妊娠期高血压疾病：流行病学、病理生理学、治疗策略及母胎结局

文献信息

中文摘要

妊娠期高血压疾病（HDP）包括慢性高血压、妊娠期高血压、子痫前期以及慢性高血压合并子痫前期，全球约5%至10%的妊娠受累，仍是孕产妇和围产期发病和死亡的主要原因。随着肥胖增加、高龄妊娠、诊断标准演变以及显著的社会经济和种族-民族差异，其负担正在上升。本综述总结了关于HDP流行病学、病理生理学、生物标志物、临床管理和长期结局的当前证据，重点介绍了近期进展和未解决的问题。在机制上，HDP的特征是全身性内皮功能障碍和血管生成失衡，特别是涉及可溶性fms样酪氨酸激酶-1（sFlt-1）、胎盘生长因子（PlGF）和可溶性内皮糖蛋白（sEng），同时伴有免疫适应不良、氧化应激以及遗传和环境因素，如内分泌干扰化学物（EDCs）和睡眠呼吸障碍（SDB）。sFlt-1/PlGF比值是疑似子痫前期短期风险评估中最经过验证的工具之一，而视网膜微血管成像可能提供全身微血管功能障碍的无创标志物。在临床上，试验证据支持将轻度慢性高血压治疗至低于140/90 mmHg，以减少不良结局而不损害胎儿生长。长期母体心血管和代谢风险因HDP表型、严重程度、发病孕龄以及相关早产或胎儿生长受限而异，而后代神经发育关联主要是观察性的，可能受早产和共同家族或社会经济因素的影响。主要基于临床前或早期转化证据支持的实验性策略包括PPARγ激动剂、胎盘靶向纳米药物和经皮耳迷走神经刺激。机器学习结合纵向多组学数据可能支持精准风险分层和个体化管理。

英文摘要

Hypertensive disorders of pregnancy (HDP) encompass chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension, affecting about 5% to 10% of pregnancies worldwide and remaining a major cause of maternal and perinatal morbidity and mortality. Their burden is increasing with rising obesity, advanced maternal age, evolving diagnostic criteria, and marked socioeconomic and racial-ethnic disparities. This review summarises current evidence on the epidemiology, pathophysiology, biomarkers, clinical management, and long-term outcomes of HDP, highlighting recent advances and unresolved questions. Mechanistically, HDP is characterised by systemic endothelial dysfunction and angiogenic imbalance, particularly involving soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), together with immune maladaptation, oxidative stress, and genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs) and sleep-disordered breathing (SDB). The sFlt-1/PlGF ratio is among the most validated tools for short-term risk assessment in suspected preeclampsia, while retinal microvascular imaging may provide a non-invasive marker of systemic microvascular dysfunction. Clinically, trial evidence supports treating mild chronic hypertension to below 140/90 mmHg to reduce adverse outcomes without compromising foetal growth. Long-term maternal cardiovascular and metabolic risks vary according to HDP phenotype, severity, gestational age at onset, and associated preterm delivery or foetal growth restriction, whereas offspring neurodevelopmental associations are largely observational and may be influenced by prematurity and shared familial or socioeconomic factors. Experimental strategies supported primarily by preclinical or early translational evidence include PPARγ agonists, placenta-targeted nanomedicine, and transcutaneous auricular vagus nerve stimulation. Machine learning combined with longitudinal multi-omics data may support precision risk stratification and individualised management.