出生体重及婴儿期体重与成年后白细胞计数的相关关系:5619例男、女性从胎儿期到成年期的随访观察

以低出生体重为标志的胎儿生长不良与成年后冠心病风险增高相关.虽然研究结果并不一致,但这种关联可能是经由冠心病的危险因子如高血压或血脂异常所介导.此外,低出生体重与成年后的胰岛素抵抗也有关,后者可导致糖尿病的发生.也可使动脉粥样硬化性疾病的风险增加.另一方面,也可能低出生体重的婴儿有一种共同因子,使他们在成年后冠心病和糖尿病风险增高.     

宫内缺氧对胎儿、新生儿及成年子代心脏功能的影响及相关研究进展

宫内缺氧是胚胎发育中的常见综合征,多见于产前期病理生理高危妊娠,或由于血管病变使子宫血流减少,使宫内胎儿供氧减少,引起胎儿生长迟缓,严重的可引起胎儿死亡。妊娠期间慢性宫内缺氧可抑制胎儿心脏功能,改变心脏基因表达,增加心肌程序性细胞死亡,还可导致心肌细胞过早退出细胞周期和心肌肥厚,这些改变不仅在围生期表现明显,而且可能通过生理和代谢的程序化控制,引起成年子代心脏结构和功能的改变,造成成年心脏对缺血-再灌注损伤的易感性增加。现就宫内缺氧对胎儿、新生儿及成年子代心脏功能的影响及相关研究进展进行综述。     

030 妇女怀孕期间高胆固醇对儿童早期动脉粥样硬化的影响:儿童早期损害结果(FELIC)的研究

儿童血浆胆固醇较低,没有动脉粥样硬化的临床表现.但动脉壁脂肪斑纹在胎儿期开始形成,如果母亲怀孕期间高胆固醇,会增加胎儿脂肪斑纹形成.在FELIC研究中证明动脉粥样硬化损害发生在儿童时期.     

超声检查评价肥胖儿童血管系统功能的价值

近年来，儿童期单纯肥胖症发生率呈上升趋势。鉴于肥胖儿童成年后动脉粥样硬化（AS）性心血管疾的发生率明显升高，对其心血管系统功能的早期检测与评价非常必要。AS被认为是小儿时期得病、成人发病的疾病，动脉内膜的脂质沉积在小儿，甚至胎儿时期即开始，表现为动脉血管内皮功能障碍以及血管内膜的节段性增厚，经过一段很长的亚临床阶段，直到血流减少到一定程度才出现缺血的临床症状。     

妊娠期糖尿病对新生儿脂代谢的影响

妊娠期糖尿病（GDM）由于糖脂代谢紊乱,不仅增加围产期母亲和子代的并发症,如妊娠期高血压、剖宫产率高、巨大儿、新生儿低血糖等,也可造成胎儿在宫内处于高营养状态,进而导致胎儿代谢紊乱,甚至流产、死胎.英国环境流行病学家巴克教授于1986年提出了成人慢性疾病胎儿起源假说,且此后有多项研究表明生命早期营养状态与成年后高血压、冠心病、脑卒中、2型糖尿病、肥胖和代谢综合征等疾病的发病率密切相关.目前,对生命早期营养状态的研究已经涉及胎儿出生体重、出生体型、食量和生长发育状况等.     

2型糖尿病的发生——节俭表现型假说

胎儿生长发育不良与其成年后糖耐量减低 (IGT)和 2型糖尿病 (T2DM)的高发生率有关。胎儿出生时的大小取决于宫内生长环境而不是遗传因素。“节俭表现型假说”认为胎儿为适应不利的宫内环境 ,改变生长发育的“程序化”过程 ,而这些改变保持下来 ,最终导致IGT、T2DM。     

实验动物和人体动脉粥样硬化的消退

在美国,动脉粥样硬化是危害成年居民的最严重疾病;半数以上的男性和很高百分比的女性死于此种疾病。动脉粥样硬化引起的死亡数和丧失劳动力,比肿瘤、糖尿病和所有感染加上意外事故所引起的总数还要多。日益增多的证据表明,动脉粥样硬化过程几乎是完全可以预防的,它基本上是可逆的。     

