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Tilburg University Antenatal maternal anxiety and stress and ... 2. Antenatal maternal stress and anxiety and the human fetus Reports from the pre-ultrasound era, both anecdotal and

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  • Tilburg University

    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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    Download date: 26. Jun. 2021

    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

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