Review
Prenatal maternal stress: effects on pregnancy and the (unborn) child

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Abstract

Background: Animal experiments have convincingly demonstrated that prenatal maternal stress affects pregnancy outcome and results in early programming of brain functions with permanent changes in neuroendocrine regulation and behaviour in offspring. Aim: To evaluate the existing evidence of comparable effects of prenatal stress on human pregnancy and child development. Study design: Data sources used included a computerized literature search of PUBMED (1966–2001); Psychlit (1987–2001); and manual search of bibliographies of pertinent articles. Results: Recent well-controlled human studies indicate that pregnant women with high stress and anxiety levels are at increased risk for spontaneous abortion and preterm labour and for having a malformed or growth-retarded baby (reduced head circumference in particular). Evidence of long-term functional disorders after prenatal exposure to stress is limited, but retrospective studies and two prospective studies support the possibility of such effects. A comprehensive model of putative interrelationships between maternal, placental, and fetal factors is presented. Conclusions: Apart from the well-known negative effects of biomedical risks, maternal psychological factors may significantly contribute to pregnancy complications and unfavourable development of the (unborn) child. These problems might be reduced by specific stress reduction in high anxious pregnant women, although much more research is needed.

Introduction

‘To begin my life with the beginning of my life, I record that I was born’. This is the first sentence in the chronicles of David Copperfield [1]. According to Ch. Dickens, human development does not start until after birth, and most scientists until the mid-20th century have also ignored the importance of life in the womb [2]. However, today we know that normal growth and development of the unborn child can be negatively influenced by a number of factors, including complications of pregnancy, infections, and teratogens.

Intrauterine exposure to medicinal and social drugs (alcohol, cocaine, tobacco) may cause structural and/or functional developmental deficits that often result in life-long physical or mental handicaps. Moreover, epidemiologic and experimental animal studies have demonstrated strong evidence that fetal exposure to an overall nutritional deficiency or a shortage of specific nutrients during a critical period may lead to permanent alterations in the development and function of a particular organ system [3], [4]. This early programming is related to the emergence of a number of diseases in later life, including cardiovascular and allergic diseases, hypertension, diabetes, and schizophrenia.

Little is known about possibly deleterious and/or programming effects on the unborn child of maternal psychologic influences or stress during pregnancy. For a long time, people thought that maternal psychic impressions would induce a structural fetal abnormality (‘maternal imagination’). For instance, it was believed that sudden fright because of a leaping hare would result in a child with a harelip. Another example of association of ideas is a child affected with ichthyosis born to a mother who has done her washing regularly in a river where fish were abundant [5]. Although these cases have to be ascribed to popular superstition, recent animal experiments have yielded sound proof that prenatal maternal stress affects the fetus resulting in life-long effects [6], [7], [8]. The aim of this review is to evaluate whether the effects of stress on the course of pregnancy and the offspring as found in many animal experiments also apply to the human situation.

Section snippets

Stress and pregnancy

In daily life, humans and animals are often confronted with situations that demand adaptation. There is stress if adaptation is with great difficulty or impossible. The physiologic and behavioural responses to stressors are generally well known, though mainly for male adults [9]. Stressors may vary from life events (e.g. divorce, serious illness or death of a relative or friend) to daily hassles (e.g. domestic affairs, financial or relational problems, and queuing). During exposure to a

Prenatal stress and complications of pregnancy

The HPA axis and the reproductive system show a complex relationship in both pregnant and non-pregnant women. The hormones of the HPA axis have strong, mainly inhibiting, effects on the HPG(onads) axis [9]. Moreover, CRH and cortisol receptors are abundant in the endometrium, myometrium, and the ovaries. It is therefore not surprising that psychologic (and physical) stress may disturb the sexual and reproductive capacities. Anovulation, oligomenorrhea, and reduced libido are often seen under

Prenatal stress and development of the central nervous system: animal experiments

Animal experiments in which the mother (rat, monkey) was exposed to various stressors during pregnancy (electric foot shock, immobilisation, unexpected loud noises, etc.) have demonstrated that this treatment results in various permanent changes in the offspring. Prenatally stressed animals show delayed motor development and exhibit, at adult age, reduced exploration and adaptive behaviour, more emotional and anxious reactions in an unfamiliar environment, impaired cognitive functions

Prenatal stress and development of the central nervous system: observations in the human

It is presently unclear if prenatal programming of brain functions also occurs in the human. We do know that exposure to an increased maternal stress level influences fetal brain growth (reduced head circumference) and that prenatally stressed infants have lower scores at neonatal neurologic examination [25].

During ultrasound observation, fetuses of high anxious women have been found to be more active than those of low anxious women [35]. This is in line with the observation of dramatically

Regulation of the maternal HPA axis

CRH is produced and secreted by the hypothalamus. It plays a central role within the HPA axis and is involved in the physiologic response to stress. CRH stimulates ACTH production and secretion by the pituitary. In turn, ACTH stimulates the production and secretion of cortisol by the adrenal cortex. Regulation of these hormones is achieved by a negative feed-back mechanism [9]. This occurs in pregnant and non-pregnant women alike, although important changes take place in the course of pregnancy

Transmission of maternal stress to the unborn baby

The question of how signals of maternal stress may reach the fetus has not been dealt with so far. It seems most logic that this occurs through (stress) hormones. Three mechanisms may be distinguished, which may operate simultaneously and may amplify each other's effects. The possible mechanisms involve: (a) reduction in blood flow to the uterus and fetus at increased levels of maternal stress; (b) transplacental transport of maternal hormones; (c) stress-induced release of placental CRH to the

Outlook

Known biomedical risk factors, such as maternal diseases, teratogenic agents, complications of pregnancy, and nutritional deficiencies and infections, explain about half of the number of cases of low birth weight and prematurity and their associated problems after birth [49]. Prenatal maternal stress and anxiety may be responsible for an important proportion of the other (unexplained) cases. This appears from recent well-performed studies that took into account medical and obstetric histories,

Acknowledgements

The authors gratefully acknowledge Mrs. A. Versluis for the preparation of the illustration.

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