamphetamine
exposed children could be extremely important to the long term prognosis for human cognitive and social development.
And indeed that is what the studies demonstrate. When methamphetamine exposed children are studied at
age eight to ten, the cavitary lesions and ventricular dilation are no longer seen (Smith 2001) . All of the children in
this study had been exposed to methamphetamine with very low levels of exposure to other drugs of abuse, including
alcohol. Children with diagnosed developmental delay, impaired growth, seizure disorders, or ADHD were
excluded. Only those children who looked perfectly normal were studied. Although these children did have signs
of metabolic changes in the basal ganglia, no cavitary lesions were found.
In a follow-up study by the same group, Chang in 2004 investigated further the changes seen in the basal
ganglia of methamphetamine exposed children. Using some of the same subjects, again excluding children with
obvious developmental delays or ADHD, significant subcortical changes were seen. Methamphetamine exposed
children had significantly smaller hippocampus, globus palidus, putamen and caudate (17-26% smaller), the same
areas that are impaired in animal models according to multiple studies.
A corresponding decrement in neuropsychological testing was also observed in these methamphetamine
exposed children. They scored lower on measures of visual-motor integration, attention, verbal memory and long
term spatial memory, all essential functions in efficient learning. Again, these were children who had not been
identified as having a developmental delay or ADHD by teachers or caregivers. These children looked perfectly
normal and were in performing normally in school, but they were challenged by the effects of their prenatal
Long term follow-up of methamphetamine exposed children over a period of up to fifteen years shows the
impact of these challenges. Billings (1994) demonstrated increased aggressive behavior and poor adjustment in
children eight to ten years old exposed to methamphetamine prenatally. The same children followed up to fifteen
years of age (Cernerud 1996 and Eriksson 2000) showed higher rates of academic failure and poor social adjustment.
These methamphetamine exposed children were three times more likely to be behind in school (15% were
one year or more behind) and had lower grades than non-exposed peers.
These long term studies did not attempt to control for alcohol exposure. Indeed 81% of these children
were also exposed to alcohol prenatally. Fetal Alcohol Syndrome has clearly been linked to significant neurobehavioral
abnormalities including ADHD, learning disability, verbal memory deficits, and mental retardation (Pie
2008). Most of these children (80%) were also exposed to nicotine, which has been linked to abnormalities of the
auditory association area (Dwyer 2008) and dysregulation of emotion and attention (Shea 2008). The majority
(78%) of these children did not live with their birth mothers throughout childhood. Many were wards of the state
and had moved from foster home to foster home, a condition that is strongly linked academic failure and delinquency
(National Center on Addiction and Substance Abuse at Columbia University 2004).
We do not know the true incidence or severity of psychomotor or neurocognitive disability in children
exposed to methamphetamine because routine drug testing is not being done, and so the majority of affected children
are not identified at birth or assessed as they mature. Human studies will always be complicated by concurrent
alcohol and other drug abuse since most meth addicts use other drugs as well. We do not yet have the necessary
data to assess the true incidence and risk of methamphetamine exposure to the development of the human brain.
7 Early Detection and Intervention
Primary prevention of drug related disability in the infant requires that the drug abusing mother be identified
and counseled early in the prenatal course so that disease and impairment is prevented. Screening of obstetric
patients for drug and alcohol abuse is required by the laws of most states, yet is inconsistently done by most providers
and even more seldom reported or acted upon during the pregnancy. This is in spite of the fact that a poor
obstetric outcome is likely in the event of drug abuse during pregnancy, and that the poor outcome is likely to be
attributed to substandard obstetric care if the existence of drug abuse has not been documented.
Prenatal screening is fraught with difficulty because of the fear that the drug abusing gravida will simply
avoid prenatal care if serious attention is directed to her drug or alcohol abuse, especially in the form of drug testing.
Screening is thus limited to verbal questioning with its attendant under-estimation of the extent of the problem
For verbal screening to be effective, questioning should be incorporated into the routine intake interview
so that a rapport is established with the health care provider and suspicion as to the intentions of the provider is
minimized. Questioning should begin with an inquiry into family history of substance abuse, ideally in the context
of a general family history review. This line of questions is less threatening to the patient and less likely to raise
resistance than a direct assault on her fitness to be a mother. If the family addiction is then recorded as an illness,
not a moral failure, the patient may be more likely to admit to her ‘addictive illness,’ than she would be to admit to
her ‘illegal drug use’ with its criminal intonations.
