From fetus to adolescent. Associations between maternal anxiety, stress and
cortisol during pregnancy and behavior and cortisol in the offspring.
Co-convenors: Bea R.H. Van den Bergh and Margarete Rieger
Methodological sound follow-up studies have shown that antenatal maternal anxiety and
stress, most probably in interaction with genetic factors, are associated with alterations in the
human offspring’s behavioral, cognitive and emotional functioning from birth until the age of
15. Animal research experimentally investigating the perinatal programming hypothesis has
demonstrated that enhanced maternal cortisol levels during pregnancy influence fetal brain
development and produce changes in the offspring’s behavior. In animal offspring,
dysregulation of the hypothalamic pituitary adrenal (HPA)-axis is found to be one of the
mechanism mediating the effect of perinatal stress. In humans underlying pathophysiological
mechanisms have been hardly studied; this symposium brings four studies together in which a
first attempt is made to do so.
The first paper studies the links between maternal cortisol during pregnancy, maternal and
fetal response to an acute stressor, and neonatal behavior, taking gender of the child into
account.
The second paper investigates whether prenatal maternal perceived stress and cortisol are
associated with behavior and temperament in infancy and with cortisol, mixed handedness
and attention problems in 5-6 -year-olds.
The third paper examines the link between maternal anxiety during pregnancy and depression
and HPA-axis functioning (i.e. cortisol day profiles) in the 14-15 year old offspring, taking
several covariates (gender, birth weight, smoking, postnatal anxiety) into account.
In the fourth paper neurocognitive functioning in 17-year olds of mothers with high versus
low/median anxiety during pregnancy is assessed using tasks typically linked to activations in
different areas of prefrontal cortex and measuring event-related potentials.
1. Fetal programming of neonatal behavior – the role of maternal cortisol in
early pregnancy and fetal sex
Margarete I. Riegera,d, Harald Wurmserb, Angelika Buske-Kirschbaumc, Mechthild
Papoušekb, Karl-Martin Pirked, Dirk Hellhammera,d
a
National Center of Competence in Research (NCCR) “Swiss Etiological Study of
Adjustment and Mental Health (sesam)”, University of Basel, Basel, Switzerland
b
Child Care Centre, Ludwig-Maximilians-University Munich, Munich, Germany
c
Biological Psychology Technical University of Dresden, Dresden, Germany
d
Department for Theoretical and Clinical Psychobiology, University of Trier, Trier, Germany
Animal studies suggest that enhanced cortisol levels during pregnancy influence fetal brain
development and produce long-term changes in offspring’s behavior. On the other hand, we
know that fetal programming may be gender-dependent. Sex differences in the prevalence of
stress related diseases or psychiatric disorders in humans are well documented. Up to now, it
is unclear which mechanisms cause gender-dependent effects of adverse prenatal conditions.
The aim of the presented study was to investigate if maternal cortisol levels and fetal sex
affect maternal and fetal response to an acute stressor and if the reactivity predicts neonatal
behavior. Heart rates of 74 mother-fetus dyads were assessed at 32-34 gestational weeks using
a cardiotocograph (HRf) and a pulse watch (HRm). Mothers were asked to collect saliva
samples in early and late pregnancy. Additionally, maternal cortisol response to the Trier
Social Stress Test (TSST) was assessed. Neonate’s behavior was evaluated using the
Brazelton Neonatal Behavioral Assessment Scale (BNBAS). Data indicate that mothers’
percentage cortisol reactivity to the TSST was positively associated to HRf (r=.29, p< .01).
Higher cortisol levels in early pregnancy predicted enhanced HRf (F=6.37, p<.05, ω2=.26).
Surprisingly we found an effect of fetal sex on maternal cortisol secretion in the TSST
(F=8.11, p<.01, ω2=.11). Although we did not found
any sex differences in HRf response, pregnant women with female fetuses showed higher
cortisol levels and a pronounced cortisol response to the TSST. FHR reactivity and recovery
to the TSST predicted Habituation as well General Irritability measured with the BNBAS.
2. Prenatal maternal stress is associated with problem behavior,
temperament and cortisol in early childhood.
Barbara M. Gutteling1,2, C. de Weerth3, & Jan K. Buitelaar1.
1
Department of Psychiatry, Radboud University Nijmegen Medical Centre, The Netherlands
2
Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, The
Netherlands and Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands
3
Department of Developmental Psychology, Radboud University Nijmegen.
