Thornburg Kent L, Marshall Nicole
Department of Medicine, School of Medicine, Oregon Health and Science University, Portland, OR; Knight Cardiovascular Institute, Center for Developmental Health, Oregon Health and Science University, Portland, OR; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR.
Knight Cardiovascular Institute, Center for Developmental Health, Oregon Health and Science University, Portland, OR; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR.
Am J Obstet Gynecol. 2015 Oct;213(4 Suppl):S14-20. doi: 10.1016/j.ajog.2015.08.030.
Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The report by David Barker and colleagues showing an inverse relationship between birthweight and mortality from ischemic heart disease was the first clear-cut demonstration of fetal programming. Because fetal growth depends upon the placental capacity to transport nutrients from maternal blood, it has been a suspected causative agent since the original Barker reports. Epidemiological studies have shown that placental size and shape have powerful associations with offspring disease. More recent studies have shown that maternal phenotypic characteristics, such as body mass index and height, interact with placental size and shape to predict disease with much more precision than does birthweight alone. For example, among people in the Helsinki Birth Cohort, who were born during 1924–1944, the risk for acquiring colorectal cancer increased as the placental surface became longer and more oval. Among people in whom the difference between the length and breadth of the surface exceeded 6 cm, the hazard ratio for the cancer was 2.3 (95% CI 1.2–4.7, p=0.003) compared with those in whom there was no difference. Among Finnish men, the hazard ratio for coronary heart disease was 1.07 (1.02–1.13, P =0.01) per 1% increase in the placental weight/birthweight ratio. Thus, it appears that the ratio of birthweight to placental weight, known as placental efficiency, predicts cardiovascular risk as well. Babies born with placentas at the extremes of efficiency are more vulnerable for adult onset chronic diseases. Recent evidence suggests that placental growth patterns are sex specific. Boys’ placentas are, in general, more efficient than those made by girls. Another recent discovery is that the size, shape and efficiencies of the placenta can change over years of time with very narrow confidence limits. This suggests that the growth of the placenta within a population of women is strongly affected by their nutritional environment. Even though it is known that an individual placenta can expand to improve its nutrient acquisition capacity in the first 2/3 of gestation, the mechanisms by which placentas grow in response to a specific nutritional environment are not known. Discovering those mechanisms is the task of the current generation of scientists. While it may seem obvious that good nutrition is highly important for women who are pregnant because it supports optimal placentation and fetal development, more research is needed to determine the mechanisms by which maternal nutrition, placenta growth and fetal health are related.
在过去的四分之一世纪里，很明显，诸如心脏病和2型糖尿病等成人慢性疾病起源于早期发育阶段。大卫·巴克及其同事的报告显示出生体重与缺血性心脏病死亡率之间呈负相关，这是胎儿编程的首个明确证据。由于胎儿生长依赖于胎盘从母体血液中运输营养物质的能力，自最初的巴克报告以来，它一直被怀疑是致病因素。流行病学研究表明，胎盘的大小和形状与后代疾病密切相关。最近的研究表明，母亲的表型特征，如体重指数和身高，与胎盘的大小和形状相互作用，比单独的出生体重更精确地预测疾病。例如，在1924年至1944年出生的赫尔辛基出生队列人群中，随着胎盘表面变得更长且更呈椭圆形，患结直肠癌的风险增加。在胎盘表面长度和宽度之差超过6厘米的人群中，与无差异的人群相比，患癌风险比为2.3（95%置信区间1.2 - 4.7，p = 0.003）。在芬兰男性中，胎盘重量/出生体重比每增加1%，冠心病的风险比为1.07（1.02 - 1.13，P = 0.01）。因此，出生体重与胎盘重量之比，即胎盘效率，似乎也能预测心血管风险。胎盘效率处于极端水平的婴儿更容易患成人慢性疾病。最近的证据表明，胎盘生长模式具有性别特异性。一般来说，男孩的胎盘比女孩的胎盘效率更高。另一个最近的发现是，胎盘的大小、形状和效率在数年时间内会发生变化，置信区间很窄。这表明女性群体中胎盘的生长受到其营养环境的强烈影响。尽管已知单个胎盘在妊娠的前三分之二阶段可以扩张以提高其营养获取能力，但胎盘如何响应特定营养环境而生长的机制尚不清楚。发现这些机制是当代科学家的任务。虽然对于孕妇来说，良好的营养对支持最佳胎盘形成和胎儿发育非常重要这一点似乎很明显，但仍需要更多研究来确定母体营养、胎盘生长和胎儿健康之间的相关机制。
