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Impaired Glucose Tolerance and Elevated Blood Pressure in Low Birth Weight, Nonobese, Young South African Adults: Early Programming of Cortisol Axis
... Extrapolating from human studies, these were projected to have the highest adult blood pressures [20,162]. Heightened HPA axis activity, particularly with increased ACTH and high plasma glucocorticoid levels, is seen in children and adults that were born underweight [163][164][165][166]. This happens in a variety of populations and precedes overt adult disease, particularly in socially disadvantaged communities such as the South African population [163,167]. ...
... Heightened HPA axis activity, particularly with increased ACTH and high plasma glucocorticoid levels, is seen in children and adults that were born underweight [163][164][165][166]. This happens in a variety of populations and precedes overt adult disease, particularly in socially disadvantaged communities such as the South African population [163,167]. In addition, previous research has indicated that infants born with lower birth weights undergo catch-up growth within the initial two years of life [168][169][170]. ...
A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.
... In diabetic pregnancy, IUGR is observed most commonly in patients with vasculopathy (retinal, renal, or chronic hypertension) [37][38][39]132]. The association between low birth weight and elevated plasma cortisol concentrations, hypertension, cardiovascular diseases, T2DM and mental disorders has been documented by epidemiological studies [133,134]. However, the impact of maternal dysregulated HPA axis function in pregestational prediabetes and its influence on fetal HPA axis and postnatal offspring development has not yet been explored. ...
Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading to adverse fetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on fetal HPA axis function and postnatal offspring development, hence this study. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone were measured in all dams and pups. Glucose tolerance and expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase in pups ACTH and corticosterone concentrations, impaired glucose tolerance and dysregulated MR and GR expression in the PD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.
... LBW in humans is associated with glucose intolerance and insulin resistance in the skeletal muscle and the whole-body in the young [75][76][77], and excessive energy intake may be regarded as a promoter of insulin resistance in humans [78]. In the current study alterations in whole-body glucose tolerance or skeletal muscle glucose uptake were not observed, however, UPI-induced IUGR/LBW was associated with an increase in total PKCε protein in the gastrocnemius muscle. ...
Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male “lean” offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload.
... her offspring is robbed of vitality" (White, 1938, p. 219). The underweight newborn runs the risk of having high blood pressure, cardiovascular diseases, diabetes, and glucose intolerance in adulthood (Levitt et al., 2013). ...
The message of the Adventist Church about the Gospel of Jesus Christ and His soon return includes not only spiritual redemption but also physical and mental restoration of humankind through a healthy lifestyle. It appears that the dissemination of the Adventist Health Message (AHM) has so far been perceived as emphasizing only certain aspects, overlooking important others, and depending only on spreading knowledge while lacking contextualization to different realities. This article presents a wholeness framework to the AHM promotion by pointing to the AHM foundation, purposes, ample coverture, and ultimate goal, while also identifying both inadequate and effective methods to promote it, and the need to consider the local situation and resources of people who receive the health message.
... There are two possible processes underpinning such non-genomic mechanisms. First, adverse in utero experiences lead to permanent alterations in physiology, resulting in an adverse intrauterine environment for the fetus (these include higher maternal blood pressure, higher maternal insulin, or elevated plasma glucocorticoids during pregnancy), inducing programming effects in the next generation (Klebanoff et al. 1999;Brown et al. 2001;Buchbinder et al. 2002;Phillips et al. 1998;Levitt et al. 2000;Reynolds et al. 2001;McTernan et al. 2001;Worthman and Kuzara 2005;Meaney 2001;Lang et al. 2003). Second, adverse in utero experiences may also influence the expression of genes without changing the nucleotide sequences of DNA, through epigenetic modification, thus inducing permanent changes in the phenotype. ...
Objectives Our research provides evidence on the intergenerational fetal programming effect by examining associations in the low birth weight (LBW, birth weight <2500 g) and intrauterine growth restriction (IUGR) status between two adjacent generations from both the maternal and paternal sides. Methods Birth certificate data of the entire Taiwanese population are used to construct three-consecutive-generational samples. The final samples consist of the third-generation children born during 1999–2006 to at least one second-generation (G2) parent born during 1978–1985. Maternal and paternal samples are distinguished based on the gender of G2. We first fit the samples with linear probability models while including extensive explanatory variables to control for myriad confounding factors. We then include G2 sibling fixed effects to account for family-specific heterogeneity. Alternative explanations of sample selection, parents’ assortative mating, and grandmothers’ postnatal investment are examined. Results We find that significant intergenerational associations in LBW and IUGR only occur matrilineally. Children born to LBW mothers are 2.28 (95% CI, 0.71–3.85; p < 0.01) percentage points, corresponding to 36%, more likely to be LBW compared to children born to non-LBW mothers who are sisters. These associations cannot be explained by the above alternative explanations. Conclusions Under G2 sibling comparisons, children born to LBW (IUGR) mothers are more likely to be LBW (IUGR), but children born to LBW (IUGR) fathers are not. The findings suggest that maternal health is pertinent and that socio-economic interventions may not yield the desired outcomes within a short period of time.
... Understanding how the effects of maternal stress during pregnancy are transmitted to the fetus(es) and the mechanisms involved in fetal programing as a result could aid the development of postnatal therapeutic interventions to reverse the detrimental effects observed in the offspring. In particular, understanding how resetting the activity of the HPA and/or HPG axis in offspring occurs following prenatal stress has important implications for humans since HPA axis hyperactivity is considered to underpin several adulthood pathologies (Levitt et al., 2000; Phillip et al., 1998) and HPG axis is involved in maintaining reproductive health (Brunton, 2013; Davies & Norman, 2002). In conclusion, the alterations in development, behavior and reproductive performance of female progeny of rats by developmental exposure of AfB1 in this study, indicated that transplacental exposure to graded doses of AfB1 (10, 20, 50 and 100 mg/kg body weight) compromised post-natal development, behavior and fertility output of the female progeny. ...
