Title Page in APA style with Running HeadAPA style AbstractInt.docx

Title Page in APA style with Running Head
APA style Abstract
Introduction
(Enter information in a bulleted format. Each bullet should be
followed by 2-4 sentences.)
*NOTE: This first table is an example. You will need to delete
the information in the table then, enter your question & data.
Results
Question: What is the relationship between academic interest
and academic performance?
Allen & Robbins (2010)
Background Theory/Past Research Quote: Page 24
“When applied to students in postsecondary education,
Holland’s theory suggests that students are more likely to be
satisfied and succeed when their interests are congruent with
their academic environments (Smart, Feldman, & Ethington,
2000).”
“In another study, first-year GPA and a measure of interest–
major congruence both had relatively large effects on whether
students changed major, suggesting that students with greater
interest–major congruence are (a) more satisfied with their
academic program and (b) more likely to graduate in a timely
fashion due to not changing majors (Allen & Robbins, 2008).”
Background Theory/Past Research: Page 24
Students are more likely to do well in college when their
interests are related to their major and academic environment
(Smart, Feldman, & Ethington as cited in Allen & Robbins,
2010). Students whose major and interests are closely related
are likely to graduate more quickly because of their low
likelihood of changing majors (Allen & Robbins as cited in
Allen & Robbins, 2008).
Research Hypothesis Quote:

“Thus, we hypothesize that higher interest–major congruence
has a positive effect on first-year academic performance. By
virtue of having greater satisfaction with students’ major,
Holland’s theory also suggests that greater interest–major
congruence will lead to students satisfying their degree
requirements earlier.”
“Thus, our second hypothesis is that interest–major congruence
has a positive direct affect on timely degree attainment (beyond
the effects of first-year academic performance).”
Research Hypothesis:
Page 25
Students with higher interest-major congruence will do better in
their first year at college. Also, Allen & Robbins hypothesized
that students with higher interest-major congruence will also
earn their degree faster.
Methods Quote:
Page 26-8
“Furthermore, 3,860 (3,072 four-year and 788 two-year) of
these students began as full-time students with expectations of
earning at least a bachelor’s (4-year) or certificate (2-year)
degree. This is the sample of students on which this study is
based.”
“To be included in the study sample, students must (a) have
taken the ACT tests of educational achievement and completed
the Unisex Edition of the ACT Interest Inventory (UNIACT;
ACT, 1995) when registering for the ACT;”
“The edition of UNIACT used in this study has 90 items (15 per
scale) that describe work-relevant activities that are familiar to
people either through participation or observation. For each
item, students indicate whether they would dislike doing the
activity, are indifferent (do not care one way or the other), or
would like doing the activity. Raw scores are derived after
summing over the 15 item responses (scores of 1, 2, or 3

correspond to the three response options);”
Methods:
Page 26-8
3,860 full-time college students were studied. Each student
completed the Unisex Edition of the ACT Interest Inventory
before entering college and had selected a major. The UNIACT
asks students to indicate how much, on a scale of 1 to 3, they
would enjoy doing different work-related activities and suggests
their interests based on this information. Researchers profiled
each major based on the UNIACT and used the correlation of
the student’s interest profile and the major’s profile to calculate
interest-major congruence. First year success was measured
using first year GPA.
Results Quotes: Page 30-2
“The path coefficient (beta weight) for interest–major
congruence (0.004) was not significant; thus, our first
hypothesis (higher interest–major congruence will have a
positive effect on first-year academic performance) was not
supported by the results for the 4-year sample.”
“The path coefficient for interest–major congruence (0.162; see
Table 3 and Figure 2) was significant. Thus, our second
hypothesis (interest–major congruence will have a positive
affect on timely degree attainment, beyond the effects of first-
year academic performance) was supported by the results for the
4-year sample. “
Results: Page 30-2
The first hypothesis that higher interest-major congruence
would have a positive effect on academic performance in the
first year was not supported. Higher interest-major congruence
was not found to correlate significantly with better first-year
performance. However, high interest-major congruence was
found to predict timely degree attainment.
Conclusions Quotes: Page 32
“We believe that college major persistence may partially
mediate the relationship of interest–major congruence and

timely degree attainment: Students are less likely to change
their academic major when they have higher interest–major
congruence (cf. Allen & Robbins, 2008; Laing, Swaney, &
Prediger, 1984), and students who switch majors are more likely
to require extra coursework and so prolong their graduation.”
“We also hypothesized that students with greater interest–major
congruence are more enthused about their coursework and thus
accumulate credit hours more quickly, leading to faster degree
attainment. This hypothesis could be tested by using a measure
of enthusiasm for academic major and coursework. We expect
that interest–major congruence will predict both major
persistence and enthusiasm for coursework and that both of
these factors will predict timely degree attainment.”
Conclusions: Page 32
Allen & Robbins conclude that the relationship between high
interest-major congruence and timely degree attainment exists
because students are unlikely to change majors if their major
represents their interests. Also, students with high interest-
major congruence may feel more enthusiastic about classes and
as a result complete credits more quickly.
Question: [ Insert your question here ]
Source 2
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Methods:
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Results: Page 30-2
Question 1: [ Insert your question here. ]
Source 3
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Methods:
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Results: Page 30-2

Source 1
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Source 2

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Source 3
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Methods:
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Results: Page 30-2
Conclusion/Discussion with proper APA style citations;
Compare, contrast and integrate information from the 6 studies
you located.
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followed by 2-4 sentences.)
References in APA style
Stress during pregnancy is associated with
developmental outcome in infancy
Anja C. Huizink,1,3 Pascale G. Robles de Medina,2 Eduard J.H.
Mulder,2
Gerard H.A. Visser,2 and Jan K. Buitelaar1
1University Medical Center Utrecht, Department of Child and
Adolescent Psychiatry and Rudolf Magnus Institute
for Neurosciences, Netherlands; 2University Medical Center
Utrecht, Department of Obstetrics, Neonatology and
Gynecology and Rudolf Magnus Institute for Neurosciences,
Netherlands; 3Department of Social Medicine,

Institute for Research in Extramural Medicine, VU University
Medical Center, Netherlands
Background: Animal studies show that prenatal maternal stress
may be related to cognitive impair-
ments in offspring. Therefore, we examined whether
psychological and endocrinologic measures of
stress during human pregnancy predicted developmental
outcome of the infant at 3 and 8 months.
Method: Self-report data about daily hassles and pregnancy-
specific anxiety and salivary cortisol levels
were collected in 170 nulliparous women in early, mid- and late
pregnancy in a prospective design, in
which healthy infants born at term were followed up after birth.
Results: High levels of pregnancy-
specific anxiety in mid-pregnancy predicted lower mental and
motor developmental scores at 8 months
(p < .05). High amounts of daily hassles in early pregnancy
were associated with lower mental devel-
opmental scores at 8 months (p < .05). Early morning values of
cortisol in late pregnancy were negat-
ively related to both mental and motor development at 3 months
(p < .05 and p < .005, respectively) and
motor development at 8 months (p < .01). On average a decline
of 8 points on the mental and motor
development scale was found. All results were adjusted for a
large number of covariates. Conclu-
sion: Stress during pregnancy appears to be one of the
determinants of delay in motor and mental
development in infants of 8 months of age and may be a risk
factor for later developmental problems.
Further systematic follow-up of the present sample is needed to
determine whether these delays are
transient, persistent or even progressive. Keywords: Prenatal
stress, development, infancy. Abbrevi-
ations: ACTH: adrenocorticotropic hormone; HPA-axis:

hypothalamic-pituitary-adrenal axis; MDI:
Mental Developmental Index; PDI: Psychomotor Developmental
Index.
In pregnant animals induced stress has been shown
to adversely affect behavioral adaptation and motor
and mental development of the offspring (Weinstock,
1997). In a series of studies, Schneider and
co-workers have shown that prenatal stressors
adversely affect the motor and mental development
of rhesus monkeys (Schneider, 1992; Schneider,
Coe, & Lubach, 1992; Schneider, Roughton, Koeh-
ler, & Lubach, 1999). Exposure to mild stress during
mid-pregnancy, operationalized as three noise
bursts over a 10-minute period five times a week,
resulted in decreased motor maturity (a delay in
learning to self-feed, low muscle tone, inferior bal-
ance reactions, a slowed response speed, poorer
coordination), and a declined attention in the first
months of life in comparison with control infants
(Schneider, 1992). Recently, Schneider et al. (1999)
showed that these effects were most profound after
exposure to stress in early gestation, but could still
be found after mid- to late gestational stress. The
same mild prenatal stressor appeared to have a
negative effect on cognition as well. A delay in object
permanence was found on a sequence of Piagetian
tasks after prenatal stress (Schneider et al., 1992).
Although the mechanisms underlying the transfer of
maternal stress to the fetus are only partly under-
stood, the hypothalamic–pituitary–adrenal (HPA)
axis presumably mediates the influence of maternal
stress on the developing fetus in animals (Weinstock,
1997; Barbazanges, Piazza, Le Moal, & Maccari,
1996; McCormick, Smythe, Sharma, & Meaney,

