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Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: Links and possible mechanisms: A review Van den Bergh, B.R.H.; Mulder, E.J.H.; Mennes, M.; Glover, V.
Published in: Neuroscience and Biobehavioral Reviews
Publication date: 2005
Link to publication in Tilburg University Research Portal
Citation for published version (APA): Van den Bergh, B. R. H., Mulder, E. J. H., Mennes, M., & Glover, V. (2005). Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: Links and possible mechanisms: A review. Neuroscience and Biobehavioral Reviews, 29(2), 237-258.
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https://research.tilburguniversity.edu/en/publications/eeea080f-8e85-407d-b95c-484c78b678b5
Review
Antenatal maternal anxiety and stress and
the neurobehavioural development of the fetus and child: links
and possible mechanisms. A review
Bea R.H. Van den Bergha,*, Eduard J.H. Mulderb, Maarten Mennesa,c, Vivette Gloverd
aDepartment of Developmental Psychology, Catholic University of Leuven (KULeuven), Tiensestraat 102, 3000 Leuven, Belgium bDepartment of Perinatology and Gynaecology, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands
cDepartment of Paediatric Neurology, University Hospital Leuven (KULeuven), Herestraat 49, 3000 Leuven, Belgium dInstitute of Reproductive and Developmental Biology, Imperial College London. Du Cane Road, London W12 0NN, UK
Abstract
A direct link between antenatal maternal mood and fetal behaviour, as observed by ultrasound from 27 to 28 weeks of gestation onwards, is
well established. Moreover, 14 independent prospective studies have shown a link between antenatal maternal anxiety/stress and cognitive,
behavioural, and emotional problems in the child. This link generally persisted after controlling for post-natal maternal mood and other
relevant confounders in the pre- and post-natal periods. Although some inconsistencies remain, the results in general support a fetal
programming hypothesis. Several gestational ages have been reported to be vulnerable to the long-term effects of antenatal anxiety/stress and
different mechanisms are likely to operate at different stages. Possible underlying mechanisms are just starting to be explored. Cortisol
appears to cross the placenta and thus may affect the fetus and disturb ongoing developmental processes. The development of the HPA-axis,
limbic system, and the prefrontal cortex are likely to be affected by antenatal maternal stress and anxiety. The magnitude of the long-term
effects of antenatal maternal anxiety/stress on the child is substantial. Programs to reduce maternal stress in pregnancy are therefore
warranted.
q 2005 Published by Elsevier Ltd.
Keywords: Pregnancy; Stress; Programming; Cortisol; Fetal behaviour; Child behaviour; Developmental neuroscience; Review
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
2. Antenatal maternal stress and anxiety and the human fetus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
2.1. Normal development of human fetal behaviour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
2.2. Antenatal maternal stress and anxiety and fetal behaviour on ultrasound observation . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
3. The short and long term links between anxiety/stress during pregnancy and the development of the child . . . . . . . . . . . . . . . . 243
3.1. Overview of results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
3.2. Controlling for the effect of confounders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
3.3. Timing of gestational stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
3.4. Magnitude of the effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
Neuroscience and Biobehavioral Reviews 29 (2005) 237–258
www.elsevier.com/locate/neubiorev
0149-7634/$ - see front matter q 2005 Published by Elsevier Ltd.
doi:10.1016/j.neubiorev.2004.10.007
* Corresponding author. Tel.: C32 16 32 58 60; fax: C32 16 32 60 55. E-mail address: [email protected] (B.R.H. Van
den Bergh).
http://www.elsevier.com/locate/neubiorev
B.R.H. Van den Bergh et al. / Neuroscience and Biobehavioral Reviews 29 (2005) 237–258238
3.5. Effects of antenatal maternal depression, a co-morbid symptom of anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
3.6. Effects of antenatal anxiety/stress on handedness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
3.7. Weaknesses of the studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
4. Two physiological mechanisms by which the maternal affective state may affect the fetus in humans . . . . . . . . . . . . . . . . . . . 251
4.1. Transfer of hormones across the placenta . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
4.2. Impaired uterine blood flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
5. Stress hormones and the developing fetal nervous system: how are they related to behavioural/emotional regulation
problems in infants and children? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
6. General conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
1. Introduction
‘And surely we are all out of the computation of our age,
and every man is some months elder than he bethinks him;
for we live, move, have a being, and are subject to the
actions of the elements, and the malices of diseases, in that
other World, the truest Microcosm, the Womb of our
Mother’(Sir Thomas Browne, Religio Medici, 1642) [1]
The question of the importance of prenatal environmen-
tal factors for development, behaviour and health, has been
scientifically studied from the 1940s onwards in humans
[1–4] and even earlier, from the 19th century onwards, in
experimental embryology (see [5,6]). The fetal program-
ming hypothesis states that the environment in utero can
alter the development of the fetus during particular sensitive
periods, with a permanent effect on the phenotype. In recent
years, the work of Barker has given a great impetus to
research in this particular field. He proposed “the fetal
origins of adult disease hypothesis”. This states that the
physiological, neuroendocrine or metabolic adaptations that
enable the fetus to adapt to changes in the early life
environment result in a permanent programming (or re-
programming) of the developmental pattern of proliferation
and differentiation events within key tissues and organ
systems and can have pathological consequences in later life
[7,8]. The key observation on which this was based was that
weight at birth was a strong risk factor for coronary heart
disease, diabetes mellitus, and obesity later in life. This
finding has been reproduced in many independent studies,
although it appears to be the ponderal index rather than birth
weight that matters (for reviews see [9] for coronary heart
disease; [10] for obesity). Most of the work on the possible
mechanisms underlying these findings have focused on
nutrition, although there is also evide