Accumulating research shows that prenatal exposure to maternal stress increases the risk for behavioral and mental health problems later in life. This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome. Effects of maternal stress on offspring neurodevelopment, cognitive development, negative affectivity, difficult temperament and psychiatric disorders are shown in numerous epidemiological and case-control studies. Offspring of both sexes are susceptible to prenatal stress but effects differ. There is not any specific vulnerable period of gestation; prenatal stress effects vary for different gestational ages possibly depending on the developmental stage of specific brain areas and circuits, stress system and immune system. Biological correlates in the prenatally stressed offspring are: aberrations in neurodevelopment, neurocognitive function, cerebral processing, functional and structural brain connectivity involving amygdalae and (pre)frontal cortex, changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous system.

“Barker’s hypothesis” emerged almost 25 years ago from epidemiological studies of birth and death records that revealed a high geographic correlation between rates of infant mortality and certain classes of later adult deaths as well as an association between birthweight and rates of adult death from ischemic heart disease. These observations led to a theory that undernutrition during gestation was an important early origin of adult cardiac and metabolic disorders due to fetal programming that permanently shaped the body’s structure, function, and metabolism and contributed to adult disease. This theory stimulated interest in the fetal origins of adult disorders, which expanded and coalesced ~5 years ago with the formation of an international society for developmental origins of health and disease (DOHaD). Here we review a few examples of the many emergent themes of the DOHaD approach, including theoretical advances related to predictive adaptive responses of the fetus to a broad range of environmental cues, empirical observations of effects of overnutrition and stress during pregnancy on outcomes in childhood and adulthood, and potential epigenetic mechanisms that may underlie these observations and theory. Next, we discuss the relevance of the DOHaD approach to reproductive medicine. Finally, we consider the next steps that might be taken to apply, evaluate, and extend the DOHaD approach.

Preterm birth represents the most significant problem in maternal-child health. The ongoing search to elucidate its underlying causes and pathophysiological mechanisms has identified maternal stress as a variable of interest. Based on emerging models of causation of complex common disorders, we suggest that the effects of maternal stress on risk of preterm birth may, for the most part, vary as a function of context. In this paper we focus on select key issues and questions that highlight the need to develop a better understanding of which particular subgroups of pregnant women, under what circumstances, and at which stage(s) of gestation, may be especially vulnerable to the potentially detrimental effects of maternal stress. Our discussion addresses issues related to the characterization and assessment of maternal stress and candidate biological (maternal-placental-fetal endocrine, immune, vascular and genetic) mechanisms. We propose the adoption of newer approaches (ecological momentary assessment) and a life-course perspective to further our understanding of the contribution of maternal stress to preterm birth.

Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested the hypothesis that stress exposure during intrauterine life is associated with shorter telomeres in adult life after accounting for the effects of other factors on LTL. LTL was assessed in 94 healthy young adults. Forty-five subjects were offspring of mothers who had experienced a severe stressor in the index pregnancy (prenatal stress group; PSG), and 49 subjects were offspring of mothers who had a healthy, uneventful index pregnancy (comparison group; CG). Prenatal stress exposure was a significant predictor of subsequent adult telomere length in the offspring (178-bp difference between prenatal stress and CG; d = 0.41 SD units; P < 0.05). The effect was substantially unchanged after adjusting for potential confounders (subject characteristics, birth weight percentile, and early-life and concurrent stress level), and was more pronounced in women (295-bp difference; d = 0.68 SD units; P < 0.01). To the best of our knowledge, this study provides the first evidence in humans of an association between prenatal stress exposure and subsequent shorter telomere length. This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk.developmental programming | fetal origin