Fetal programming/Bibliography

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A list of key readings about Fetal programming.
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Journal articles


  • Ojha, S., Saroha, V., Symonds, M. E., and Budge, H. (2013) Excess nutrient supply in early life and its later metabolic consequences. Clin Exp Pharmacol.Physiol [epub ahead of pint, Jan 26].
    • Abstract: Suboptimal nutrition in early life, both in utero and during infancy, are linked to increased risk of adult obesity and its associated adverse metabolic health problems. Excess nutrient supply during early life, can lead to metabolic programming in the offspring. Such overnutrition can occur in offspring of obese mothers, offspring of mothers who gain excess weight during gestation, infants of diabetic mothers and infants who undergo rapid growth, particularly weight gain, during early infancy. Postnatal overnutrition is particularly detrimental for infants who are born small for gestational age who are often overfed to attain "catch-up growth." Potential mechanisms include resetting of hypothalamic energy sensing and appetite regulation, altered adipose tissue insulin sensitivity and impaired brown adipose tissue function. More detailed understanding of the mechanisms involved could enable development of therapeutic strategies for ameliorating the ill effects of metabolic programming. Research in this field could potentially identify optimal and appropriate preventative interventions for a burgeoning population at risk of increased mortality and morbidity from obesity and its concomitant metabolic conditions.
  • Barker DJ, Thornburg KL. (2013) Placental programming of chronic diseases, cancer and lifespan: A review. Placenta 34:841-5.
    • Abstract (reformatted): Particular paths of fetal growth are now known to predict a range of disorders in adult life. This is thought to reflect fetal programming, the phenomenon whereby nutrition and other influences during development set the body's organs and systems for life.
    • The thesis of this review is that normal variations in the processes of placental development lead to variations in the supply of nutrients to the fetus and programme a small number of key systems that are linked to later disease. A baby's growth and nutrition depend both on the function of the placenta, reflected in its gross morphology at birth, and on the mother's lifetime nutrition, reflected in her height and weight. In many studies, the effects of placental size and shape on later disease have been examined within different categories of mother's body size.
    • The review shows that variations in gross placental morphology at birth predict a wide range of disorders in later life. Any particular placental phenotype seems to predict a limited number of diseases. Further research into the links between the processes of placentation and the morphology of the placenta at birth is now required.
    • We need to know more about the relative importance of nutrient flow, nutrient balance and the timing of nutritional events in determining disorders in later life. We also need to understand why, compared to other placental mammals, the human placenta is so variable in its morphology and functional capacity.


  • Symonds ME, Pope M, Budge H. (2012) Adipose tissue development during early life: novel insights into energy balance from small and large mammals. Proc Nutr Soc 71:363-70.
    • Abstract: Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.
  • Symonds ME, Pope M, Sharkey D, Budge H. (2012) Adipose tissue and fetal programming. Diabetologia 55:1597-606.
    • Abstract: Adipose tissue function changes with development. In the newborn, brown adipose tissue (BAT) is essential for ensuring effective adaptation to the extrauterine environment, and its growth during gestation is largely dependent on glucose supply from the mother to the fetus. The amount, location and type of adipose tissue deposited can also determine fetal glucose homeostasis. Adipose tissue first appears at around mid-gestation. Total adipose mass then increases through late gestation, when it comprises a mixture of white and brown adipocytes. BAT possesses a unique uncoupling protein, UCP1, which is responsible for the rapid generation of large amounts of heat at birth. Then, during postnatal life some, but not all, depots are replaced by white fat. This process can be utilised to investigate the physiological conversion of brown to white fat, and how it is re-programmed by nutritional changes in pre- and postnatal environments. A reduction in early BAT deposition may perpetuate through the life cycle, thereby suppressing energy expenditure and ultimately promoting obesity. Normal fat development profiles in the offspring are modified by changes in maternal diet at defined stages of pregnancy, ultimately leading to adverse long-term outcomes. For example, excess macrophage accumulation and the onset of insulin resistance occur in an adipose tissue depot-specific manner in offspring born to mothers fed a suboptimal diet from early to mid-gestation. In conclusion, the growth of the different fetal adipose tissue depots varies according to maternal diet and, if challenged in later life, this can contribute to insulin resistance and impaired glucose homeostasis.
