P4 Paediatric Vascular Assessment substudy

Preeclampsia is a hypertensive disorder of pregnancy characterised by new onset hypertension at ≥ 20 weeks’ gestation accompanied by maternal organ dysfunction and/ or fetal compromise. This hypertensive exposure in pregnancy has known long-term consequences for both the mother and child.\n\nPresently, the mechanisms for these cardiometabolic, immunological and neurodevelopmental consequences in the child aren’t well characterised, but epigenetic changes in development and premature biological aging may play a role in the development of these long-term morbidities.\n\nTo investigate, we assessed genome-wide DNA methylation and biological aging in the blood of 2–5 year-old children with (n=20) or without (n=20) previous intrauterine exposure to preeclampsia. Exposure to preeclampsia was associated with 69 differentially methylated regions (DMRs) proximal to both known and novel candidate genes. Biological aging, as determined by two telomere length quantification methods and an epigenetic clock, was found to not be statistically different between the preeclampsia exposure and normotensive pregnancy groups.

子痫前期（preeclampsia）是一类妊娠高血压疾病（hypertensive disorder of pregnancy），以妊娠满20周及以上时新发高血压，并伴随母体器官功能障碍（maternal organ dysfunction）和/或胎儿窘迫（fetal compromise）为典型特征。此类妊娠期间的高血压暴露，已被证实会对母体与子代产生长期健康影响。

目前，子代出现的此类心血管代谢（cardiometabolic）、免疫及神经发育相关后遗症的致病机制尚未被充分阐释，但发育过程中的表观遗传改变与过早生物学衰老（biological aging），可能在这类长期病症的发生发展中起到一定作用。

为探究相关致病机制，本研究对2至5岁儿童的血液样本开展了全基因组DNA甲基化（genome-wide DNA methylation）与生物学衰老（biological aging）水平检测：其中20名儿童曾在宫内暴露（intrauterine exposure）于子痫前期，另外20名儿童的母体妊娠期间血压正常。研究发现，子痫前期宫内暴露与69个位于已知及新候选基因近端的差异甲基化区域（DMRs）存在关联。通过两种端粒长度（telomere length）定量方法与表观遗传时钟（epigenetic clock）测定的生物学衰老水平，在子痫前期暴露组与正常血压妊娠组之间未发现统计学显著差异。