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代写coursework,Weight Cardiovascular Heart
发表日期:2013-09-19 08:32:58 | 来源:assignment.cc | 当前的位置:首页 > 代写coursework > 正文

Introduction

In 1989, Dr. David Barker and his colleagues, working in University of Southampton, suggested that lower weight of an infant at birth and during infancy had a direct correlation with a higher risk of cardiovascular disease later in life. Later studies conformed to the idea that poor nutritional conditions of the mother resulted in low birth weight, which was associated with subsequent development of coronary heart disease, hypertension and diabetes type II. He compiled his findings and postulated ‘Barker’s Hypothesis’, now renamed as ‘Fetal Origins Hypothesis’.

‘Fetal Origins Hypothesis proposes that coronary heart disease originates through responses to under nutrition during fetal life and infancy, which permanently changes the body’s structure, physiology, and metabolism.’(1)

It was suggested that low birth weight, at full term, indicated malnourishment. Therefore, it was implied that the fetus made physiological adjustments to prepare itself for life. Consequently, changes in the fetus’ physiology and metabolism, made it more prone to chronic diseases in adulthood. Further, it shed light on the dramatic consequences of increases in weight after the age of two years. It proposed that the risk of developing coronary heart disease and diabetes type II rapidly increases due to weight gain after the age of two years.(1)

Prenatal Period

The prenatal period is divided into an embryonic period and a fetal period. After conception, the embryonic period lasts for 8 weeks. During this period, all the body organs are formed and the embryo forms a distinctly human appearance. Further, morphogenesis starts after the third week of development. The end of the embryonic period marks the beginning of the fetal period. Anatomically, the fetal period manifests by the vascular penetration of the humerus. The fetus is not as prone to damage as the embryo was to environmental exposures during the embryonic period. This phase is marked by growth and development of major structures already formed in the fetus.

Genes play a vital role in the development of necessary organs of the body. Environmental influences can disrupt the functioning of ‘imprinted genes’ resulting in inhibited growth, thus affecting the birth weight. Consequently, there is a higher risk of chronic diseases developing in later life. These imprinted genes are prone to alterations as they are functionally haploid and have different controlling mechanisms than the rest of the genome. (2)

Malnourishment can disrupt the fetus’ cell cycles and slow down their cellular division. Therefore, the fetus physiologically adapts by favoring development of vital organs, such as the brain, over the growth of non essential organs such as kidney (nephron mass) and the pancreas (beta cell mass).Consequently, these developmental adaptations, in response to deficient maternal-placental nutrient supply, may be the root of future chronic diseases later in life.(3)

Birth Mass and Diabetes Mellitus

A number of studies have showed the correlation with low birth weight and insulin resistance. Preston studies show the direct relationship between low birth weight and insulin resistance, measured using the ponderal index. (4) Table 1 shows the relationship between reduced birth weight and diabetes type II. (5)

Possible Mechanism:

Maternal malnourishment results in a decrease in insulin production and increase in peripheral insulin resistance. Subsequently, more glucose is diverted towards the brain and heart and less towards tissues, such as skeletal muscle, which are more insulin dependant.(6)Therefore, muscles become resistant to insulin. Consequently, later in life, when adequate nutrients are available, peripheral insulin resistance can cause glucose intolerance and diabetes. (6) The Preston studies conform to the idea that undernourished babies have muscles which become resistant to insulin. (4)

On average, there are one million nephrons in a normal kidney. (7) However, maternal under nutrition can change the progamme of development. According to Widdowson and Mccance, malnourishment can result in decreased number of cells. (4) Further, studies show that low birth weight result in a decreased number of nephrons and associated increase in glomerular volume. (7)