A suboptimal in utero environment can have detrimental effects on the pregnancy and long-term adverse "programing" effects on the offspring. Aflatoxin B1 is one of the potent reproductive toxicants and currently detected in both milk and tissues. This article focuses on the effects of prenatal exposure to graded doses of aflatoxin B1 on the pregnancy outcomes of dams and postnatal developments of the female offspring, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats were injected intramuscularly with vehicle or aflatoxin B1 (10, 20, 50 or 100 μg/kg body weight/day) on days 12-19 of gestation. At parturition, newborns were observed for clinical signs of toxicity and survival. The female offspring were examined through a battery of tests in order to evaluate their developmental, behavioral and reproductive end points. All animals were born alive. The litter size of the aflatoxin B1 treated rats was comparable to the controls. However, the birth weight of the pups in the experimental group was significantly lower when compared to controls. Significant and persistent lags in cliff avoidance, negative geotaxis, surface rightening activity and ascending wire mesh, with a delay in elapsed time for vaginal opening were detected in the female progeny exposed to aflatoxin B1 during embryonic development. The locomotor activity and exploratory behavior in experimental females were significantly decreased than that of controls. Embryonic exposure to aflatoxin B1 also resulted in prolonged stress response, irregular estrus and suppressed fertility output in the progeny at their adulthood. These results indicate that in utero exposure to aflatoxin B1 severely compromised postnatal development of neonatal rats and caused irregular estrus that was accompanied by suppressed fertility output.
... Störungen der HPA-Achsen Aktivität bei Erwachsenen mit geringem GeburtsgewichtVerschiedene Studien konnten zeigen, dass bei Erwachsenen, die als SGA geboren wurden, die Aktivität der HPA-Achse sowohl in Ruhe als auch nach Stimulierung im Vergleich zu Plasma als auch der Blutdruck signifikant höher waren als bei Erwachsenen mit einem normalen Geburtsgewicht und stellten dadurch eine Beziehung zwischen niedrigem Geburtsgewicht, erhöhter HPA-Achsen Aktivität sowie Bluthochdruck her.Antwort in Reaktion auf eine pharmakologische Stimulation durch Gabe von ACTH, welches die Nebennierenrinde zur Cortisolproduktion und -ausschüttung anregt, fielen bei Erwachsenen, welche bei der Geburt untergewichtig waren, signifikant höher aus[15,16].Ferner reagierten in einer Studie von Wüst, Entringer et al.[12] Erwachsene, welche als SGA geboren wurden, stärker auf einen experimentellen psychosozialen Stressreiz im Sinne einer erhöhten HPA-Antwort als Probanden, die als AGA geboren wurden. Die Cortisol-Werte in Ruhe waren hingegen in dieser Studie in beiden Gruppen nicht unterschiedlich.Cortisolwertes. ...
... Schwangerschaftswoche mit synthetischen Glucocorticoiden behandelt, um die neonatale Morbidität und Mortalität zu vermindern. In verschiedenen Studien konnte belegt werden, dass synthetische antenatale Glucocorticoide in diesen Fällen die Inzidenz eines schweren Atemnotsyndroms reduzieren können (12,48), aber auch das Risiko für die Entstehung einer bronchopulmonalen Dysplasie (57), intraventrikulären Hämorrhagie (33), nekrotisierenden Enterocolitis (8) und Frühgeburtlichkeit assoziierten Mortalität (12,48) signifikant vermindern. ...
1. Zusammenfassung
Hintergrund. Es besteht die Vermutung, dass eine erhöhte fetale Glucocorticoid- Exposition
in utero einen permanenten Einfluss auf das Gleichgewicht und die Regulierung der fetalen
Hypothalamus- Hypophysen- Nebennieren- Achsen – (HPA- Achsen-) Funktion haben
könnte. Eine Veränderung des Gleichgewichts der HPA- Achse könnte dabei Auswirkungen
auf verschiedene Organsysteme haben und zu der Entstehung von metabolischen und
kardiovaskulären Erkrankungen führen. So sind veränderte Plasmacortisolwerte im
Erwachsenenalter assoziiert mit dem Risiko für das Auftreten eines metabolischen Syndroms
mit gestörter Glucosetoleranz, arterieller Hypertonie und Dyslipidämie. In der vorliegenden
Studie wurde die Reaktivität des HPA- Achsen- Systems bei gesunden Neugeborenen
analysiert, welche im Rahmen einer Lungenreifungsinduktion (LRI) wegen der Gefahr einer
Frühgeburtlichkeit einer antenatalen Betamethason- Verabreichung ausgesetzt waren. Diese
wurden mit Neugeborenen ohne pränatale Steroidexposition verglichen.
Methoden. Cortisol- und Cortisonwerte wurden im Speichel von Neugeborenen vor und
nach einem Stressreiz gemessen. Als Stressreiz diente der schmerzhafte Fersenstich einer
routinemässigen Blutentnahme 72 bis 94 Stunden nach Geburt (Guthrie Test).
Speichelproben von 23 Kindern mit Lungenreifungsinduktion und von 40 Kontrollen wurden
in Ruhe und 20 Minuten nach dem Fersenstich entnommen und auf Cortisol- und Cortison-
Konzentrationen analysiert.
Resultate. Während die Kontroll- Gruppe einen signifikanten Anstieg der Cortisol- und
Cortison- Werte 20 Minuten nach dem Stressereignis als Zeichen einer normalen
Stressreaktivität der HPA- Achse zeigte, war bei der LRI- Gruppe die Cortisol- und Cortison
Ausschüttung deutlich reduziert. Mögliche Einflussfaktoren auf die Cortisolreaktion, wie das
Gestationsalter, das Geburtsgewicht, der Zeitpunkt der Lungenreifungsinduktion und das
Geschlecht zeigten keinen signifikanten Einfluss auf die Ergebnisse.
1. Zusammenfassung 5
Interpretation. Gesunde Neugeborene, welche intrauterin eine einmalige
Lungenreifungsinduktion mit 2x12mg Betamethason vor der 34. Schwangerschaftswoche
(SSW) erhalten haben, zeigen noch 8 Wochen später eine signifikante Veränderung der
physiologischen Reaktivität der HPA- Achse auf einen Stressreiz. Diese Ergebnisse geben
Grund zu der Vermutung, dass bereits eine einmalige Lungenreifungsinduktion die HPAAchsen-
Aktivität dauerhaft verändern und somit einen Risikofaktor für die Entstehung von
Erkrankungen im späteren Leben darstellten könnte.
Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic–pituitary–adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.
Objective:
Low birthweight (bw) and unfavourable intrauterine conditions have been associated with metabolic sequelae in later life, but little is known about their impact on glucocorticoid metabolism. We studied monozygotic twins with intra-twin bw-differences to analyse the long-term impact of bw on glucocorticoid metabolism.