1995). In primates, the effects of a mild stressor
during pregnancy could be mimicked by prenatal
exposure to adrenocorticotropic hormone (ACTH)
during a 2-week period (Schneider, 1992).
In humans, the effects of naturally occurring
stressors on birth outcome have been studied in
prospective designs. There is substantial evidence
that maternal stress is associated with premature
delivery and lower birth weight adjusted for gesta-
tional age (Glynn, Wadhwa, Dunkel-Schetter, Chicz-
Demet, & Sandman, 2001; Dunkel-Schetter, 1998;
Copper et al., 1996; Lou et al., 1994; Wadhwa,
Sandman, Aporto, Dunkel-Schetter, & Garite, 1993)
and with a smaller head circumference (Lou et al.,
1994). The latter finding may reflect suboptimal
brain development and may be a predictor of im-
paired cognitive development (Hack et al., 1991;
Ounsted, Moar, & Stott, 1988). One previous study
investigated the effect of stress during pregnancy on
the postnatal development of human infants (Van
den Bergh, 1990). Measures of general anxiety in the
third trimester of pregnancy were positively correla-
ted with a difficult temperament of the infant at 10
weeks and 7 months after birth, but were unrelated
to infant mental or motor development (Van den
Journal of Child Psychology and Psychiatry 44:6 (2003), pp
810–818
� Association for Child Psychology and Psychiatry, 2003.
Published by Blackwell Publishing, 9600 Garsington Road,
Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148,
USA

iluonokhalm1
Highlight
Bergh, 1990). A recent large prospective epidemio-
logical study found that prenatal maternal anxiety
predicted behavioral and emotional problems in
children at 4 years (O’Connor, Heron, Golding,
Beveridge, & Glover, 2002).
The present prospective longitudinal study was
designed to examine the effects of stress in human
pregnancy on both motor and mental development
early in life. We took account of several potential
confounders. To avoid confounding influence of
prematurity and previous pregnancies, only infants
were included born near term of nulliparous women.
We used two aspects of prenatal maternal stress in
early, mid-, and late pregnancy as predictors of in-
fant outcome: daily hassles and pregnancy anxiety.
Daily hassles, rather than major life events, may be
seen as proximal measures of stress and have been
found to affect health more rapidly than major
life events (DeLongis, Coyne, Dakof, Folkman, &
Lazarus, 1982; McEwen & Seeman, 1999). Preg-
nancy anxiety reflects a unique aspect of human
pregnancy. In a previous study, we showed the ex-
istence of pregnancy anxieties which were only partly
related to measures of general anxiety and depres-
sion (Huizink, 2000). Therefore, we were interested
in the effect of daily hassles and pregnancy anxiety
in pregnancy on later infant development.
The hypothalamic–pituitary–adrenal (HPA) axis
has been found to be one of the mediators of the
effects of prenatal maternal stress on the developing

fetus in animal studies (e.g., Weinstock, 1997;
Weinstock, Matlina, Maor, Rosen, & McEwen, 1992;
Fride, Dan, Feldon, Halevy, & Weinstock, 1986;
McCormick et al., 1995). Therefore, physiological
parameters reflecting the activity of the maternal
HPA axis during pregnancy were also included as
predictors of postnatal infant development. For that
purpose, cortisol day profiles were assessed in early,
mid-, and late pregnancy.
Methods
Participants
Nulliparous women with a singleton pregnancy were
recruited from the outpatient clinic of the Department
of Obstetrics of the University Medical Center Utrecht
(UMCU). The clinic is a first-line referral center where
the majority of pregnant women seen carry a low to
normal risk status and have their pregnancy supervised
by midwives. The UMCU is located outside the city of
Utrecht and attracts a mixed rural and urban popula-
tion of patients. Eligibility criteria were: first-time sin-
gleton pregnancy resulting in birth after 37 weeks of
gestation, no major pregnancy complications, no major
birth complications, Apgar scores >7, and good health
of the baby. Women were excluded from the study if
they were not fluent in Dutch, used drugs, or used
medication with risks for the fetus. The institutional
review board at the UMCU approved the study. All
participants gave written informed consent.
Study design and measures
The participants were included in a prospective longi-
tudinal study with assessments at 15–17 weeks (early

pregnancy), 27–28 weeks (mid-pregnancy), and 37–38
weeks of gestation (late pregnancy), and at 10 days and
at 3 and 8 months after birth. At study entry, data were
collected on demographic characteristics, and on ob-
stetric, medical and psychiatric histories. The assess-
ments at early, mid- and late pregnancy included
ultrasound recording of fetal behavior to be reported
elsewhere, and a set of self-report questionnaires on
various aspects of stress during pregnancy.
Predictors
To predict infant development, we used two different
aspects of maternal stress, which were only moderately
intercorrelated in each period of pregnancy (r’s ranging
from –.03 to .26). The first psychological predictor was
the rate of occurrence of daily hassles in the past
months, as measured by the Everyday Problem List
(Vingerhoets, Jeninga, & Menges, 1989). Examples of
items are ‘You could not find important belongings’ and
‘You were trapped in a traffic jam’. Cronbach’s alphas
were >.85. Daily hassles have been found to be associ-
ated with increased cortisol secretion in adult males
(Van Eck, Berkhof, Nicolson, & Sulon, 1996).
The second predictor, pregnancy anxiety, was as-
sessed by means of the Pregnancy Related Anxieties
Questionnaire-Revised (PRAQ-R; Huizink, 2000). This
questionnaire was developed by confirmatory factor
analysis from the PRAQ of Van den Bergh (Van den
Bergh, 1990) and consisted of ten items that fitted to a
three-factor model: fear of giving birth, fear of bearing a
physically or mentally handicapped child, and concern
about one’s own appearance. We used two subscales in
the present study: fear of giving birth (3 items; scores
ranging from 3 to 15) and fear of bearing a physically or

mentally handicapped child (4 items; scores ranging
from 4 to 20). Examples of items are: ‘I am worried
about the pain of contractions and the pain during de-
livery’ (fear of giving birth) and ‘I am afraid the baby will
be mentally handicapped or will suffer from brain
damage’ (fear of bearing a physically or mentally han-
dicapped child). The items were answered on a 5-point
scale, ranging from ‘never’ to ‘very often’. Cronbach’s
alpha’s of the subscales were all >.76 throughout
pregnancy. In another study, we found that only 17% of
the variance in pregnancy anxiety could be explained by
general trait anxiety and depression measures (Huiz-
ink, 2000). It has been shown that pregnancy anxiety
rather than general anxiety was related to birth out-
come and activation of the neuroendocrine axis in
pregnancy (Killingsworth Rini, Dunkel-Schetter, Wad-
wha, & Sandman, 1999; Wadhwa et al., 1993).
The concentration of cortisol in maternal saliva was
taken as an endocrinologic measure of maternal stress.
Salivary cortisol levels reliably reflect levels of the un-
bound hormone in blood (Meulenberg & Hofman, 1990;
Kirschbaum & Hellhammer, 1989). Seven saliva sam-
ples were collected every two hours between 8:00 a.m.
and 8:00 p.m., to obtain cortisol daytime curves in each
of the three periods of pregnancy. All samples were
stored at –70 �C until assayed. Salivary cortisol was
Prenatal stress and infant development 811
measured without extraction using an in-house com-
petitive radioimmunoassay employing a polyclonal
anticortisol-antibody (K7348). [1,2]-3 H(N)-Hydrocorti-
sone (NET 185, NEN-DUPONT, Dreiech, Germany) was

used as a tracer following chromatic verification of its
purity. The lower limit of detection was 0.5 nmol/L and
interassay variation was 11.0%, 8.2%, and 7.6% at 4.7,
9.7 and 14.0 nmol/L, respectively (n ¼ 20). Reference
values for adults are 4–28 nmol/L at 8:00 a.m. The
early morning (8 a.m.) cortisol level is a dynamic
measure and was thought to reflect the early morning
peak as an anticipatory stress response. It was entered
as a predictor in the present study. Also, the mean
cortisol secretion during the day (from 8:00 a.m. to 8:00
p.m.) was entered as a predictor in the present study.
The psychological and endocrinologic predictors proved
to be uncorrelated, except for the 8 a.m. cortisol value
and daily hassles (r ¼ .27, p < .05) in late pregnancy.
Outcome variables
The main dependent measures were the developmental
indices of the infant at the age of 3 and 8 months after
birth as assessed by the Bayley Scales of Infant Devel-
opment (BSID; Bayley, 1969) in a standard test situ-
ation. The examinations were performed by a
psychologist who was blind to the data on stress during
pregnancy. The BSID has been translated and validated
in a Dutch population of infants (Van der Meulen &
Smrkovky, 1983) and results in a Mental Develop-
mental Index (MDI) and a Psychomotor Developmental
Index (PDI). The MDI is designed to assess sensory-
perceptual acuities, discriminations, and the ability to
respond to these; the early acquisition of ‘object con-
stancy’ and memory, learning, and problem-solving
ability; vocalizations and the beginnings of verbal
communication; and early evidence of the ability to
form generalizations and classifications. The PDI is a
measure of the degree of body control, coordination of
the large muscles, and finer manipulatory skills of the

hands and fingers.
Confounders
Data on other factors from the prenatal, perinatal and
postnatal periods that may influence infant develop-
ment served as covariates in our analyses. The educa-
tional level and professional level of the pregnant
woman and her partner (Van Westerlaak, Kropman, &
Collaris, 1976) defined socio-economic status (SES).
Smoking (number of cigarettes smoked per day) and
alcohol-intake (number of beverages per week) were
assessed by self-report in each period of pregnancy.
Biomedical risk factors during pregnancy were added
up in a cumulative score (1 point per factor). Perinatal
covariates included birth weight (in grams) and gesta-
tional age at birth (in weeks). Also, complications dur-
ing delivery were taken into account, by calculating a
cumulative score (1 point per factor). Postnatal covari-
ates were breastfeeding, psychological well-being and
perceived stress of the mother at 3 and 8 months fol-
lowing childbirth. Psychological well-being was de-
termined by the Dutch version of the General Health
Questionnaire (GHQ-30; Koeter & Ormel, 1991). This
questionnaire contains 30 questions to be answered on
a 4-point scale. Cronbach’s alpha was .92. Perceived
stress was assessed with a Dutch translation of the 14-
item Perceived Stress Scale (Cohen & Williamson,
1987). The scale measures perceived stress over the last
month on a 4-point scale, ranging from ‘never’ to ‘al-
ways’. Cronbach’s alpha was .92. Postnatal depression
scores were determined by means of the 10-item Edin-
burgh Postnatal Depression Scale (EPDS; Cox, Holden,
& Sagovsky, 1987). Cronbach’s alpha was .86.