Possible Mechanisms

Fetal growth restriction has adverse effects on kidney development. According to Brenner and Mackenzie, such restrictions result in decrease in number of nephrons. In addition to that they proposed that there is an associated increase in glomerular filtration rate and hydrostatic pressure. Consequently, there is an increase in the risk of developing glomerular sclerosis.(8) In order to maintain adequate kidney function, the reduced number of glomeruli undergo hypertrophy and hyperfiltration. Subsequently, intraglomerular hypertension is compromised, further damaging the kidney and increasing nephron loss. (7) Moreover, Keijzer-Veen and colleagues recognized an inverse relationship between birth weight and serum creatinine implying that low birth weight was associated with a higher risk of developing progressive renal failure. (8) Diagram 1 shows a summary of events leading to kidney failure. (7)

Link between Birth Weight and Hypertension

Kidney is a vital organ in controlling blood pressure. The association of intrauterine events with kidney development imply there effect on development of hypertension. Initially described by Guyton, the kidney’s role in the rennin-angiostatin-aldosterone system and its homeostatic functions are well accepted.(7) In addition to that, number of studies have showed a direct association of low birth weight and development of hypertension in adult life. The link between birth weight and hypertension was first demonstrated by Barker and Osmond in a cohort of 46 to 64 year olds. (7) According to the Helsinki studies, there was inverse correlation between birth weight and blood pressure.

Possible Mechanisms

Brenner and Chertow postulated that decreasednephron number associated with retarted fetal growth could increaserisk of hypertension and chronic renal disease/failure. (9)They also hypothesized about a concept known as ‘nephron dosing.’ They suggested that reduced number of nephrons for a constant body mass resulted in an imbalance between the load to be excreted and capacity of the nephron. As a result, the infant is prone to hypertension later in life. Further, experimental work has shown how decreased numbers of nephrons activate renin-angiotensin system to maintain glomerular filtration rate. Therefore, sodium and water retention increases resulting in increase in blood pressure. (9) In addition to that, lack of stretchiness in vessel walls and excess glucocorticoids, which induce expression of angiotensin related molecules, make the infant more prone to hypertension later in life.(4,8) Diagram 2 summarizes the effect of reduced number of nephrons. (9)

Birth Mass and Cardiovascular Disease

Diabetes type II, kidney disease and hypertension are potential causal agents of cardiovascular disease. As illustrated above, the relationship between low birth weight and the diseases mentioned, there is an indirect link to cardiovascular disease. Furthermore, a small number of studies have shown the inverse association between mass at birth with cardiovascular disease in later life. (10) Scarcities of food supply to mothers results in the fetal programme to adapt to a situation where undernourishment is the norm. However, when these individuals turn obese in later years, they have an increased risk of cardiovascular disease.

Prevalence of cardiovascular disease (CVD) risk factorclustering (percentage of individuals with at least 3 of systolic blood pressure, glucose and triglycerides in the highest sex-specific tertile,and HDL cholesterol in the lowest tertile) within joint tertiles of birthweight and adult body mass index (BMI) among men and women born during the Institute of Nutrition of Central America and Panama (INCAP) supplementation study in one of 4 study villages in Guatemala; 1969–1976, and examined in 1997–1999.

Criticisms

All hypotheses need thorough measures of refutation. A number of criticisms have been raised with regard to the Fetal Origins Hypothesis. It has been suggested that coronary heart disease in later life is associated with one or more confounding factors including parental features, such as low socioeconomic status, genetic and environmental factors resulting in coronary heart disease. Hübinette and colleagues concluded from their research that low birth mass and development of coronary heart disease later in life is resultant from the combination of genetic factors and unmeasured maternal influences that function independently of birth weight. (12)

Moreover, studies conducted in Southampton have certain inconsistencies. In those studies, measures of actual nutrition were not recorded. ‘Early nutrition isinferred indirectly from fetal and infant growth, and fetalgrowth especially is a doubtful surrogate measure. Thus evenif we take the findings as valid we still must ask whether nutritionor some other effect is being measured.’(13) In short, maternal nutrition is not equivalent to fetal nutrition. Additionally according to Kramer & Joseph (1996), there is significant selection bias in the retrospective studies conducted. (14)

Furthermore, most of the studies done till now take into account two points in time to measure the weight- one at birth and one later in life. Without another transitional measuring point, it is hard to differentiate whether cardiovascular diseases are linked to fetal and postnatal exposures or are merely elements of postnatal growth. (15)