生命早期肠道菌群的形成及影响因素

从受孕开始至2周岁这1 000 d被称为“生命早期1 000 d”,是机体健康可塑性最强的阶段,是生长发育的第一个关键时期,也是预防成年慢性非传染性疾病的“机遇窗口期”。在这个关键时期遇到的不同因素可能会影响肠道微生物组成,从而影响以后的患病风险,例如特异性疾病、代谢紊乱、动脉粥样硬化性疾病和神经系统疾病等。本文将主要对出生前胎儿、新生儿及3岁以前婴幼儿时期肠道菌群的形成及其出生后受胎龄、分娩方式、喂养方式、食物、抗生素等因素的影响机制进行综述,为相关临床疾病治疗奠定基础,对保障人类长期健康提供新思路。     

周围动脉内膜-中层厚度在动脉粥样硬化中的应用

动脉粥样硬化为一进行性疾病 ,其病程一般在儿童时就开始至成年的中后期才表现出临床症状。冠心病常发生在一生中职业生涯最好的时刻。因此 ,如何早期发现和防治动脉粥样硬化 ,就显得尤为重要。近年来研究表明高频超声测量周围动脉血管壁的内膜 中层厚度 (intima mediathickness ,IMT)的变化不仅被认为动脉粥样硬化的早期改变 ,而且被作为研究冠状动脉粥样硬化的间接指标和窗口。1　动脉IMT增加是动脉粥样硬化的早期标志超声显像所测IMT与组织学上的IMT有很好的一致性。在超声影像上动脉的IMT是指第一条线状较高强回声 (管腔 内膜界…     

出生时身长体重可预测60～70岁时机体下丘脑-垂体-肾上腺轴对社会心理应激的反应

胎儿时期的环境可能对成年后一些常见疾病的易感性有重大影响,如心血管疾病、2型糖尿病及抑郁症.下丘脑-垂体-肾上腺轴(HPAA)在人一生中的发展过程可能是连接两者的关键因素.许多关于人类的流行病学调查已经显示,出生时体重低或早产儿成年后HPAA活性增高.     

Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: a theoretical review

BACKGROUND: Despite good evidence that ethanol abuse in adulthood is more likely the earlier human adolescents begin drinking, it is unclear why the early onset of drinking occurs in the first place. A review of experimental studies with animals complemented by clinical, epidemiologic and experimental studies with humans supports the idea that precipitating conditions for ethanol abuse occur well before adolescence, in terms of very early exposure to ethanol as a fetus or infant. Experimental studies with animals indicate, accordingly, that ethanol intake during adolescence or adulthood is potentiated by much earlier exposure to ethanol as a fetus or infant. METHODS: Two broad theoretical frameworks are suggested to explain the increase in affinity for ethanol that follows very early exposure to ethanol, one based on effects of mere exposure and the other on associative conditioning. Studied for 50 years or more in several areas of psychology, "effects of mere exposure" refers to enhanced preference expressed for flavors, or just about any stimuli, that are relatively familiar. An alternative framework, in terms of associative conditioning, is guided by this working hypothesis: During ethanol exposure the fetus or infant acquires an association between ethanol's orosensory (odor/taste) and pharmacological consequences, causing the animal subsequently to seek out ethanol's odor and taste. RESULTS AND CONCLUSIONS: The implication that ethanol has rewarding consequences for the fetus or young infant is supported by recent evidence with perinatal rats. Paradoxically, several studies have shown that such early exposure to ethanol may in some circumstances make the infant treat ethanol-related events as aversive, and yet enhanced intake of ethanol in adolescence is nevertheless a consequence. Alternative interpretations of this paradox are considered among the varied circumstances of early ethanol exposure that lead subsequently to increased affinity for ethanol.     

Environmental and genetical aspects of the link between pregnancy, birth size, and type 2 diabetes

Exposure of the fetus to the intrauterine milieu can have profound effects on the health of the offspring in adulthood. These observations are highly reproducible in many populations worldwide although the mechanisms behind them remain elusive. The 'thrifty phenotype' hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. Results of a series of studies demonstrate the powerful influence of the mother's metabolic state on whether the emerging adult develops obesity and hyperinsulinemia. Importantly, these attributes can be passed on to the next generation non-genetically and can be reversed and prevented. Such hypothesis has been expanded on by the "Developmental Origins of Health and Disease" (DOHaD) hypothesis which describes the origin of adult disease in terms of fetal developmental 'plasticity' or the ability of the fetus to respond to poor in-utero conditions. A wealth of epidemiological evidence has provided a convincing link between a sub-optimal gestational environment and an increased propensity to develop adult onset metabolic disease. In this paper the factors that participate in the programming of the fetus and infants that lead to endocrine dysfunction in postnatal life are reviewed.     