Early prenatal identification of a drug or alcohol problem permits primary prevention of the neonatal complications
– the ideal situation – rather than just damage containment obtainable with neonatal drug testing. Prenatal
identification requires an informed, concerned and honest patient, who has been apprised of the risks drug abuse
poses to her and her baby’s health, a non-judgmental attitude on the part of the medical provider, and the availability
of appropriate inpatient or outpatient treatment facilities.
Since primary prevention often is not accomplished, we are left with damage containment measures that focus on
identification of the affected newborns and rehabilitation of their mothers after delivery. But even post delivery
‘damage control’ interventions are often not carried out because of poor detection of drug and alcohol abuse in the
neonatal stage. The period of hospitalization presents our best opportunity to detect and intervene in the addiction
process because of the prolonged period of intense observation by skilled professionals in the labor and delivery
suite. Professionals trained in recognition of the signs of addiction can identify mothers and infants with risk factors
for addiction and in most states can order a neonatal drug test at the slightest hint of a problem. The most seriously
affected children are likely to be identified in this way, however not all drug addicts look, act, and smell like
drug addicts. Not all labor and delivery professionals are alert to the signs and symptoms of addiction, and not all
doctors and hospitals permit drug testing on their favored (insured) patients. Some doctors and hospitals, wishing
to avoid all the hassle associated with drug testing, do testing on only the most egregious cases, missing many affected
children. The extremely short hospitalizations for delivery that are now common also limit the ability of
trained professionals to observe mothers over an extended time and recognize abnormal patterns of behavior and
failures in bonding.
Most children exposed to drugs of abuse are not identified at birth, and most of them go home with their
drug abusing parents without any intervention. These children, who have already been exposed to a potent neurotoxin,
are then exposed to poor nutrition, domestic violence and child abuse, infectious diseases, and a host of environmental
problems associated with poverty and addiction. They are at significant risk for academic and social
failure if their problems are not addressed in a proactive manner. Proactive intervention however demands that we
know at the infancy or preschool stage that a child is at risk for drug or alcohol related developmental challenges.
Early identification offers us the opportunity to intervene in the development of a child and reduce the likelihood
of a poor outcome.
Despite a long history of neonatal testing for medical problems and inborn errors of metabolism in our
newborns (e.g. PKU and hypothyroid) the United States has no systematic program for testing all neonates for exposure
to neurotoxic drugs of abuse. This is in spite of the large numbers of children thought to suffer from these
exposures and the ease of testing by meconium or hair analysis. (Garcia - Bournissen F 2007). Testing is instead
based on stereotypes and behavioral indications that may unfairly stigmatize some segments of the population and
at the same time fail to detect the majority of cases. Basic public health science tells us that this is a totally inadequate
system of detection of a major public health risk.
Large numbers of affected children are missed when testing is based solely on risk factors. In a large
study of universal meconium drug testing, 44% of all neonates in an inner city hospital tested positive for illicit
drug exposure. The majority of children with prenatal exposure to illegal drugs appeared normal at birth, and so
would not have been tested under most protocols. Only one in four drug abusing mothers admitted to their drug use
on questioning in the perinatal setting (Ostrea 1992). Of those who admitted to drug use at any time during pregnancy,
around 90% of their infants had a positive meconium drug screen at birth.
Current neonatal indications for drug testing include obvious withdrawal symptoms, low birth weight,
neurobehavioral abnormalities, seizures, stroke, cardiac problems and NEC in a term baby. Only severely affected
infants will display symptoms this severe – around 4% of methamphetamine positive neonates (Smith 2003). Most
methamphetamine affected children (>50%) do not have any significant withdrawal symptoms, but are still at risk
for developmental delay or learning disability. Identification of these children is essential for effective intervention
to prevent social and academic failure.
