Vulnerability to Prenatal Glucocorticoids Programs Infant Development

描述（由申请人提供）：合成糖皮质激素（GCs）被广泛应用于有早产风险的孕妇，以促进胎儿肺成熟，并已证实对早产儿的呼吸功能和生存有好处（Crowley, 1995）。具有讽刺意味的是，这种用于促进早产儿生存的常见产前治疗可能会增加早产和发育障碍的风险，特别是在脆弱的胎儿中。这是合理的因为:(i) GC治疗刺激胎盘CRH生产导致增加1.5折CRH浓度持续至少一周(Korebrits et al ., 1998; Marinoni et al ., 1998),(2)提高胎盘CRH在妊娠期与早产有关,可能在因果通路(睡魔et al ., 1994; Wadhwa et al ., 1998;睡魔et al ., 1999;史密斯et al ., 2002;睡魔et al ., 2003; Wadhwa et al ., 2004;睡魔et al ., 2006;（iii）产前暴露于CRH升高与发育障碍有关（Sandman et al., 1999; Davis et al., 2005; Class et al., 2008; Ellman et al., 2008，初步研究）。本应用的目的是表征胎盘CRH对GC治疗的反应，并确定最易受GC治疗负面影响的胎儿。该应用将确定胎盘对GC治疗的CRH反应的大小是否与出生结局和婴儿发育有关。胎盘对合成GC治疗的反应将通过对150名有早产迹象的非裔美国人和白种人单胎妊娠妇女的连续血浆样本收集来确定。样本将在糖皮质激素治疗前和治疗后一周内收集。婴儿发育将在6个月和12个月时用标准化的实验室措施进行评估。该项目将确定胎盘CRH对糖皮质激素治疗的反应程度是否与以下风险相关：(i)早产妇女的分娩时间加快，（ii）婴儿生理应激反应性增加，（iii）婴儿恐惧气质和（iv）婴儿精神和神经运动迟缓。

DESCRIPTION (provided by applicant): Synthetic glucocorticoids (GCs) are widely administered to pregnant women at risk for preterm delivery to enhance fetal lung maturation and have established benefits for respiratory functioning and survival among preterm infants (Crowley, 1995). Ironically, this common prenatal treatment given to promote survival among preterm infants may increase the risk of preterm birth and developmental impairments, particularly among vulnerable fetuses. This is plausible because: (i) GC treatment stimulates placental CRH production resulting in a 1.5 fold increase in CRH concentrations that persists for at least one week (Korebrits et al., 1998; Marinoni et al., 1998), (ii) elevated placental CRH during this gestational period is associated with preterm birth and may be in the causal pathway (Sandman et al., 1994; Wadhwa et al., 1998; Sandman et al., 1999; Smith et al., 2002; Sandman et al., 2003; Wadhwa et al., 2004; Sandman et al., 2006; Smith et al., 2009) and (iii) prenatal exposure to elevated CRH is associated with developmental impairments (Sandman et al., 1999; Davis et al., 2005; Class et al., 2008; Ellman et al., 2008, Preliminary Studies). The goal of the present application is to characterize the placental CRH response to GC therapy and to identify fetuses who are most susceptible to negative consequences resulting from GC treatment. This application will determine if the magnitude of the placental CRH response to GC treatment is associated with birth outcome and infant development. The placental response to synthetic GC treatment will be determined with the serial collection of maternal plasma samples in 150 African American and Caucasian women with singleton pregnancies who present with signs of preterm labor. Samples will be collected before and during the week following glucocorticoid treatment. Infant development will be evaluated with standardized laboratory measures at 6 and 12 months. This project will determine if the magnitude of the placental CRH response to glucocorticoid treatment will be associated with risk for: (i) accelerated time to delivery among women in preterm labor, (ii) increased infant physiological stress reactivity, (iii) infant fearful temperament and (iv) infant mental and neuromotor delays.