Increased LDL cholesterol and CRP in infants of mothers with type 1 diabetes

BACKGROUND: Proatherogenic stimuli during foetal life may predispose to development of atherosclerosis in adulthood. Elevated plasma low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) expression is associated with increased risk of atherosclerosis. METHODS AND RESULTS: In this study, we examined how maternal type 1 diabetes affects foetal plasma LDL cholesterol and CRP. In comparison with healthy mothers, the plasma LDL cholesterol was not increased in the mothers with diabetes, however, the umbilical-cord plasma LDL cholesterol was increased in their infants. CRP was increased in infants of mothers with diabetes and high haemoglobin A1c (HbA1c, >/= 6.2%). Human placenta expresses microsomal triglyceride transfer protein (MTP), which facilitates secretion of apolipoprotein B-containing lipoproteins. Microsomal triglyceride transfer activity was slightly higher (11%) in placentas from mothers with diabetes and HbA1c >/= 6.2% compared with the controls. CONCLUSION: The results suggest that maternal type 1 diabetes increases the foetal plasma LDL cholesterol and CRP concentration and thus might predispose the offspring to development of atherosclerosis. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Mismatched pre- and postnatal nutrition leads to cardiovascular dysfunction and altered renal function in adulthood

The early life environment has long-term implications for the risk of developing cardiovascular (CV) disease in adulthood. Fetal responses to changes in maternal nutrition may be of immediate benefit to the fetus, but the long-term effects of these adaptations may prove detrimental if nutrition in postnatal life does not match that predicted by the fetus on the basis of its prenatal environment. We tested this predictive adaptive response hypothesis with respect to CV function in sheep. We observed that a mismatch between pre- and postnatal nutrient environments induced an altered CV function in adult male sheep that was not seen when environments were similar. Sheep that received postnatal undernutrition alone had altered growth, CV function, and basal hypothalamo-pituitary-adrenal axis activity in adulthood. Prenatal undernutrition induced greater weight gain by weaning compared with the prenatal control diet, which may provide a reserve in the face of a predicted poor diet in later life. In an adequate postnatal nutrient environment (i.e., relatively mismatched), these offspring exhibited cardiac hypertrophy and altered CV function in adulthood. These data support the concept that adult CV function can be determined by developmental responses to intrauterine nutrition made in expectation of the postnatal nutritional environment, and that if these predictions are not met, the adult may be maladapted and at greater risk of CV disease. Our findings have substantial implications for devising strategies to reduce the impact of a mismatch in nutrition levels in humans undergoing rapid socio-economic transitions in both developing and developed societies.     

Evolutionary interactions between diabetes and development

Because of the complications of diabetes affecting the mothers and their fetus/newborns are less known, this review examined the epidemiologic and mechanistic issues involved in the developmental programming of diabetic mothers. This overview showed that sperm, egg, zygote or blastocyst derived from diabetic parents may develop into offspring with high risk of any type of diabetes, even if placed in a normal uterus, producing developmental delay, embryopathy, geno- and cyto-toxicity, teratogenic changes, free radicals and apoptosis. These early insults may then lead to an increased rate of miscarriage and congenital anomalies depending on free radicals signaling and cell-death pathways involved by the diabetogenic agents. Furthermore, sperm, egg, zygote or blastocyst from normal parents will have an increased risk of diabetes if placed in a diabetic uterus. Interestingly, diabetes has deleterious effect on male/female reproductive functions and on the development of the blastocysts/embryos. Indeed, this review hypothesized that the long-term effects of diabetes during the pregnancy (gestational diabetes) may influence, generally, on the health of the embryos, newborns (perinatal life) and adulthood. However, there are obvious species differences between pregnant women and animal models. Thus, maintaining normoglycaemia during pregnancy may play an important role in a healthy life for the newborns.     

Schilddr��senerkrankungen und Schwangerschaft

Pregnancy causes a number of physiological alterations in thyroid hormone metabolism that need to be distinguished from the pathophysiological states of thyroid dysfunction. Both hypothyroidism and thyrotoxicosis may impair the course of pregnancy and may negatively affect the fetus. In particular, maternal hypothyroidism may lead to irreparable and detrimental deficits in the neurocognitive development of the fetus. Autoimmune thyroid disease is the most common cause of thyroid dysfunction in pregnancy. Hashimoto's thyroiditis is associated with impaired fertility and miscarriage, and may first manifest in pregnancy due to the increased thyroid hormone requirement. Graves' disease often shows a characteristic course in pregnancy with amelioration of thyrotoxicosis in the second half of pregnancy and exacerbation after delivery. In addition transplacental passage of maternal TSH receptor antibodies may lead to thyrotoxicosis in the fetus and/or newborn.     

