Fetal origins of neonatal lung disease: understanding the pathogenesis of bronchopulmonary dysplasia.

摘要

in the early 1990s, Barker and colleagues (4) proposed that early events occurring before birth could produce later onset cardiovascular disease in the adult. This "fetal origins hypothesis" sparked the beginning of a new way of thinking among clinical and basic scientists. Over the years, numerous reports have added to this idea that a key to understanding complex human diseases is to consider the pathology occurring as early as the fetal stages of development (3, 15, 17, 24, 25). The fetal lung appears to be particularly vulnerable to these processes (14). Animal studies have demonstrated marked structural abnormalities and cellular dysfunction Secondary to intrauter-ine processes such as inflammation and hypoxia-ischemia (6,9, 27). In this issue, Rozance and colleagues (21) utilize a sheep model of hyperthermia-induced placental insufficiency to comprehensively study fetal lung changes of intrauterine growth restriction (IUGR). They provide compelling evidence that the fetal lung is markedly altered by IUGR, with a degree of structural change and cellular dysfunction so significant that IUGR could be considered an independent risk factor for the development of later bronchopulmonary dysplasia (BPD). These and related findings in other animal models, combined with what has been reported in clinical observations, provide compelling evidence for the fetal origins of BPD (5, 16, 18-20).