Conclusions

Recent systematic overviews show strong inverse associations between birth weight and cardiovascular disease, diabetes type II, hypertension and kidney disease. (15) Taking into account its criticisms, it would be safe to conclude that retarded fetal growth is linked with increase in risk of developing the above mentioned diseases in later life. Barker’s hypothesis has created awareness on a large scale level defining the importance of maternal nourishment and its effects on causing subsequent disease in future. In addition to that, explanations regarding genetic and environmental influences, and confounding factors such as socioeconomic status cannot be excluded with regard to their effect on the development of chronic disease later life. On the whole, the fetal origins hypothesis has been a discovery and a very important one leading to a whole new explanation of the development of chronic diseases in adult life.

Summary

In short, fetal development is dramatically influenced by environmental factors including chemical, physical and biological factors. Consequently, fetal programming results in physiological adaptations affecting fetal growth and birth weight. Moreover, compensatory effects result in disturbances in normal growth of crucial organs. As a result birth weight is reduced. Furthermore, post natal increase in weight as an attempt to rectify the low birth weight is harmful to the child in the later years as it further increases the risk of cardiovascular disease. Lastly, these influences can be passed on from generation to generation. (16)

Literature Cited

(1) The Science - The Barker Theory. Available at: http://thebarkertheory.org/science.html. Accessed 3/22/2008, 2008.

(2) Young LE. Imprinting of genes and the Barker hypothesis. Twin Research 2001 Oct;4(5):307-317.

(3) Bihl GR. Intrauterine growth and disease in later life--Barker and beyond. South African Medical Journal.Suid-Afrikaanse Tydskrif Vir Geneeskunde 2003;93(10):757-760.

(4) Barker DJ. The fetal origins of coronary heart disease. Eur.Heart J. 1997 Jun;18(6):883-884.

(5) Barker DJ. Adult consequences of fetal growth restriction. Clinical Obstetrics & Gynecology 2006 Jun;49(2):270-283.

(6) de Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Aust.N.Z.J.Obstet.Gynaecol. 2006 Feb;46(1):4-14.

(7) Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension 2006 Mar;47(3):502-508.

(8) Lackland DT. Mechanisms and fetal origins of kidney disease.[comment]. Journal of the American Society of Nephrology 2005 Sep;16(9):2531-2532.

(9) Bagby SP. Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming. J.Nutr. 2007 Apr;137(4):1066-1072.

(10) Lawlor DA, Ronalds G, Clark H, Smith GD, Leon DA. Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: findings from the Aberdeen Children of the 1950s prospective cohort study. Circulation 2005 Sep 6;112(10):1414-1418.

(11) Stein AD, Conlisk A, Torun B, Schroeder DG, Grajeda R, Martorell R. Cardiovascular disease risk factors are related to adult adiposity but not birth weight in young guatemalan adults. J.Nutr. 2002 Aug;132(8):2208-2214.

(12) Poulter NR. Birthweights, maternal cardiovascular events, and Barker hypothesis. The Lancet, 2001 6/23;357(9273):1990-1991.

(13) Paneth N, Susser M. Early origin of coronary heart disease (the "Barker hypothesis"). BMJ 1995 Feb 18;310(6977):411-412.

(14) Langley-Evans SC. Fetal programming of cardiovascular function through exposure to maternal undernutrition. Proc.Nutr.Soc. 2001 Nov;60(4):505-513.

(15) Gillman MW. Epidemiological challenges in studying the fetal origins of adult chronic disease. Int.J.Epidemiol. 2002 Apr;31(2):294-299.

(16) Sobsey D. Fetal Programming: Implications for Development and Developmental Disability. Available at: http://209.85.173.104/search?q=cache:2dpttiNsV2YJ:www.ualberta.ca/~jpdasddc/ARTICLES/2000(2)/pp71-75SobseyFetal.pdf+Fetal+Programming:+Implications+for+Development+and+Developmental+Disability&hl=en&ct=clnk&cd=1&gl=uk. Accessed 4/14/2008, 2008.