Developmental programming of cardiovascular disorders: Focus on hypertension

Increasing evidence suggests that adult cardiovascular disorders, e.g. hypertension, can be “programmed” in utero. The mechanisms that affect the developing fetus and lead to future cardiovascular disease are not fully established. This review addresses the possible involvement of maternal nutrition, sex steroids and other endocrine factors in the programming of hypertension in adulthood. Some possible mechanisms of subsequent development of hypertension in adulthood, such as elevated sympathetic and renin–angiotensin system activity, and failure of nephron development, also are discussed. Previous studies suggest that maternal undernutrition could be a major factor in fetal programming, but in light of the increased worldwide prevalence of obesity, maternal overnutrition is now receiving increased attention. Special emphasis is given here to this phenomenon. Obesity is associated with increased serum and tissue levels of proinflammatory cytokines, and loss of sensitivity to the adipokine leptin. It is postulated that this causes dysregulation of the hypothalamo–pituitary–adrenal axis, resulting in increased levels of circulating glucocorticoids. These factors could play a major role in programming, during the in utero period, of future hypertension in the offspring of obese mothers.     

Prenatal exposure to interleukin-6 results in hypertension and increased hypothalamic-pituitary-adrenal axis activity in adult rats

During pregnancy, systemic inflammatory responses induce cytokines that may stress the fetus and contribute to cardiovascular and neuroendocrine dysfunction in adulthood. We evaluated the effects of early and late prenatal exposure to IL-6 on mean systolic arterial pressure (MSAP) and hypothalamic-pituitary-adrenal (HPA) axis regulation in male and female rats at 5-24 wk of age. MSAP and ACTH and corticosterone levels were measured basally and in response to a novel environment, immobilization stress, and stimulation with corticotropin-releasing factor (CRF) and ACTH. In addition, mRNA expression and protein levels of glucocorticoid receptor, mineralocorticoid receptor, CRF receptor type 1, and CRF were estimated in brain areas thought to mediate central effects of corticosteroids on the HPA axis and on central neuroendocrine regulation of MSAP. Both early and late prenatal IL-6 exposure led to hypertension, which was evident in females at 5 wk of age. In adult rats, basal ACTH and corticosterone levels were elevated, the responses to stress and stimulation tests were of extended duration, and circadian rhythm during the light period was flattened and reversed. Mineralocorticoid receptor and glucocorticoid receptor mRNA expression was reduced in the hippocampus, the CRF level was increased in the hypothalamus, and CRF receptor type 1 mRNA expression was increased in the pituitary. These findings suggest that fetal stress induced by prenatal exposure to IL-6 leads to hypertension and dysregulation of HPA axis activity during adulthood.     

Childhood Obesity and Cardiovascular Disease Risk: Working Toward Solutions

The prevalence of obesity in childhood is high and continues to increase globally. It is currently estimated that 381 million children worldwide have overweight or obesity. This disease stems from multiple complex pathways that can present early in life. This is particularly concerning because childhood obesity is associated with cardiovascular risk factors that can lead to early atherosclerosis and premature cardiovascular disease (CVD). Hypertension, dysglycemia, dyslipidemia, and systemic inflammation are associated with vascular changes in childhood, and these contribute to increased risk of cardiovascular events in adulthood if not adequately treated. Interventions to treat childhood obesity include multicomponent family-based behaviour modification programs, which have been demonstrated to have moderate short-term effects on weight-related outcomes; their effects on cardiovascular risk factors, however, are less well understood. Although supervised, structured exercise interventions result in improvements in blood pressure, inflammation, carotid artery intima media thickness, dysglycemia, dyslipidemia, and endothelial dysfunction in children with obesity in the short term, our understanding of how to translate these interventions into long-term sustainable exercise or physical activity recommendations remains uncertain. Research focus in these areas will help in treating childhood obesity and associated CVD risk factors to prevent CVD development in adulthood.     

Intrauterine growth, the vascular system, and the metabolic syndrome

There is substantial evidence linking birth size with the risk of developing cardiovascular disease and its major biological risk factors in adulthood. The fetal origins hypothesis proposes that these diseases originate through adaptations, which the fetus makes when it is undernourished. These adaptations may be cardiovascular, metabolic, or endocrine. They permanently change the structure and function of the body. Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus. The purpose of this article is to examine some of the more recent epidemiological associations between low birth weight and adult atherosclerotic vascular disease and its risk factors. We will also discuss mechanisms that might explain these associations.