Running head: PRENATAL EXPOSURE AND BEHAVIOR 1
Prenatal Alcohol and Nicotine Exposure and the Subsequent Cognitive and Behavioral
Deficits Seen in Children
Abigail Stewart
A Senior Thesis submitted in partial fulfillment
of the requirements for graduation
in the Honors Program
Liberty University
Spring 2016
PRENATAL EXPOSURE AND BEHAVIOR 2
Acceptance of Senior Honors Thesis
This Senior Honors Thesis is accepted in partial
fulfillment of the requirements for graduation from the
Honors Program of Liberty University.
______________________________
Kimberly Brown, DNP
Thesis Chair
______________________________
Terri Page, MSN
Committee Member
______________________________
Daniel Logan, Ed.D.
Committee Member
______________________________
Brenda Ayres, Ph.D.
Honors Director
______________________________
Date
PRENATAL EXPOSURE AND BEHAVIOR 3
Abstract
Prenatal alcohol and nicotine exposure have well known physiological effects on the
fetus. However, it is the goal of this thesis to inform the reader of of the deleterious
effects that these substances can have on cognitive and behavioral development in
children. A literature review in relation to this topic was conducted through online
databases using key words. Though some of the results were inconsistent, enough
evidence exists for women to be educated on the increased risks for cognitive and
behavioral deficits in children exposed to alcohol and nicotine in utero.
PRENATAL EXPOSURE AND BEHAVIOR 4
Prenatal Alcohol and Nicotine Exposure and the Subsequent Cognitive and Behavioral
Deficits Seen in Children
Alcohol and tobacco smoke are known to have deleterious effects on birth
outcomes in neonates born to women who have used these substances during pregnancy.
However, research is indicating that the effects of these legal substances are manifold and
persist throughout childhood, possibly even into adulthood. The aim of this thesis is to
show that prenatal alcohol and nicotine exposure cause cognitive and behavioral deficits
that can be seen throughout childhood. The following pages will describe the researched
biological effects of alcohol and nicotine on the developing fetus. This will be followed
by a literature review of studies researching the effects of prenatal alcohol and nicotine
exposure on cognition and behavior in children.
Biological Effects of Alcohol
Alcohol exposure causes damage to the central nervous system (CNS) of the
developing fetus. Depending on the timing and amount of exposure, there may be
different effects. This results in the variation in symptoms that are present in fetal
alcohol spectrum disorders (FASD). New magnetic resonance imaging (MRI)
technologies are being used to track brain changes in people exposed to alcohol
prenatally, which has enabled discoveries related to specific areas of the brain and how
they respond to alcohol exposure (Warren, Hewitt, & Thomas, 2011). Up to this point, a
few of the regions that have been noted to be especially vulnerable include the frontal
cortex, regions of the cerebellum, the corpus callosum, and the hippocampus. A certain
type of MRI, known as diffusion tensor imaging (dtMRI), is able to notice changes in
white matter nerve tracts. These changes in children with prenatal alcohol exposure
PRENATAL EXPOSURE AND BEHAVIOR 5
(PAE) are thought to be related to alterations in information processing (Warren et al.,
2011).
As stated in Warren et al. (2011), embryonic frog models exposed to alcohol
experienced altered gene expression leading to microcephaly, growth retardation, and
microphthalmia. In humans, the oxidative stress that is induced by prenatal alcohol
exposure may cause altered timing of apoptosis which can interfere with neuronal
development, possibly leading to the above symptoms.
Abnormalities have been found in the size of the corpus callosum as a result of
alcohol exposure, leading to difficulties in verbal learning in this population. In addition,
alcohol may cause basal ganglia volume reduction. This effect may result in lower
intelligence quotient (IQ) scores. Other research suggests teratogenic effects of alcohol
on the cerebellum, resulting in fine and gross motor delays and therefore affecting
balance and motor control in this population (Coles, 2011; Dorrie, Focker, Freunscht, &
Hebebrand, 2014).
Biological Effects of Nicotine
Nicotine is one of the many compounds present in tobacco smoke. It has the
ability to cross both the placental and the blood-brain barriers in the developing fetus and
it has been found at a 15% higher concentration in the fetus than in the mother. When the
developing fetus’s central nervous system (CNS) is exposed to nicotine, the nicotinic
acetylcholine receptors (nAChR) are stimulated, triggering neurodevelopmental events.
Therefore, the normal timing of these neurodevelopmental processes, such as the
migration of nerve cells and the initiation of axons and dendrites, is altered because
PRENATAL EXPOSURE AND BEHAVIOR 6
nicotine produces the actions that are usually initiated by acetylcholine. As a result,
abnormal changes are made within the CNS (Blood-Siegfried & Rende, 2010).
Nicotine also desensitizes neurotransmitter action in prenatal exposure and
decreases epinephrine and norepinephrine production. Due to neurotransmitter reduction
in areas such as the frontal cortex, the fetus may be predisposed to conditions like
attention deficit/hyperactivity disorder (ADHD). In ADHD, children have the inability to
suppress input, which is related to dysregulation of neurotransmitters in the frontal cortex
and, therefore, the inablity to regulate impulse control and stimuli. Because of nicotine’s
effects on neurotransmitters, ADHD in children who were prenatally exposed to tobacco
smoke may be directly related to nicotine (Blood-Siegfried & Rende, 2010).
In addition, alterations in the serotonergic and dopaminergic pathways can lead to
emotional dysregulation, leading to the externalizing behaviors seen in many children
who were prenatally exposed to nicotine. These behavioral traits may also be linked to a
greater risk for mental illness in this population, including an increased prevalence of
nicotine addiciton. Learning deficits are also found in children prenatally exposed to
nicotine. The hippocampus, the part of the brain involved in sequential learning and
short-term memory, is thought to be damaged by prenatal nicotine exposure, therefore
leading to these deficits. However, the hippocampus continues to develop after birth.
Because of this, it is hypothesized that postnatal smoking may also contribute to
cognitive deficits (Blood-Siegfried & Rende, 2010; Ellis, Berg-Nielsen, Lydersen, &
Wichstrom, 2012).
