Elsevier

Neurobiology of Aging

Volume 24, Supplement 1, May–June 2003, Pages S53-S60
Neurobiology of Aging

Prenatal stress and cognitive development and temperament in infants

https://doi.org/10.1016/S0197-4580(03)00050-2Get rights and content

Abstract

Studies in rodents and nonhuman primates indicate that maternal stress during pregnancy can influence the developing fetus, resulting in delay of motor and cognitive development and impaired adaptation to stressful situations. These effects may be mediated by the hypothalamic–pituitary–adrenal (HPA) axis. We examined whether stress during pregnancy predicted developmental outcome of human infants in a prospective design. Self-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in nulliparous pregnant women. Dependent measures were scores on the Bayley Scales of Infant Development and on temperamental questionnaires at 3 and 8 months. Pregnancy-specific anxiety in mid pregnancy predicted lower mental and motor developmental scores at 8 months. Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months and motor development at 8 months. Pregnancy-specific anxiety explained 7% of the variance of test-affectivity and goal-directedness at 8 months. Increased maternal stress during pregnancy seems to be one of the determinants of temperamental variation and delay of development of infants and may be a risk factor for developing psychopathology later in life.

Introduction

In pregnant animals, induced stress adversely affects behavioral adaptation and motor and mental development of the offspring [41]. Stress in early or mid gestation in nonhuman primates resulted in impaired motor development, declined attention, and delayed cognitive development of offspring in the first year of life [29]. Though these findings have not yet been replicated in humans, there is increasing appreciation of the relevance of the prenatal stress paradigm for the human situation.

In ancient times, it was already a common belief that the emotional state of a mother may affect the child she is carrying [12]. Prospective studies have substantiated this belief by reporting that maternal stress during pregnancy is associated with an adverse obstetric outcome, as reflected in increased risk for premature delivery, or low birth weight for gestational age [20], [23].

Recently, it was further found that prenatal stressors of human life were associated with a significantly smaller head circumference, when corrected for birth weight [20]. The aim of this paper is to review animal models on prenatal stress and to summarize our own work on the influence of prenatal stress on temperamental and cognitive development in human infants.

Section snippets

Effect of prenatal stress on behavior of rodent offspring

Aspects of development that could be influenced by prenatal stress in rodents were the early physical and motor development, exploration in a novel environment, disturbance behavior under stressful conditions, and social and sexual behaviors. Prenatal stress was associated with lower birth weights of the pups [42] and compromised early motor development [11], [15]. Prenatal stress further affected the behavior of rodent offspring in a novel situation, with prenatally stressed offspring showing

Prenatal stress and behavior of nonhuman primate offspring

Prenatally stressed rhesus macaque infants had lower birth weights and compromised physical growth, and exhibited retarded motor development and shorter attention spans when compared to infants born to nonstressed mothers [28]. When tested at 6 months of age in a novel environment, the prenatally stressed infants presented with significantly more disturbance behaviors and lower amounts of exploratory behaviors compared to controls [29]. In addition, half of the prenatally stressed infants

Prenatal stress and learning abilities of offspring

Studies on learning abilities of the offspring of stressed mothers have revealed impairments on a number of tasks. Early work has adduced evidence for impairments of discrimination learning [15], reversal of a learning set on a T-maze and acquisition of an operant response [33] in the offspring of prenatally stressed rats. The results of two recent studies, however, are conflicting. Using crowding combined with one daily painful experiences as stressors in Wistar rats, learning acquisition in a

Prenatal stress and the HPA axis

There is abundant evidence of an overactive and dysregulated HPA axis in the offspring of prenatally stressed animals. First, a number of studies have measured higher levels of circulating glucocorticoids under baseline conditions in adult rodents that were exposed to stress when in utero [14], [22], [43], [44]. Female rodent offspring appear to be more sensitive to the effects of prenatal stress on the HPA axis [22], [43], which is in accordance with the observation that normal baseline levels

Possible mechanisms explaining the altered regulation of HPA axis after prenatal stress

There are several possibilities to explain such an overactivity and altered feedback regulation of the HPA axis: (1) downregulation of receptors in the hippocampus, the hypothalamus, the pituitary or adrenal glands; (2) decreased sensitivity of the receptors at any of these levels; and (3) alteration in CRH levels, or altered levels or affinity of plasma binding proteins [8]. Though not all of these mechanisms which may underlie alterations in feedback regulation of the HPA axis after prenatal

Prospective study on stress in human pregnancy-design

Prospective studies on the influence of the emotional state of the pregnant mother on infant temperament are sparse. One small previous study investigated the effect of stress during pregnancy on the postnatal development of human infants [39]. Measures of general anxiety in the third trimester of pregnancy were positively correlated with a difficult temperament of the infant at 10 weeks and 7 months after birth, but were unrelated to infant mental or motor development. We started a prospective

Findings of prenatal stress on cognitive development and temperament in infants

MANCOVAs were performed with a high-low contrast set on the predictor variable as between-subject factor, the MDI and PDI scores at 3 and 8 months as dependent variables, and gestational age at birth, birth weight and the postnatal stress and depression level of the mother as covariates. An overall effect of daily hassles on 8 months scores was found to show a trend towards significance, after correction for these covariates (F=2.31, P=0.10). A significant overall effect was found of fear on

Conclusion

Stress during pregnancy, as reflected by a high amount of daily hassles in early pregnancy or strong fear of giving birth in mid pregnancy, was associated with an average decline of 8-points in mental and psychomotor developmental scores of the infant 8 months after birth. The effects of pregnancy anxiety remained significant after adjusting for possible confounders, such as SES, maternal age, birth weight, gestational age, biomedical risks during pregnancy, perinatal complications, and the

Acknowledgements

This work was supported by the Van der Gaag Stichting and the Royal Academy of Sciences (Buitelaar), the Praeventiefonds (Buitelaar, Visser), the University Medical Center Utrecht (Buitelaar, Visser), and the Rudolf Magnus Institute for Neurosciences (UMCU).

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