Statistical analysis
Categorical or interval-scaled covariates (SES, maternal
age, gestational age, birth weight, postnatal stress and
depression of the mother) were tested for their re-
lationships with the dependent and the independent
variables by means of correlations (Pearson product-
moment or Spearman rank-order correlations where
appropriate) and regression analysis. Only covariates
which were significantly related to the predictors and
dependent variables were included in further analyses.
For each predictor one MANCOVA was performed, with
MDI and PDI scores at 3 months and 8 months as
dependent variables, resulting in 4 tests in each
pregnancy period. A high–low contrast on the between-
subjects factor represented the upper and lower quar-
tile scores on the predictors. Dichotomous covariates
(smoking and alcohol use, infants’ sex, breastfeeding)
were entered as a between-subjects factor in the MAN-
COVA. Only in case of a significant multivariate Ho-
telling’s T2 test were univariate analyses performed
subsequently to locate the source of the difference. The
clinical relevance of prenatal predictors was explored in
logistic regression analyses that attempted to differen-
tiate mental and motor scores below the lower quartile
from scores above the upper quartile. The associations
between continuous predictor variables and the dicho-
tomized dependent variables in the logistic regression
models are reported as standardized odds ratios (SOR)
and 95% confidence intervals (CI). The SOR represents
the change in risk due to one standard deviation change
in the independent variable. With all tests, statistical
significance was assumed at the level of p < .05. Given
the exploratory set-up of the study and the reasonable
though not large sample size, the alpha level was not
corrected for multiple comparisons. In this way, an

adequate balance was established between the risk for
type I and type II errors.
Results
Descriptive analyses
Two hundred and thirty women satisfied the inclu-
sion and exclusion criteria and agreed to participate
in the study. To check for selection bias, we ap-
proached 70 non-participants of whom 69% (n ¼ 48)
returned the questionnaire that collected data on the
mental health status (trait-anxiety), appraisal of
pregnancy, maternal age, educational level, em-
ployment status, and health behavior during preg-
nancy (smoking and drinking habits). Comparisons
812 Anja C. Huizink et al.
were made between a random sample of participants
(n ¼ 52) and non-participants by means of t-tests
and Chi-square tests. Participants smoked more
than did non-participants (23% versus 7%, p < .01).
On all other aspects, non-participants did not differ
from participants. Of the 230 women who completed
the questionnaires on the first occasion, 217 and
172 did so on the second and third occasion, re-
spectively. The main reasons for the drop in the
number of participants towards late pregnancy were
delivery before 37 weeks of gestation, or delivery
before the assessment in late pregnancy had taken
place; other reasons were lack of interest, lack of
time, stillbirth, pregnancy complications that re-
quired intensive follow-up, or relocation to another

city. Only healthy infants born near term (more than
37 completed weeks of gestation) were included in
the follow-up study after birth, to remain free from
confounding factors involved with prematurity or
health problems of the infant. The total number of
mother–infant dyads with complete datasets, inclu-
ding an assessment of infant development at 3 and 8
months of age, was 170. Cortisol data of the third
prenatal measurement was not complete, due to the
fact that the last sample of cortisol was collected in
the week after the last prenatal visit, which was
planned near term. Other reasons for incomplete
cortisol data throughout pregnancy were insufficient
amounts of collected saliva. The sample of partici-
pants consisted largely of Caucasian middle class
women, although both lower and higher social clas-
ses were represented (Table 1). The majority of
women (93.7%) lived together with their partner, ei-
ther in wedlock or unmarried. We noted the following
biomedical risks during pregnancy: pregnancy
complications (n ¼ 30: 17.6%), use of medication
during pregnancy (n ¼ 25: 14.7%), medication with
risks for the fetus (n ¼ 4: 2.4%), fertility problems
(n ¼ 48: 28.2%), in vitro fertilization (n ¼ 13: 7.6%),
high blood pressure (n ¼ 15: 8.8%), gestational dia-
betus mellitus (n ¼ 3: 1.8%), gynecological risk
(n ¼ 12: 7.1%), and pre-existent disease (n ¼ 12:
7.1%). Since only 7 participants reported smoking
more than 10 cigarettes per day, smoking was coded
as a dichotomous variable: non-smokers, and
smokers of 1 or more cigarettes per day. Further,
since only 11 subjects consumed more than 2 alco-
hol-containing beverages per week, a dichotomous
variable was created: non-drinkers, and drinkers of
1 or more beverages/week. We observed the follow-

ing perinatal complications: intrapartum complica-
tions (n ¼ 25: 14.7%), use of medication during
delivery (n ¼ 88: 51.8%), elective caesarean section
(n ¼ 24: 14.1%), and artifical delivery due to fetal
distress (n ¼ 20: 11.8%). Descriptives of the poten-
tial covariates are summarized in Table 1 as well.
Descriptives of the scores on the predictor and
dependent variables are presented in Table 2. The
MDI scores at 3 and 8 months of age were signifi-
cantly correlated (r ¼ .26, p < .0005), and so were
the PDI scores at these ages (r ¼ .23, p < .0005). The
MDI and PDI scores were highly correlated at both 3
months (r ¼ .52, p < .0005) and 8 months (r ¼ .38,
p < .0005).
Table 1 Descriptives of potential covariates of the prenatal,
perinatal and postnatal periods (N ¼ 170). Values are presented
as
proportions or as mean (SD) and range
Prenatal
Maternal age, years 31.3 (4.9)
Socioeconomic status:
Educational level mother Low 13.6% Middle 67.5% High 18.9%
Educational level partner Low 23.4% Middle 59.8% High 16.8%
Professional level mother Low 8.0% Middle 54.6% High 37.4%
Professional level partner Low 18.0% Middle 29.2% High
52.8%
Paid job 87.4% (44.7% full-time, 55.3% part-time)
Ethnic background Caucasian (96%)
Smoking (cigarettes/day) Smokers (1 or more cig/day) n ¼ 29;
Non-smokers: n ¼ 141
Alcohol-intake (beverages/week) Drinkers (1 or more
beverage/week) n ¼ 26; Non-drinkers: n ¼ 144
Biomedical risks:

Cumulative score 1.0 (1.2), range 0–5
Number of risks No risk: n ¼ 85, 1 or more risks, n ¼ 85
Perinatal
Birth weight, grams 3386 (487)
Gestational age at birth, weeks 39.6 (1.9)
Sex 84 boys, 86 girls
Perinatal complications:
Cumulative score 1.0 (1.3), range 0–5
Postnatal
Psychological well-being (GHQ-30) 4.7 (5.1), range 0–25
Perceived stress 25.9 (5.8), range 14–45
Postnatal depression (EPDS) 15.8 (4.6), range 10–32
*low level: primary school, high-school education; middle
level: secondary school education; high level: college or
academic
education.
Psychological stress measures during pregnancy
and infant mental and motor development
MANCOVAs were performed with a high–low contrast
set on the predictor variable as between-subject
factor, the MDI and PDI scores at 3 and 8 months as
dependent variables, and gestational age at birth,
birth weight and the postnatal stress and depression
levels of the mother as covariates. An overall effect of
daily hassles in early pregnancy on 8-month scores
was found to show a trend towards significance, after
correction for these covariates (F ¼ 2.31, p ¼ .10).
No effect of daily hassles in mid- or late pregnancy
was found on infant development. A significant

overall effect was found of fear of giving birth in
mid-pregnancy on 8-month scores of infant devel-
opment (F ¼ 5.04, p < .005). Subsequent univariate
analyses (Table 3 and Figure 1) revealed that a high
amount of daily hassles in early pregnancy was as-
sociated with lower MDI scores at 8 months (F ¼ 3.9,
p ¼ .05). Strong fear of giving birth in mid-pregnancy
was associated with lower MDI and PDI scores at
8 months (F ¼ 5.58, p < .05 and F ¼ 7.67, p < .01,
respectively). Strong fear of giving birth in late
pregnancy was associated with lower MDI scores at
8 months (F ¼ 5.34, p < .05). No effect was found of
fear of bearing a handicapped child on infant
development.
Logistic regression showed that of the two different
aspects of maternal stress (daily hassles, pregnancy
anxieties), daily hassles in early pregnancy were an
independent risk factor for low (i.e., £ P25) MDI
scores of infants at 8 months of age (SOR ¼ 1.1, 95%
CI 1.02–1.18). Logistic regression furthermore
showed that high levels of fear of giving birth in mid-
pregnancy increased the risk of having an infant
with a low (i.e., £ P25) PDI score at 8 months of age
(SOR ¼ 1.3, CI 1.12–1.56).
Endocrinologic stress measures during pregnancy
and infant mental and motor development
A MANCOVA, with a high–low contrast on the 8 a.m.
salivary cortisol level in late pregnancy as between-
subject factor, the MDI and PDI scores at 3 and
8 months as dependent variables, and gestational
age at birth, birth weight and the postnatal stress
and depression level of the mother as covariates,

showed a significant overall effect (F ¼ 4.61,
p < .05). In univariate follow-up tests high cortisol
was related to lower MDI scores at 3 months of age
(F ¼ 6.38, p < .05) and lower PDI scores at both 3
and 8 months of age (F ¼ 9.15, p < .005; and
F ¼ 9.38, p < .005) (see Table 3). Cortisol in early
and mid-pregnancy did not show overall significant
effects on infant development.
Table 2 Descriptives of the psychological and endocrinologic
predictors
Predictors Mean SD Range N
Psychological
Daily hassles T1 10.0 6.3 0–45 170
Daily hassles T2 7.8 5.5 0–26 170
Daily hassles T3 6.4 4.3 0–23 170
Fear of giving birth T1 6.2 2.9 3–15 170
Fear of handicapped child T1 9.3 3.5 4–20 170
Endocrinologic
Cortisol 8 AM T1 19.8 7.4 6.0–44.2 142
Cortisol 8 AM T2 23.3 6.8 9.3–41.0 130
Cortisol 8 AM T3 23.6 6.3 2.5–43.0 85
Cortisol mean value T1 10.6 2.3 5.2–19.8 142
Dependent variables
MDI 3 months 114.9 15.0 71–150 170
MDI 8 months 117.7 15.5 76–150 170
PDI 3 months 101.3 13.7 61–150 170
PDI 8 months 109.4 13.5 77–150 170

T1 ¼ 15–17 weeks of gestational age; T2 ¼ 27–28 weeks of
gestational age; T3 ¼ 37–38 weeks of gestational age.
Table 3 Stress during pregnancy and mental and motor
developmental scores at 3 and 8 months. Means and standard
deviations
(in brackets) are presented
MDI PDI
3 months 8 months 3 months 8 months
Low High Low High Low High Low High
Psychological measure of stress
Early pregnancy
Daily hassles 114 (15) 112 (13) 120 (15)* 113 (15) 103 (16) 98
(10) 110 (12) 109 (11)
Mid pregnancy
Fear of giving birth 115 (17) 112 (12) 122 (15)* 114 (11) 102
(17) 99 (8) 114 (12)** 106 (13)
Late pregnancy
Fear of giving birth 117 (17) 113 (13) 123 (17)* 116 (15) 101
(17) 101 (12) 114 (14) 108 (12)
Endocrinologic measure of stress
Late pregnancy
Cortisol 8 AM 117 (13)* 107 (14) 117 (14) 112 (13) 103 (7)**
95 (9) 114 (16)* 102 (10)
*post-hoc univariate analyses p < .05; ** post-hoc univariate
analyses p < .01.