PRENATAL EXPOSURE AND BEHAVIOR 7
Prenatal Alcohol Exposure and the Literature
The following information was collected from research articles published within
the last five years. A search was conducted through CINAHL Plus using key words in
order to obtain peer-reviewed journal articles. Specific information on these articles can
be found in Table 1 in the appendix.
Purpose and Patient Population
Studies on the cognitive and behavioral effects of PAE have been conducted all
over the world. Robinson et al. (2010) studied 2,868 pregnant women and their children
at an obstetric hospital in Western Australia. However, only 1,860 mother-child pairs
were able to participate all the way through the study. The children in this study were
born between 1989 and1991 and a 14-year follow up study evaluated them between
2003-2006, as well as at the ages of two, five, eight, and ten. This longitudinal study
assessed the relationship between prenatal alcohol exposure and child behavioral
development, with a specific focus on light-moderate drinking.
Another longitudinal study in this review studied 2,264 mother-child pairs from a
Swedish antenatal clinic. Again, only 1,868 women participated at the second follow up,
which was at 32 weeks’ gestation. Though this is a longitudinal study as well, it is only
in the beginning stages, therefore the current information only details intra-pregnancy
alcohol consumption, the labor process, and characteristics of the newborns. This is an
ongoing study that is being used to determine the effects of low-moderate maternal
alcohol intake on the neuropsychological development of the child over time (Comasco,
Hallberg, Helander, Oreland, Sundelin-Wahlsten, 2012).
PRENATAL EXPOSURE AND BEHAVIOR 8
Proven, Ens, & Beaudin (2014) analyzed the language abilities, including
strengths and weaknesses, of 124 school-aged children with a clinical diagnosis of Partial
Fetal Alcohol Syndrome (pFAS) or Alcohol Related Neurodevelopmental Disorder
(ARND). These children resided in Canada and their ages ranged from five to eighteen.
Within this study, a specific focus was placed on age and gender and the specific effects
of prenatal alcohol exposure in these populations. Graham et al. (2013) studied the
presence of sluggish cognitive tempo (SCT) in children with PAE and with or without
ADHD. Two hundred and seventy-two children between the ages of eight and sixteen,
along with their caregivers, were recruited from five different sites across the United
States in order to determine if an association exists between PAE and decreased cognitive
abilities.
The focus of a study by Peles et al. (2014) was to determine the effects of and
compliance to a Brief Intervention, which involved the interviewer explaining to the
women the harmful effects of alcohol and other substance abuse upon both them and their
babies and giving them tips for cutting down and quitting. These 108 Israeli women were
recruited at less than or equal to 30 weeks’ gestation as a result of presenting to a hospital
in Israel with medical complications. Though Peles at al. did not conduct a longitudinal
study, their research did provide insight on the confounding factors in the family
environment that may contribute to the development of behavioral disorders in children
exposed to alcohol prenatally.
A similar study was conducted as a cohort study of 907 mother-child pairs in
Dublin, Ireland from 2010-2011. The intent was to determine if women heed the medical
advice of their midwives to abstain from alcohol while pregnant and breastfeeding.
PRENATAL EXPOSURE AND BEHAVIOR 9
Again, this study contributed information regarding the correlations between specific
maternal characteristics and alcohol consumption during pregnancy (Dunney, Muldoon,
& Murphy, 2015).
The other research articles in this review provided more focused information from
different studies on the neurobehavioral profile of children who have been exposed to
alcohol prenatally. Jacobson, Carter, & Jacobson (2013) gave a commentary on the
behavioral effects of prenatal alcohol exposure observed by Day and colleagues
throughout childhood and into young adulthood. Pei, Denys, Hughes, & Rasmussen
(2011) surveyed the prevalence of mental health issues seen in people with fetal alcohol
spectrum disorders (FASD). The classification of FASD encompasses multiple disorders,
but there is not a profile that is specific to behavioral deficits. Mattson & Riley (2011)
conducted a review in order to obtain more information on establishing a neurobehavioral
profile of affected individuals who do not show physical signs of prenatal alcohol
exposure. Their goal was to develop criteria that would aid in the identification and
prompt treatment of these children.
Coles (2011) discussed the barriers to detecting FASD in children and sought to
provide ways to distinguish between behavioral and developmental disorders caused by
prenatal alcohol exposure vs. other causes. Another review, by Dorrie et al. (2014),
focused on the central nervous system consequences of PAE. In addition, new research
advances are being made regarding the long term effects of PAE and Warren et al. (2011)
highlight these advances.
PRENATAL EXPOSURE AND BEHAVIOR 10
Methods
The majority of these studies gathered information through parental
questionnaires and interviews with the parent(s), although sometimes the child was
involved in the process as well. Assessment of prenatal alcohol exposure was primarily
conducted through the use of a self-reporting tool called the Alcohol Use Disorders
Identification Test (AUDIT). Comasco et al. (2012), Dunney et al. (2015), and Peles et
al. (2014) specifically cited the use of this tool. This questionnaire consists of ten items
that assess the quantity and frequency of maternal alcohol exposure during pregnancy.
Due to the information often being gathered after pregnancy, the data collected from the
AUDIT is retrospective data, which carries with it a level of bias. Despite the possibility
of false reporting, the AUDIT is a well established tool that has been useful in obtaining
results regarding PAE.
There are two main ways of determining prenatal alcohol exposure. The first is
through maternal report, either prospectively or retrospectively, as mentioned above. The
second is through a dysmorphology examination, which involves documenting physical
markers such as short palpebral fissures, a smooth philtrum, a thin vermillion border, and
small brain size. These characteristics are thought to be associated with heavy alcohol
exposure during a specific time frame in the first trimester, resulting in the profile that is
known as Fetal Alcohol Syndrome (FAS). However, as this thesis argues, there are
behavioral and cognitive deficits that result from PAE, even in those children who do not
have these physical characteristics. Therefore, it is necessary to determine a more
accurate tool for assessing PAE in order for the disorder to be acknowledged in children
whose mothers may give a false report (Mattson & Riley, 2011).
