Long-term health consequences of birth by cesarean section

摘要 每年有近130万例剖腹产，导致三分之一的婴儿出生 全国范围内。如果有适应症，剖腹产可以降低母亲和胎儿的发病率和死亡率。然而， 许多剖宫产没有明确的医学指征，导致严重的孕产妇和 围产期发病率和死亡率。越来越多的证据也表明，对后代的风险可能会延伸到 慢性--非传染性疾病。一致的证据表明，通过剖腹产出生的人处于 儿童患肥胖症的风险增加，肥胖率在成年后持续较高， 剖腹产带来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、结直肠癌)、心血管疾病 疾病和2型糖尿病。然而，关于剖腹产与风险因素相关的数据 慢性病风险的生物标记物仍然很少。关于生物的信息也很少。 剖腹产与子代慢性病风险之间关系的潜在机制。这 提案解决了这些知识差距。具体地说，我们建议通过以下方式评估出生关系 青春期开始的剖腹产--乳腺癌的既定危险因素； 慢性病风险的生物标记物--包括有丝分裂、炎症、胰岛素抵抗、血脂的标记物 新陈代谢和脂肪组织活动；以及身体成分的纵向轨迹(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(目标3和4)，以进一步获得 了解剖腹产对健康的长期影响的生物学基础。

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.