  • Almond K, Bikker P, Lomax M, Symonds ME, Mostyn A. (2012) The influence of maternal protein nutrition on offspring development and metabolism: the role of glucocorticoids. Proc Nutr Soc 71:198-203.
    • Abstract: The consequences of sub-optimal nutrition through alterations in the macronutrient content of the maternal diet will not simply be reflected in altered neonatal body composition and increased mortality, but are likely to continue into adulthood and confer greater risk of metabolic disease. One mechanism linking manipulations of the maternal environment to an increased risk of later disease is enhanced fetal exposure to glucocorticoids (GC). Tissue sensitivity to cortisol is regulated, in part, by the GC receptor and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2. Several studies have shown the effects of maternal undernutrition, particularly low-protein diets, on the programming of GC action in the offspring; however, dietary excess is far more characteristic of the diets consumed by contemporary pregnant women. This study investigated the programming effects of moderate protein supplementation in pigs throughout pregnancy. We have demonstrated an up-regulation of genes involved in GC sensitivity, such as GC receptor and 11beta-HSD, in the liver, but have yet to detect any other significant changes in these piglets, with no differences observed in body weight or composition. This increase in GC sensitivity was similar to the programming effects observed following maternal protein restriction or global undernutrition during pregnancy.


  • Koletzko B, Symonds ME, Olsen SF. (2011) Programming research: where are we and where do we go from here?. Am J Clin Nutr 94:2036S-43S.
    • Abstract: Convincing evidence has accumulated to show that both pre- and postnatal nutrition preprogram long-term health, well-being, and performance until adulthood and old age. There is a very large potential in the application of this knowledge to promote public health. One of the prerequisites for translational application is to strengthen the scientific evidence. More extensive knowledge is needed (eg,
      • on effect sizes of early life programming in contemporary populations,
      • on specific nutritional exposures,
      • on sensitive time periods in early life,
      • on precise underlying mechanisms, and
      • on potential effect differences in subgroups characterized by, eg, genetic predisposition or sex).
    • Future programming research should aim at filling the existing gaps in scientific knowledge, consider the entire lifespan, address socioeconomic issues, and foster innovation. Research should aim at results suitable for translational application (eg, by leading to health-promoting policies and evidence-based dietary recommendations in the perinatal period). International collaboration and a close research partnership of academia, industry, and small and medium enterprises may strengthen research and innovative potential enhancing the likelihood of translational application. The scientific know-how and methodology available today allow us to take major steps forward in the near future; hence, research on nutritional programming deserves high priority.
  • Speakman JR, Levitsky DA, Allison DB et al. (2011) Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech 4:733-45. [pii;10.1242/dmm.008698 [doi] Abstract/Full-Text].
    • Abstract: The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the 'obesity epidemic'--the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models--the general intake model and the dual intervention point model--that address this issue and might offer better ways to understand how body fatness is controlled.
  • Sebert SP, Dellschaft NS, Chan LL et al. (2011) Maternal nutrient restriction during late gestation and early postnatal growth in sheep differentially reset the control of energy metabolism in the gastric mucosa. Endocrinology 152:2816-26. [pii;10.1210/en.2011-0169 [doi] Abstract/Full-Text].