PRENATAL EXPOSURE AND BEHAVIOR 11
A few studies used the identification of alcohol metabolites in neonatal meconium
samples to determine PAE. In Jacobson et al.’s (2013) commentary on Day and
colleagues longitudinal study, they noted that maternal self-report of alcohol
consumption was validated by recognized cognitive defects in the children, as well as
alcohol metabolites in meconium samples. This validation is ideal; however, Mattson &
Riley (2011) stated that testing for metabolites in meconium is only helpful for
determining the presence of alcohol exposure later in pregancy.
The Child Behavior Checklist (CBCL) was used by Robinson et al. (2010) and
Graham et al. (2013) to evaluate emotional and behavioral problems in children at
different ages. This questionnaire is usually filled out by the parent(s) of the child, but in
some cases the researchers also had the child’s school teacher fill it out. The results were
similer enough, though, that the conclusions were drawn from the parental
questionnaires. When completed, the CBCL provides three z-scores, each of which
corresponds with either total behavior, internalizing behavior, or externalizing behavior.
The higher the score, the more problematic the child’s emotions and behaviors (Robinson
et al., 2010).
In addition to the CBCL, Graham et al. (2013) used the Sluggish Cognitive
Tempo (SCT) questionnaire to assess cognitive ability. The SCT tool is used to reveal
deficits in sustained attention, including sluggishness, hypoactivity, varying alertness,
and daydreaming. High SCT scores are associated with internalizing behaviors, such as
depression, anxiety, obsessions, and social phobias. This questionnaire is filled out by
the parents.
PRENATAL EXPOSURE AND BEHAVIOR 12
In the study by Proven et al. (2014), the Clinical Evaluation of Language
Fundamentals (CELF-4) was used to assess the language profile of school-aged childen
exposed to alcohol prenatally. Different test forms were used for different age groups.
Score categories for the CELF-4 include the Core Language Score, which quantifies the
child’s general language ability, and the language indices, which include five
subcategories (receptive language, expressive language, language content, language
structure, and language memory) that give more detailed information on language and
communication. Language delay is rated as severe, moderate, mild, average, or above
average.
Discussion
In the research on PAE and the associated behavioral and cognitive effects in
children, it is difficult to establish strictly causative relationships between these deficits
and PAE. However, many correlations and associations are present and conclusions may
still be drawn from this data.
Multiple studies in this review found a postive correlation between nicotine use
and drinking during pregnancy, including Comasco et al. (2012). This finding was
supported by Dorrie et al. (2014), with the additional associations of multiple substance
use, low socioeconomic status, greater mean age, fewer prenatal visits, and a greater total
amount of years of alcohol consumption. Similar to the association with low
socioeconomic status, Petes et al. (2014) found that women who drank during pregnancy
were less educated and less likely to be in a relationship. In Dunney et al. (2015), older
age (35-39), smoking, private health care, and a history of illicit drug use were also
positively correlated with alcohol consumption. Robinson et al. (2010) found specifically
PRENATAL EXPOSURE AND BEHAVIOR 13
that a higher alcohol intake during the first trimester was associated with smoking during
pregnancy. The above findings indicate the possibility of other factors playing a role in
the development of neurobehavioral disorders in children subject to PAE.
The longitudinal study of behavioral development by Robinson et al. (2010)
revealed interesting findings regarding the effects of low to moderate PAE. Both light
and moderate drinking at 18 weeks gestation resulted in a decrease in CBCL scores,
indicating better behavior. In addition, fewer behavioral problems were noted over 14
years in children whose mothers were light drinkers (two to six standard drinks per week)
during their first trimester than in children whose mothers did not drink at all. The
authors suppose that the self-control that is necessary to engage in light-moderate
drinking may be a factor that speaks to the parenting skills of the mother, therefore
resulting in better behavior in these chldren. As many pregnancies are unexpected, this
study may be able to give peace of mind to those mothers who continue drinking during
their first trimester because the pregnancy is unexpected and they did not know that they
were pregnant.
However, Robinson et al. (2010) and others also found supporting evidence for
the detrimental effects of PAE on behavior. Both occasional drinking at 34 weeks
gestation and heavy drinking at any time resulted in higher CBCL scores in children,
indicating poorer behavior. With heavy drinking, increased behavioral problems were
noted in children in all three categories (total, internalizing, and externalizing), but these
results were not statistically significant due to the small sample size of heavy drinkers
studied. According to Matson & Riley (2011), compared to other children with similar
traits (such as low intelligence quotient [IQ]), alcohol-exposed children experienced
PRENATAL EXPOSURE AND BEHAVIOR 14
impairment in externalizing behaviors and adaptive skills. Due to these findings, conduct
disorder is common in this population. However, Dorrie et al. (2014) propose that the
risk for this disorder can be reduced if the children are raised in stable homes.
Language is another area that was highly reported about by these studies. Proven
et al. (2014) discovered that almost 70% of the children they studied with pFAS or
ARND scored a rating of “severe” on the Core Language Index, indicating
communication impairments. In addition, there were no significant differences in
language scores among the two diagnoses (pFAS and ARND). These children showed
poor performance in both expressive and receptive language abilities. Dorrie et al.
(2014) also noted that reduced language comprehension and some hearing impairments
have been discovered in this population, which would contribute to a delay in language
development.
Coles (2011) defined issues that PAE can cause in a child’s memorization
capabilities. These children tend to have problems with learning new material and with
memorization, due to deficits in executive functioning, such as in active working
memory, planning, problem solving, and organization. Though they have normal long-
term memory abilities, achieving this level of memory may take more trials because these
children process information more slowly and therefore require more time to attain
mastery. Visual-spatial deficits have also been noted in this population, often indicated
by problems with handwriting, clumsiness, and mathematics. Dorrie et al. (2014)
supported this finding by stating that mathematics is often a problem area for children
with FASD, due to the inability to mentally represent and manipulate numbers.
PRENATAL EXPOSURE AND BEHAVIOR 15
Some of these studies also attempted to determine the differences in ADHD in
children exposed to alcohol prenatally as compared to other children with ADHD.
Mattson & Riley (2011) discovered that alcohol exposed children had greater
impairments related to visual-spatial reasoning, problem solving, and flexibility, as well
as encoding and shift aspects of attention. Coles (2011) described difficulties in children
with FASD in regulating arousal and in self-control, which often manifests as ADHD.