Methods:
46 monozygotic twin-pairs with bw-differences of <1SDS (concordant; n = 29) and ≥1SDS (discordant; n = 17) were recruited. At 6.9 years (mean age), saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Results:
We found significant or highly significant intra-twin correlations in all twin pairs at 3/4 (cortisol), respectively 4/4 (cortisone) time points. Graphic evaluation of the diurnal cortisol patterns for each twin pair showed a distinct alignment in all groups. Analyses of the change of intra-twin differences over the day by mixed linear modelling showed no intra-twin differences in diurnal patterns. Regression analyses of intra-twin differences at 7:00 h showed a significant influence of catch-up growth, indicating lower cortisol concentrations in smaller twins with more catch-up growth (adj.R²=0.159, p = 0.014, ß=-3.71, F(1,42) = 9.15, f²=0.19).
Conclusion:
In monozygotic twins with intra-twin bw-differences, intra-twin catch-up growth showed a moderate influence on intra-twin differences in morning cortisol concentrations. We observed no differences regarding diurnal patterns. In contrast, in all groups, we found significant intra-twin correlations for cortisol and cortisone over the day and a pronounced graphic alignment of cortisol diurnal patterns. We therefore suggest a predominant significance of the genetic background compared with bw-differences on cortisol metabolism.
Objective:
To assess the relationship between Hypothalamic-Pituitary-Adrenal (HPA) axis activity, vascular function and insulin sensitivity in healthy adults.
Design:
Open observational study.
Patients:
Thirty healthy adults were studied at the Endocrine Research Unit, Repatriation General Hospital, Adelaide, Australia.
Measurements:
HPA activity was assessed from the serum cortisol 30 minutes after 1 µg ACTH1-24 (Novartis Pharmaceuticals, NSW, Australia). Subjects with a cortisol below (n=15) and above (n=15) the median were categorized as low and high responders respectively. Reactive hyperaemia index (RHI) was measured fasting to estimate endothelial function. Matsuda index was calculated from glucose and insulin concentrations collected fasting and 30 minutely for two hours after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). The primary endpoint was the difference in RHI between low and high responders.
Results:
There were no significant differences in age (61±9 vs 64±7 years, p=0.19), BMI (26±3 vs 24±4 kg/m2, p=0.25) and sex (p=0.71) between low and high responders. High responders had a lower RHI (2.1±0.2 vs 2.6±0.2, p=0.04) than low responders and there was a negative association between RHI and peak cortisol post ACTH1-24 (ß = -0.56, p <0.01). There were no significant differences in Matsuda index (15.0 ± 2.4 vs 22.7 ± 5.2, p = 0.19) between high and low responders.
Conclusion:
In healthy adults, endothelial dysfunction is likely to contribute to the association between HPA hyperactivity and increased cardiovascular risk. As insulin sensitivity was not different in high and low responders, endothelial dysfunction is not primarily secondary to insulin resistance. This article is protected by copyright. All rights reserved.
Nutritional, hormonal, and other aspects of the gestational and infancy environments have effects on biology and metabolism that persist into adulthood to influence risk for cardiovascular, metabolic and other diseases of aging. These effects are examples of developmental plasticity, which involves modified growth of organs and tissues and durable epigenetic changes that influence gene expression. In this chapter, we first review the evidence linking early environments to adult health, including discussion of underlying developmental and epigenetic mechanisms and their possible evolutionary function. We then explore the applicability of these principles to two public health problems: the rapid rise of chronic diseases in lower and middle income nations, and the persistent health disparities within societies that map onto social categories such as race or class. The developmental processes reviewed here show how buffering infants and pregnant women from social and nutritional stressors could help promote healthy aging in future generations.
Adolescent pregnancy (occurring < age 20) is considered a public health problem that creates and perpetuates inequities, affecting not only women, but societies as a whole globally. The efficacy of current approaches to reduce its prevalence is limited. Most existing interventions focus on outcomes without identifying or addressing upstream social and biological causes. Current rhetoric revolves around the need to change girls’ individual behaviours during adolescence and puberty. Yet, emerging evidence suggests risk for adolescent pregnancy may be influenced by exposures taking place much earlier during development, starting as early as gametogenesis. Furthermore, pregnancy risks are determined by complex interactions between socio-structural and ecological factors including housing and food security, family structure, and gender-based power dynamics. To explore these interactions, we merge three complimentary theoretical frameworks: “Eco-Social”, “Life History” and “Developmental Origins of Health and Disease”. We use our new lens to discuss social and biological determinants of two key developmental milestones associated with age at first birth: age at girls’ first menstrual bleed (menarche) and age at first sexual intercourse (coitarche). Our review of the literature suggests that promoting stable and safe environments starting at conception (including improving economic and social equity, in addition to gender-based power dynamics) is paramount to effectively curbing adolescent pregnancy rates. Adolescent pregnancy exacerbates and perpetuates social inequities within and across generations. As such, reducing it should be considered a key priority for public health and social change agenda.
Objective The objective of this study is to study the profile of apolipoprotein E (APOE) gene polymorphism and lipid profile among intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) neonates. This is an observational study. This study was done at the neonatal unit of a teaching hospital in South India. All consecutively born IUGR neonates (cases) of more than 32 weeks' gestational age and AGA neonates (controls) were enrolled for the study. Genomic DNA extraction was done from a total of 102 peripheral venous blood samples. Genotyping of the APOE rs429358 and rs7412 defining the ε2, ε3, and ε4 alleles was done by polymerase chain reaction–restriction fragment length polymorphism method. Prefeed venous blood was collected and analyzed for lipid profile estimation. The allelic frequencies of cases versus control were ε2—9 (8.7%) versus 3 (2.9%); ε3—88 (84.6%) versus 81 (79.4%); and ε4–7 (6.7%) versus 18 (17.6%). The frequency of ε4 isoform allele, associated with adult onset of metabolic diseases was less among the IUGR group. The mean total cholesterol (TC), Low-Density Lipoprotein (LDL), High-Density Lipoprotein, and triglyceride (TG) were 107.59 ± 35.99, 51.69 ± 24.68, 21.75 ± 9.58, and 151.22 ± 61.84 mg/dL, respectively, in the IUGR group. The mean TC and LDL levels in IUGR group were marginally higher than AGA neonates (107 ± 35.99 vs. 100.37 ± 22.69 mg/dL and 51.69 ± 24.68 versus 46.9 ± 19.51 mg/dL, p > 0.05). In both groups, the mean TC and TGL levels were elevated in the ε4 isoform subgroup (p > 0.05). In our study, the ε2 allele was the second most predominant APOE isoform and the ε4 allele of the APOE gene associated with adult-onset diseases was not increased among IUGR neonates. Neonates with ε4 allele showed an abnormal lipid profile in both study groups suggesting a possible association.