    • Abstract: Fetal growth restriction followed by accelerated postnatal growth contributes to impaired metabolic function in adulthood. The extent to which these outcomes may be mediated centrally within the hypothalamus, as opposed to in the periphery within the digestive tract, remains unknown. In a sheep model, we achieved intrauterine growth restriction experimentally by maternal nutrient restriction (R) that involved a 40% reduction in food intake through late gestation. R offspring were then either reared singly to accelerate postnatal growth (RA) or as twins and compared with controls also reared singly. From weaning, all offspring were maintained indoors until adulthood. A reduced litter size accelerated postnatal growth for only the first month of lactation. Independently from postnatal weight gain and later fat mass, R animals developed insulin resistance as adults. However, restricted accelerated offspring compared with both the control accelerated and restricted restricted offspring ate less and had higher fasting plasma leptin as adults, an adaptation which was accompanied by changes in energy sensing and cell proliferation within the abomasum. Additionally, although fetal restriction down-regulated gene expression of mammalian target of rapamycin and carnitine palmitoyltransferase 1-dependent pathways in the abomasum, RA offspring compensated for this by exhibiting greater activity of AMP-activated kinase-dependent pathways. This study demonstrates a role for perinatal nutrition in the peripheral control of food intake and in energy sensing in the gastric mucosal and emphasizes the importance of diet in early life in regulating energy metabolism during adulthood.
  • Sebert S, Sharkey D, Budge H, Symonds ME. (2011) The early programming of metabolic health: is epigenetic setting the missing link? Am J Clin Nutr 94:1953S-8S. [pii;10.3945/ajcn.110.001040 [doi] Abstract/Full-Text].
    • Abstract: Adult health is dependent, in part, on maternal nutrition and growth during early life, which may independently affect insulin sensitivity, body composition, and overall energy homeostasis. Since the publication of the "thrifty phenotype hypothesis" by Hales and Barker (Diabetologia 1992;35:595-601), animal experiments have focused on establishing the mechanisms involved, which include changes in fetal cortisol, insulin, and leptin secretion or sensitivity. Intrauterine growth retardation can be induced by either prolonged modest changes in maternal diet or by more severe changes in uterine blood supply near to term. These contrasting challenges result in different amounts of cellular stress in the offspring. In addition, shifts in the transcriptional activity of DNA may produce sustained metabolic adaptations. Within tissues and organs that control metabolic homeostasis (eg, hypothalamus, adipose tissue, stomach, skeletal muscle, and heart), a range of phenotypes can be induced by sustained changes in maternal diet via modulation of genes that control DNA methylation and by histone acetylation, which suggests epigenetic programming. We now need to understand how changes in maternal diet affect DNA and how they are conserved on exposure to oxidative stress. A main challenge will be to establish how the dietary environment interacts with the programmed phenotype to trigger the development of metabolic disease. This may aid in the establishment of nutrigenomic strategies to prevent the metabolic syndrome
  • Fainberg HP, Budge H, Symonds ME. (2011) The conflicting effects of maternal nutrient restriction and early-life obesity on renal health. Proc Nutr Soc 70:268-75. [pii;10.1017/S0029665110004921.]
    • Abstract: Epidemiological and animal studies have demonstrated that early-life nutrition alters the metabolic responses and generates structural changes in complex tissues, such as the kidneys, which may lead to a reduction in the offspring lifespan. Independently, obesity induces a spontaneous low-grade chronic inflammatory response by modulating several of the major metabolic pathways that ultimately compromise long-term renal health. However, the combined effects of maternal nutrition and early-life obesity in the development of renal diseases are far from conclusive. Previous results, using the ovine model, demonstrated that the combination of a reduction in fetal nutrition and juvenile obesity induced a series of adaptations associated with severe metabolic syndrome in the heart and adipose tissue. Surprisingly, exposure to an obesogenic environment in the kidney of those offspring produced an apparent reduction in glomerulosclerosis in relation to age- and weight-matched controls. However, this reduction in cellular apoptosis was accompanied by a rise in glomerular filtration rate and blood pressure of equal intensity when compared with obese controls. The intention of this review is to explain the adaptive responses observed in this model, based on insights into the mechanism of renal fetal programming, and their potential interactions with some of the metabolic changes produced by obesity.
  • Symonds ME, Budge H, Perkins AC, Lomax MA. (2011) Adipose tissue development--impact of the early life environment. Prog Biophys Mol Biol 106:300-6. [pii;10.1016/j.pbiomolbio.2010.11.008 [doi] Abstract/Full-Text].