However, with FASD alone, children have fewer behavioral problems but greater deficits
in the encoding of information and in being able to effectively switch tasks. In ADHD,
the problems lie in focus and sustaining attention. Dorrie et al. (2014) conveyed these
same findings in relation to the differences between the neurobehavioral profiles of
children with FASD and children with ADHD. Graham et al. (2013) reported that some
of the items on the SCT tool were higher (indicating greater cognitive deficits) in children
exposed to alcohol prenatally, independent of ADHD status, indicating the possibility to
use this tool to determine characteristics of PAE in children who do not have ADHD.
Jacobson et al. (2013) and Pei et al. (2011) both found that the effects of PAE
continue throughout childhood and even into adulthood. Specifically, this population is
at high risk for psychiatric diagnoses and these symptoms may be more likely than other
symptoms of FASD to persist into adulthood. The development of psychiatric disorders
may be due in part to the deficits in emotional executive functioning which can manifest
in social interactions and decision making skills, as stated by Dorrie et al. (2014).
Mattson & Riley (2011) came to a similar conclusion, based upon the fact that children
exposed to alcohol prenatally displayed impairment in social cognition and facial
emotion processing ability.
PRENATAL EXPOSURE AND BEHAVIOR 16
Limitations
Research studies are never all-encompassing. Therefore, limitations that
complicate the interpretation of the results are inevitable. One of the greatest limitations
among these studies is the possibility for response bias, as alcohol consumption during
pregnancy was self-reported. Coles (2011) reported that, in some cases, underdiagnosis
of FASD may be related to the unreliability of exposure information that is obtained, due
to many children presenting later in life and being removed from their biological mother
by that time. Dysmorphic features are sometimes subtle and therefore may also be
underreported, as noted by Warren et al. (2011). Computer recognition of these features
is being developed in order to aid in underdiagnosis in children with dysmorphic features.
Underreporting of alcohol use and/or neurobehavioral symptoms must be accounted for
when interpreting the results of these studies.
Another limitation found in most of these studies was the inability to control for
confounding factors. There are many environmental and genetic factors, such as the
caregiving environment, comorbid diagnoses, parental disorderts, etc., that may play a
role in the development of neurobehavioral disorders in this population of children.
Coles (2011) explains that, at present, there is no way to determine whether comorbidities
such as ADHD, depression, etc. are the direct results of PAE or if they are due to a
combination of genetics, environment, and exposure. For instance, in the study by
Proven et al. (2014), comorbid diagnoses and the child’s environment were not even
analyzed in the study. There are many factors that contribute to the development of
children with FASD and it is unfortunately impossible at present to control for all of
these factors.
PRENATAL EXPOSURE AND BEHAVIOR 17
A few of these studies, including Comasco et al. (2012) and Dunney et al. (2015),
experienced a loss of a portion of their participants throughout the study. They
determined that their losses were random and not pertaining to a specific population, but
it is still an important limitation to note. In addition, many of the sample sizes of children
and/or mothers were small, namely Peles et al. (2014), Proven et al. (2014), and Graham
et al. (2013).
Although some of the studies were longitudinal, those that were not were forced
to rely upon an increased amount of retrospective data. Proven et al. (2014) reported a
specific limitation in their data collection tool, the CELF-4, because it has not been used
much to date for research analysis purposes. Lastly, Robinson et al. (2010) noted a
limitation in their assessment of specific patterns of drinking, such as binge drinking, due
to data on weekly drinking being obtained as an average. Therefore, data related to the
specific timing and volume of alcohol exposure is unknown.
Conclusion
The results from the above studies have shown many detrimental neurobehavioral
effects of PAE in children. Even though some of the results were inconsistent, there is
enough evidence, though not related to a proven causative relationship, that children are
at a significant risk for developing cognitive and behavioral deficits when exposed to
alcohol prenatally. This knowledge should be an encouragement to healthcare
professionals to impress upon their patients that there is no safe level of PAE. Women
need to be properly educated regarding the harmful effects of alcohol consumption during
pregnancy on the neurobehavioral development of their children. In addition, as Dorrie
et al. (2014) suggest, physicians and psychiatrists need to consider FASD related
PRENATAL EXPOSURE AND BEHAVIOR 18
diagnoses more frequently when children present with developmental delays and
behavioral disorders. Accurate diagnosis will enable more proper and focused treatment
of these children.
Prenatal Nicotine Exposure and the Literature
The following articles were collected in the same manner as the previous set,
using different key words. This search was used to determine the results of research
regarding the cognitive and behavioral effects throughout childhood of prenatal nicotine
exposure via tobacco smoke. Specific information on these articles can be found in Table
2 in the appendix.
Purpose and Patient Population
All of these studies are retrospective in nature, meaning that the children were
evaluated based upon maternal report of prenatal nicotine exposure. Motlagh et al.
(2010) studied 222 chlidren between the ages of seven and eighteen with either ADHD,
Tourette’s Syndrome, both conditions, or neither condition. The purpose of this study
was to assess the pre- and perinatal risk factors associated with ADHD and Tourette’s,
with heavy maternal smoking being one of the supposed risk factors.
Mei-Dan et al. (2015) conducted a study in Montreal, Canada, surveying women
who gave birth from 2001-2007. Out of these 20,938 deliveries, 1,646 of them were to
smoking mothers. The goal was to assess for a dose-response relationship between
perinatal outcomes and maternal smoking. Though this study did not follow the babies
throughout childhood, the risk for dose-related adverse outcomes was assessed. Ellis et
al. (2012) studied four year-old children in Trondheim, Norway to determine if a
relationship exists between prenatal smoking and psychiatric disorders in preschoolers.
PRENATAL EXPOSURE AND BEHAVIOR 19
All children born in 2003 and 2004 in Trondheim were invited to participate. Nine
hundred and ninety-five parent-child pairs participated all the way through the study.
Yang, Decker, & Kramer (2013) worked with a cohort of Belarusian children
around six and a half years of age who were either exposed prenatally to maternal
smoking or exposed postnatally to maternal or paternal smoking. The purpose of this
study was to find relationships between prenatal and postnatal tobacco smoke exposure
and growth and development in the children. A cohort study by Ruckinger et al. (2010)
was similar, except that the children studied were ten years-old and the goal was to
specifically determine the behavioral problems in these children and the relationship that
these problems had to prenatal and/or postnatal tobacco exposure. These children and
their parents were from Munich or Wesel, Germany, and the children were born between
1995 and 1998. Five thousand nine hundred and ninety-one children began the study, but
only 2,862 had completed information throughout the whole study.