Current maternal indications for neonatal drug testing include a known history of drug abuse, lack of prenatal
care, home delivery or precipitous delivery, preterm labor, poor weight gain in pregnancy, hypertension without
proteinuria, abruption, fetal distress, sexually transmitted disease, and obvious intoxication. Poor, single, or
homeless mothers are much more likely to be tested for drug abuse than mothers who are employed and have stable
The currently practiced methods for drug testing of neonates rely heavily on stereotypes of how drug
abusing mothers typically behave. This approach is dangerous and misleading for two reasons. First, women from
disadvantaged backgrounds may fit the ‘profile’ of the drug abusing mother and may be selected for testing at a
higher rate. This risk factor based testing leads to a stigmatized feeling of reproach, being held under suspicion
merely for being poor or unmarried or homeless.
Secondly, stereotype based drug testing misses many infants whose mothers do not fit the ‘profile’ but
who are abusing illegal drugs, especially methamphetamine. Methamphetamine differs from other major drugs of
abuse in that many low dose users do not consider themselves ‘drug users.’ Methamphetamine abusers are often
well educated highly functioning individuals, working two jobs, highly driven and successful. They use methamphetamine
to work harder and longer, get more focus and enhance attention, or to lose weight and/or preventweight gain. They
consider methamphetamine a ‘medication’ not a ‘drug’ and so will deny ‘drug use.’ Methamphetamine
users frequently do not fit the stereotype of the ‘addict.’ Drug testing based on stereotypes misses this
sizable population of mothers, and so their methamphetamine exposed newborns are not detected.
Universal drug testing offers a major improvement to our current protocols based on perceived risk factors.
State laws to provide for testing of all newborns for exposure to drugs of abuse, just as we currently test all
neonates for PKU and thyroid dysfunction, would permit detection of the vast majority of drug affected newborns.
The basis for testing for PKU and thyroid dysfunction is that early intervention is life saving and prevents severe
disability in affected children. This rationale also applies to the drug exposed newborn. Identified mothers could be
offered treatment and counseling, and a major cause of child abuse would be prevented. Children could be
screened for learning disabilities and receive the special attention they need to develop normally.
We currently screen children for learning disabilities in early elementary school, long after the best window
of opportunity for intervention- birth to age three- has passed. Universal neonatal testing for drug exposure
would permit earlier intervention in the child’s cognitive and social development, and would also permit earlier
intervention for the mothers of drug exposed children allowing more of them to obtain the treatment they need to
preserve the family. None of these interventions can happen if we do not know a newborn has been exposed to
If all newborns were tested, no mother would feel singled out or stigmatized, and no affected children
would be missed. Counseling and follow-up could be offered to mothers and their children and early detection of
learning difficulties could be facilitated. Early detection could lead to better outcomes for children and their families
as addictions are identified in earlier stages when treatment outcomes are more favorable. Earlier detection of
the subtle learning disabilities associated with methamphetamine exposure permits educational intervention to
mitigate the long term impact of these challenges.
The major limitation of universal neonatal drug testing is that it would only detect late second and third
trimester use, and would miss those children whose mothers didn’t like the hyperemesis treatment offered by their
obstetrician, and elected to use their college friend’s hangover treatment instead. These women are extremely
unlikely to admit to drug use, and if their children exhibit learning difficulties or neurologic injury, they will find
someone else to blame.
Another limitation is the incidence of false positive results even with the use of gas chromatography or
mass spectrometry confirmation testing. Meconium screens are not reliable for PCP exposure – the use of dextromethorphine
(Robitussin) cough medicine is enough to make the PCP screen positive. The meconium screen would
also be positive for amphetamines in the case of prescription use of stimulants such as Adderall and Desoxyn.
These drugs are not recommended for use in pregnancy (Category C) as alternative treatments are readily available
for their indications.
But the most common reason for failure to obtain a drug test is denial, usually based on stereotyping of
the mother and fear of offending the favored (insured) patient. Patients are in denial, their families are in denial,
and often healthcare workers join them in the assurance that everything must be just fine. A good mother like her
couldn’t possibly be using illegal drugs. Denial is generally discouraged in the medical field since lives are at risk
if a serious diagnosis is missed.