    • Abstract: Increasing experimental and observational evidence in both animals and humans suggests that early life events are important in setting later fat mass. This includes both the number of adipocytes and the relative distribution of both brown and white adipose tissue. Brown adipose tissue is characterised as possessing a unique uncoupling protein (UCP)1 which enables the rapid generation of large amounts of heat and is most abundant in the newborn. In large mammals such as sheep and humans, brown fat that is located around the major internal organs, is largely lost during the postnatal period. However, it is retained in small and discrete areas into adulthood when it is sensitive to environmental cues such as changes in ambient temperature or day length. The extent to which brown adipose tissue is lost or replaced by white adipose tissue and/or undergoes a process of transdifferentiation remains controversial. Small amounts of UCP1 can also be present in skeletal muscle which now appears to share the same common precursor cell as brown adipose tissue. The functional consequences of UCP1 in muscle remain to be confirmed but it could contribute to dietary induced thermogenesis. Challenges in elucidating the primary mechanisms regulating adipose tissue development include changes in methylation status of key genes during development in different species, strains and adipose depots. A greater understanding of the mechanisms by which early life events regulate adipose tissue distribution in young offspring are likely to provide important insights for novel interventions that may prevent excess adiposity in later life.
  • Hyatt MA, Gardner DS, Sebert S et al. (2011) Suboptimal maternal nutrition, during early fetal liver development, promotes lipid accumulation in the liver of obese offspring. Reproduction 141:119-26. [pii;10.1530/REP-10-0325 [doi] Abstract/Full-Text].
    • Abstract: Maternal nutrition during the period of early organ development can modulate the offspring's ability to metabolise excess fat as young adults when exposed to an obesogenic environment. This study examined the hypothesis that exposing offspring to nutrient restriction coincident with early hepatogenesis would result in endocrine and metabolic adaptations that subsequently lead to increased ectopic lipid accumulation within the liver. Pregnant sheep were fed either 50 or 100% of total metabolisable energy requirements from 30 to 80 days gestation and 100% thereafter. At weaning, offspring were made obese, and at ~1 year of age livers were sampled. Lipid infiltration and molecular indices of gluconeogenesis, lipid metabolism and mitochondrial function were measured. Although hepatic triglyceride accumulation was not affected by obesity per se, it was nearly doubled in obese offspring born to nutrient-restricted mothers. This adaptation was accompanied by elevated gene expression for peroxisome proliferator-activated receptor gamma (PPARG) and its co-activator PGC1alpha, which may be indicative of changes in the rate of hepatic fatty acid oxidation. In contrast, maternal diet had no influence on the stimulatory effect of obesity on gene expression for a range of proteins involved in glucose metabolism and energy balance including glucokinase, glucocorticoid receptors and uncoupling protein 2. Similarly, although gene expressions for the insulin and IGF1 receptors were suppressed by obesity they were not influenced by the prenatal nutritional environment. In conclusion, excess hepatic lipid accumulation with juvenile obesity is promoted by suboptimal nutrition coincident with early development of the fetal liver.


  • Symonds ME. (2010) Epigenomics - Grand Challenge: Much more than the Developmental Origins of Adult Health and Disease. Front Genet 1:1. [doi Abstract/Full-Text].
  • Hyatt MA, Keisler DH, Budge H, Symonds ME. (2010) Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep. J Endocrinol 204:173-9. [pii;10.1677/JOE-09-0358 [doi] Abstract/Full-Text].