 

介绍
1989年,大卫·巴克博士和他的同事,在南安普敦大学的工作,建议低体重的婴儿在出生婴儿时期的风险较高的心血管疾病,在以后的生活有直接的关联。后来的研究符合营养条件差,母亲的想法,导致低出生体重,这是冠状动脉心脏疾病,高血压和II型糖尿病相关的后续发展。他编写了他的研究结果,推测巴克的假说“ ,现更名为”胎儿起源假说“ 。
(1) “胎儿起源假说,冠状动脉心脏疾病的起源,通过反应在胎儿期和起步阶段,永久改变身体的结构,生理和代谢营养。
有人提出,低出生体重,足月,表示营养不良。因此,有人暗示,胎儿生理调整生活作好准备。因此,在胎儿的生理和代谢变化,使得它更容易在成年后的慢性疾病。此外,它揭示重量增加后的戏剧性后果两岁。 (1)它建议两岁后迅速发展冠状动脉心脏疾病和II型糖尿病的风险增加,由于体重增加。
胎儿期
胎儿期分为胚胎期和胎儿期。受孕后,胚胎时期持续8周。在此期间,所有的身体器官的形成和胚胎形成了人类特有的外观。此外,形态发展的第三个星期后开始。胚胎期的结束,标志着胎儿时期开始的。解剖学上,胎儿期表现由血管渗透肱骨。胎儿是不容易损坏,胚胎是在胚胎时期的环境风险。此阶段的特点是主要结构已经形成在胎儿的生长和发展。
基因在必要的身体器官的发展中起到了至关重要的作用。环境影响,扰乱了正常运作的“印记基因” ,从而抑制细菌的生长,从而影响出生体重。因此,有慢性疾病,在以后的生活发展的风险较高。这些印迹基因是容易改变的,因为它们是功能单倍体,比基因组中的其余部分的不同的控制机制。 (2)
营养不良可以破坏胎儿的细胞周期,减缓他们的细胞分裂。因此,胎儿生理利于发展的重要器官,如脑,非必要的器官,如肾(肾单位质量) ,胰腺(胰岛β细胞质量)的生长相适应,因此,这些发展适应,响应于(3)产妇胎盘的营养供应缺乏,可能是未来慢性疾病的根源在以后的生活。
出生质量与糖尿病
大量的研究表明,低出生体重和胰岛素抵抗的相关性。普雷斯顿的研究表明,低出生体重和胰岛素抵抗之间的直接关系,采用重量指数。 (4)表1示出减少出生体重和II型糖尿病之间的关系。 (5)
可能的作用机制:
产妇营养不良降低外周胰岛素抵抗胰岛素的产生和增加的结果。随后,更多的葡萄糖被转移对大脑和心脏和以下对组织如骨骼肌,更多的胰岛素依赖型(6)因此,肌肉对胰岛素产生抗性。因此,在以后的生活,提供充足的养分时,外周胰岛素抵抗可导致葡萄糖不耐症和糖尿病。 (6)的普雷斯顿研究符合的想法,营养不足的婴儿肌肉对胰岛素产生抗性的。 (4)
平均而言,在一个正常的肾脏,有一万肾。 (7)不过,产妇营养不足可以改变发展上程序。根据威多森和麦坎斯,营养不良可导致细胞数量减少。 (4)此外,有研究表明,低出生体重导致肾单位数目减少,相应增加,肾小球体积。 (7)
可能的机制
胎儿生长受限肾脏发育有不良影响。据布伦纳和Mackenzie ,这样的限制导致肾单位数量减少。此外,他们建议,有一个相关的肾小球滤过率的增加,静水压力。因此,存在的风险发展肾小球硬化(8) ,为了维持足够的肾功能的增加,数量减少,肾小球经过肥大和高滤过。随后,肾小球内高血压被攻破,进一步损害肾,增加肾的损失。 (7)此外, Keijzer VEEN和同事确认这意味着低出生体重是与发展进行性肾功能衰竭的风险较高的出生体重和血清肌酐之间的反比关系。 (8)图1显示了一个总结导致肾功能衰竭的事件。 (7)
出生体重与高血压之间的联系