8. Denial Doesn’t Work
Denial on a societal scale is just as dangerous as denial on an individual level. Our reluctance to ‘label’
drug affected children results in a complete inability to assist them since we do not know who they are. Universal
drug testing of neonates would break down barriers to treatment and intervention for children and their families.
Family drug courts could assure compliance with treatment on the part of parents and assemble the wide range of
services and programs that could prevent the disintegration of these fragile families.
When affected children are missed, opportunities for intervention are missed. We lose opportunities to
impact the child and family with drug treatment options, prevent child abuse and neglect, improve cognitive performance
and prevent academic failure. We miss the opportunity to prevent second generation drug abuse in these
children as they grow up with poor self esteem and fall into delinquency. Universal drug testing offers us an inroad
to identify and assist families and children at risk. We would be remiss if we fail to take action.
AÃ§ikgÃ¶z O, GÃ¶nenÃ§ S, Kayatekin BM, PekÃ§etin C, Uysal N et al. (2000) The effects of a single dose of
methamphetamine on lipid peroxidation levels in the rat striatum and prefrontal cortex. Eur Neuropsychopharmacol.
Acevedo SF, de Esch IJ, Raber J. (2007) Sex and histamine dependent long term cognitive effects of methamphetamine exposure. Neuropsychopharmacology, 32(3), 665-72.
Aseltine RH, Gore S, Gordon J (2000) Life Stress, anger, and anxiety, and delinquency: An empirical test of general
strain theory. J Health Social Beh, 41, 256-75.
Bays J (1991) Fetal vascular disruption with prenatal exposure to cocaine or methamphetamine Letter to the Editor
Pediatrics 87, 416-7.
Billings L Eriksson M, Jonsson B, Steneroth G, Zetterstrom R. (1994) The influence of environmental factors on
behavioral problems in eight year old children exposed to amphetamine during fetal life. Child Abuse and Neglect
Brecht ML, Greenwell L, Anglin MD. (2007) Substance use pathways to methamphetamine use among treated
users. Addict Behav. 32(1), 24-38.
Cernarud L, Eriksson M, Jonsson B, Steneroth G, Zetterstrom R. (1996) Amphetamine addiction during pregnancy:
14 year follow-up of growth and school performance. Acta Pediatr 85, 204-8.
Chang L, Smith LM, LoPresti C, Yonekura LM et al. (2004) Smaller subcortical volumes and cognitive deficits in
children with prenatal methamphetamine exposure. Psychiatry Research Neuroimaging 132, 95-106.
Cho AK, Melega WP, Kuczenski R, Segal DS. (2001) Relevance of pharmacokinetic parameters in animal models
of methamphetamine abuse. Synapse 39, 161-6.
Cohen JB, Greenberg R, Uri J, Halpin M, Zweben JE. (2007) Women with methamphetamine dependence: research
on etiology and treatment. Psychoactive Drugs, 4, 347-51.
Derauf C, LaGasse LL, Smith LM, Grant P, Shah R, et al. (2007) Demographic and psychosocial characteristics of
mothers using methamphetamine during pregnancy: preliminary results of the infant development, environment,
and lifestyle study (IDEAL). Am J Drug and Alcohol Abuse 33, 281-9.
Dixon SD. (1989) Effects of transplacental exposure to cocaine and methamphetamine on the neonate. Western J
Med. 150(4), 436-42.
Dixon SD, Bejar R. (1989) Echoencephalographic findings in neonates associated with maternal cocaine and
methamphetamine use: incidence and clinical correlates. J Pediatrics 115, 770-8.
Dwyer JB, Broide RS, Leslie FM. (2008) Nicotine and brain development. Birth Defects Res C Embryo Today 84
Elliott RH, Rees GB. (1990) Amphetamine ingestion presenting as eclampsia. Can J Anaesth 37, 130 –133.
Eriksson M, Larsson G, Zetterström R. (1981) Amphetamine addiction and pregnancy II Pregnancy, delivery and
the neonatal period. Socio-medical aspects. Acta Obstet Gynecol Scand, 60(3), 253-9.