    • Abstract: Maternal parity influences size at birth, postnatal growth and body composition with firstborn infants being more likely to be smaller with increased fat mass, suggesting that adiposity is set in early life. The precise effect of parity on fat mass and its endocrine sensitivity remains unclear and was, therefore, investigated in the present study. We utilised an established sheep model in which perirenal-abdominal fat mass (the major fat depot in the neonatal sheep) increases approximately 10-fold over the first month of life and focussed on the impact of parity on glucocorticoid sensitivity and adipokine expression in the adipocyte. Twin-bearing sheep of similar body weight and adiposity that consumed identical diets were utilised, and maternal blood samples were taken at 130 days of gestation. One offspring from each twin pair was sampled at 1 day of age, coincident with the time of maximal recruitment of uncoupling protein 1 (UCP1), whilst its sibling was sampled at 1 month, when UCP1 had disappeared. Plasma leptin was lower in nulliparous mothers than in multiparous mothers, and offspring of nulliparous mothers possessed more adipose tissue with increased mRNA abundance of leptin, glucocorticoid receptor and UCP2, adaptations that persisted up to 1 month of age when gene expression for interleukin-6 and adiponectin was also raised. The increase in fat mass associated with firstborn status is therefore accompanied by a resetting of the leptin and glucocorticoid axis within the adipocyte. Our findings emphasise the importance of parity in determining adipose tissue development and that firstborn offspring have an increased capacity for adipogenesis which may be critical in determining later adiposity.


  • Symonds ME, Sebert SP, Hyatt MA, Budge H. (2009) Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol 5:604-10. [pii;10.1038/nrendo.2009.195 [doi] Abstract/Full-Text].
    • Abstract: The primary markers of the metabolic syndrome are central obesity, insulin resistance and hypertension. In this review, we consider the effect of changes in maternal nutrition during critical windows in fetal development on an individual's subsequent predisposition to the metabolic syndrome. The fetal origins of obesity, cardiovascular disease and insulin resistance have been investigated in a wide range of epidemiological and animal studies; these investigations highlight adaptations made by the nutritionally manipulated fetus that aim to maintain energy homeostasis to ensure survival. One consequence of such developmental plasticity may be a long term re-setting of cellular energy homeostasis, most probably via epigenetic modification of genes involved in a number of key regulatory pathways. For example, reduced maternal-fetal nutrition during early gestation to midgestation affects adipose tissue development and adiposity of the fetus by setting an increased number of adipocyte precursor cells. Importantly, clinically relevant adaptations to nutritional challenges in utero may only manifest as primary components of the metabolic syndrome if followed by a period of accelerated growth early in the postnatal period and/or if offspring become obese.
  • Symonds ME, Sebert SP, Budge H. (2009) The impact of diet during early life and its contribution to later disease: critical checkpoints in development and their long-term consequences for metabolic health. Proc Nutr Soc 68:416-21. [pii;10.1017/S0029665109990152 [doi] Abstract/Full-Text].
    • Abstract: Changes in maternal diet at different stages of reproduction can have pronounced influences on the health and well-being of the resulting offspring, especially following exposure to an obesogenic environment. The mechanisms mediating adaptations in development of the embryo, placenta, fetus and newborn include changes in the maternal metabolic environment. These changes include reductions in a range of maternal counter-regulatory hormones such as cortisol, leptin and insulin. In the sheep, for example, targeted maternal nutrient restriction coincident with the period of maximal placental growth has pronounced effects on the development of the kidney and adipose tissue. As a consequence, the response of these tissues varies greatly following adolescent-onset obesity and ultimately results in these offspring exhibiting all the symptoms of the metabolic syndrome earlier in young adult life. Leptin administration to the offspring after birth can have some long-term differential effects, although much higher amounts are required to cause a response in small compared with large animal models. At the same time, the responsiveness of the offspring is gender dependent, which may relate to the differences in leptin sensitivity around the time of birth. Increasing maternal food intake during pregnancy, either globally or of individual nutrients, has little positive impact on birth weight but does impact on liver development. The challenge now is to establish which components of the maternal diet can be sustainably modified in order to optimise the maternal endocrine environment through pregnancy, thus ensuring feto-placental growth is appropriate in relation to an individual's gender and body composition.
