The impact of severe asthma during pregnancy on placental function and fetal hypothalamic-pituitary-adrenal function

这项研究将研究妊娠期用于控制严重哮喘的糖皮质激素是否会影响胎盘和胎儿功能。众所周知，妊娠期严重哮喘与低出生体重婴儿有关，但导致婴儿发育迟缓的事件尚不清楚。然而，在动物和人类怀孕期间，婴儿对母亲糖皮质激素的暴露增加会导致婴儿生长受限。因此，我们建议在妊娠期间增加糖皮质激素的摄入量以治疗哮喘，改变胎盘的功能，并允许胎儿暴露于母亲的糖皮质激素，从而改变胎儿的发育。我们将检查胎盘血流，并测量一些可能参与控制胎盘血流的胎盘酶，这些酶来自轻、中、重度哮喘患者，并将其与非哮喘女性进行比较。我们将使用多普勒超声观察胎盘在子宫内的血流，并在胎盘分娩后观察体外的胎盘血流。我们想通过测量一种源于胎儿的激素雌三醇来了解胎儿是否受到母亲增加糖皮质激素摄入量的影响。我们将在整个怀孕期间测量雌三醇，因为在母亲的尿液中很容易检测到它。这些研究将告诉我们，用于治疗哮喘的糖皮质激素摄入是否会对怀孕期间的胎盘和婴儿产生影响。这些研究将在科学和临床上做出重大贡献。在科学层面上，我们将能够检查怀孕期间母亲糖皮质激素摄入量增加如何影响胎盘机制，以及这些变化是否会影响胎儿，临床上，这项研究的结果将使我们能够优化怀孕期间的哮喘治疗，从而改善婴儿的结局。

This study will examine whether the glucocorticoids administered for the control of severe asthma during pregnancy affects placental and fetal function. It is known that severe asthma during pregnancy is associated with low birth weight babies but the events that cause reduced growth of the baby are unknown. However in both animal and human pregnancies, increased exposure of the baby to glucocorticoids from the mother causes growth restriction of the baby. Therefore we propose that the increased intake of glucocorticoids for the treatment of asthma during pregnancy changes how the placenta functions and allows the fetus to be exposed to maternal glucocorticoids causing changes in fetal development. We will examine placental blood flow and measure some placental enzymes that may be involved in the control of blood flow in placentas collected from women with mild, moderate and severe asthma and compare them to non-asthmatic women. We will look at placental blood flow in utero using Doppler ultrasound and also in vitro after the placenta is delivered. We want to see if the fetus is affected by increased intake of glucocorticoids by the mother by measuring a hormone estriol, which originates from the fetus. We will measure estriol throughout pregnancy as it can easily be detected in the mothers' urine. These studies will tell us if glucocorticoid intake for the treatment of asthma can exert effects on the placenta and baby during pregnancy. These studies will make a significant contribution both scientifically and clinically. At a scientific level we will be able to examine how increased maternal glucocorticoid intake during pregnancy affects placental mechanisms and whether these changes affect the fetus and clinically the outcome of this study will allow us to optimize asthma therapy during pregnancy so that we can improve the outcome for the baby.