Background
Individuals who were born prematurely (PT), with low birth weight (LBW), or small for gestational age (SGA) appear to present a set of permanent changes that make them more susceptible to develop chronic non-communicable diseases (CNCD) in adult life.
Aim
Investigating the association between PT birth, LBW or SGA at birth and CNCD incidence in adult life.
Methods
Systematic review with meta-analysis of studies available in three databases - two of them are official (PubMed and Web of Science) and one is gray literature (OpenGrey) - based on pre-established search and eligibility criteria.
Results
Sixty-four studies were included in the review, 93.7% of them only investigated one of the exposure variables (46.7% LBW, 35.0% PT and 18.3% SGA at birth), whereas 6.3% investigated more than one exposure variable (50.0% LBW and PT; 50.0% SGA and PT). There was association among all exposure variables in the following outcomes: cardiometabolic (CMD) and glycidic metabolism (GMD) disorders, changes in body composition and risk of developing metabolic syndrome (MS). Female sex was identified as risk factor in the exposure-outcome association. Eighteen (18) articles were included in the meta-analysis. There was positive association between LBW and incidence of CMD (OR: 1.25 [95%CI: 1.11; 1.41]; 07 studies), GMD (OR: 1.70 [95%CI: 1.25; 2.30]; 03 studies) and MS (OR: 1.75 [95%CI: 1.27; 2.40]; 02 studies) in adult life. PT was positively associated with CMD (OR: 1.38 [95%CI: 1.27; 1.51]; 05 studies).
Conclusions
LBW and PT are associated with CMD and GMD development, as well as with the risk of developing MS in adult life.
During low-intensity exercise stages of the lactate threshold test, blood lactate concentrations gradually diminish due to the predominant utilization of total fat oxidation. However, it is unclear why blood glucose is also reduced in well-trained athletes who also exhibit decreased lactate concentrations. This review focuses on decreased glucose and lactate concentrations at low-exercise intensity performed in well-trained athletes. During low-intensity exercise, the accrued resting lactate may predominantly be transported via blood from the muscle cell to the liver/kidney. Accordingly, there is increased hepatic blood flow with relatively more hepatic glucose output than skeletal muscle glucose output. Hepatic lactate uptake and lactate output of skeletal muscle during recovery time remained similar which may support a predominant Cori cycle (re-synthesis). However, this pathway may be insufficient to produce the necessary glucose level because of the low concentration of lactate and the large energy source from fat. Furthermore, fatty acid oxidation activates key enzymes and hormonal responses of gluconeogenesis while glycolysis-related enzymes such as pyruvate dehydrogenase are allosterically inhibited. Decreased blood lactate and glucose in low-intensity exercise stages may be an indicator of recovery ability in well-trained athletes. Athletes of intermittent sports may need this recovery ability to successfully perform during competition.
Type 2 diabetes and metabolic syndrome (MetS) are metabolic diseases, which are characterized by hyperglycemia, dyslipidemia, hypertension, and insulin resistance along with alterations in glycerophospholipid-, sphingolipid-, and cholesterol-derived lipid mediators. These conditions are accompanied by induction of oxidative stress, low-grade inflammation along with marked changes in neural membrane signaling, and endothelial dysfunction. Long-term consumption of western diet contributes to the pathogenesis of type 2 diabetes and MetS. Modification of diet, exercise, and optimal sleep (lifestyle) may play an important role in protection from type 2 diabetes and MetS. These changes also delay the onset of stroke, Alzheimer’s disease, and vascular dementia.
Low birth weight is associated with hypertension. Low birth weight can result from fetal growth restriction (FGR) or prematurity. FGR is postulated to impact blood pressure (BP) by developmental programming. This systematic review and meta-analysis studies BP in human and animal offspring following FGR. Pubmed and Web of Science were searched for studies reporting on BP after placental insufficiency induced FGR compared with normal growth controls. Primary outcome was mean absolute BP difference (ΔBP mm Hg [95% CI]). Meta-analysis was performed using random-effects models. Subgroup analyses were executed on species, sex, age, pregnancy duration, and stress during BP readings. Due to large interspecies heterogeneity, analyses were performed separately for human (n=41) and animal (n=31) studies, the latter restricted to rats (n=27). Human studies showed a ΔBP between FGR and controls of −0.6 mm Hg ([95% CI, −1.7 to 0.6]; I ² =91%). Mean ΔBP was −2.6 mm Hg (95% CI, −5.7 to 0.4) in women versus −0.5 mm Hg (95% CI, −3.7 to 2.7) in men. Subgroup analyses did not indicate age, gestational age, and stress during measurements as sources of heterogeneity. In rats, mean BP was 12.0 mm Hg ([95% CI, 8.8–15.2]; I ² =81%) higher in FGR offspring. This difference was more pronounced in FGR males (13.6 mm Hg [95% CI, 10.3–17.0] versus 9.1 mm Hg [95% CI, 5.3–12.8]). Subgroup analyses on age showed no statistical interaction. BP readings under restrained conditions resulted in larger BP differences between FGR and control rats (15.3 mm Hg [95% CI, 11.6–18.9] versus 5.7 mm Hg [95% CI, 1.1–10.3]). Rat studies confirm the relation between FGR and offspring BP, while observational studies in humans do not show such differences. This may be due to the observational nature of human studies, methodological limitations, or an absence of this phenomenon in humans.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov . Unique identifier: CRD42018091819.
Background:
Small-for-gestational-age (SGA) birth bears an enhanced risk of developing hypertension, obesity, insulin resistance and mental health disorders in later life as a consequence of adaptive processes in utero. Only a small number of studies on pain perception in SGA infants exist. These are indicative of a blunted stress response to pain in SGA newborns.
Aim:
We initiated a pilot study investigating differences in postoperative pain perception between SGA and appropriate-for-gestational-age (AGA) infants.