Increasing evidence is being found on the effects of maternal prenatal stress on postnatal
outcome in humans. However, studies differ methodologically in how prenatal stress is
determined and in how long the offspring are followed. For example, relations between
prenatal maternal stress hormones (especially cortisol) and postnatal outcome have only been
investigated in babies and infants. One of the aims of the present study was to obtain more
insight on the effects of prenatal maternal cortisol as well as reported stress, on the postnatal
outcome. To this end, associations between different forms of prenatal maternal stress, and
several postnatal child outcome measures, were investigated prospectively and longitudinally.
Child variables included behavior and temperament, cortisol stress reactions, lateralization,
and memory and learning. The results of our study in more than 100 mother-child pairs
showed that reported prenatal maternal stress was related to problem behavior and
temperamental problems in toddlers as well as in school-aged children. Also, prenatal
maternal cortisol levels were related to higher levels of cortisol in 5-year-olds during stressful
situations. And finally, reported maternal prenatal stress was related to more mixed
handedness, and more attention problems when the children were 6 years old.
3. Cortisol and depression in 14-15 year olds are linked to maternal anxiety
during pregnancy
Bea R.H. Van den Bergh1, Ben Van Calster2, Tim Smits3, Lieven Lagae4, Sabine Van Huffel5
1
Department of Psychology, K.U.Leuven., Leuven, Belgium
2
Deptartment of Electrical Engineering, K.U.Leuven, Leuven, Belgium
3
Centre for Ethics, K.U.Leuven, Leuven, Belgium
4
Department of Paediatric Neurology, K.U.Leuven, Leuven, Belgium
5
Deptartment of Electrical Engineering, K.U.Leuven, Leuven, Belgium
The relationship between the hypothalamic-pituitary-adrenal (HPA)-axis dysregulation and
susceptibility for psychopathology has been observed in several studies. Elevated basal levels
of cortisol are associated with depression in children and adults. Experimental animal research
testing the perinatal progamming hypothesis has demonstrated that dysregulation of HPA-axis
may result from perinatal stress and can lead to depressive-like behavior later in life. The aim
of the present study is to investigate the link between maternal anxiety during pregnancy,
HPA-axis functioning and depression in adolescence. Our longitudinal study started with 86
healthy mothers and their firstborn children. The sample has been assessed at 12-22, 23-31
and 32-40 weeks postmenstrual age and at 1, 10, 28 weeks and at ages 8-9, 14-15 and 17 after
birth. Besides other variables, maternal anxiety was measured on all occasions, using the State
Trait Anxiety Inventory. The adolescents (n=58) provided 3 saliva samples during a week-end
day: within 30 minutes after awakening (approximately 9 PM), at noon (approximately 12h45
PM) and in the evening (approximately 20h30). Depression was measured with the Children’s
Depression Inventory. Multiple regressions revealed that maternal anxiety at 12-22 weeks of
pregnancy influences diurnal salivary cortisol as well as depression in the 14-15 year old
offspring. Intriguing influences of several covariates – smoking during pregnancy, gender,
birth weight, postnatal maternal anxiety on HPA-axis functioning and depression are
discussed.
4. Cognitive Functioning at age 17 is related to antenatal maternal anxiety.
Maarten Mennes1,2, Peter Stiers2, Lieven Lagae3, Bea Van den Bergh1
1 Department of Psychology, K.U.Leuven., Leuven, Belgium
2 Laboratorium voor Neuropsychologie, K.U.Leuven, Leuven, Begium.
3 Department of Paediatrics, K.U.Leuven, Leuven, Belgium
Anxiety and stress experienced by the mother during pregnancy are reported to have a
negative association with the development of the fetus, child, and even adolescent.
Associations were found with emotional, behavioral and recently also with cognitive
development. The aim of the present study was to extend the findings of the follow-up study
of Van den Bergh et al. (Neuroscience and Biobehavioral Reviews, 29,259-269; Pediatric
Research in press) of specific cognitive impairment seen in 14/15 year old adolescents of
mothers who experienced high levels of anxiety during their pregnancy. Cognitive
functioning of 49 17-year old adolescents was assessed using tasks typically linked to
activations in different areas of prefrontal cortex. An association was found between high
maternal anxiety during week 12-22 of pregnancy and performance on a dual task and on a
response shifting task. Working memory, cued visual attention and external response
inhibition on the other hand were not related to antenatal maternal anxiety. These results
could be linked to the orbitofrontal cortex. It is hypothesized that the specific impairments
found, could be linked to subtle aberrations or fetal programming during the development of
prefrontal cortical areas and networks. In the same sample event-related potentials (ERP)
were used to investigate actual brain processes.