Prasad Jaya, Van Steenwinckel Juliette, Gunn Alistair J, Bennet Laura, Korzeniewski Steven J, Gressens Pierre, Dean Justin M
Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.
Inserm, Neurodiderot, Université de Paris, 75019 Paris, France.
Int J Mol Sci. 2024 Dec 3;25(23):12999. doi: 10.3390/ijms252312999.
The combination of hypertension with systemic inflammation during pregnancy is a hallmark of preeclampsia, but both processes also convey dynamic information about its antecedents and correlates (e.g., fetal growth restriction) and potentially related offspring sequelae. Causal inferences are further complicated by the increasingly frequent overlap of preeclampsia, fetal growth restriction, and multiple indicators of acute and chronic inflammation, with decreased gestational length and its correlates (e.g., social vulnerability). This complexity prompted our group to summarize information from mechanistic studies, integrated with key clinical evidence, to discuss the possibility that sustained or intermittent systemic inflammation-related phenomena offer hints about viable therapeutic targets, not only for the prevention of preeclampsia, but also the neurobehavioral and other developmental deficits that appear to be overrepresented in surviving offspring. Importantly, we feel that carefully designed hypothesis-driven observational studies are necessary if we are to translate the mechanistic evidence into child health benefits, namely because multiple pregnancy disorders might contribute to heightened risks of neuroinflammation, arrested brain development, or dysconnectivity in survivors who exhibit developmental problems later in life.
孕期高血压与全身炎症反应并存是先兆子痫的一个标志,但这两个过程也传递了有关其先兆和相关因素(如胎儿生长受限)以及潜在相关子代后遗症的动态信息。先兆子痫、胎儿生长受限以及急性和慢性炎症的多种指标越来越频繁地相互重叠,同时孕周缩短及其相关因素(如社会脆弱性)也日益常见,这使得因果推断变得更加复杂。这种复杂性促使我们团队总结来自机制研究的信息,并结合关键临床证据,来探讨持续或间歇性全身炎症相关现象不仅为预防先兆子痫,也为预防存活子代中似乎高发的神经行为及其他发育缺陷提供可行治疗靶点线索的可能性。重要的是,我们认为,如果要将机制证据转化为对儿童健康有益的成果,精心设计的假设驱动观察性研究是必要的,这主要是因为多种妊娠疾病可能会增加幸存者发生神经炎症、脑发育停滞或连接障碍的风险,而这些幸存者在生命后期会出现发育问题。