Discussion
Stress during pregnancy, as reflected by a high
amount of daily hassles in early pregnancy or strong
fear of giving birth in mid-pregnancy, was associated
with an average decline of 8 points in mental and
psychomotor developmental scores of the infant
8 months after birth (Table 3). The effects of preg-
nancy anxiety remained significant after adjusting
for possible confounders, such as SES, maternal
age, birth weight, gestational age, biomedical risks
during pregnancy, perinatal complications, and the
mothers’ postnatal stress and depression levels. The
effect on mental development at 8 months appeared
to be non-linear since it was only found when high–
low contrast groups were formed. In contrast, the
negative effect of fear of giving birth on psychomotor
development at 8 months proved to be linear. Corti-
sol levels in saliva at 8 a.m. in late pregnancy as an
endocrinologic index of stress was also linearly re-
lated to psychomotor development at 3 and 8 months
and mental development at 3 months. Overall, the
negative effects of prenatal stress on developmental
outcome were more clearcut at 8 than at 3 months.
Relevant issues are greater measurement error of
developmental outcome at 3 months due to less
reliability and less variation in the scores.
At first sight, the effects of prenatal stress on in-
fant development seem to be rather mild. The pre-
sent study, however, probably provides an
underestimate of the influence of prenatal stress on
infant development, because the follow-up was lim-
ited to healthy infants born near term, and stress
effects that are mediated by an adverse birth out-

come (Dunkel-Schetter, 1998; Copper et al., 1996;
Wadhwa et al., 1993) were not taken into account in
our study. Another consideration is that the adverse
effects on infant development were found when
studying the influence of commonly occurring and
relatively minor stressors rather than that of
experimentally induced stress such as applied in
animal designs or of circumscribed major life-events.
Nonetheless, our results concur with evidence from
studies in monkeys indicating that experimental
prenatal stress induced neuromotor deficits in off-
spring (Schneider et al., 1999; Schneider, 1992;
Schneider et al., 1992). We note that although the
MDI is classified as a ‘mental developmental index’,
over half of the items contributing to the MDI be-
tween the age of 3 and 8 months are motor or sen-
sorimotor tasks. A recent large study showed effects
of prenatal maternal anxiety on child behavior at
4 years (O’Connor et al., 2002). The effects found in
the present study and in the few other prospective
human studies (O’Connor et al., 2002; van den
Bergh, 1990) are small, but appear to be consistent.
The effects of prenatal stress and anxiety on the in-
fant appear to be on various aspects of behavior and
development, suggesting a diffuse effect. The clinical
relevance of our findings is apparent from the in-
creased risk of obtaining developmental scores below
the lowest quartile, given high amounts of daily
hassles and distress in early pregnancy and a strong
fear of giving birth in mid-pregnancy. It is further
important to note that Bayley test scores of mental
development in infancy were found to correlate
significantly with intelligence test scores in later
childhood (Laucht, Esser, & Schmidt, 1994; Siegel,
1989).

We examined two relatively independent aspects of
the emotional state of pregnant women as potential
predictors of infant development. Pregnancy anxiety
represented as fear of giving birth in mid-pregnancy
emerged as the strongest predictor. Pregnancy
anxiety reflects a unique element of human preg-
nancy and was previously found to predict adverse
pregnancy outcome (Killingsworth Rini et al., 1999).
Since pregnancy anxiety is not quite comparable
with the stressors applied in studies in rodents and
non-human primates, replication should be sought
130
120
110
100
130
120
110
100
90
80
9
5
%

C
l m
e
n
ta
l d
e
ve
lo
p
m
e
n
t
9
5
%
C
l m
o
to
r
d
e
ve
lo

p
m
e
n
t
Fear of giving birth in mid pregnancy
and mental development at 3 and 8 months
Cortisol at 8 am in late pregnancy
and motor development at 3 and 8 months
N= 58 58 75 75 37 37
low mediate high
N= 24 24 38 38 22 22
low mediate high
= 3 months scores
= 8 months scores
Figure 1 Effect of high fear of giving birth in mid-pregnancy on
mental development (left) and of high cortisol at 8 a.m.
in late pregnancy on motor development (right). The error bars
reflect 95% confidence intervals
in future human studies. Van den Bergh (1990)
showed that measures of general anxiety in the third
trimester of pregnancy were unrelated to infant
mental or motor development. Our measures of
pregnancy anxiety, on the contrary, were related to

infant mental and motor development. In another
study, we found that pregnancy anxiety was only
partly related to measures of general anxiety, and we
suggested that pregnancy-related anxiety may be a
rather distinctive syndrome (Huizink, 2000). There-
fore, it might be of interest to focus on pregnancy
anxiety as predictor of infant development in future
human studies.
Our findings underline the importance of the
study of relatively minor but stressful daily hassles
in addition to pregnancy anxiety in the identification
of pregnant women with psychological high-risk
status. Thus far, the results of stress reduction
programs in pregnancy are inconclusive (Villar et al.,
1992). The present study suggests that a sharper
focus on pregnancy anxieties and daily hassles may
increase the effectiveness of intervention studies.
It remains difficult to establish during which
period of pregnancy exposure to stress matters most
in affecting the postnatal development of the infant.
Our stress measures throughout pregnancy are
correlated over time and thus are not independent.
Measurement of effects of stress during a particular
period in pregnancy on fetal behavior and physiology
would provide more short-cut information about the
timing issue of stress exposure. Studies in rhesus
macaques reported sensitivity to prenatal stress to
peak during early gestation and to taper off during
later gestation (Schneider et al., 1999). Further, the
California earthquake in 1994 was perceived as most
stressful when it occurred early in pregnancy com-
pared with late pregnancy (Glynn et al., 2001). In
addition, stress experienced early in pregnancy was
associated with shorter gestational length in this

earthquake study (Glynn et al., 2001). We found the
strongest effects on infant development of psycholo-
gical measures of stress and cortisol in mid- to late
pregnancy. O’Connor et al. (2002) found that anxiety
at 32 weeks of gestation had the strongest effect
on later child behavior, which is comparable to our
results.
The relationship between psychological and endo-
crinologic measures of stress in pregnancy may be
complicated by the physiologic changes in neuro-
endocrine function during pregnancy. The fetal-
placental-decidual unit produces steroids and
peptides hormones, among them corticotropin-
releasing hormone (CRH). Maternal cortisol creates a
positive feedback loop, by stimulating the synthesis
and release of placental CRH which in turn further
activates the maternal HPA-axis. As a result, over the
course of pregnancy there is a progressive increase
in maternal plasma levels of stress hormones, in-
cluding CRH, ACTH and cortisol. This may have
implications for the responsivity of the HPA-axis to
stress. Indeed, only in late pregnancy was the early
morning value of cortisol correlated with psycholo-
gical measures of stress.
The mechanisms that underlie the association
between prenatal stress and infant development are
unknown. There are a number of plausible hypo-
theses. First, maternal stress may reduce uteropla-
cental blood flow since cortisol and catecholamines
are known to affect vessel tone (Teixeira, Fisk, &
Glover, 1999). Reduced supply of oxygen and nu-
trients to the fetus in turn mobilizes a response of the
fetal HPA-axis that is operative from mid-pregnancy

on. Second, maternal stress may lead to increased
production of placental CRH that further activates
the fetal HPA-axis (Majzoub & Karalis, 1999). Third,
maternal cortisol may be directly transported across
the placenta and enter the fetal circulation. The fetus
is relatively protected from raised levels of maternal
cortisol by the 11 ß-hydroxysteroid dehydrogenase
(11 ß-HSD) enzyme in the placenta that metabolizes
cortisol to inactive cortisone. In spite of this, how-
ever, maternal cortisol has been found to account for
about 40% of the variance in fetal concentrations of
cortisol in high stress conditions (Gitau, Cameron,
Fisk, & Glover, 1998).
A common element of these hypotheses is that the
fetus is exposed to excess levels of cortisol. Studies
in the rat indicate that the fetal brain is protected
from glucocorticoids (in rat: corticosterone) by 11
ß-HSD which is highly expressed in all areas of the
brain in mid-pregnancy (Diaz, Brown, & Seckl,
1998). The expression of 11-HSD, however, is dra-
matically reduced in the last period of pregnancy,
which allows glucocorticoids to interact with their
receptor systems and influence brain development
(Diaz et al., 1998). This would fit with our finding of
the association between cortisol in late pregnancy
and infant developmental outcome. Glucocorticoids
are critical in promoting neuronal and glial matura-
tional events under normal circumstances but are
neurotoxic in high concentration (Uno et al., 1994).
In particular, the hippocampus is highly vulnerable
to excess levels of glucocorticoids that may lead to
dose-dependent degeneration and depletion of hip-
pocampal pyramidal neurons (Uno et al., 1994) and
persistent reductions in hippocampal glucocorticoid
receptor systems (Barbazanges et al., 1996; Maccari

et al., 1995).
Animal studies provide extensive documentation
that prenatal stress results in persisting alterations
of the regulation of the HPA-axis and concomitant
lifelong problems in behavioral adaptation (Wein-
stock, 1997) and neurocognitive deficits (Schneider
et al., 1999; Schneider & Coe, 1993). Early neuro-
motor dysfunction in children has been associated
with academic, cognitive, and behavioral problems
at later ages (Gillberg & Gillberg, 1989). Decades
ago, Bayley (1969) stated: ‘Motor abilities play im-
portant roles in the development of the child’s ori-
entation toward its environment, and they influence
the quality of its interaction with the environment.
Locomotion and control of the body serve to enlarge
the potential sphere for new and varied experiences
and for individual choices in seeking or avoiding
different kinds of experience.’ Thus, the effects of
prenatal stress on early motor and mental develop-
ment may hamper the subsequent development of
the child in various ways. We are currently involved
in a further follow-up of our sample to examine
whether the negative effects of prenatal stress on
developmental outcome at 3 and 8 months are
transient, persistent or even progressive, and to gain
more insight into the neurobiological basis of these
effects.
Acknowledgement