A Swedish study by Lundberg et al. (2010) analyzed 172,182 conscripted males
around 18 years of age that were born to Nordic mothers. The goal was to determine the
association between prenatal maternal smoking and young adult intellectual outcomes,
taking into account parental and birth characteristics. In order to control for familial
factors, 14,722 of these males were sibling pairs. Both Cope (2015) and Tiesler &
Heinrich (2014) performed reviews on the relationship between prenatal nicotine
exposure and the behaviors and adverse effects that result in the exposed children.
Methods
The most common method used to detect nicotine exposure in these studies was
maternal self-report. Motlagh et al. (2010), Mei-Dan et al. (2015), Ellis et al. (2012),
PRENATAL EXPOSURE AND BEHAVIOR 20
Lundberg et al. (2010), Yang et al. (2013), and Ruckinger et al. (2010) all utilized this
retrospective method. In Ruckinger et al. (2010), mothers were classified as heavy
smokers if they smoked greater than five cigarettes per day and light smokers if they
smoked less than five cigarettes per day. Tiesler & Heinrich (2014) reported that nicotine
and/or its metabolites can also be detected in the urine, cord serum, meconium, amniotic
fluid, hair, or nails. However, these methods may not be as effective because they can
only detect recent exposure.
Three studies, Ellis et al. (2012), Ruckinger et al. (2010), and Yang et al. (2013),
utilized the Strengths and Difficulties Questionnaire (SDQ) to assess child behavior. The
SDQ consists of five behavioral scales related to emotional symptoms, conduct problems,
hyperactivity/inattention, peer-relationship problems, and a prosocial scale. Yang et al.
(2013) also used the Weschler Abbreviated Skills of Intelligence (WASI) to determine
cognitive ability. In Lundberg et al. (2010), intellectual performance in the cohort of
male participants was tested in four dimensions: logical/inductive, verbal, spatial, and
theoretical/technical.
In addition to using questionnaires, Ellis et al. (2012) utilized the Preschool Age
Psychiatric Assessment and conducted semi-structured diagnostic interviews with the
child and parent(s). When interpreting their results, these researchers controlled for
parental confounders such as personality disorders, anxiety, depression, alcohol use,
incarceration, capacity to pay bills, etc.
Discussion
Ruckinger et al. (2010) determined that of the 2,862 children that had complete
information throughout the study, those who were exposed to nicotine prenatally were at
PRENATAL EXPOSURE AND BEHAVIOR 21
the greatest risk for behavioral problems at ten years of age. These risks were higher in
children exposed to heavy prenatal tobacco exposure than in children exposed to light or
no tobacco smoke. Interestingly, postnatal exposure was also associated with behavioral
problems, but the results were much less significant. Yang et al. found similar results in
their cohort of six and a half year-old children. Children exposed to prenatal smoking,
maternal postnatal smoking, and/or paternal postnatal smoking had slightly lower IQ
scores, as well as higher total cognitive difficulties and externalizing behaviors.
Multiple studies found an association between prenatal nicotine exposure and the
development of ADHD. When controlling for confounding factors, Ellis et al. (2012)
found that prenatal smoking predicted ADHD and oppositional defiant disorder (ODD) in
four year-olds, as well as a cormorbid diagnosis of the two. Ruckinger et al. (2010)
supported this finding in their study of ten year-olds when they discovered that one of the
strongest associations with abnormal behavior on the SDQ in children that were exposed
to nicotine prenatally was hyperactivity/inattention. This is in line with previous research
that has found greater abnormalities in externalizing behaviors in children prenatally
exposed to tobacco smoke.
In the study by Motlagh et al. (2010), there was a high association between heavy
maternal smoking and the development of ADHD. Severe maternal psychosocial stress
was also found to be associated with this disorder. However, stress and heavy smoking
were independently associated with ADHD, indicating that both factors may lead to this
condition separately. These factors were associated with Tourette’s Syndrome as well,
but the findings were less significant. A conflicting study was conducted by Thapar et al.
(cited in Tiesler & Heinrich, 2014) that compared the effects of maternal smoking on the
PRENATAL EXPOSURE AND BEHAVIOR 22
risk for ADHD in children who were genetically related and unrelated to the gestational
carrier. The results showed that there was an increased risk for ADHD in those children
who were genetically related, but no association in those who were carried by a surrogate.
Another study by Gaysina et al. (cited in Tiesler & Heinrich, 2014), focused on
discovering whether or not a genetic component between prenatal alcohol exposure and
conduct disorders/externalizing behaviors existed. Three different mother-child pairs
were studied: those that were genetically related, children who were adopted at birth, and
children who were adopted at conception. Regardless of genetics, chlidren who were
prenatally exposed to maternal smoking had a greater risk of developing conduct
problems.
Lundberg et al. (2010), in their study of young conscripted Swedish males,
discovered in the unadjusted analysis of prenatal smoking and intellectual performance
that there was an increased risk for poor intellectual performance in male offspring of
women who were moderate or heavy smokers during pregnancy. These results remained
significant when adjusting for confounding factors, such as birth and parental
characteristics. The sibling subset of this study revealed an increased risk for poor
intellectual performance in both sons when the mother smoked during the first
pregnancy, regardless of whether or not she smoked during the second pregnancy. But if
she smoked only during the second pregnancy, neither son was at an increased risk for
poor intellectual outcomes. Therefore, according to these results, prenatal smoke
exposure does not influence intellectual performance. This suggests the influence of
genetic/environmental factors in the development of intellectual deficits in children
exposed to nicotine prenatally.
PRENATAL EXPOSURE AND BEHAVIOR 23
Limitations
As mentioned earlier, the assessment of prenatal alcohol exposure in these studies
was primarily through maternal self report. With this type of retrospective data, there is
always the possibility for inaccurate results due to faulty memory, fear of judgment, etc.
