Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, 56100, Pisa, Italy.
Intern Emerg Med. 2013 Apr;8 Suppl 1:S41-5. doi: 10.1007/s11739-013-0925-y.
Low birthweight is associated with increased rates of coronary heart disease, stroke, hypertension and non-insulin-dependent diabetes during adult life. This is thought to be the consequence of a 'programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may, hence, result from adaptations to a condition where placental nutrient supply fails to match fetal demand. Recently, compensatory feto-placental up-regulation of the nitric oxide system during fetal growth restriction (FGR) was shown. Particularly, restricted hypoxic fetuses present an elevation of nitrites and a reduction of asymmetric dimethylarginine. S-nitrosohemoglobin is consumed under hypoxic conditions. These events are followed by nitric oxide pathway down-regulation postnatally, increasing susceptibility to cardiovascular disorders later in life. The relative hyperoxia would favor any such occurrence through depletion of tetrahydrobiopterin secondary to oxygen radical formation. This concept may lead to new therapeutic strategies, based on tetrahydrobiopterin supplementation, free-radical scavenging, L-arginine administration and/or inhaled NO therapy in FGR hypoxic newborns, to improve their postnatal adaptation and to reduce the risk of metabolic pathologies in adult age.
低出生体重与成年后患冠心病、中风、高血压和非胰岛素依赖型糖尿病的几率增加有关。这被认为是“编程”的结果，即在生命早期的一个关键敏感时期，刺激或损伤对结构、生理学和新陈代谢产生持久的影响。因此，胎儿的编程可能是由于对胎盘营养供应无法满足胎儿需求的情况的适应。最近，在胎儿生长受限 (FGR) 期间，胎儿-胎盘一氧化氮系统的代偿性上调已经得到证实。特别是，受限缺氧胎儿的亚硝酸盐水平升高，不对称二甲基精氨酸减少。在缺氧条件下，S-亚硝基血红蛋白被消耗。这些事件随后导致出生后一氧化氮途径下调，增加了成年后患心血管疾病的易感性。相对高氧会通过氧自由基形成导致四氢生物蝶呤耗竭而有利于任何此类发生。这一概念可能会导致新的治疗策略，基于四氢生物蝶呤补充、自由基清除、L-精氨酸给药和/或 FGR 缺氧新生儿吸入一氧化氮治疗，以改善其出生后适应，并降低成年后患代谢性疾病的风险。
