Long-term health consequences of birth by cesarean section

摘要 每年有近130万例剖腹产手术，导致三分之一的儿童出生 全国范围有指征时，剖宫产可降低母亲和胎儿的发病率和死亡率。然而，在这方面， 许多剖腹产者没有明确的医学指征，导致严重的孕产妇死亡率增加， 围产期发病率和死亡率。越来越多的证据还表明，对后代的风险可能会扩大到 慢性非传染性疾病。一致的证据表明，通过剖腹产出生的人在一个 儿童时期肥胖的风险增加，成年后肥胖率持续较高， 通过剖腹产出生的长期健康后果可能会增加风险 肥胖相关的慢性疾病，包括常见的癌症（乳腺癌，前列腺癌，结肠直肠癌），心血管疾病 2型糖尿病的治疗方法然而，关于剖宫产与危险因素或 慢性病风险的生物标志物仍然很少。关于生物学的信息也很少。 剖腹产和后代慢性疾病风险之间关系的潜在机制。这 这些建议弥补了这些知识差距。具体而言，我们建议通过以下方式评估出生关系： 青春期开始剖宫产--乳腺癌的一个确定的危险因素; 慢性疾病风险的生物标志物-包括有丝分裂、炎症、胰岛素抵抗、脂质 代谢和脂肪组织活性;以及身体组成的纵向轨迹（目标1和2）。 此外，我们建议评估剖宫产与纵向轨迹的关系， 全基因组DNA甲基化模式和肠道微生物组（目的3和4），以便进一步获得 了解剖腹产的长期健康后果的生物学基础。

ABSTRACT Nearly 1.3 million cesareans are performed each year, resulting in the birth of one third of all children nationwide. When indicated, cesarean sections reduce morbidity and mortality to mother and fetus. However, many cesareans do not have a clear medical indication leading to an increase in serious maternal and perinatal morbidity and mortality. Increasing evidence also suggests that risks to offspring may extend to chronic-non communicable conditions. Consistent evidence shows that individuals born by cesarean are at an increased risk of obesity as children and that higher rates of obesity persist through adult life, raising the possibility that the long-term health consequences of being born by cesarean may extend to an increased risk of obesity-related chronic conditions including common cancers (breast, prostate, colorectal), cardiovascular disease and type 2 diabetes. However, data on the association of birth by cesarean with risk factors for or biomarkers of chronic disease risk remains scarce. There is also a paucity of information regarding the biologic mechanisms underlying the relation between cesarean delivery and offspring chronic disease risk. This proposal addresses these knowledge gaps. Specifically, we propose to evaluate the relation of birth by cesarean with pubertal onset –an established risk factor for breast cancer; with longitudinal trajectories in biomarkers of chronic disease risk –including markers of mitogenesis, inflammation, insulin resistance, lipid metabolism and adipose tissue activity; and with longitudinal trajectories in body composition (Aims 1 and 2). In addition, we propose to evaluate the relation of birth by cesarean section with longitudinal trajectories in whole genome DNA methylation patterns and gut microbiome (Aims 3 and 4) in order to gain further understanding on the biological underpinnings of the long-term health consequences of birth by cesarean.