This research was supported by the Van der Gaag
Stichting and the Praeventiefonds (28-2685).
Correspondence to
A.C. Huizink, Department of Social Medicine, Insti-
tute for Research in Extramural Medicine, VU
University Medical Center, Van der Boechorststraat
7, 1081 BT Amsterdam, The Netherlands; Email:
[email protected]
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Manuscript accepted 14 August 2002
Appendix A: Pregnancy anxiety
Fear of giving birth:
I am worried about the pain of contractions and the
pain during delivery.
I am anxious about the delivery because I have never

experienced one before.
I am worried about not being able to control myself
during labor and fear that I will scream.
Fear of bearing a physically or mentally
handicapped child:
I am afraid the baby will be mentally handicapped or
will suffer from brain damage.
I am afraid our baby will be stillborn, or will die
during or immediately after delivery.
I am afraid that our baby will suffer from a physical
defect or worry that something will be physically
wrong with the baby.
I sometimes think that our child will be in poor
health or will be prone to illnesses.
This document is a scanned copy of a printed document. No
warranty is given about the accuracy of the copy.
Users should refer to the original published version of the
material.
J Abnorm Child Psychol (2006) 34:789–798
DOI 10.1007/s10802-006-9054-7
O R I G I N A L PA P E R

Does Maternal Prenatal Stress Adversely Affect the Child’s
Learning and Memory at Age Six?
Barbara M. Gutteling · Carolina de Weerth ·
Noortje Zandbelt · Eduard J. H. Mulder ·
Gerard H. A. Visser · Jan K. Buitelaar
Published online: 25 October 2006
C© Springer Science+Business Media, LLC 2006
Abstract Prenatal maternal stress has been shown to affect
postnatal development in animals and humans. In animals,
the morphology and function of the offspring’s hippocampus
is negatively affected by prenatal maternal stress. The present
study prospectively investigated the influence of prenatal
maternal stress on learning and memory of 112 children (50
boys, 62 girls, Age: M = 6.7 years, SD = 8.4 months), with
the Test of Memory and Learning (TOMAL). Maternal stress
levels were determined three times during pregnancy by self-
report questionnaires. Furthermore, maternal saliva cortisol
samples were used as a measure of hypothalamus-pituitary-
adrenal axis functioning. Results of hierarchical multivariate
B. M. Gutteling
Department of Child and Adolescent Psychiatry, Utrecht
University Medical Center and the Rudolf Magnus Institute of
Neuroscience,
Utrecht, The Netherlands
B. M. Gutteling (�) · J. K. Buitelaar
Department of Psychiatry (961), Radboud University Nijmegen
Medical Centre,
P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
e-mail: [email protected]
C. de Weerth
Department of Developmental Psychology, Radboud University

Nijmegen,
Nijmegen, The Netherlands
N. Zandbelt
Department of Psychiatry, Radboud University Nijmegen
University Medical Centre, Nijmegen and Department of
Developmental Psychology, Radboud University Nijmegen,
Nijmegen, The Netherlands
E. J. H. Mulder · G. H. A. Visser
Department of Perinatology and Gynaecology, Utrecht
University
Medical Center,
Utrecht, The Netherlands
regression analyses showed that maternal life events mea-
sured during the first part of pregnancy were negatively as-
sociated with the child’s attention/concentration index, while
controlling for overall IQ, gender, and postnatal stress. No
associations were found between prenatal maternal cortisol
and the offspring’s learning and memory.
Keywords Prenatal maternal stress . Learning . Memory .
Child
Barker’s (1995) hypothesis of fetal programming opened the
field for extensive research into the fetal origins of diseases
at adult age. The hypothesis states that the environment in
utero can alter the development of the fetus during particular
sensitive periods, with a permanent effect on the set point of
physiological systems and the phenotype in later years. The
prenatal environment can be affected by external prenatal
factors, such as maternal smoking (Cnattingius, Granath,
Petersson, & Harlow, 1999), maternal alcohol intake
(Henriksen et al., 2004), and maternal use of drugs dur-

ing pregnancy (Thadani et al., 2004), all of which can result
in worse birth outcomes. Furthermore, the in utero environ-
ment can be influenced by internal prenatal factors, which are
likewise related to a less optimal postnatal outcome. One of
these factors, prenatal maternal stress, can have long-lasting
consequences on the development of the offspring (Gitau,
Fisk, & Glover, 2001; Huizink, Mulder, & Buitelaar, 2004a;
Weinstock, 2001). In animal studies, prenatal maternal stress
has been shown to affect postnatal physical outcome, and the
development, behavior, and stress responses of the offspring
(Huizink et al., 2004a; Mulder et al., 2002; Weinstock, 1997;
Weinstock, 2001). Furthermore, in humans, prenatal mater-
nal stress is related to a poor birth outcome (low birth weight,
premature delivery, and a small head circumference; Gitau
et al., 2001; Mulder et al., 2002), to a difficult temperament
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790 J Abnorm Child Psychol (2006) 34:789–798
(Gutteling et al., 2005b; Huizink, Robles de Medina,
Mulder, Visser, & Buitelaar, 2002; van den Bergh, 1990),
and to behavioral and emotional problems in toddlers and in
children (Gutteling et al., 2005b; O’Connor, Heron, Golding,
Beveridge, & Glover, 2002).
The mechanisms involved in transduction of prenatal ma-
ternal stress to the fetus are only partly understood, but three
possible mechanisms have been proposed: 1) transplacen-
tal transport of cortisol to the fetus, 2) release of placental
hormones, induced by prenatal maternal stress, 3) maternal
stress-induced decreases of the blood flow to the placenta
(Huizink et al., 2004a). These mechanisms could act inde-
pendently or in concert.

Particularly the hippocampus has been shown to be sensi-
tive to the neurotoxic effects of high levels of endogeneous or
exogeneous steroid hormones or of fetal hypoxia (Sapolsky,
Uno, Rebert, & Finch, 1990). For example; treatment of mid-
aged rats with corticosterone was associated with impaired
hippocampus dependent spatial learning (Bodnoff et al.,
1995). Further, in humans, acute glucocorticoid treatment
with dexamethasone or prednisone was associated with de-
creased declarative memory performance (Newcomer, Craft,
Hershey, Askins, & Bardgett, 1994; Wolkowitz et al., 1990).
Recently, research in humans has also been carried out on
the influence of prenatal maternal stress on the child’s cogni-
tive functioning. The influence of prenatal stress (State-Trait
Anxiety Inventory: STAI; Spielberger, Gorsuch, & Leshene,
1970) on attention and working memory was studied. More
cognitive problems were found in prenatally stressed chil-
dren at 8- to 9-years of age (van den Bergh & Marcoen,
2004), and in adolescence (van den Bergh et al., 2005a).
These problems could be due to negative effects of prena-
tal anxiety on the fetus’ hippocampus. On the other hand,
O’Connor, Heron, Golding, and Glover (2003) did not find
associations between prenatal maternal stress (Crown-Crisp
index, Birtchnell, Evans, & Kennard, 1988) and attention
problems in 6-year old children. However, van den Bergh
and colleagues (2004, 2005a) measured prenatal stress at
12–22 weeks of gestation, while O’Connor et al. (2003)
measured stress at 18 and 32 weeks prenatally. These differ-
ences in pregnancy assessment moments could at least partly
explain the lack of consensus in results. From the above, it
is clear that further research on the relations between pre-
natal maternal stress and its timing, and offspring cognitive
development, is necessary before solid conclusions on these
issues can be drawn.

The goal of the present study is to test the hypothesis
that prenatal maternal stress is associated with a poor per-
formance on memory and learning tasks in the 6-year-old
offspring. Further, if so, to obtain more insight into which
period of pregnancy is most sensitive for these effects, and
to determine which stress factors play the most important
role. A recent review on the differential effects of the tim-
ing of stress during pregnancy concluded that the results of
16 studies were inconsistent in this respect (van den Bergh
et al., 2005b). Therefore, we chose not to hypothesize about
which period in pregnancy would be most vulnerable for the
prenatal stress effects.
Method
Participants
This study is part of an ongoing prospective longitudinal
project which investigated the influence of prenatal mater-
nal stress factors and endocrine factors on fetal behavior
and postnatal development. A total of 230 mothers were ini-
tially recruited from a population of women who visited the
Outpatient Clinic of the Department of Obstetrics of the Uni-
versity Medical Center Utrecht, The Netherlands, between
January 1996 and July 1998. Eligibility criteria were: Dutch
fluency, no drug use, no use of medication with risks for the
fetus, first-time singleton pregnancy resulting in birth after
37 weeks of gestation, no major pregnancy or birth com-
plications, Apgar scores > 7, and good health of the baby.
All women were 15–17 weeks pregnant of their first single-
ton child and participated on a voluntary basis. The local
ethics committee approved the study and the participants
gave written informed consent. The maternal written con-
sent and child assent (verbally by the investigator) were (re)-
established at the time of follow-up testing. Participants were

asked to fill out questionnaires on stress and possible con-
founding variables, such as educational level and smoking, at
15–17 weeks, 27–28 weeks, and 37–38 weeks of gestation.
The first and last measurement moments were chosen to take
place as early and late in pregnancy as possible, and the
second measurement moment was taken as an extra mea-
surement in between. In the Netherlands women have their
first medical check at approximately 12–16 weeks of ges-
tation, and this was therefore the first opportunity to invite
mothers to participate in the study.
Of the 230 women who completed the questionnaires on
the first occasion, 217 completed the questionnaires on the
second occasion and 172 on the third occasion. Of these 172
mother-child pairs, 32 were excluded because of medical rea-
sons, such as preterm delivery, stillbirth, child’s illness, and
serious pregnancy complications, or because they delivered
twins.
The present follow-up study took place between March
2004 and August 2004 when the children were between 5
and 8 years old. A total of 145 participants who were still
taking part of the longitudinal study were invited to partic-
ipate in this follow-up study (five of the mother-child pairs
participated in this postnatal part of the study but not in one
of the earlier phases). Of these 145 children, 113 actually
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Table 1 Descriptives of maternal and child characteristics
Maternal characteristics
Maternal age (years) 32.2 (SD = 5.0)
Maternal education:
Low educational level (primary school) 4%
Middle educational level (high school) 54%
High educational level (college or academic
education).

