Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa).
Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa).
Am J Obstet Gynecol MFM. 2021 Nov;3(6):100473. doi: 10.1016/j.ajogmf.2021.100473. Epub 2021 Sep 2.
Barker pioneered the idea that the epidemic of coronary heart disease in Western countries in the 20th century, which paradoxically coincided with improved standards of living and nutrition, has its origin in fetal life. Indeed, there is substantial evidence associating low birthweight because of fetal growth restriction with an increased risk of vascular disease in later adult life. These conclusions led to the second part of the Barker hypothesis, the thrifty phenotype, in which adaptation to undernutrition in fetal life leads to permanent metabolic and endocrine changes. Such changes are beneficial if the undernutrition persists after birth but may predispose the individual to obesity and impaired glucose tolerance if conditions improve. The hypothesis assumes that a poor nutrient supply during a critical period of in utero life may "program" a permanent structural or functional change in the fetus, thereby altering the distribution of cell types, gene expression, or both. The fetus, in response to placental undernutrition and to maintain sufficient vascular supply to the brain, decreases resistance to blood flow in the middle cerebral artery. Simultaneously, because of the limited blood supply to the fetus, the arterial redistribution process is accompanied by increased resistance to flow to other fetal vital organs, such as the heart, kidneys, liver, and pancreas. It may explain why individuals exposed to ischemic changes in utero develop dyslipidemia, lower nephron number, and impaired glucose tolerance, all factors contributing to metabolic syndrome later in life. Nevertheless, support for the hypotheses comes mainly from studies in rodents and retrospective epidemiologic studies. This review focused on ultrasound and Doppler studies of human fetal growth restriction in several fetal organs: the placenta, fetal circulation, brain, heart, kidneys, adrenal glands, liver, and pancreas. Support for the hypothesis was provided by animal studies involving conditions that create fetuses with growth restriction with effects on various fetal organs and by human studies that correlate impaired fetal circulation with the in utero development and function of fetal organs.
巴克尔率先提出了这样一种观点，即 20 世纪西方国家冠心病的流行，与生活水平和营养水平的提高相矛盾，其起源于胎儿期。事实上，有大量证据表明，由于胎儿生长受限导致的低出生体重与成年后血管疾病风险增加有关。这些结论导致了巴克尔假说的第二部分，即节俭表型，即胎儿期适应营养不良会导致永久性的代谢和内分泌变化。如果出生后营养不良持续存在，这些变化是有益的，但如果情况改善，个体可能容易肥胖和糖耐量受损。该假说假设，在胎儿期的关键时期，如果营养供应不足，可能会“编程”胎儿发生永久性的结构或功能改变，从而改变细胞类型、基因表达或两者的分布。胎儿为了应对胎盘营养不足和维持大脑足够的血管供应，会降低大脑中动脉的血流阻力。同时，由于胎儿的血液供应有限，动脉重新分布的过程伴随着流向其他胎儿重要器官（如心脏、肾脏、肝脏和胰腺）的血流阻力增加。这也许可以解释为什么在子宫内暴露于缺血性变化的个体发展为血脂异常、肾小球数量减少和糖耐量受损，所有这些因素都是导致成年后代谢综合征的原因。然而，这些假说的支持主要来自于啮齿动物研究和回顾性流行病学研究。本综述重点关注了人类胎儿生长受限在几个胎儿器官中的超声和多普勒研究：胎盘、胎儿循环、大脑、心脏、肾脏、肾上腺、肝脏和胰腺。动物研究为该假说提供了支持，这些研究涉及到会导致胎儿生长受限并对各种胎儿器官产生影响的情况，而人类研究则表明胎儿循环受损与胎儿器官在子宫内的发育和功能有关。
