Department of Obstetrics, Wilhelmina Children's Hospital Birth Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Academic Unit of Human Development and Health, University of Southampton, Southampton, UK.
Acta Physiol (Oxf). 2017 Jan;219(1):241-259. doi: 10.1111/apha.12702. Epub 2016 May 26.
Pregnancy is a critical time for long-term blood pressure regulation in both mother and child. Pregnancies complicated by placental insufficiency, resulting in pre-eclampsia and intrauterine growth restriction, are associated with a threefold increased risk of the mother to develop hypertension later in life. In addition, these complications create an adverse intrauterine environment, which programmes the foetus and the second generation to develop hypertension in adult life. Female offspring born to a pregnancy complicated by placental insufficiency are at risk for pregnancy complications during their own pregnancies as well, resulting in a vicious circle with programmed risk for hypertension passing from generation to generation. Here, we review the epidemiology and mechanisms leading to the altered programming of blood pressure trajectories after pregnancies complicated by placental insufficiency. Although the underlying mechanisms leading to hypertension remain the subject of investigation, several abnormalities in angiotensin sensitivity, sodium handling, sympathetic activity, endothelial function and metabolic pathways are found in the mother after exposure to placental insufficiency. In the child, epigenetic modifications and disrupted organ development play a crucial role in programming of hypertension. We emphasize that pregnancy can be viewed as a window of opportunity to improve long-term cardiovascular health of both mother and child, and outline potential gains expected of improved preconceptional, perinatal and post-natal care to reduce the development of hypertension and the burden of cardiovascular disease later in life. Perinatal therapies aimed at reprogramming hypertension are a promising strategy to break the vicious circle of intergenerational programming of hypertension.
妊娠是母婴长期血压调节的关键时期。胎盘功能不全导致的子痫前期和宫内生长受限等妊娠并发症，使母亲在以后的生活中发生高血压的风险增加三倍。此外，这些并发症会造成宫内环境不良，从而使胎儿和第二代在成年后易发生高血压。在胎盘功能不全的妊娠中出生的女性后代，在自己的妊娠期间也有发生妊娠并发症的风险，从而形成了一个恶性循环，即高血压的遗传风险代代相传。在这里，我们回顾了胎盘功能不全导致的血压轨迹改变的流行病学和机制。尽管导致高血压的潜在机制仍在研究中，但在暴露于胎盘功能不全后，母亲体内存在血管紧张素敏感性、钠处理、交感神经活动、内皮功能和代谢途径的几种异常。在儿童中，表观遗传修饰和器官发育障碍在高血压的编程中起着至关重要的作用。我们强调，妊娠可以被视为改善母婴长期心血管健康的机会窗口，并概述了预期从改善孕前、围产期和产后护理中获得的潜在收益，以降低高血压的发生和以后生活中心血管疾病的负担。针对高血压重编程的围产期治疗是打破高血压代际编程恶性循环的有前途的策略。
