Prenatal Undernutrition and Autonomic Function in Adulthood

Rooij, Susanne R. de; Jones, Alexander; Phillips, David I. W.; Osmond, Clive; Karemaker, John M.; Roseboom, Tessa J.; Painter, Rebecca C.

doi:10.1097/psy.0000000000000393

Cited by 8 publications

(7 citation statements)

References 24 publications

(34 reference statements)

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“…These observations reproduce findings in children who experienced IUGR in whom altered cardiac morphometry and function have been identified, including a reduced stroke volume accompanied by an increased heart rate to maintain cardiac output at rest (Crispi et al 2010). Increased resting heart rates have also been documented in some studies of adults who were low birth weight (Phillips & Barker, 1997), although this is not a consistent finding (de Rooij et al 2016).…”

Section: In Vivo Cardiac Functionsupporting

confidence: 78%

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Postnatal undernutrition alters adult female mouse cardiac structure and function leading to limited exercise capacity

Ferguson

Monroe

Heredia

et al. 2019

The Journal of Physiology

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Key points Impaired growth during fetal life can reprogramme heart development and increase the risk for long‐term cardiovascular dysfunction. It is uncertain if the developmental window during which the heart is vulnerable to reprogramming as a result of inadequate nutrition extends into the postnatal period. We found that adult female mice that had been undernourished only from birth to 3 weeks of age had disproportionately smaller hearts compared to males, with thinner ventricle walls and more mononucleated cardiomyocytes. In females, but not males, cardiac diastolic function, and heart rate responsiveness to adrenergic stimulation were limited and maximal exercise capacity was compromised. These data suggest that the developmental window during which the heart is vulnerable to reprogramming by inadequacies in nutrient intake may extend into postnatal life and such individuals could be at increased risk for a cardiac event as a result of strenuous exercise. Abstract Adults who experienced undernutrition during critical windows of development are at increased risk for cardiovascular disease. The contribution of cardiac function to this increased disease risk is uncertain. We evaluated the effect of a short episode of postnatal undernutrition on cardiovascular function in mice at the whole animal, organ, and cellular levels. Pups born to control mouse dams were suckled from birth to postnatal day (PN) 21 on dams fed either a control (20% protein) or a low protein (8% protein) isocaloric diet. After PN21 offspring were fed the same control diet until adulthood. At PN70 V̇O2, max was measured by treadmill test. At PN80 cardiac function was evaluated by echocardiography and Doppler analysis at rest and following β‐adrenergic stimulation. Isolated cardiomyocyte nucleation and Ca2+ transients (with and without β‐adrenergic stimulation) were measured at PN90. Female mice that were undernourished and then refed (PUN), unlike male mice, had disproportionately smaller hearts and their exercise capacity, cardiac diastolic function, and heart rate responsiveness to adrenergic stimulation were limited. A reduced left ventricular end diastolic volume, impaired early filling, and decreased stored energy at the beginning of diastole contributed to these impairments. Female PUN mice had more mononucleated cardiomyocytes; under resting conditions binucleated cells had a functional profile suggestive of increased basal adrenergic activation. Thus, a brief episode of early postnatal undernutrition in the mouse can produce persistent changes to cardiac structure and function that limit exercise/functional capacity and thereby increase the risk for the development of a wide variety of cardiovascular morbidities.

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Section: In Vivo Cardiac Functionsupporting

confidence: 78%

“…Increased resting heart rates have also been documented in some studies of adults who were low birth weight (Phillips & Barker, ), although this is not a consistent finding (de Rooij et al . ).…”

Section: Discussionmentioning

confidence: 97%

Postnatal undernutrition alters adult female mouse cardiac structure and function leading to limited exercise capacity

Ferguson

Monroe

Heredia

et al. 2019

The Journal of Physiology

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“…It is intriguing that, in contrast to influential theories (e.g. 12), two papers failed to find evidence for cardiovascular mechanisms linking early-life adversity with child and adult physical health outcomes (1, 13). In addition to these neurobiological mechanisms, papers in the special issue highlight the importance of psychosocial mechanisms in the association between early adversity and health.…”

mentioning

confidence: 98%

“…Yet, the pathways explored here are by no means exhaustive, some papers represent fields in their infancy in terms of bridging social and biological sciences (e.g. social epigenetics), and some papers failed to find support for mechanisms widely argued to play a role in the link between adversity and health despite strong study designs (e.g., (13)). A multitude of fundamental questions about the pathways linking adverse early environments to the onset of disease remain unanswered.…”

mentioning

confidence: 99%

Mechanisms Underlying the Association Between Early-Life Adversity and Physical Health: Charting a Course for the Future

2016

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Early life adversities (ELA) are associated with subsequent pervasive alterations across a wide range of neurobiological systems and psychosocial factors that contribute to accelerated onset of health problems and diseases. In this article, we provide an integrated perspective on recent developments in research on ELA, based on the articles published in this Special Issue of Psychosomatic Medicine. We focus on: (1) the distinction between specific versus general aspects of ELA in terms of the nature of exposure (e.g., physical and sexual abuse, emotional abuse or neglect, relative socioeconomic deprivation), biological and behavioral correlates of ELA, and differences across diseases; (2) the importance of timing in the critical phases of exposure to ELA; and (3) adaptive versus dysfunctional responses to ELA and their consequences for biological and behavioral risk factors for adverse health outcomes. This article concludes with outlining important new targets for research in this area, including the neurobiology of affect as mechanism linking ELA to adverse health outcomes, and the need for large-scale longitudinal investigations of multi-system processes relevant to ELA in diverse samples, starting prenatally, continuing to late adolescence, and with long-term follow-up assessments that enable evaluation of incident disease outcomes.

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“…Studies presented here examine mechanisms involved in the association of early-life adversity with physical health outcomes that emerge early in development, such as asthma (23–25) and chronic pain (26), global measures of physical health in childhood and adolescence (27, 28) (Hagan, Whalen), as well as intermediate phenotypes that predate the onset of disease, including adiposity (29), body mass index (24), and biomarkers of cardiometabolic risk (30). Specific physiological mechanisms investigated encompass epigenetic modifications (29, 31), alterations in cellular aging (32) and inflammatory processes (23, 33), disruptions in stress response systems including the hypothalamic-pituitary-adrenal axis and autonomic nervous system (27, 31, 34), cardiovascular and metabolic changes (30), and altered pain signaling (35). At the psychosocial level, the role of mental health (24, 25, 28), social support (24), and family relationship quality (27) are also explored as mechanisms.…”

mentioning

confidence: 99%

Introduction to the Special Issue of Psychosomatic Medicine: Mechanisms Linking Early-Life Adversity to Physical Health

McLaughlin

Lane²,

Bush

2016

Psychosom Med

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Prenatal Undernutrition and Autonomic Function in Adulthood

Cited by 8 publications

References 24 publications

Postnatal undernutrition alters adult female mouse cardiac structure and function leading to limited exercise capacity

Postnatal undernutrition alters adult female mouse cardiac structure and function leading to limited exercise capacity

Mechanisms Underlying the Association Between Early-Life Adversity and Physical Health: Charting a Course for the Future

Introduction to the Special Issue of Psychosomatic Medicine: Mechanisms Linking Early-Life Adversity to Physical Health

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