Eriksson M, Jonsson B, Steneroth G, Zetterström R. (2000) Amphetamine abuse during pregnancy: environmental
factors and outcome after 14-15 years. Scand J Public Health 28(2), 154-7.
Forrester MB, Merz RD. (2006) Comparison of trends in gastroschisis and prenatal illicit drug use rates. J Toxicol
Environ Health A 69, 1253-9.
Forrester MB, Merz RD. (2007) Risk of selected birth defects with prenatal drug use, Hawaii 1986-2002. J Toxicol
Environ Health A 70, 7-18.
Garcia-Bournissen F, Rokach B, Karaskov T, Koren G. (2007) Methamphetamine detection in maternal and neonatal hair: implications for fetal safety. Arch Dis Child Fetal Neonatal Ed. 92, F332-3.
Gomez-DeSilva J, Silva MC, Tavares T. (1998) Developmental exposure to methamphetamine : a neonatal model
in the rat. Ann NY Acad Sci 844, 310-13
Gomez-DeSilva J, de Miguel R, Fernandez-Ruiz J, Summavielle T, Tavares MA. (2004) Effects of neonatal exposureto methamphetamine: catecholamine levels in brain areas of the developing rat. Ann NY Acad Sci 1025, 602-
Gonzalez Castro F, Barrington EH, Walton MA, Rawson RA. (2000) Cocaine and methamphetamine: differential
addiction rates. Psychol Addict Behav 14, 390-6.
Hansen RL, Struthers JM, Gospe SM Jr. (1993) Visual evoked potentials and visual processing in stimulant drug
exposed infants. Dev Med Child Neurol 35, 798-805.
Heller A, Bubula N, Lew R, Heller B, Won L. (2001) Gender dependent enhanced adult neurotoxic response to
methamphetamine following fetal exposure to the drug. Pharmacol Exp Ther 298, 769-79.
Hildebrandt K, Teuchert –Noodt G, Dawirs RR. (1999) A single neonatal dose of methamphetamine suppresses
dentate granule cell proliferation in adult gerbils which is restored to control values by acute doses of haloperidol.
J Neural Transmission 106, 549-558.
Hoyme HE, Jones KL, Dixon SD, Jewett T, Hanson JW, et al. (1990) Prenatal Cocaine exposure and fetal vascular
disruption. Pediatrics 85(5), 743-7.
Jeng W, Wong AW, Ting-A-Kee R, Wells PG. (2005) Methamphetamine enhanced embryonic oxidative DNA
damage and neurodevelopmental deficits. Free Radic Biol Med 39, 317-26.
Knight EM, James H, Edwards CH, Spurlock BG, Oyemade UJ et al (1994) Relationships of serum illicit drug
concentrations during pregnancy to maternal nutritional status. J Nutr. 124, 973S-980S.
Nair MP, Mahajan S, Sykes D, Bapardekar MV, Reynolds J et al. (2006) Methamphetamine modulates DC SIGN
expression by mature dendritic cells. J Neuroimmune Pharmacol 1(3), 296-304.
National Center on Addiction and Substance Abuse at Columbia University (2004) Criminal Neglect: Substance
Abuse, Juvenile Justice, and the Children Left Behind.
Mahajan SD, Hu Z, Reynolds JL, Aalinkeel R, Schwartz SA, Nair MP. (2006) Methamphetamine modulates gene
expression patterns in monocyte derived mature dendritic cells: implications for HIV-1 pathogenesis. Mol Diagn
Ther 10, 257-69.
Mahoney JJ 3rd, Kalechstein AD, De La Garza R 2nd, Newton TF. (2008) Presence and persistence of psychotic
symptoms in cocaine versus methamphetamine dependent participants Am J Addiction, 17(2), 83-98.
McCann UD, Kuwabara H, Kumar A, Palermo M, Abbey R, et al. (2007) Persistent cognitive and dopamine transporterdeficits in abstinent methamphetamine users. Synapse, 62(2), 91-100.
McKetin R, McLaren J, Lubman DI and Hides L. (2006) The Prevalence of psychotic symptoms among methamphetamine users. Addiction 101(10), 1473-8.
Oro AS, Dixon SD. (1987) Perinatal Cocaine and methamphetamine exposure: maternal and neonatal correlates.
