Hellström Ann, Ley David, Hansen-Pupp Ingrid, Hallberg Boubou, Ramenghi Luca A, Löfqvist Chatarina, Smith Lois E H, Hård Anna-Lena
Department of Ophthalmology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Department of Pediatrics, Institute of Clinical Sciences, Lund University and Skane University Hospital, Lund, Sweden.
Am J Perinatol. 2016 Sep;33(11):1067-71. doi: 10.1055/s-0036-1586109. Epub 2016 Sep 7.
The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.
极早产儿的新生儿期通常表现为对宫外生活的艰难适应,营养供应不足且生长因子水平低下,导致生长发育不良和高发病率。长期的多系统并发症包括因脑损伤导致的认知、行为和运动功能障碍,以及持续至成年期的视觉和听力缺陷及代谢紊乱。胰岛素样生长因子1(IGF-1)是胎儿生长以及包括视网膜在内的大多数器官尤其是中枢神经系统发育的主要调节因子。发育中的大脑中的葡萄糖代谢受IGF-1控制,IGF-1还能刺激分化并防止细胞凋亡。极早产出生后,IGF-1的血清浓度降至极低水平,并在围产期发育的大部分时间内保持较低水平。已发现新生儿血清IGF-1浓度低与脑和视网膜生长不良以及伴有多器官疾病(如脑室内出血、早产儿视网膜病变、支气管肺发育不良和坏死性小肠结肠炎)的总体生长不良之间存在密切关联。实验和临床研究表明,早期补充IGF-1可改善分解代谢状态下的生长,并减少缺氧/缺血事件后的脑损伤。目前正在进行一项多中心II期研究,以确定静脉注射人重组IGF-1直至达到正常宫内血清浓度是否能改善生长发育并降低与早产相关的发病率。