Transmitting biological effects of stress in utero: Implications for mother and offspring

doi:10.1016/j.psyneuen.2013.05.018

Psychoneuroendocrinology

Volume 38, Issue 9, September 2013, Pages 1843-1849

https://doi.org/10.1016/j.psyneuen.2013.05.018 Get rights and content

Summary

The developing foetus makes adaptations to an adverse in utero environment which may lead to permanent changes in structure and physiology, thus ‘programming’ the foetus to risk of ill health in later life. Epidemiological studies have shown associations between low birth weight, a surrogate marker of an adverse intrauterine environment, and a range of diseases in adult life including cardiometabolic and psychiatric disease. These associations do not apply exclusively to low birth weight babies but also to newborns within the normal birth weight range. Early life stress, including stressors in the prenatal and early postnatal period, is a key factor that can have long-term effects on offspring health. Animal studies show this is mediated through changes in the maternal and foetal hypothalamic-pituitary-adrenal axes resulting in foetal exposure to excess glucocorticoids. Data in humans are more limited but support that the biological effects of stress in utero may be transmitted through changes in glucocorticoid action or metabolism. Common contemporary physical and social stressors of maternal obesity and socio-economic deprivation impact on the maternal response to pregnancy and the prevailing hormonal milieu that the developing foetus will be exposed to. Prenatal stress may also be compounded by early postnatal stresses such as childhood maltreatment with resultant adverse effects for the offspring. Understanding of the mechanisms whereby these stressors are transmitted from mother to foetus will not only improve our knowledge of normal foetal development but will also help identify novel pathways for early intervention either in the periconceptional, pregnancy or the early postpartum period.

Section snippets

Maternal stress and early life programming of disease

The early life environment is not only crucial for setting the growth trajectory of the foetus but is now recognised as a key factor contributing to disease susceptibility in later life (Barker, 1995). Thus the developing foetus adapts to an insult in utero with permanent changes in structure, physiology and metabolism which are initially beneficial for survival. In later life, particularly when there is a mismatch between the early and later life environment (Gluckman et al., 2005), these

Exposure to excess glucocorticoids as a mediator of maternal stress effects on the developing foetus

One of the key hormonal systems thought to transmit the effects of maternal stress to the developing foetus is the hypothalamic-pituitary-adrenal (HPA) axis. Many studies in rodent models have demonstrated that the effects of prenatal stress are at least partly mediated via the HPA axis through exposure to excess glucocorticoids (Harris and Seckl, 2011). Data are less clear-cut in humans, particularly as many studies have shown little correlation between maternal anxiety levels and maternal

Contemporary early life stressors influencing offspring outcome

In modern society maternal obesity and low socio-economic status are examples of pertinent physiological and social stressors for women during pregnancy (Fig. 1). Despite major advances in health in developed countries there remain major discrepancies in disease according to social class. Lower socioeconomic position is associated with increased risk of morbidity and premature mortality from physical and mental disorders, and confers similar trans-generational consequences on the offspring. The

Long term effects of prenatal and early postnatal stress for mother and child

There is much evidence that women who have developed a physical illness in pregnancy such as pre-eclampsia are at later risk of hypertension and cardiovascular disease (Melchiorre et al., 2011), suggesting that pregnancy is itself a physiological stressor, and an adverse metabolic response to pregnancy predicts later vulnerability to disease. So are there any long-term consequences for a mother who has experienced psychosocial stress in pregnancy? Follow up studies of women exposed to extreme

Implications and future research

Understanding of the mechanisms whereby stressors are transmitted from mother to foetus will not only improve our knowledge of normal foetal development but also identify novel pathways for early intervention either in the preconception, pregnancy or early postpartum period. Initial findings suggest that a simple stress management instruction can improve maternal mood and reduce morning cortisol levels during pregnancy (Urizar et al., 2004). High self-efficacy and daily uplifts seem to have a

Contributors

RMR wrote the first draft of the manuscript. JL, CB, PG and KR carried out additional edits to the manuscript. All authors approved the final draft.