43%
Smoking during first trimester of pregnancy 16%
Alcohol during first trimester of pregnancy 20%
Child characteristics Mean (SD)
Birth weight (grams) 3404 (496)
Gestational age (days) 280 (8.6)
Note: SD = Standard Deviation.
participated in the home testing procedure. Loss of partic-
ipants was due to lack of time (n = 4), not being able to
reach the participants due to the family having moved away
(n = 18), lack of interest (n = 7), school problems (n = 2) and
illness of mother’s partner (n = 1). One child was unwilling
to cooperate during the test-session (n = 1).
The children who participated in the present study
(n = 112) and those who had participated at approxi-
mately 16 weeks of gestation (n = 217) were compared
by independent t-tests to check whether there was at-
trition bias based upon maternal differences. No signifi-
cant differences between the groups were found in gen-
der, t(1,112) = − .46, p = .65; maternal educational levels, t
(1,112) = − 1.06, p = .32; early period maternal stress ques-
tionnaires, Daily hassles, t(1,107) = − .63, p = .53, Fear of
giving birth, t(1,102) = 1.44, p = .14, Fear of having a handi-
capped child, t(1,102), p = .85, Life events, t(1,115) = − .48
p = .64; or cortisol data, Morning cortisol, t(1,99) = .34,
p = .74, Evening cortisol, t(1,100) = 1.02, p = .31, Slope,
t(1,99) = − .36, p = .72.
Furthermore, the children who participated in the present
study (n = 113) and those whose temperament and problem
behavior was measured at the age of 27-months (n = 110)

were compared. No significant differences were found for
temperament, t(1,110) = − .36, p = .72 or problem behavior,
t(1,108) = − .07, p = .94.
Of the 112 children who participated, 50 were boys and
62 were girls. The mean age of the children was 6.7 years
(SD = 8.4 months). A t-test for independent samples showed
no significant difference in age between boys and girls (Mean
age boys = 6.6 years and the mean age for girls = 6.9 years,
t(1,110) = 1.87, p = .07).
Missing data
About 10% of the prenatal stress data, which were measured
three times during pregnancy, were missing. For each partic-
ular variable at each assessment moment, the missing values
were replaced with the mean score of the group as a whole.
Although the imputation with group means smoothes the data
by reducing differences among the participants, it was pre-
ferred above other alternatives, such as imputation with the
subject’s score on the missing variable at another assessment
moment, because the prenatal maternal stress variables were
not stable throughout pregnancy (i.e. increased or decreased
over time, see Table 2).
Measures
Prenatal maternal questionnaire measures. Several mater-
nal questionnaires were collected in the three pregnancy
periods. First, the frequency of daily hassles, in the past
2 months, was measured with the Everyday Problem List
(Alledaagse Problemen Lijst, APL; Vingerhoets, Jeninga, &
Menges, 1989). This questionnaire is based on different ques-
tionnaires: the Daily Life Experience Questionnaire (Stone
& Neale, 1982), the Daily Hassles Scale (Kanner, Coyne,
Schaefer, & Lazarus, 1981), and the Everyday Problem Scale

(Burks & Martin, 1985). This self-report questionnaire was
used to assess the number of daily hassles during the past
2 months. Mothers completed the list by marking ‘yes’ or
Table 2 Descriptives of the prenatal and postnatal maternal
stress factors
Stress factor
First period of pregnancy
N; Mean (SD)
Second period of
pregnancy N; Mean (SD)
Third period of pregnancy
N; Mean (SD)
Postnatal mean at 3 and 8 months
postpartum N; Mean (SD)
Daily hassles 105; 9.9 (5.8) 111; 8.1 (6.1) 104; 6.9 (4.5)
Life events 112; 283.2 (132.0) 112; 159.2 (115.2) 112; 141.1
(123.2)
Fear of having a
handicapped child
86; 9.1 (3.4) 85; 8.3 (2.6) 85; 8.3 (2.8)
Fear of giving birth 86; 5.5 (2.6) 85; 5.4 (2.6) 86; 5.5 (2.5)
Perceived stress 111; 25.6 (4.7)
Morning cortisol (nmol/l) 79; 19.7 (5.9) 77; 24.0(6.7) 56;
23.6(6.8)
Evening cortisol (nmol/l) 80; 5.2 (2.0) 77; 8.3 (2.7) 56; 12.4
(3.7)
Slope 81; − 2.39 (3.09) 76; − 1.57 (2.97) 56; − 4.41 (4.25)
Note. N = number of participants; SD = Standard Deviation.

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‘no’ on 49 items, which were very diverse in nature (e.g.
‘You had to wait long for an appointment’, ‘You couldn’t
be yourself’, ‘You had problems with friends’). The APL
has been proven reliable and valid in a non-problem sample
(Vingerhoets et al., 1989). Re-test (1 week later) reliability
of a normative sample was .85. Norm values are available
for the non-pregnant population. Norm scores of a commu-
nity sample showed that < 9 is normal, 10–16 is high, and
> 17 is very high. Internal consistency was adequate for the
present study sample (Cronbach’s α = .84 in the first period
of pregnancy, α = .81 in the second period, and α = .96 in
the third period).
Second, the impact score on the Life Events Questionnaire
(Vragenlijst Recent Meegemaakte Gebeurtenissen (VRMG);
Van de Willige, Schreurs, Tellegen, & Zwart, 1985) was in-
cluded. The Life Events Questionnaire was used to measure
the negative emotionality or ‘impact’ of the ‘participants’
life events of the past year (at 15–17 weeks of gestation) or
past 2 months (at 27–28 weeks of gestation and at 38–39
weeks of gestation). The impact score of this questionnaire
is based on the Social Readjustment Rating Questionnaire
(Holmes & Rahe, 1967). The participants rate the negative
impact of the events they experienced within a list of 63
possible events on 5-point Likert scales (ranging from ‘very
negative’ to ‘not negative’). The higher the impact score, the

more life event-related negative emotionality had been expe-
rienced by the subject. Each of these scores is then multiplied
by a standard score indicating the impact of that specific life
event. For example, dying of a partner or family member is
multiplied by 100, moving is multiplied by 20, and being a
victim of a criminal offence is multiplied by 53. The result-
ing values are then summed up into a total score that is used
for analysis. Thus, the total score is partly determined by
how negative the participant rated a life event, and partly by
an objective ‘stressor’ weight given to each particular event.
More information on this questionnaire can be obtained from
the first author. No norm values, reliability or validity scales
of norm groups are available for this questionnaire. The in-
ternal consistency for this study sample was adequate for
the three pregnancy periods (Cronbach’s α = .70 for the first
period, α = .76 for the second period, and α = .77 for the last
period).
Third, pregnancy related anxiety was measured with the
Pregnancy Related Anxiety Questionnaire-Revised, PRAQ-
R (van den Bergh, 1990). This self-report questionnaire con-
sists of 34 items, and has three subscales. Questions concern
specific fears and worries related to pregnancy. The items
are answered nominally, on a 5-point Likert scale (ranging
from ‘never’ to ‘very often’). Scores can range from 3 to
15 for the scale “fear of delivery” and from 4 to 20 for the
scale “fear of a handicapped child”. No norm values nor
reliability or validity evidence for community samples are
available. For this study, two scales were used: “fear of bear-
ing a physically or mentally handicapped child” (4 items) and
“fear of giving birth” (3 items) (Huizink, Robles de Medina,
Mulder, Visser, Buitelaar, 2004b). This choice was based on
earlier findings between these scales and postnatal outcome
in the same study sample (Gutteling, de Weerth, & Buite-
laar, 2004, 2005a; Gutteling et al., 2005b). For the present

study sample, construct validity was supported, since factor
analysis showed that pregnancy-related anxiety in general
and both subscales in particular were distinctively different
from general anxiety (Huizink et al., 2004b). Also, the in-
ternal consistency was satisfactory for both subscales during
the total pregnancy (Cronbach’s α = .79–.83 for fear of giv-
ing birth, and α = .87–.88 for fear of a handicapped child;
Huizink et al., 2004b).
Prenatal maternal cortisol measures. Cortisol saliva sam-
ples were collected in each of the three periods of preg-
nancy (15–17 weeks, 27–28 weeks, and 37–38 weeks of
gestation) on a pre-selected day every 2 h between 8 a.m.
and 8 p.m. Mothers were asked to keep strictly to the sam-
pling times. However, because electronic sampling time de-
vices were not used, compliance can only be assumed. The
mothers collected saliva by means of special cotton swabs
(Salivettes, Sarstedt Inc., Germany) and stored the samples
in their refrigerator until mailing them to the hospital. Fur-
thermore, mothers were instructed to perform their normal
daily activities and asked not to perform vigorous physical
activities.
Samples were stored at − 20◦C until analysis. The
cortisol concentrations were measured without extraction,
using an in house competitive radioimmunoassay with
polyclonal anticortisol-antibody (K7348). [1,2 − 3H(N)]-
Hydrocortisone (NET 185, NEN-DUPONT, Dreiech, Ger-
many) was used as a tracer after chromatographic verifica-
tion of its purity. The lower limit of detection was 0.5 nmol/L
and inter-assay variation was 11.0; 8.2; and 7.6% at 4.7; 9.7
and 14.0 nmol/L respectively (N = 20).
Because earlier results in this longitudinal project showed
associations between prenatal morning cortisol and postnatal
child characteristics (Gutteling, et al., 2004, 2005a; Huizink,

