Vulnerability to Prenatal Glucocorticoids Programs Infant Development

描述(申请人提供)：合成糖皮质激素(GC)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存活有好处(Crowley，1995)。具有讽刺意味的是，这种为促进早产儿存活而进行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的产生，导致CRH浓度增加1.5倍，并持续至少一周(Korea brits等人，1998；Marinoni等人，1998)，(Ii)胎盘CRH在这个妊娠期升高与早产有关，并可能是因果途径(Sandman等人，1994；Wadhwa等人，1998；Sandman等人，1999；Smith等人，2002；Sandman等人，2003；Wadhwa等人，2004；Sandman等人，2006；(3)产前暴露于CRH升高与发育障碍有关(Sandman等人，1999年；Davis等人，2005年；Class等人，2008年；Ellman等人，2008年，《初步研究》)。本申请的目的是表征胎盘CRH对GC治疗的反应，并确定哪些胎儿最容易受到GC治疗的负面后果的影响。这项应用将确定胎盘CRH对GC治疗的反应是否与出生结局和婴儿发育有关。对150名有早产迹象的单胎妊娠非裔美国人和高加索女性的母体血浆样本的系列收集，将确定胎盘对合成GC治疗的反应。样本将在糖皮质激素治疗前和治疗后一周内采集。婴儿的发育将在6个月和12个月时用标准化的实验室测量进行评估。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有关：(I)早产妇女分娩时间加快，(Ii)婴儿生理应激反应增加，(Iii)婴儿恐惧气质和(Iv)婴儿智力和神经运动迟缓。 公共卫生相关性：使用合成糖皮质激素进行产前治疗是早产妇女的一种常见治疗方法。这项调查将确定哪些胎儿容易受到产前糖皮质激素治疗对分娩结局和婴儿发育的负面影响。

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. PUBLIC HEALTH RELEVANCE: Prenatal treatment with synthetic glucocorticoids is a common therapy given to women in preterm labor. This investigation will identify fetuses who are vulnerable to the negative consequences of prenatal glucocorticoid treatment for birth outcome and infant development.