Role of funding source

This work had no particular funding source.

Conflict of interest

RMR, JL, CB, PG and KR all declare that there is no actual or potential conflict of interest related to the submitted manuscript.

Acknowledgement

No additional funding source was received for this work.

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Citation Excerpt :
Additionally, stress may suppress the developing immune system (Merlot et al., 2008), which could account for the higher incidence of respiratory and other infections in the infants. There is also evidence that the effects of prenatal stress on child development could be mediated via the hypothalamic-pituitary-adrenal (HPA) axis through exposure to excess glucocorticoids (cortisol in human beings) (Reynolds et al., 2013; Hantsoo et al., 2019), with possible effects on brain structure and physiology related to cognitive and executive functions (Bock et al., 2015; Teicher et al., 2016). And finally, mothers’ behavior may change in response to stressful events—specifically, stress may induce high-risk behaviors such as drinking alcohol, smoking, poor diet, etc., and these behaviors may in turn affect fetal development and health (Dunkel-Schetter, 2009; Clark et al., 2021).
We estimate the impact of prenatal stress on early childhood development outcomes known as “middle years” or intermediate outcomes, which has not been studied previously. Using a unique measure of actual maternal stress induced by a large earthquake, we find that relative to children that were not exposed, in utero maternal stress reduces children’s cognitive skills and socio-emotional problems by age 3, and that the effects are heterogeneous. The negative impacts on cognitive skills occur during the first trimester of pregnancy and are found among both low and high-income children, and boys and girls. The harmful effects on socio-emotional behaviors occur when stress is experienced in the last trimester of pregnancy.
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Transmitting biological effects of stress in utero: Implications for mother and offspring

Summary

Section snippets

Maternal stress and early life programming of disease

Exposure to excess glucocorticoids as a mediator of maternal stress effects on the developing foetus

Contemporary early life stressors influencing offspring outcome

Long term effects of prenatal and early postnatal stress for mother and child

Implications and future research

Contributors

Role of funding source

Conflict of interest

Acknowledgement

Schizophr. Res.

Psychoneuroendocrinology

Schizophr. Res.

Lancet

Biol. Psychol.

Psychoneuroendocrinology

Neurosci. Biobehav. Rev.

Trends Ecol. Evol.

Horm. Behav.

Biol. Psychiatry

Biol. Psychol.

Biol. Psychiatry

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Early Hum. Dev.

Biol. Psychiatry

J. Psychiatr. Res.

Biol. Psychol.

Neurosci. Biobehav. Rev.

Psychoneuroendocrinology

Clin. Perinatol.

Biol. Psychiatry

Prog. Neurobiol.

Behav. Brain Res.

Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis

Psychol. Med.

Developing and mature oligodendrocytes respond differently to the immune cytokine interferon-gamma

J. Neurosci. Res.

Fetal origins of coronary heart disease

Br. Med. J.

Effects of lifestyle intervention in obese pregnant women on gestational weight gain and mental health: a randomized controlled trial

Int. J. Obes. (Lond.)

Maternal pregnancy-specific anxiety is associated with child executive function at 6–9 years age

Stress

Impaired executive function mediates the association between maternal pre-pregnancy body mass index and child ADHD symptoms

PLoS ONE

Maternal pre-pregnancy obesity and child ADHD symptoms, executive function and cortical thickness

Eur. J. Psychotraumatol.

Ecological momentary assessment of maternal cortisol profiles over a multiple-day period predicts the length of human gestation

Psychosom. Med.

Early life nutrition and metabolic programming

Ann. N.Y. Acad. Sci.

Prevalence of obesity and trends in the distribution of body mass index among US Adults, 1999–2010

JAMA

Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids

Hypertension

The association between the acute psychobiological stress reactivity in second-trimester pregnant women and amniotic fluid cortisol and cortisone

Eur. J. Psychotraumatol.