Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models because these would enable use of powerful transgenic methods. Therefore, we have characterized a mouse model of chronic ES, which was provoked in mouse pups by abnormal, fragmented interactions with the dam. Dam-pup interaction was disrupted by limiting the nesting and bedding material in the cages, a manipulation that affected this parameter in a dose-dependent manner. At the end of their week-long rearing in the limited-nesting cages, mouse pups were stressed, as apparent from elevated basal plasma corticosterone levels. In addition, steady-state mRNA levels of CRH in the hypothalamic paraventricular nucleus of ES-experiencing pups were reduced, without significant change in mRNA levels of arginine vasopressin. Rearing mouse pups in this stress-provoking cage environment resulted in enduring effects: basal plasma corticosterone levels were still increased, and CRH mRNA levels in paraventricular nucleus remained reduced in adult ES mice, compared with those of controls. In addition, hippocampus-dependent learning and memory functions were impaired in 4- to 8-month-old ES mice. In summary, this novel, robust model of chronic early life stress in the mouse results in acute and enduring neuroendocrine and cognitive abnormalities. This model should facilitate the examination of the specific genes and molecules involved in the generation of this stress as well as in its consequences.

Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother-child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre-and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.developmental programming | fetal origins | hypothalamus-pituitaryadrenal axis | depression | emotion regulation

The consequences of prenatal maternal stress for infant mental and motor development were examined in 125 full term infants at 3, 6 and12 months of age. Maternal cortisol and psychological state were evaluated five times during pregnancy and at 3, 6 and 12 months postpartum. Exposure to elevated concentrations of cortisol early in gestation was associated with a slower rate of development over the first postnatal year and lower scores on the mental development index of the Bayley Scales of Infant Development (BSID) at 12 months. Elevated levels of maternal cortisol late in gestation, however, were associated with accelerated development over the first year and higher scores on the BSID at 12 months. Elevated levels of maternal pregnancy specific anxiety early in pregnancy were independently associated with lower scores on the BSID at 12 months. These associations could not be explained by postnatal maternal psychological stress, stress related to parenting, prenatal medical history, socioeconomic factors or child race, sex or birth order. These data suggest that maternal cortisol and pregnancy specific anxiety have programming influences on the developing fetus. Prenatal exposure to the same signal, cortisol, had opposite associations with infant development based on the timing of exposure. Keywords pregnancy; cortisol; stress; infant development; cognition; prenatal; depression; anxiety; fetal programmingThe prenatal period is a time of rapid change during which fetal organs and organ systems are forming and are vulnerable to both organizing and disorganizing influences. These influences on the fetus have been described as programming; the process by which a stimulus or insult during a vulnerable developmental period has a long-lasting or permanent effect. The effects of programming are dependent on the timing of the exposure and on the developmental stage of organ systems. There is convincing support for fetal programming of adult health outcomes, however, the evidence comes primarily from retrospective studies that rely on birth phenotype (e.g., small size at birth or preterm delivery) as an index of fetal development (Barker, 1998(Barker, , 2002. It is unlikely, however, that birth phenotype alone is the cause of subsequent health outcomes. Birth phenotype, instead, reflects fetal adaptation to exposures that shape the structure and function of physiological systems that underlie health and disease risk (Gluckman & Hanson, 2004;Morley, Blair, Dwyer, & Owens, 2002 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptpurpose of the present study was to investigate the programming influence of biological and psychosocial indicators of prenatal maternal stress for fetal development and to evaluate the effects of timing of exposure to stress on infant development. Fetal Programming: The Role of Glucocorticoids (GCs)For a number of reasons GCs have been proposed as a primary candidate for fetal programming. Glucocorticoids, cortisol in humans, are steroid hormones that play a critical ...

Prenatal psychosocial predictors of infant birth weight and length of gestation were investigated in a prospective study of 120 Hispanic and 110 White pregnant women. Hypotheses specifying that personal resources (mastery, self-esteem, optimism), prenatal stress (state and pregnancy anxiety), and sociocultural factors (income, education, ethnicity) would have different effects on birth outcomes were tested using structural equation modeling. Results confirmed that women with stronger resources had higher birth weight babies ((3 = .21), whereas those reporting more stress had shorter gestations (|3 =-.20). Resources were also associated with lower stress ((3 =-.67), being married, being White, having higher income and education, and giving birth for the first time. There was no evidence that resources buffered the effects of stress. The importance of personal resources in pregnancy is highlighted along with implications for understanding the etiology of adverse birth outcomes.