Cope (2015) advocates for testing for cotinine, a metabolite of nicotine, in the urine or
saliva instead of using maternal self report. However, these tests will only be positive if
the woman has smoked within the past three days, making it necessary to use maternal
self report to obtain more detailed data.
Another limitation of many of theses studies was the inability to control for
genetic and environmental factors. Ruckinger et al. (2010) and Yang et al. (2013) did not
assess for parental psychological states and genetic factors. Similarly, Ellis et al. (2012)
did not control for ADHD in the mother. Lundberg et al. (2010) were unable to control
for maternal alcohol consumption, parental intellectual abilities, and behavioral problems.
In addition, prenatal and postnatal smoke exposure were not distinguished.
None of these studies were longitudinal and Motlagh et al. (2010) had a small
sample size. In the study by Ellis et al. (2012), the criteria for diagnosing psychiatric
disorder was based on the past three months when six months is required for true
diagnosis. Ruckinger et al. (2010) had a similar limitation. In their study, the SDQ was
used to assess for behavioral problems. However, this tool is only used for screening
purposes and is not diagnostic.
Conclusion
The results regarding the cognitive and behavioral effects of prenatal nicotine
exposure in children are inconsistent. But despite the inability to establish a concrete
PRENATAL EXPOSURE AND BEHAVIOR 24
causal relationship, Tiesler & Heinrich (2014) state that the known effects of prenatal
nicotine exposure should be enough to support the discontinuation of use. Longitudinal
studies are needed in order to be able to assess the cognitive and behavioral states of the
children throughout childhood.
Further Study
The areas for future study regarding prenatal substance exposure and childhood
development are many. For instance, numerous substances beyond alcohol and nicotine
are used during pregnancy. Though the physical effects of these substances have been
researched, there is a lack of information on varying types of prenatal exposures and their
effects on language development and communication. In addition, language performance
in fetal alcohol spectrum disorders over time and the effectiveness of interventions in this
population requires supplementary data in order to make treatments more effective
(Proven et al., 2014).
Another open area of study is the specific effect of environmental tobacco smoke
(ETS) exposure on the developing fetus. Some research studies have attempted to take
into account paternal smoking as a factor in nicotine exposure, but this factor is rarely
isolated. Therefore, the results are often conflicting. For example, children exposed to
nicotine prenatally are at a higher risk than the average child for developing ADHD.
However, children whose mother was exposed to environmental tobacco smoke during
pregnancy surprisingly have this same risk. ETS exposure is commonplace. Discovering
new evidence regarding its lasting effects in prenatally exposed children may inspire
awareness and lead to decreased exposure (Tiesler & Heinrich, 2014).
PRENATAL EXPOSURE AND BEHAVIOR 25
The outcome of maternal alcohol consumption on the infant while breastfeeding
is a factor that is often omitted from studies, according to Dunney et al. (2015). This
factor may be found in conjunction with prenatal alcohol use; however, the isolated
effects of alcohol consumption during the breastfeeding period are unknown. Related to
both prenatal alcohol and nicotine exposure, there is more information needed on the type
and prevalence of internalizing disorders manifested in childhood. Tiesler & Heinrich
(2014) reviewed some studies that supported the association of prenatal nicotine exposure
with these disorders, while others found no association at all. Further study is needed to
determine accurate correlation.
The above areas for future study are only a few of the countless areas in need of
further research. The examples given were chosen because they were noted as gaps in the
literature reviewed for this study or as important follow up questions necessary to build
upon the current research.
Review
The literature regarding the behavioral and cognitive effects of prenatal alcohol
and nicotine exposure provides compelling associations with deficits in these areas.
Though absolute causation has not been proven up to this point, the above research
indicates that these substances present a great enough risk that they should be avoided
during pregnancy.
Only a few of the studies in this review were longitudinal. In the future, it will be
necessary to conduct a greater number of longitudinal studies that control for other
factors that may interfere with behavior and cognition in children. However, because
there are well known risks associated with consumption of these substances during
PRENATAL EXPOSURE AND BEHAVIOR 26
pregnancy, perhaps the focus should be on education of women and prevention of use
during pregnancy. This would be the best possible way to avoid the cognitive and
behavioral deficits in children that are most likely associated with prenatal use of alcohol
and nicotine.
PRENATAL EXPOSURE AND BEHAVIOR 27
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Robinson, M., Oddy, W.H., McLean, N.J., Jacoby, P., Pennell, C.E., de Klerk, N.H.,
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1139-1152. doi:10.1111/j.1471-0528.2010.02596.x
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Hoffman, U., Kramer, U., Berdel, D., von Berg, A., Bayer, O., Wichmann, H.E.,
von Kries, R., & Heinrich, J. (2010). Prenatal and postnatal tobacco exposure and
behavioral problems in 10-year old children: Results from the GINI-plus
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154. doi:10.1289/ehp.0901209
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Warren, K. R., Hewitt, B. G., & Thomas, J. D. (2011). Fetal alcohol spectrum disorders:
Research challenges and opportunities. Alcohol Research & Health, 34(1), 4-14.
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Yang, S.M., Decker, A., & Kramer, M.S. (2013). Exposure to parental smoking and child
growth and development: A cohort study. BMC Pediatrics 13(104), 1-10. doi:
10.1186/1471-2431-13-104
PRENATAL EXPOSURE AND BEHAVIOR 31
Appendix
Table 1
Study
Patient
Characteristics
Instruments
Method
Results
Limitations
1) Coles, 2011
-Children with FASD
-Factors to take into
consideration:
Evidence for prenatal
alcohol exposure,
caregiving
environment,
comorbidities, and
differential diagnosis
-Mean IQ of around 70
-Damage to the central
and peripheral nervous
systems resulting in fine
and gross motor delays,
affecting balance and
motor control
-Visual-spatial deficits,
indicated by problems in
these areas: handwriting,
clumsiness, and
mathematics
-Deficits in executive
functioning, such as in
active working memory,
planning, problem
solving, and organization
-Difficulties in regulating
arousal and in self-
control, often manifesting
as ADHD
-At present, there is
no way to determine
whether
comorbidities, such as
ADHD, depression,
etc., are the direct
results of prenatal
alcohol exposure or if
they are due to a
combination of
genetics,
environment, etc.
