Antenatal insulin-like growth factor-I and perinatal growth, survival and function of the growth restricted fetus.

出生前生长不良或宫内生长受限(IUGR)，如妊娠阶段的轻、短或瘦，极大地增加了出生前、出生后和婴儿期患病和死亡的风险。IUGR增加了窒息、血糖控制不良、体温过低、呼吸困难、神经问题和免疫功能低下的风险，其中许多持续存在。IUGR是产科和新生儿最常见的临床问题之一，澳大利亚出生的IUGR婴儿中约6%在非土著社区出生，7%至17%在土著社区出生。尽管这些对个体一生健康的不利影响，我们目前还没有任何有效的治疗IUGR的方法。小婴儿大多是由于出生前氧气和营养素供应不足，这是由于母亲为胎盘提供氧气和营养素的能力受损，或者由于胎盘本身功能不佳。这种宫内营养不良不仅会减缓生长速度，还会损害一系列身体功能的发育，从而增加IUGR患病和死亡的风险。用于治疗IUGR的产前治疗方法需要恢复氧气和营养的供应，或者促进生长和功能发育。我们发现，给IUGR胎儿注射一种主要的促生长激素，胰岛素样生长因子-I(IGF-I)，可以促进其生长，因为IUGR胎儿的IGF-I水平较低。因此，该项目将确定在IUGR胎儿中直接给予这种激素是否会恢复出生前的发育和生长，改善功能，从而改善出生后的存活和健康。如果成功，IUGR产前治疗的第一个有效方法将被确定，并将为设计一系列治疗方案提供必要的知识，以最好地恢复IUGR胎儿体内IGF的丰度，以改善围产期和以后的结局。

Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.