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