Robles de Medina, Mulder, Visser, & Buitelaar, 2003), the 8
a.m. values of each pregnancy period were used as indepen-
dent variables. Additionally, the evening (8 p.m.) values and
slopes of the cortisol curves for each pregnancy period were
included as independent variables in an exploratory fashion.
SPSS version 12.1 was used to calculate the slope that con-
sisted of the 7 diurnal measurements. It was calculated as
follows: We performed general linear modeling using the
mothers as random factor, the slope as the dependent fac-
tor and the 7 cortisol variables (8 a.m. till 8 p.m.) as the
covariates. The Beta’s of the main effects were considered
the slope. This slope in cortisol levels throughout the day is
related to the shape of the circadian curve and to recovery
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from daily stress, and as such is often used to study relations
between HPA axis activity and behavior (see e.g. Li et al.,
2005; White, Gunnar, Larson, Donzella, & Barr, 2000). Be-
cause the cortisol data were not normally distributed, we
transformed with logarithm and used the transformed data in
the regression analyses.
Child measures. The children’s learning and memory func-
tion was assessed with the neuropsychological Test of Mem-
ory and Learning (TOMAL, Reynolds & Bigler, 1994). The
TOMAL is intended to measure memory and learning in
children and adolescents between the ages of 5 and 20 years.
It consists of 14 subtests, 10 of which form the core subtests.
Several indexes can be calculated to provide information
on specific components of memory. The use of compos-

ite indexes is recommended, because their results are more
reliable than those of the individual subtests (Reynolds &
Bigler, 1994). Five composite indexes can be calculated.
These indexes are the Attention/Concentration Index (ACI),
the Associative Recall Index (ARI), the Free Recall Index
(FRI), the Learning Index (LI), and the Sequential Recall
Index (SRI). All indexes have a mean of 100 and a standard
deviation of 15 (Reynolds & Bigler, 1994).
The TOMAL has shown good reliability (both internal
consistency and stability; e.g. all used subtests show an in-
ternal consistency of Cronbach’s alphas of above .74, with
63% of the subtests revealing coefficients of above .90) as
well as a good validity (content, construct and criterion va-
lidity; Reynolds & Bigler, 1994). However, the memory and
learning test is only validated in American children.
The first author translated the TOMAL into Dutch. In
order to help avoid possibly biased results due to anxiety,
nervousness and other interfering symptoms (Reynolds &
Bigler, 1994), the TOMAL was administered in the home
environment of each child. Four trained master students
and the first author administered the TOMAL, which took
approximately 1.5 h to complete. There were no significant
differences in children’s scores among the different test
leaders.
In our sample, the reliability for the total TOMAL was
adequate (Cronbach’s α = .77 for internal consistency of the
10 core subtests). This is considered in accordance with the
findings of the sample of the original authors. Internal con-
sistency was moderate to good for the ACI, the LI, and the
SRI (all α’s > .65) but low for the ARI and the FRI (both
lower than α = .60). Both the ACI and the SRI contain the
subtests digits forward, letters forward, and manual imita-
tion, all indicators of concentration and working memory.

Because of the overlap between these two indexes and the
earlier findings of associations between prenatal maternal
stress and attention and concentration (van den Bergh &
Marcoen, 2004), we decided to use the ACI in the analyses.
Since the ACI and the LI showed good reliability and are
completely non-overlapping indices from the TOMAL, they
were used as the dependent variables in the analyses.
Confounding variables. The following possible confounding
variables were assessed: child’s gender, gestational age, and
birth weight, maternal age, maternal educational level, prena-
tal smoking (yes/no) and alcohol use (yes/no), and postnatal
maternal stress. Postnatal maternal stress levels were deter-
mined when the children were 3 and 8 months old with the
State-Trait Anxiety Index (STAI; Spielberger et al., 1970)
and the Perceived Stress Scale (PSS, Cohen & Williamson,
1987). The STAI measured anxiety in two ways. Namely
state anxiety that is conceptualized as a transitory emotional
anxiety and trait anxiety that refers to relatively stable prone-
ness to anxiety. The STAI-state contains 20 statements that
ask the respondent how she feels at the moment (e.g. ‘I feel
upset’, ‘I feel at ease’). Individuals respond to each item on a
four-point Likert scale, indicating the frequency with which
they feel like the statement (‘not at all’—‘very much so’).
The STAI-trait contains 20 statements that ask the respon-
dent how she generally feels (e.g. ‘I am a steady person’,
‘I lack self-confidence’), and which are also answered on
4-point Likert scales (‘almost never’- ‘almost always’). The
PSS measured perceived stress during the last month, on a 4-
point Likert scale varying from ‘never’ to ‘always’ (e.g. ‘how
often have you felt nervous and “stressed”?’, ‘how often have
you felt that things were going your way?’). The question-
naire is reported valid and reliable (Cohen & Williamson,
1987).

Pearson’s correlations showed significant relations be-
tween the 3 and 8 months’ measurements for both ques-
tionnaires. Therefore, mean scores over these ages were cal-
culated and used as measures of early postnatal stress and
possible confounding variables.
Finally, because IQ is known to be closely related to mem-
ory and learning abilities (Ackerman, Beier, & Boyle, 2005),
the results of an intelligence test were included as a con-
founding variable in the analyses. IQ was measured by using
four subtests of the Dutch version of the Wechsler Intelli-
gence Scale for Children III (WISC III, Wechsler, 2002).
The four subtests were similarities, vocabulary (both verbal
subtests), picture completion, and block design (both per-
formance subtests). All subtests have a mean of 10 and a
SD of 3 (Wechsler, 2002). A sum score of the subtests was
calculated (IQ-score) and used as a possible confounding
variable.
Statistical analyses
Hierarchical multiple regression analyses were performed to
investigate the links between prenatal stress and memory and
learning. Confounding variables that were significantly cor-
related (at the .05 level or below) to the dependent variables
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Table 3 Correlations between the prenatal stress variables and
memory and learning
DH1 DH2 DH3 Birt1 Birt2 Birt3 Child1 Child2 Child3 LE1 LE2

ACI LI
DH1 .04 .12
DH2 .56∗ ∗ .03 .11
DH3 .41∗ ∗ .72∗ ∗ .14 .07
Birth1 −.03 .08 .15 −.03 .03
Birth2 −.02 .13 .15 .76∗ ∗ −.08 .02
Birth3 .05 .22∗ .23∗ .63∗ ∗ .74∗ ∗ .08 .07
Child1 −.12 .02 .10 .28∗ ∗ .17 .16 −.00 −.14
Child2 .03 .10 .22∗ .32∗ ∗ .21∗ .33∗ ∗ .61∗ ∗ .04 −.19
Child3 .07 .16 .27∗ ∗ .18 .17 .31∗ ∗ .56∗ ∗ .74∗ ∗ .01 −.10
LE1 .29∗ ∗ .16 .15 .16 .19 .21∗ −.04 .01 −.01 −.16 .02
LE2 .16 .19∗ .14 .09 .14 .19∗ .10 .13 .14 .66∗ ∗ −.13 −.01
LE3 .08 .19∗ .19∗ .09 .13 .20∗ .03 .04 .05 .60∗ ∗ .71∗ ∗ −.10
.11
Note.∗ ∗ Correlation is significant at the 0.01 level.
∗ Correlation is significant at the 0.05 level. Abbreviations: DH
= Daily hassles, LE = Life
events, Child = fear of having a handicapped child, Birth = Fear
of giving birth, ACI = Attention/concentration index, LI =
Learning index,
1 = pregnancy period 1, 2 = pregnancy period 2, 3 = pregnancy
period 3.
were included as predictors in the regression analyses
together with the prenatal stress levels. Regression analyses
were carried out separately for the prenatal maternal stress
factors, and for the maternal cortisol data. With all tests,
p-values < 0.05 were considered statistically significant.
Outliers and influential data points were determined using
Cook’s distance and leverage values. When Cook’s distance
was greater than 1 or the leverage had a greater value than
2p/N (p is the number of parameters) the data point was
considered an outlier. Eliminating the influential data points
(n = 1) did not change the results.

Results
Preliminary analyses
Maternal measures. The total group results for prenatal ma-
ternal stress variables are presented in Table 2. The partici-
pants showed normal levels of stress scores.
Prenatal maternal stress variables. Correlations among
the mean prenatal maternal stress variables were in gen-
eral low to modest. Table 3 shows the correlations
among the prenatal maternal stress variables, and between
these variables and the memory and learning outcome
variables.
Cortisol data. The three cortisol measures within each as-
sessment period were mostly modestly to strongly correlated,
and measures between adjacent periods were also often mod-
estly correlated: those of period 1 with period 2, and those
of period 2 with period 3 (see Table 4).
Relations between prenatal maternal stress questionnaire
data and cortisol data. The correlations between prenatal
maternal stress and prenatal cortisol of each pregnancy pe-
riod were non-significant.
Child measures. The children showed normal memory and
learning scores on the TOMAL indexes (ACI, M = 99.5,
SD = 11.1, range = 71–120; LI, M = 101.1, SD = 15.3,
Table 4 Correlations between the prenatal cortisol variables and
memory and learning
Morning 1 Evening 1 Slope 1 Morning 2 Evening 2 Slope 2
Morning 3 Evening 3 ACI LI