肾脏是控制血压的重要器官。肾脏发育宫内事件的关联意味着有高血压的发展影响。盖顿最初描述,肾脏的作用的肾素 - 血管抑素 - 醛固酮系统和它的自我平衡功能以及接受(7)此外,许多研究都显示,低出生体重和成年高血压发展的一个直接的关联生活。在一组46至64岁的巴克和Osmond首次证实出生体重与高血压之间的联系。 (7)根据的赫尔辛基研究,出生体重和血压之间的逆相关。
可能的机制
布伦纳和Chertow的假设, decreasednephron数与胎儿生长retarted相关可能increaserisk高血压和慢性肾疾病/失败。 (9) ,此外还假设关于一个概念被称为'肾单位药量。他们建议的肾单位数量减少被排出体外的负载和容量的肾单位之间的不平衡导致一个恒定的身体质量。其结果是,婴儿容易出现高血压以后的生活中。另外,实验工作已经表明,肾单位数量减少激活肾素 - 血管紧张素系统,以维持肾小球滤过率。因此,钠和水的潴留增加,从而导致血压上升。 (9)此外,在血管壁的伸展性和过量的糖皮质激素,血管紧张素相关分子的诱导表达缺乏,使婴儿更容易出现高血压以后的生活。 (4,8)图2总结了数量减少的效果肾单位。 (9)
出生质量与心血管疾病
II型糖尿病,肾脏疾病和高血压是心血管疾病的潜在因果代理。如上图所示,低出生体重之间的关系及上述疾病,是心血管疾病的一个间接的联系。此外,也有少数研究显示出生时患有心血管疾病在以后的生活质量之间的负相关。 (10)稀缺的粮食供给计划,以适应胎儿营养不良是常态的情况下母亲的结果。然而,当这些人把肥胖在以后的岁月里,他们有心血管疾病的风险增加。
心血管疾病(CVD )的风险factorclustering (个人至少有3个收缩期血压,血糖和甘油三酯在性别特异性最高的前三分之一的比例,而高密度脂蛋白胆固醇最低三分之一)在联合四分位出生体重和成年体重患病率指数(BMI)的营养研究所中美洲和巴拿马( INCAP )的补充研究4个研究在危地马拉的村庄之一, 1969年至1976年期间出生的男性和女性,并探讨了在1997-1999年间。
批评
所有的假设都需要彻底的措施反驳。胎儿起源假说方面已经提出了一些批评。有人曾建议,在以后的生活中是与一个或多个混杂因素,包括父母的功能,如低社会经济地位,遗传和环境因素导致冠状动脉心脏病冠状动脉心脏疾病。 Hübinette和他的同事们从他们的研究中得出结论,低出生冠状动脉心脏疾病,在以后的生活质量和发展是遗传因素和不可测产妇的影响独立运作的出生体重相结合的结果。 (12)
此外,在南安普敦进行的研究有一定的不一致。在这些研究中,实际的营养措施没有记录。 “早期营养间接isinferred的胎儿和婴幼儿的生长,尤其是fetalgrowth一个呆账代理措施。因此, evenif我们采取有效的结果,我们仍然要问是否nutritionor其他一些效果正在测量。 “ (13)总之,产妇的营养是不是相当于胎儿的营养。此外,根据克莱默约瑟夫(1996) ,有显着的选择进行的回顾性研究中的偏见。 (14)
此外,大多数的研究至今时间来衡量的重量在出生以后的生活中考虑两点。如果没有另一个过渡测量点,它是很难区分是否有心血管疾病与胎儿和出生后的风险或仅仅是出生后生长的元素。 (15)
结论
最近的系统概述显示出生体重和心血管疾病, II型糖尿病,高血压和肾脏病的强逆之间的关联。 (15)考虑到其的批评,这将是安全的结论,胎儿生长迟缓与发展在以后的生活中上述疾病的风险增加。巴克的假设已经创建的意识造成随后在未来的疾病定义产妇营养的重要性及其影响进行了大规模的水平。此外,关于遗传和环境的影响,以及混杂因素,如社会经济地位的解释不能排除其效果方面的慢性疾病的发展以后的生活。就整体而言,胎儿起源假说已经发现一个非常重要的,导致慢性疾病在成年生活中的发展到了一个全新的解释。