Methods:
Pain and alertness levels of 10 formerly SGA and 14 AGA infants at the age 0.5-2 years were evaluated by the FLACC scale, Steward and Aldrete Scores following hernia repair, reconstructive surgery of hypospadia and orchidopexy. In addition, the postoperative consumption of non-steroidal anti-inflammatory drugs was compared between SGA and AGA.
Results:
Postoperative pain and alertness levels were not significantly different in SGA and AGA children. We did not observe significant group differences regarding the consumption of non-steroidal anti-inflammatory drugs.
Conclusion:
While previous studies were suggestive of a suppressed stress response to pain in SGA newborns, these findings did not fully translate into an altered response to pain beyond the newborn age. Further studies in a larger cohort seem necessary to verify this finding.
The importance of ensuring adequate choline intakes during pregnancy is increasingly recognized. Choline is critical for a number of physiological processes during the prenatal period with roles in membrane biosynthesis and tissue expansion, neurotransmission and brain development, and methyl group donation and gene expression. Studies in animals and humans have shown that supplementing the maternal diet with additional choline improves several pregnancy outcomes and protects against certain neural and metabolic insults. Most pregnant women in the U.S. are not achieving choline intake recommendations of 450 mg/day and would likely benefit from boosting their choline intakes through dietary and/or supplemental approaches.
Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in programming of insulin resistance later in life. Spontaneous IUGR in the guinea pig, due to natural variation in litter size, produces offspring with asymmetric IUGR and neonatal catch-up growth. We hypothesized that spontaneous IUGR and/or accelerated neonatal growth would impair insulin sensitivity in adult guinea pigs. Insulin sensitivity of glucose metabolism was determined by hyperinsulinemic-euglycemic clamp (HEC) in 38 (21 male, 17 female) young adult guinea pigs from litters of two-to-four pups. A subset (10 male, 8 female) were infused with d-[3-3H]glucose before and during the HEC to determine rates of basal and insulin-stimulated glucose utilization, storage, glycolysis, and endogenous glucose production. n males, the insulin sensitivity of whole body glucose uptake ( r = 0.657, P = 0.002) and glucose utilization ( r = 0.884, P = 0.004) correlated positively and independently with birth weight, but not with neonatal fractional growth rate (FGR10-28). In females, the insulin sensitivity of whole body and partitioned glucose metabolism was not related to birth weight, but that of endogenous glucose production correlated negatively and independently with FGR10-28 ( r = -0.815, P = 0.025). Thus, perinatal growth programs insulin sensitivity of glucose metabolism in the young adult guinea pig and in a sex-specific manner; impaired insulin sensitivity, including glucose utilization, occurs after IUGR in males and impaired hepatic insulin sensitivity after rapid neonatal growth in females.
Background
Low birth weight has been associated with subsequent risks of obesity and certain chronic diseases, but evidence for this association is limited for Chinese population.
Methods
We analyzed data from two population‐based prospective cohort studies, the Shanghai Women’s Health Study and the Shanghai Men’s Health Study to examine the association. Information on self‐reported birth weight was collected at the baseline in‐person interview. Anthropometric measurements were taken at the study enrollment. Information on T2DM diagnoses was self‐reported, and diagnoses of hypertension were based on self‐reports and measured blood pressures at baseline and follow‐up surveys.
Results
11 515 men and 13 569 women provided information on their birth weight and were included in this study. Nonlinear associations were observed for birth weight with baseline body mass index (BMI), waist circumference (WC), waist‐to‐hip ratio (WHR) and waist‐to‐height ratio (WHtR) (p values for nonlinearity < 0.05), and low birth weight was linked with lower BMI, smaller WC, but larger WHR and WHtR. An excess risk of T2DM was observed for low birth weight (<2500 g) versus birth weight of 2500‐3499 g since baseline (HR: 1.17; 95%CI: 0.92‐1.49) and birth (1.29; 1.07‐1.54), whereas the HRs for hypertension were 1.13 (1.01‐1.27) and 1.20 (1.11‐1.30), respectively. The risk of the diseases decreased as birth weight increased up to ~4000 grams; further increases in birth weight did not convey additional benefits.
Conclusion
Our results suggest that low birth weight, an index of poor intrauterine nutrition, may influence health risks later in life in Chinese population.
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Objective
The objective of this study was to identify subgroups with distinct fat and fat‐free growth patterns in the first 6 months of life and describe predictors of these different patterns.
Methods
A total of 510 apparently healthy Ethiopian infants were followed from birth to 6 months of age. Each infant had at least three and up to six repeated measurements of fat and fat‐free mass using air‐displacement plethysmography. Latent class trajectory analyses were used to categorize infants in groups with distinct body composition patterns.
Results
Four distinct fat mass and two fat‐free mass growth patterns were identified. Of the infants measured, 5% presented a delayed fat growth pattern and 3% presented a catch‐up fat growth pattern involving low birth weight but a significant fat growth velocity from 2.5 to 6 months. A large class had a high fat level at birth and an accelerated fat growth pattern in early infancy. Fat‐free growth was represented by two distinct classes with less variability. Catch‐up growth was primarily seen in fat mass.
Conclusions
We identified distinct patterns of delayed, catch‐up, and accelerated fat growth in early infancy. This variability is not detected in regular anthropometric assessment and could be a mechanism linking early growth with later obesity and cardiometabolic risk.
Objective:
We conducted a review of the evidence on the relationship between birth weight and BP among African children and adolescents. Medline, EMBASE, Global Health and Web of Science databases were searched for publications to October 2016. Papers reporting the relationship between birth weight and BP among African children and adolescents were assessed. Bibliographies were searched for further relevant publications. Selected papers were summarized following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. In total, 16 papers from 13 studies conducted in nine African countries (Nigeria, Republic of Seychelles, Gambia, Democratic Republic of Congo, Cameroon, South Africa, Algeria, Zimbabwe and Angola) were reviewed. Eight studies were cohorts, while five were cross-sectional. The relationship between birth weight and later BP varied with age of the participants. Studies in neonates showed a consistently positive association, while predominantly inverse associations were seen among children, and studies in adolescents were inconsistent. Based on the limited number of studies identified, the relationship between birth weight and later BP may vary with age in African children and adolescents. Not all studies adequately controlled for confounding, notably gender or age. Whether the inverse relationship between birth weight and BP in later life observed in Western settings is also seen in Africa remains unclear.