Morning 1 −.03 .12
Evening 1 .24∗ −.08 −.06
Slope 1 .22 .36∗ ∗ .00 .06
Morning 2 .15 −.11 −.08 −.03 −.14
Evening 2 .18 .37∗ ∗ .31∗ −.03 −.16 −.04
Slope 2 .31∗ .37∗ ∗ .27∗ .37∗ ∗ .74∗ ∗ −.12 −.15
Morning 3 −.03 −.11 −.05 .34∗ .15 .33∗ .13 .10
Evening 3 .06 .09 .22 .14 .33∗ .40∗ ∗ .45∗ ∗ .11 .15
Slope 3 .01 .06 .09 .23 .31∗ .49∗ ∗ .65∗ ∗ .85∗ ∗ .18 .22
Note. ∗ Correlation is significant at the 0.05
level.∗ ∗ Correlation is significant at the 0.01 level.
Abbreviations: ACI = Attention/concentration index,
LI = Learning index, 1 = pregnancy period 1, 2 = pregnancy
period 2, 3 = pregnancy period 3.
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Table 5 Hierarchical regression analyses of the prenatal
maternal stress predictors measured during the first period of
pregnancy and postnatal
memory and learning
Attention/concentration index Learning index
R-square df p-value R-square df p-value
Model 1 .25 4;110 .00∗ ∗ .18 4;110 .00∗ ∗
Beta t p-value Beta t p-value
(Constant) 7.81 .00∗ ∗ 5.67 .00∗ ∗

WISC .47 5.52 .00∗ ∗ .41 4.63 .00∗ ∗
Gender .21 2.44 .02∗ .13 1.51 .14
Postnatal perceived stress .02 .18 .86 −.06 −.72 .47
Smoking −.03 −.38 .71 −.08 −.94 .35
R-square change df p-value R-square change df p-value
Model 2 .05 8;110 .00∗ ∗ .03 8;110 .00∗ ∗
Beta t p-value Beta t p-value
(Constant) 8.22 .00∗ ∗ 5.73 .00∗ ∗
Daily hassles −.01 −.07 .94 .08 .82 .41
Life events −.22 −2.42 .02∗ −.01 −.13 .90
Fear of giving birth −.02 −.18 .86 .09 .94 .35
Fear of having a handicapped child −.06 −.66 .51 −.16 −1.71 .09
WISC .49 5.79 .00∗ ∗ .40 4.38 .00∗ ∗
Gender .18 2.16 .03∗ .16 1.75 .08
Postnatal perceived stress .03 .37 .71 −.08 −.83 .41
Smoking .03 .31 .76 −.10 −1.03 .31
range 53–125) and the WISC (M = 43.3, SD = 7.6, range
= 29–63).
Relations between confounding variables and dependent
variables. An analysis of the correlations (Pearson or Spear-
man, where appropriate) between the continuous confound-
ing variables; gestational age, birth weight, maternal age,
and maternal educational level, and the TOMAL indexes
indicated significant positive correlations between the IQ-
scores and the learning and memory variables (ACI and IQ
r(1,110) = .46, p < .01, LI and IQ r(1,110) = .39, p < .01).
Since smoking, alcohol use, and gender were dichotomous
variables, independent t-tests were performed to investigate
differences in memory and learning performance behavior
between the groups. No significant results were found for

smoking and alcohol use. Results showed that girls per-
formed better than boys on the ACI, t(1,110) = 2.0, p = .05.
Based on these results, IQ and gender were included in the
regression analyses as confounding variables. Furthermore,
smoking was also entered in the analyses, because earlier
results within the same study sample have shown signifi-
cant effects of maternal smoking (Gutteling et al., 2005b).
Postnatal perceived stress and postnatal state anxiety cor-
related significantly (r(1,108) = .68, p < .01). Therefore, we
decided to exclude the STAI, as earlier in this longitudinal
study postnatal maternal perceived stress had been found to
influence the effect of prenatal stress on postnatal outcome
(Gutteling et al., 2005b).
Main analyses
Hierarchical regressions were conducted using prenatal
stress and cortisol levels to predict the ACI index and the
learning index. At step one of each regression, confounding
variables (IQ, gender, smoking and postnatal stress) were
entered, and at step two the predictor (either prenatal stress
or cortisol levels) was added to see if it contributed unique
incremental variance in the outcome variable. Separate anal-
yses were performed for the prenatal maternal stress scores
and the cortisol levels (entering both types of variables to-
gether does not alter the results). The analyses showed that
the impact score of life events measured during the first pe-
riod of pregnancy was negatively associated with the atten-
tion/concentration index (ACI). The models for the prenatal
maternal stress factors of the first pregnancy period are pre-
sented in Table 5.
No significant associations were found for prenatal ma-
ternal stress measures assessed later in pregnancy, nor for
prenatal maternal cortisol levels.

Discussion
Our main finding was in the expected direction, i.e. that
a higher negative impact of maternal life events measured
during the first period of pregnancy (15–17 weeks) pre-
dicted lower scores on the 6-year-old child’s attention/
Springer
concentration index (ACI). This result is similar to that of
van den Bergh and colleagues (van den Bergh & Marcoen,
2004; van den Bergh et al., 2005a) who studied the influence
of prenatal stress on attention and working memory at
childhood and adolescence. The authors did not find
significant results for stress measured later in pregnancy,
and concluded that prenatal stress in early pregnancy was
associated with more cognitive problems in both childhood
and adolescence. These findings point in the direction of
possible programming effects of early maternal pregnancy
stress on the fetal brain, resulting in attention and concentra-
tion problems in childhood and adolescence. Future studies
using, for example, functional Magnetic Resonance Imaging
should give more insight in which area of the human brain
is particularly affected by prenatal maternal stress.
Our results are not in line with those of O’Connor et al.
(2003) who showed no associations between prenatal ma-
ternal anxiety and attention problems, measured by parental
reports, in 6-year old children. Furthermore, we did not find
an association between prenatal stress and attention prob-
lems, measured with the Child Behavior Checklist at 5-years
of age in this sample (Gutteling, de Weerth, & Buitelaar,

submitted). However, it is important to note that the associ-
ations between prenatal maternal stress and attention were
consistently found when the information on the offspring’s
attention was obtained by neuropsychological or develop-
mental tests and/or trained observers’ information, such as
in the present and earlier studies (van den Berg et al., 2005a,
2005b; Huizink et al., 2002), while no associations were
found when using questionnaires filled in by the mother
(Gutteling et al., submitted, O’Connor et al., 2002). Because
the effects found in the different studies are significant but
of small effect size, it is possible that the mothers of young
children are not aware of memory and/or attention deficits,
as these might only be detectable through specialized tests
and observations.
In the present study, the offspring’s’ learning and mem-
ory scores were associated only with the negative impact of
life events and not with other prenatal maternal stress vari-
ables. Earlier reports of the same longitudinal study showed
the offspring’s’ temperament and cortisol levels to be related
to other indicators of prenatal maternal stress, namely daily
hassles, perceived stress and fear of having a handicapped
child (Gutteling et al., 2004, 2005a, 2005b). However, the
measures of prenatal maternal stress are all different in na-
ture and assess different aspects of the stress and anxiety
experienced by the pregnant women. This is reflected in the
weak to modest correlations among the women’s scores on
the different questionnaires. These variations in experienced
stress measured by the different questionnaires could also
be reflected in different effects on maternal physiology that
in turn could produce different effects on postnatal outcome.
Nonetheless, the findings with life events of the present study
are in line with earlier published reports of other researchers.
Lee, Chang and Lung (2006) also determined negative asso-
ciations between prenatal maternal life events and offspring

attention and concentration problems in a retrospective study.
Also Obel (2003) reported life events in the first and second
trimester of pregnancy to be related to attention problems in
the offspring.
No relationships were found between prenatal mater-
nal basal cortisol measures and the child’s memory and
learning. Apparently, prenatal maternal basal cortisol as as-
sessed in this study is not related to memory and learning in
6-year-old children. Earlier results of this longitudinal study
showed positive relations between prenatal maternal corti-
sol and offspring cortisol reactivity levels (Gutteling et al.,
2004, 2005a), but no relation between maternal cortisol and
offspring behavior (Gutteling et al., 2005b). However, it is
possible that series of maternal cortisol samples taken on 1
day per pregnancy period, as was the case in our study, do not
adequately reflect a pregnant woman’s physiological stress
status. Future studies should measure basal cortisol on series
of days, cortisol reactivity to stressors (de Weerth & Buite-
laar, 2005), and also sample other HPA axis hormones, such
as CRH and ACTH, in order to more rigorously investigate
possible links between physiological measures of maternal
pregnancy HPA axis functioning and offspring memory and
learning.
There are several possible explanations for finding only
one association between our prenatal maternal stress mea-
sures, and the offspring’s learning and memory scores. First,
the mothers in our study group had low to moderate stress
levels. Perhaps higher stress levels are necessary for obtain-
ing more general and severe learning and memory deficits.
Second, it is known that negative effects of cortisol levels on
memory performance appear in aged humans (Lupien et al.,
2005). Also, memory impairment as a result of early mater-
nal deprivation has been found to become more visible in
aged rats as compared to younger rats (Oitzl, Workel, Flut-

tert, Frosch, & de Kloet, 2000). It is therefore possible that
greater effects of prenatal stress on memory and learning
are not yet very visible in the children of the present study.
Longitudinal studies and follow-ups are therefore necessary
to obtain more insight into the long-term effects of prenatal
maternal stress on memory and learning.
Limitations of the present study are the relatively small
sample size, and the lack of a genetic informed design, which
precludes to take account of the influence of genetic factors.
Maternal genetic vulnerability factors, which can be passed
on to the child, are most probably at least partly responsi-
ble for both prenatal maternal stress levels and the child’s
memory and learning. Finally, clinical cut-off scores of the
TOMAL are unavailable for the Dutch population; therefore
the clinical relevance of the differences in memory/attention
performance is not clear.
Springer
The overall conclusion from this study is that in a women
with low to moderate levels of early pregnancy mater-
nal stress, higher levels of stress appear to be associated
with slight decreases in attention/concentration scores in the
school-aged offspring. More research is needed to determine
whether these effects can be replicated in other populations,
and whether they become larger with age and in the off-
spring of pregnant women with abnormally high amounts of
prenatal stress.
Acknowledgments The authors wish to express their gratitude to
the

parents and children who participated in this study, to Anja C.
Huizink
and Pascale G. Robles de Medina for data collection in the
prenatal
phase, to Reinier K. J. Hoogendorp for his helpful comments,
and
to the Van der Gaag Stichting (KNAW) and the Praeventie
fonds for
financial support (Zorg Onderzoek Nederland, 28-2685).
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