Natalya Igosheva & Vivette Glover
Institute of Reproductive and Developmental Biology, Imperial College, London, London, UK

https://doi.org/10.36866/pn.56.36

Our recent work (Igosheva et al. 2004) suggests that if the mother is stressed while she is pregnant this may permanently alter the cardiovascular reactivity of her child. This is probably due to fetal programming.

This concept has become well known through the work of David Barker (Barker, 1995). He and his colleagues have shown that being small at birth is a risk factor for later cardiovascular disease and associated illnesses such as diabetes. Barker has 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 early life environment result in a permanent programming (or re-programming) of the developmental pattern of proliferation and differentiation events within key tissue and organ systems and have pathological consequences in later life. Barker and his group have mainly looked at the nutrition of the fetus to explaining the possible mechanisms underlying these findings.

A second field of work, originally in animal models, has shown that if the mother is stressed while she is pregnant this alters the later behaviour of her offspring. In particular, the offspring show an increased stress response when exposed to a new stressor (Weinstock, 2001).

In animal studies it is possible to control for possible confounders, such as alterations in parenting behaviour after prenatal stress, by cross-fostering all the offspring to new unstressed mothers (Schneider et al. 1999).

In both rats and monkeys the underlying mechanisms are starting to be understood. It has been shown that the exposure to prenatal stress re-programmes the main stress response system of the offspring. The function of the hypothalamic-pituitary-adrenal axis, which makes the stress hormone cortisol, is permanently altered, and this is associated with changes in the neurochemistry of the hippocampal region of the brain (Matthews, 2002). The link between antenatal maternal anxiety and child behavioural problems has recently also been shown in humans. The children of mothers who were particularly anxious while pregnant (in the top 15%) were found to be at double the risk for later behavioural problems such as attention deficit/hyperactivity (O’Connor et al. 2002).

Our recent research (Igosheva et al. 2004) suggests that these two areas of study, prenatal stress and cardiovascular function, may be more linked than previously realised. In this study, pregnant rats were mildly stressed during the final week of their pregnancy, by exposing them to light and restraint. A control group were studied in parallel with no such prenatal stress. All the newborn pups were then cross-fostered to new mothers and all these offspring were studied when they were 6 months old. The basal characteristics of all the offspring were the same. However, when subjected to a new mild stress, those animals whose mothers had been exposed to stress during pregnancy showed a much larger increase in systolic blood pressure than did the controls (Fig. 1). Their blood pressure also took longer to recover back to normal. Prenatally stressed rats also showed a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, more prolonged heart rate responses to acute stress and delayed recovery. Most of these effects were more pronounced in the females than in the males.

Thus it seems that prenatal stress may also have a permanent effect on the cardiovascular system. As prenatal stress can also cause smaller babies, it is one possible mechanism underlying the Barker findings. Such a pattern of haemodynamic responses to stress would have significant consequences for adult cardiovascular health if it also occurs in humans. Much more research will clearly be needed to establish this. However, it may be that a new way to prevent the development of predisposition to a range of health problems will be to ensure that pregnant mothers have as stress free a time as possible.

Acknowledgments

The research was supported by grants from the Royal Society, CRDF and the Ministry of Education of the Russian Federation.

References

Barker DJ (1995). Fetal origins of coronary heart disease. BMJ 311, 171-174.

Igosheva N, Klimova O, Anishchenko T & Glover V (2004). Prenatal stress alters cardiovascular responses in adult rats. J Physiol 557, 273-285.

Matthews SG (2002). Early programming of the hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab 13, 373-380.

O’Connor TG, Heron J & Glover V (2002). Antenatal anxiety predicts child behavioral/emotional problems independently of postnatal depression. J Am Acad Child Adolesc Psychiatry 41, 1470-1477.

Schneider M L, Roughton EC, Koehler AJ & Lubach GR (1999). Growth and development following prenatal stress exposure in primates: an examination of ontogenetic vulnerability. Child Dev 70, 263-274.

Weinstock M (2001). Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65, 427-451.