Fetal programming has been delivered in the last years in many papers in different medical specialties, and it claims the pregnancy as the most susceptible period in which cellular changes occur in order to adapt to morbid processes that eventually will take place as pathologies in the infant, teenager or in the adult individual, such as obesity, dyslipidemia, metabolic syndrome, arterial hypertension, ischemic heart disease, metabolic diseases as diabetes mellitus type 2, psychiatric diseases as schizophrenia, anxiety, bipolarity, depression and neurological diseases as autist spectrum disorders, epilepsy, Alzheimer and Parkinson. To analyze the different nutritional, genetic and obstetric pathologies that can influence the programming of the individuals in the fetal stage oriented towards a better programming of the society from prenatal consultation. Maternal nutritional basis of an accurate fetal programming makes the obstetricians the main protagonist of the proper prenatal management in order to have in a medium and long term a healthier society, with lower incidence of these common diseases. Conclusions: Good prenatal management involves an individual with adequate phenotypic programming to decrease the incidence of adult diseases. The role of the obstetrician is essential to define a healthier society in the future.
Fetal programming refers to abnormal somatic and functional development of target tissues in response to over nutrition or to adverse stimulus with a deficient supply of nutrients and oxygen through the placenta that is experienced during crucial periods of fetal growth. These early responses may have an impact on metabolic processes and hormonal homeostasis resulting in functional aberrations and metabolic diseases during childhood tracking into adulthood. The greater propensity to obesity is characterized by central and visceral adipose tissue deposit, lack of skeletal muscle development and insulin resistance related cardio metabolic risk factors. Nutritional programming during early infancy is influenced by accelerated postnatal growth induced by hypercaloric over nutrition that seems to be independent of birth weight. Although controversies may exist, breastfeeding must be encouraged since multiple advantages including obesity prevention have been described. The recognition that intrauterine insult as well as early life nutritional experiences have a role in the etiology of obesity epidemic suggests that interventional measures should be directed towards improvement of a healthy nutrition in mothers, babies, infants and children.
Objective:
To evaluate associations between low birth weight (LBW) and anthropometry, body composition, physical fitness, and gross motor coordination among schoolchildren from Maputo, Mozambique.
Methods:
A total of 353 children aged 7 to 10 years old from both genders born in Maputo (Mozambique) were sampled. The sample was divided into two groups: LBW (n = 155) and normal birth weight (NBW, n = 198). Body composition measurements and indices weight-for-age, height-for-age, and weight-for-height were assessed. Physical fitness was assessed by handgrip strength, flexibility, agility, long jump, and running speed. Gross motor coordination was evaluated by using the Korper Koordination Test fur Kinder (KTK) battery.
Results:
LBW children were lighter and smaller than NBW children with reduced indices for weight-for-age and height-for-age. They also showed a reduced performance in handgrip strength and sideways movement tests. These differences remained significant even after adjustment for age, gender, body size, and fatness skinfold thickness.
Conclusion:
LBW seems to be the major factor that influences anthropometry, and is a predictor of low muscle strength and low performance on sideways movement tests. This result suggests that growth faltering in LBW children is associated with adverse health consequences, even after controlling for gender, age, fatness, and body size.
Fetal growth and function are regulated and influenced by a multitude of complex factors including genetic profile of the embryo, maternal predispositions, placental state, fetal and maternal hormonal environment, and adequate nutrient and oxygen supply to the developing fetus. Every abnormal change that occurs during this sensitive developmental period programs health condition of the individual in postnatal life – the phenomenon known as “fetal programming.” One of the most prevalent disorders affecting fetal development rate in almost 10 % of all pregnancies is fetal growth restriction (FGR) – a very complex and multifactorial disorder that often results in multiple adverse perinatal and postnatal complications including death. A growing number of studies over the last few decades confirms that the complex interaction between genetic constitution, prenatal and early postnatal environment determines the growth and development of the fetus and defines the susceptibility to certain disorders in adult life, like cardiovascular disease, neurobehavioral and metabolic disorders. Considering the high prevalence of FGR and the progressing availability of intervention strategies, it is of the highest clinical relevance to detect potential health risks as early as possible, to introduce timely preventive interventions and to adapt the life style in order to improve the long-term outcome of FGR cases.
The early life environment is crucial for later life health including mental health and cognitive function. Exposure to glucocorticoids in utero is thought to be a key underlying mechanism. Here we review the evidence from both animal and human studies that alterations in fetal exposure to glucocorticoids impact on fetal brain development with implications for neurodevelopment and life-long mental health and cognitive function.
Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological
process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns
improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via
serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986–1988). Size
at birth was classified using birth weight-for-gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks’ gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable
analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (β = 0.24 (95% confidence interval
(CI): 0.18, 0.31), β = 0.16 (95% CI: 0.09, 0.23), β = 0.08 (95% CI: 0.01, 0.16), and β = 0.37 (95% CI: 0.22, 0.52), respectively).
However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R2 increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional
insight into child growth beyond that obtained from absolute size at birth.
During the last 2 decades evidence suggesting a role for prenatal diet in the development of adult disease has built up. One of the mechanisms that has been proposed to mediate this association is fetal programming of the stress response. It has been hypothesized that poor nutritional circumstances during gestation can alter the set points of the stress response resulting in lifelong over- or underactivation of the response, which subsequently causes disease. Support for the fetal programming of the stress response hypothesis has come from animal experiments as well as from human studies. Animal studies have mainly been performed in rats, guinea pigs, and sheep. In these studies, pregnant animals were fed a restricted diet after which functioning of the stress systems, the Hypothalamic–Pituitary–Adrenal (HPA)-axis and the Autonomic Nervous System (ANS), was measured in the offspring. Overall, results show that maternal food restriction induces growth retardation in the offspring as well as several alterations in the development of the HPA-axis and the ANS. Due to obvious ethical constrictions to manipulate the maternal diet research in humans has mainly focused on the effects of birth weight as an indirect measure of the fetal environment. Most birth-weight studies have shown an overactive HPA-axis and ANS in response to stress in people with low birthweight. Only two studies in humans have directly measured the effects of prenatal diet on stress responsiveness in later life. The Motherwell Study found that fasting cortisol concentrations and cortisol responses to a psychological stress protocol were elevated in men and women whose mothers consumed a diet consisting of high meat and fish intake and low green vegetables intake. The Dutch Famine Birth Cohort Study investigated the effects of prenatal exposure to the Dutch famine, which happened at the end of World War II in the Netherlands. Men and women who were exposed to the famine in utero did not show altered functioning of the HPA-axis. However, men and women exposed to the famine during early gestation did show greater blood pressure responsiveness to a psychological stress protocol. It can be concluded that prenatal diet definitely affects stress responsiveness in later life. The exact effect, how it happens, to what extent, and which factors are of importance, remains to be clarified. It seems justified though, to inform women of the importance of a balanced diet during pregnancy for the health of their babies.