PRENATAL EXPOSURE AND BEHAVIOR 32
2) Comasco et
al., 2012
-2264 mother-child
pairs
-Swedish antenatal
clinic
-The AUDIT alcohol
consumption self-
report tool
-Statistical
significance p<0.05
-Alcohol biomarker
blood tests (CDT and
PEth)
-Longitudinal study
-229 of 1868 women
admitted to consuming
alcohol during
pregnancy, ranging from
monthly to multiple times
a week
-Nicotine use before
and/or during pregnancy
was positively correlated
with those who drank
during pregnancy
-Babies born to women
who drank during
pregnancy had a higher
birthweight (3,665 g vs.
3,518 g)
-Only 1868 women
participated at second
follow-up, which was
at 32 weeks’ gestation
-Response bias must
be taken into account,
as alcohol
consumption was self-
reported
-9% of the women
who were invited to
participate declined
3) Dorrie et
al., 2014
-Children exposed to
alcohol prenatally
-Reduced head
circumference,
prevalence of epileptic
seizures, growth deficits,
corpus callosum
abnormalities which may
lead to impaired verbal
learning ability, basal
ganglia volume reduction
possibly resulting in
lower IQ scores
-There is no long-
term data on FASD
outcome beyond the
age of 30
PRENATAL EXPOSURE AND BEHAVIOR 33
4) Dunney et
al., 2015
-Cohort study of 907
women
-Dublin, Ireland
-2010-2011
-The questionnaire
used was developed
from the AUDIT-C
and the T-ACE
survey tools.
-Data analysis with
the Statistical
Package for Social
Sciences (SPSS)
-95% confidence
intervals
-Alcohol consumption
was positively correlated
with older age (35-39),
private health care, Irish
nationality, cigarette use,
and a history of illicit
drug use.
-The possibly for
underreporting of
prenatal alcohol
consumption due to
self-reporting
-There was a loss of
participants
5) Graham et
al., 2013
- 272 children,
between the ages of 8
and 16, and their
caregivers
-Participants were
recruited from five
different sites across
the U.S.
-The Child Behavior
Checklist (CBCL)
parental
questionnaire
-The SCT parental
questionnaire
-Data analyzed using
the SPSS
-The alcohol exposed
groups showed
significant elevations in
SCT. However, the
children who were
exposed to alcohol but
did not have ADHD had
significantly lower SCT
scores compared to those
who had ADHD.
-The number of
children in each
category was
different.
-IQ was not
controlled for in this
study.
6) Jacobson et
al., 2013
-Children with
FASD, followed into
adulthood
-126-item Achenbach
Adult Self-Report
-Maternal self-report
of alcohol
consumption
validated by
recognized cognitive
defects and alcohol
metabolites in
meconium samples
-The effects of prenatal
alcohol exposure are
permanent and continue
into adulthood
-Concentrated levels of
alcohol, such as multiple
drinks on one occasion,
as opposed to one drink
on different occasions,
are thought to have a
PRENATAL EXPOSURE AND BEHAVIOR 34
greater effect on the
fetus, but in this study
there was just as much of
an effect in those who
were consistent drinkers
7) Mattson &
Riley, 2011
-Children who have
no physical
characteristics of
prenatal alcohol
exposure
-Two main ways of
determining prenatal
alcohol exposure:
maternal report,
prospectively or
retrospectively, or a
dysmorphology
examination
-Compared to other
children with similar
traits (such as low IQ),
the alcohol-exposed
children experienced
impairment in
externalizing behavior,
adaptive skills, and
verbal learning.
-When comparing
alcohol-exposed children
with ADHD with other
children with ADHD,
alcohol-exposed children
had greater impairments
related to visual-spatial
reasoning, problem
solving, flexibility, as
well as encoding and
shift aspects of attention.
-The studies that have
been done have each
only focused on one
aspect of the alcohol
phenotype. It is not
possible for one study
to simultaneously
account for every
aspect.
-Environmental,
genetic, or other
factors may interact
with the fact of
alcohol exposure,
therefore creating the
possibility for more
profiles.
8) Pei et al.,
2011
-Children with
comorbid FASD and
-Computer-based
literature review of
-As compared with other
symptoms of FASD,
-Sample sizes are
often small
PRENATAL EXPOSURE AND BEHAVIOR 35
mental health issues
peer-reviewed
journals and book
chapters
psychiatric symptoms
tend to persist into
adulthood and may
increase
-Prevalence of FASD in
the US is 9-10 in every
1000 births
-More research
needed relating these
findings to
environmental
protective factors
9) Peles et al.,
2014
-108 pregnant women
at gestational week
less than or equal to
30 weeks
-Hebrew-speaking
women presenting to
a hospital in Israel
-They were recruited
because they
presented to the
hospital with medical
complications
-Questionnaires used
include AUDIT C
and TWEAK for
alcohol use,
Fagerstrom for
nicotine exposure,
and the addiction
severity index (ASI)
for other substance
use
-These women were
interviewed to
determine exposure
to alcohol, nicotine,
and/or psychoactive
substances. Those
who were exposed
were given the
opportunity to
participate in a Brief
Intervention (BI). 46
of the 108 were
exposed and 41
participated in the BI.
-As a result of the BI,
self-report of exposure
was reduced for the
duration of the
pregnancy, but then
increased after birth.
-The association of
the studied group with
a lesser amount of
education may be
related to poor
lifestyles and health
habits, leading to the
medical conditions
that brought them in –
this was not a part of
the study
10) Proven et
al., 2014
-124 school-aged
children with a
clinical diagnosis of
FASD – ages 5-18
-CELF-4 language
test
-Data analyzed using
SPSS, level of
significance of
p<0.05
-Poor performance across
the board related to both
expressive and receptive
language abilities
-Almost 70% scored a
rating of “severe” on the
-No children with
FAS were included
-The CELF-4 has not
been used much to
date for research
analysis purposes
PRENATAL EXPOSURE AND BEHAVIOR 36
Core Language Index,
indicating
communication
impairments
-Co-morbid diagnoses
and environment were
not analyzed in this
study
11) Robinson
et al., 2010
-2868 pregnancies
between 1989-1991
with a 14-year follow
up of the children
between 2003 and
2006 – 1860
participated all the
way through
-Obstetric hospital in
Western Australia
-The CBCL parental
questionnaire
-For reporting their
level of alcohol
intake, the women
were given five
categories to choose
from: no drinking,
occasional, light,
moderate, and heavy.