Pediatrics, 111(4), 571-8.
Ostrea EM, Brady M, Gause S, Raymundo AL, Stevens M. (1992) Drug Screening of Newborns by Meconium
Analysis: A Large-Scale, Prospective, Epidemiologic Study. Pediatrics 89, 107-113.
Pei JR, Rinaldi CM, Rasmussen C, Massey V, Massey D. (2008) Memory patterns of acquisition and retention of
verbal and nonverbal information in children with fetal alcohol spectrum disorders. Can J Clin Pharmacol, 15(1),
Samuels SI, Maze A, Albright G. (1979) Cardiac arrest during cesarean section in a chronic amphetamine abuser.
Anesth Analg. 58, 528 –530.
Shea AK, Steiner M. (2008) Cigarette smoking during pregnancy. Nicotine Tob Res 10(2), 267-78.
Smith LM, Chang L, Yonekura ML, Grob C, Osborne D, et al. (2001) Brain proton magnetic resonance spectroscopyin children exposed to methamphetamine in utero. Neurology 57, 255-60.
Smith L, Yonekura ML, Wallace T, Berman N, Kuo J et al. (2003) Effects of prenatal methamphetamine exposure
on fetal growth and drug withdrawal symptoms in infants born at term. J Dev Behav Pediatr 24, 17-23.
Smith LM, LaGasse LL, Derauf C, Grant P, Shah R. (2006) The infant development, environmental, and lifestyle
study: effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth. Pediatrics 118, 1149-56.
Stek AM, Fisher BK, Baker RS, Lang U, Tseng CY, et al. (1993) Maternal and fetal cardiovascular responses to
methamphetamine in the pregnant sheep. Am J Obstet Gyncecol. 169(4), 888-97.
Stewart JL, Meeker JE (1997) Fetal and infant deaths associated with maternal methamphetamine abuse. J Analytic
Toxic 21, 515-7.
Struthers JM, Hansen RL. (1992) Visual recognition memory in drug-exposed infants. Behav Pediatr 13, 108-11.
Talloczy Z Martinez J, Joset D, Ray Y, GÃ¡cser A et al. (2007) Methamphetamine inhibits antigen processing,
presentation, and phagocytosis. Plos Pathog. 4, e28.
Torfs CP, Velie EM, Oechsli FW, Bateson TF, Curry CJ. (1994) A Population based study of gastroschisis: demographic,pregnancy, and lifestyle risk factors. Teratology 50(1), 44-53.
Vorhees CV, Skelton MR, Williams MT. (2007) Age dependent effects of neonatal methamphetamine exposure on
spatial learning. Behav Pharmacol 18, 549-2.
Weissman AD Caldecott-Hazard S. (1995) Developmental neurotoxicity to methamphetamines. Clin Exp PharmacolPhysiol 22, 372-4.
Wells PG, Bhuller Y, Chen CS, Jeng W, Kasapinovic S, et al. (2005) Molecular and biochemical mechanisms in
teratogenesis involving reactive oxygen species. Toxicol Appl Pharmacol 207(2 Suppl), 354-66.
Williams MT, Moran MS, Vorhees CV. (2004) Behavioral and growth effects induced by low dose methamphetamineadministration during the neonatal period in rats. Int J Dev Neurosci 22, 273-83
Williams MT Brown RW, Vorhees CV. (2004) Neonatal methamphetamine administration induces region specific
long term neuronal morphologic changes in the rat hippocampus, nucleus accumbens, and parietal cortex. Eur J
Neurosci 19, 3165-70.
Won L, Bubula N, Heller A. (2001) Methamphetamine concentrations in fetal and maternal brain following prenatal
exposure. Neurotoxicol Teratol. 23(4), 349-54.
Yamamoto BK, Bankson MG (2005) Amphetamine neurotoxicity: cause and consequence of oxidative stress. Crit
Rev Neurobiol. 17, 87-117.
Ye L, Peng JS, Wang X, Wang YJ, Luo GX, Ho WZ. (2008) Methamphetamine enhances hepatitis C virus replication in human hepatocytes. J Viral Hepat 15, 261-70