Low birth weight and a rapid weight gain in early childhood may lead to an increased risk for developing cardiovascular disease later in life, such as hypertension and dyslipidaemia. In this study, we examined the associations between size at birth, relative weight gain in infancy and childhood with specific cardiovascular disease risk factors in early adulthood. Adolescents (
n
=1935) from the Birth to Twenty plus (BT20+) cohort were included in the analysis. The following were treated as exposure variables: weight at birth, and relative conditional weight gain (CW), independent of height, between ages 0–24 months and 24–48 months. Outcomes were serum lipids and body composition variables at age 18 years. After adjusting for sex and other confounders, early life exposures were not associated with adolescent lipid profile. Following adjustment for sex and height (body size), birth weight [β=0.704 (0.40, 1.01)], CW 0–24 [β=1.918 (1.56, 2.28)] and CW24–48 [β=1.485 (1.14, 1.82)] accounted for 48% of the variance in fat mass. However, birth weight [β=0.773 (0.54, 1.01)], CW 0–24 [β=1.523 (1.24, 1.80)] and CW24–48 [β=1.226 (0.97, 1.49)] were also positively predicted and accounted for 71% of the variance in fat mass in adolescence (
P
<0.05). Our data suggests that birth weight and weight gain during infancy and early childhood independent of linear growth are related to adolescent body composition but not blood lipid profiles in an urban African population.
Introduction:
Birth weight has been considered an important marker of the nutritional transition in developing countries.
Objective:
To evaluate the influence of birth weight on body composition and physical fitness of young men born in Maputo, Mozambique.
Methods:
One hundred and seventy-nine students (aged 19 to 22 years) were divided into four groups (low birth weight < 2.500 g, LBW, n = 49; insufficient birth weight ≥ 2.500 g and < 3.000 g, IBW, n = 27; normal birth weight ≥ 3.000 g and < 3.999 g, NBW, n = 74; and high birth weight > 3.999 g, HBW, n = 31). Anthropometry and body composition were measured. Physical fitness was assessed by handgrip strength, muscle endurance, flexibility, agility, and running speed.
Results:
IBW showed lower values of body mass and fat free mass while LBW and HBW had high values of hip circumference, suprailiac, subscapular and abdominal skinfold when compared to NBW. LBW and HBW showed a high percentage of individuals with low performance in flexibility, right handgrip, agility, abdominal resistance, arms strength, and horizontal long jump. Around 70% of HBW showed low performance in the running speed test.
Conclusion:
Both low and high birth weight can influence adult adiposity and the performance in physical fitness tests.
Objective: A dysfunction of the sympathetic nervous system may contribute to the development of hypertension and obesity in subjects with low birth weight (LBW). The present study examines resting sympathetic nerve traffic and its baroreflex modulation to the muscle vascular bed in healthy LBW subjects.
Design: Case–control studies of 13 healthy LBW subjects (< 2500 g at term) aged 20–30 years and 13 normal birth weight subjects (NBW; 3200–3700 g) closely matched for age, gender and body mass index.
Methods: Muscle sympathetic nerve activity (MSNA) recordings from the superficial peroneal nerve, blood pressure and heart rate were obtained at rest, during an inspiratory apnoea and a cold pressor test. Baroreflex function was evaluated by short-term infusion of nitroprusside and phenylephrine, respectively, in nine subjects of each group.
Results: During resting conditions burst frequency was significantly lower in LBW subjects (LBW: 24.7 ± 2.4; NBW: 34.4 ± 2.1 bursts/min, P < 0.05). When normalized for the different baseline values, baroreflex-mediated changes in MSNA were similar in both groups. Maximal MSNA levels in response to inspiratory apnoea and the cold pressor test did not differ between the groups. Blood pressure and heart rate were similar in LBW and NBW subjects both at rest and during sympatho-excitatory manoeuvres.
Conclusions: Subjects born too small for their gestational age show a significantly lower sympathetic nerve activity under baseline conditions. Given the different baseline values, the sympathetic response to haemodynamic alteration is not affected in LBW subjects, and maximal activation during non-haemodynamic sympatho-excitatory manoeuvres is preserved.
This chapter reviews evidence that the risk of type 2 diabetes mellitus (T2DM) in adult life may be set by factors operating early in the life course of an individual. There is consistent evidence linking small size at birth to T2DM in later life. This association appears to be mediated through insulin resistance and to be at least partially explained by the effects of environmental exposure in utero. However, this small baby syndrome is unlikely to be the main explanation for ethnic differences in rates of diabetes and insulin resistance, where genetic factors are important. The effects of reduced fetal growth in diabetes risk are modest compared with the effects of other factors that may be amenable to intervention: exposure to maternal hyperglycemia and obesity.
The field of life course epidemiology has expanded rapidly since this book was first published. The purpose of this field is to study how biological and social factors during gestation, childhood, adolescence, and earlier adult life independently, cumulatively, and interactively influence later life health and disease. Contributors to this edition capture the excitement of the developing field and assess the latest evidence regarding sources of risk to health across the life course and across generations. The chapters on life course influences on cardiovascular disease, diabetes, blood pressure, respiratory disease, and cancer have been updated and extended. New chapters on life course influences on obesity, biological ageing, and neuropsychiatric disorders have been added. Life course explanations for disease trends and for socioeconomic differentials in disease risk are given more attention in this edition, reflecting recent developments in the field. The section on policy implications has been expanded, assessing the role of interventions to improve childhood social circumstances, as well as interventions to improve early growth. Emerging new research themes and the theoretical and methodological challenges facing life course epidemiology are highlighted.