  • Budge H, Sebert S, Sharkey D, Symonds ME. (2009) Session on 'Obesity'. Adipose tissue development, nutrition in early life and its impact on later obesity. Proc Nutr Soc 68:321-6. [pii;10.1017/S0029665109001402 [doi] Abstract/Full-Text].
    • Abstract: It is now apparent that one key factor determining the current obesity epidemic within the developed world is the extent to which adipose tissue growth and function can be reset in early life. Adipose tissue can be either brown or white, with brown fat being characterised as possessing a unique uncoupling protein (uncoupling protein 1) that enables the rapid generation of heat by non-shivering thermogenesis. In large mammals this function is recruited at approximately the time of birth, after which brown fat is lost, not normally reappearing again throughout the life cycle. The origin and developmental regulation of brown fat in large mammals is therefore very different from that of small mammals in which brown fat is retained throughout the life cycle and may have the same origin as muscle cells. In contrast, white adipose tissue increases in mass after birth, paralleled by a rise in glucocorticoid action and macrophage accumulation. This process can be reset by changes in the maternal nutritional environment, with the magnitude of response being further determined by the timing at which such a challenge is imposed. Importantly, the long-term response within white adipocytes can occur in the absence of any change in total fat mass. The present review therefore emphasises the need to further understand the developmental regulation of the function of fat through the life cycle in order to optimise appropriate and sustainable intervention strategies necessary not only to prevent obesity in the first place but also to reverse excess fat mass in obese individuals.


  • Robert A. Waterland and Karin B. Michels. (2007) Epigenetic Epidemiology of the Developmental Origins Hypothesis. Annual Review of Nutrition Vol. 27: 363-388.
    • Abstract: Extensive human epidemiologic and animal model data indicate that during critical periods of prenatal and postnatal mammalian development, nutrition and other environmental stimuli influence developmental pathways and thereby induce permanent changes in metabolism and chronic disease susceptibility. The biologic mechanisms underlying this “developmental origins hypothesis” are poorly understood. This review focuses on the likely involvement of epigenetic mechanisms in the developmental origins of health and disease (DOHaD).We describe permanent effects of transient environmental influences on the developmental establishment of epigenetic gene regulation and evidence linking epigenetic dysregulation with human disease.We propose a definition of “epigenetic epidemiology” and delineate how this emerging field provides a basis from which to explore the role of epigenetic mechanisms in DOHaD


  • Godfrey KM. (2002) The Role of the Placenta in Fetal Programming—A Review. Placenta 23, Supplement A, Trophoblast Research, 16, S20–S27. | available online here.
    • The fetal origins hypothesis proposes that adult cardiovascular and metabolic disease originate through developmental plasticity and fetal adaptations arising from failure of the materno-placental supply of nutrients to match fetal requirements. The hypothesis is supported by experimental data in animals indicating that maternal nutrition can programme long term effects on the offspring without necessarily affecting size at birth.
    • There is now evidence linking body composition in pregnant women and the balance of nutrient intake during pregnancy with raised levels of cardiovascular risk factors in the offspring.
    • Maternal body composition and diet are thought to affect fetal development and programming as a result of both direct effects on substrate availability to the fetus and indirectly through changes in placental function and structure. Alterations in placental growth and vascular resistance, altered nutrient and hormone metabolism in the placenta, and changes in nutrient transfer and partitioning between mother, placenta and fetus all have important effects on the fetal adaptations thought to be central to programming.
    • Future interventions to improve placental function are likely to have lifelong health benefits for the offspring.


  • Saavedra JM, Dattilo A. Early nutrition and long-term health : mechanisms, consequences, and opportunities. Amsterdam: Elsevier/Woodhead Publishing; 2017. xliv, 576 pages p.
    • The provision of nutrients to an individual begins from the time they are conceived, and maternal nutrition, prior to and during gestation can have profound and long-lasting consequences. The concept of “nutritional programming” in the first 1000 days, described as the process and mechanisms by which nutrition, related dietary behaviors, and the environment during pregnancy and early life determine future health and risk of disease in later life helps explain some of these effects…