总结
总之,胎儿的发育显着影响的环境因素,包括化学,物理和生物因素。因此,影响胎儿生长和出生体重的生理适应胎儿的编程结果。此外,补偿效果的关键器官的正常生长造成干扰。其结果是减少出生体重。此外,产后增加的重量是有害的,作为一种尝试,以纠正低出生体重的孩子在以后的几年,因为它进一步增加了心血管疾病的风险。最后,这些影响可以通过一代又一代。 (16)
参考文献
(1)科学 - 巴克理论。适用于: http://thebarkertheory.org/science.html 。访问2008年3月22日, 2008年。
(2)年轻LE 。印迹基因和巴克假设。双床研究2001年10月4(5) :307- 317 。
(3)宝途GR 。胎儿宫内发育和疾病在以后的生活 - 巴克尔和超越。南非医学Journal.Suid Afrikaanse Tydskrif的VIR Geneeskunde 2003 ,93 (10) :757- 760 。
(4)巴克DJ 。冠状动脉心脏疾病的胎儿起源。 Eur.Heart J. 1997 , 18(6) :883 -884 。
(5)巴克DJ 。胎儿生长受限的成人后果。临床妇产科2006年6月, ​​49(2) :270- 283 。
(6) ,哈丁JE de Boo对于HA 。成人病(巴克)假说的发展起源。 Aust.N.Z.J.Obstet.Gynaecol 。 2006年2月46(1) :4 - 14 。
(7)赞迪 - 内贾德K, VA LUYCKX , :布伦纳BM 。成人高血压和肾脏疾病:胎儿编程的作用。高血压2006年3月, 47(3) :502 -508 。
(8)拉克兰DT 。机制和肾脏疾病的胎儿起源。 [评论] 。 [美国肾脏病学会2005年9月, 16(9) :2531 -2532 。
( 9 )巴格比SP 。产妇营养,低肾单位数目,以及在以后的生活中高血压:营养编程的途径。 J.Nutr 。 2007年4月, 137 (4) :1066 - 1072 。
(10)劳勒DA , Ronalds G ,克拉克ħ ,史密斯GD ,莱昂DA 。出生体重呈负相关事件冠状动脉心脏疾病和​​中风的个体出生在20世纪50年代: 20世纪50年代的前瞻性队列研究,从香港仔儿童的调查结果。循环2005年9月6日, 112 (10) :1414 -1418 。
(11)斯坦AD ,托伦科恩利斯克甲,乙,施罗德DG , Grajeda ŗ ,马尔托雷尔R.心血管疾病的危险因素与成人肥胖,但没有出生体重在年轻的危地马拉成人。 J.Nutr 。 2002年8月, 132 (8) :2208 -2214 。
(12)保尔特NR 。出生体重,母亲的心血管事件,和巴克假说。 “柳叶刀”杂志, 2001年6/23 , 357 ( 9273 ) :1990 - 1991 。
(13)潘氏N, Susser M.早期起源的冠状动脉心脏疾病( “巴克假说” ) 。 BMJ 1995年2月18日, 310 ( 6977 ) :411- 412 。
(14)兰利 - 埃文斯SC 。心血管功能,通过暴露产妇营养不良的胎儿编程。 Proc.Nutr.Soc 。 2001年11月, 60(4) :505 -513 。
(15)吉尔曼兆瓦。成人慢性疾病的胎儿起源研究的流行病学挑战。 Int.J.Epidemiol 。 2002年4月; 31(2) :294 -299 。
(16) Sobsey D.胎儿编程:发展和发育残疾的影响。适用于:访问4/14/2008 , 2008年。