Glucocorticoids (Cortisol and corticosterone) have a host of biological effects inbrain and body, underpinning adaptive responses to stress and maintaining criticalaspects of basal metabolism (de Kloet 2004). Many neural and glial systems aremodified by glucocorticoids and their target genes include neurotransmitter systems,receptors, ion channels, cytoskeletal proteins, enzymes, second messengersystems, and metabolism. Acute rises of glucocorticoid levels are adaptive responsesto diurnal cues or stress, facilitating survival pathways and inhibiting immediatelyunhelpful processes such as digestion and inflammation. In contrast, chronicelevations of glucocorticoids (e.g., Cushing's syndrome) are detrimental to homeostasisat all phases of life from embryogenesis to senescence (de Kloet 1991, 2004).In the central nervous system (CNS), chronic glucocorticoid excess exerts profoundadverse effects, producing neuropsychiatric dysfunction (depression, psychosis),cognitive impairments, structural deterioration, and neuroendocrine abnormalities(McEwen 1999, 2003). Conversely, chronic severe deficiency of glucocorticoids(Addison's disease) is also deleterious, reducing an organism's survival in stressfulcircumstances and associating with reduced mood and hippocampal neuronal loss(Sloviter et al. 1989). Thus, it is obviously crucial that glucocorticoid levels arestrictly controlled. This is ensured by negative feedback control of the hypothalamic-pituitary-adrenal (HPA) axis. Glucocorticoids act predominantly by binding tointracellular receptors of two types; lower-affinity, widely distributed glucocorticoidreceptors (GR) and higher-affinity mineralocorticoid receptors (MR), whichhave a restricted tissue distribution (de Kloet 1991, 2004). In the hippocampus,where GR and MR are both highly expressed, both receptors bind the same glucocorticoidligands in vivo. Because the genes regulated by GR and MR in the hippocampusare largely distinct (Vreugdenhil and de Kloet 1998), nuclear accessory factors(coactivators and corepressors (Jenkins et al. 2001)) and the fine kinetics ofreceptor-DNA binding are also likely to be important. However, is the product of circulating steroid levels and this transcriptional machinery all there is to glucocorticoidbiology?
Introduction The series of epidemiological studies that set the ball rolling for DOHaD research, by linking data from old obstetric and child health records to adult outcomes, were based in (so-called) developed countries. In brief, they showed that adult cardiovascular disease, type 2 diabetes and the metabolic syndrome were increased in people who were light or thin at birth and during infancy, gained weight or body mass index (BMI) rapidly in childhood, and became overweight or obese adults (Barker 1989, Hales et al. 1991, Barker et al. 1993, Osmond et al. 1993, Forsen et al. 1997, 1999, Eriksson et al. 2001, 2003). The associations with accelerated childhood weight gain and adult obesity were strongest in those who were smallest at birth. These findings led to the ‘fetal origins’ and ‘thrifty phenotype’ hypotheses, which proposed that undernutrition during early development, and a mismatch between undernutrition at this time and later overnutrition and obesity, are crucial factors in the development of these adult diseases (Barker 1989, 1995, Hales and Barker 1992) The concept that cardiovascular disease and type 2 diabetes, generally considered diseases of affluence, have their origins in transition from poverty and undernutrition offered an explanation for the epidemics of coronary heart disease that swept Europe and the USA in the mid twentieth century (Barker et al. 1989). These appeared first in higher socioeconomic groups (the first to experience transition) and later shifted to the less advantaged (the last to experience improvements in fetal and infant nutrition). © P. D. Gluckman and M. A. Hanson 2006 and Cambridge University Press, 2009.
Introduction A clear relationship exists between intrauterine development and predisposition to postnatal disease. It is now understood that pre- and periconceptional nutritional status, glucocorticoid exposure and immediate postnatal development including catch-up growth may all contribute to these influences of early development on later-life disease. Barker and colleagues have described in detail the potential influence that an adverse intrauterine environment could play in the risk of developing particular diseases later in life (Barker 1994a, 1994b, 1995). It has been proposed that resetting of endocrine axes controlling growth and development could be one pathway for the developmental programming of later health and wellbeing. The fetal hypothalamic-pituitary-adrenal (HPA) axis in particular is highly vulnerable to changes in the intrauterine environment. Fetal HPA axis activity increases with gestation in most species and contributes to increased fetal levels of circulating glucocorticoids (Fowden et al. 1998). Even subtle changes in the intrauterine environment can disrupt the delicate balance of fetal HPA development and glucocorticoid production and can therefore alter long-term HPA activity and function. HPA hyperactivity has been demonstrated in animals after prenatal undernutrition (Lingas et al. 1999), prenatal stress (Takahashi and Kalin 1991) and maternal synthetic glucocorticoid administration (Uno et al. 1990, Sloboda et al. 2000). Programming of the fetal HPA axis during development appears to play a central role in the link between fetal growth and long-term disease in adulthood. Prenatal programming of HPA axis function may increase the risk of developing cardiovascular and metabolic diseases. © P. D. Gluckman and M. A. Hanson 2006 and Cambridge University Press, 2009.
The ‘fetal origins of adult disease (FOAD)’ hypothesis proposes that developmental programming during gestation may influence adult health and disease [1]. It suggests a process where events occurring at critical, or sensitive, periods of fetal development, permanently alter structure, physiology, or metabolism. These changes predispose affected individuals to diseases in later life.
Barker and his colleagues were the first to develop the concept of FOAD based on significant associations between low birthweight and the risk of chronic diseases in adulthood, including coronary artery disease, hypertension and stroke, type 2 diabetes, and osteoporosis. Several other groups confirmed associations between birthweight and adult health in other populations. These adverse intrauterine environments include gestational diabetes mellitus (GDM), intrauterine undernutrition and pre-eclampsia, which are common and severe gestational complications. Furthermore, certain antenatal nutritional disturbances can increase the risk of diseases later in life without affecting fetal growth. In this chapter, we will discuss the evidence related to adverse intrauterine environment and embryo-fetal origins of diseases.
Research on nutrition in the pediatric clinic is increasingly concerned with the health of neonates and children rather than with their nutritional needs. Indeed, it is becoming increasingly clear that poor or excessive nutrition, above all in the first periods of life, has an important impact on the development of chronic metabolic diseases, both in the pediatric age and in adulthood. To improve the understanding of the relations among nutrition, integrated metabolism, and health, nutritionists are evaluating the metabolomic approach has an important tool to establish single nutritional phenotypes, that is, the way in which diet interacts with individual's metabolisms so as to provide a complete definition of their health and diseases.
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