-Longitudinal
regression models
used
-Light and moderate
drinking at 18 weeks
showed a decrease in
CBCL scores, indicating
better behavior
-Heavy drinking was
associated with higher
CBCL scores = poorer
behavior
-Fewer behavioral
problems were noted
over the 14 years in
children whose mothers
were light drinkers (2-6
standard drinks per week)
during their first trimester
than in children whose
mothers did not drink at
all
-Because weekly
drinking was
averaged, there was
no way to test for
binge drinking
episodes, therefore
specific patterns of
drinking could not be
assessed.
12) Warren et
al., 2011
-Neonates and
children with FASD
-MRI technology is being
used to track brain
changes in people
exposed to alcohol
-Dysmorphic features
are sometimes subtle
and therefore
underreported.
PRENATAL EXPOSURE AND BEHAVIOR 37
prenatally, which has
enabled discoveries
related to specific areas
of the brain and how they
respond to alcohol
exposure.
Computer recognition
of these features is
being developed.
PRENATAL EXPOSURE AND BEHAVIOR 38
Table 2
Study
Patient
Characteristics
Instruments
Method
Results
Limitations
1) Cope, 2015
-Women who smoked
during pregnancy and
their fetuses
-Damage to the fetus:
intrauterine growth
retardation, altered
gene expression
leading to an
increased risk of
neural tube defects,
decreased pulmonary
function possibly
leading to asthma in
children, impairment
of neurological
development,
increased risk of colic
-Testing needs to be
biological since self-
report is often
inaccurate.
2) Ellis et al.,
2012
-4 year-old children in
Trondheim, Norway
-All children born in
2003-2004 and their
parents were invited
to participate-995
participated all the
way through
-Preschool Age
Psychiatric
Assessment
-The SDQ parental
questionnaire
-Semi-structured
diagnostic interview
-When controlling for
confounding factors,
prenatal smoking
predicted ADHD and
ODD in 4 year-olds,
as well as a comorbid
diagnosis.
-Did not control for
ADHD in the mother
-Retrospective study
requiring information
from four years prior
-Criteria for
diagnosing disorders
was based on the past
three months when
PRENATAL EXPOSURE AND BEHAVIOR 39
six months is required
for a true diagnosis
3) Lundberg et
al., 2010
-172,182 conscripted
Swedish males
(around 18 years of
ago) born to Nordic
mothers, with 14,722
of these males being
sibling pairs
-Intellectual
performance tested in
four dimensions:
logical/inductive,
verbal, spatial, and
theoretical/ technical.
-Proc Genmond in
SAS with 95%
confidence intervals
-According to this
study, prenatal smoke
exposure does not
influence intellectual
performance.
-Prenatal and
postnatal smoke
exposure were not
distinguished
-Inability to control
for maternal alcohol
consumption, parental
intellectual abilities
and behavioral
problems
4) Mei-Dan et
al., 2015
-Montreal, Quebec,
Canada
-Women who gave
birth from 2001-2007
-20,938 deliveries,
1646 to smoking
mothers
-Higher rates of
adverse outcomes
(compared to non-
smoking women)
were also seen in
women who only
smoked five or less
cigarettes per day
-This is a
retrospective study
5) Motlagh et
al., 2010
-222 children between
7 and 18 with either
ADHD, Tourette’s,
both conditions, or
neither condition
-Cognitive ability and
mental health were
assessed via different
rating scales
-Independent
association of heavy
maternal smoking and
severe maternal
psychosocial stress
and the development
of ADHD.
-Much of the data
collected about the
pre- and perinatal
history was based
upon maternal self-
report
-Small sample size
PRENATAL EXPOSURE AND BEHAVIOR 40
6) Ruckinger et
al., 2010
-5,991 children and
their parents from
Munich and Wesel
Germany, born
between 1995-1998
-The SDQ parental
questionnaire
-Poisson regression
models were used to
obtain relative risk
estimates
-Data analyzed from
the German Infant
Nutritional
Intervention (GINI),
an ongoing birth
cohort study
-Of the 2,862 children
that had complete
information
throughout the study,
those who were
exposed to tobacco
prenatally were at the
greatest risk for
behavioral problems
at 10 years of age.
-The SDQ is used for
screening. It is not
diagnostic.
-This study did not
confound for parental
psychological
problems.
-Information based
upon maternal self-
report
7) Tiesler &
Heinrich,
2014
-Children who were
prenatally exposed to
nicotine
-Detection of nicotine
exposure:
retrospective or
prospective maternal
report, nicotine or its
metabolites, such as
cotinine in urine, cord
serum, meconium,
amniotic fluid, hair,
nails
-ADHD, with
hyperactivity or
inattention: children
exposed to nicotine
prenatally are at a
higher risk for
developing this
disorder, but so are
children whose
mother was exposed
to ETS during
pregnancy
-Regardless of
genetics, children
who were exposed
prenatally to maternal
smoking had a greater
-Results are
conflicting regarding
the effects of ETS
exposure
PRENATAL EXPOSURE AND BEHAVIOR 41
risk of developing
conduct problems.
8) Yang et al.,
2013
-A cohort of
Belarusian children
around 6.5 years of
age who were either
exposed prenatally to
maternal smoking or
exposed postnatally to
maternal or paternal
smoking
-The Weschler
Abbreviated Skills of
Intelligence (WASI)
-The SDQ parental
questionnaire
-Cluster-adjusted
multivariable
regression
-Children exposed to
prenatal smoking,
maternal postnatal
smoking, and/or
paternal postnatal
smoking had slightly
lower IQ scores, as
well as higher total
difficulties and
externalizing
behaviors.
-This study did not
assess parental
psychological states
and genetic factors.
-There is always the
possibility for
underreporting of
maternal smoking,
especially due to
prenatal smoking
prevalence in the
studied population
being lower than the
national average
PRENATAL EXPOSURE AND BEHAVIOR 42
