Vulnerability to Prenatal Glucocorticoids Programs Infant Development

描述（由申请人提供）：合成糖皮质激素（GC）广泛用于有早产风险的孕妇，以促进胎儿肺成熟，并已确定对早产儿的呼吸功能和存活率有益（Crowley，1995）。具有讽刺意味的是，这种常见的产前治疗，以促进早产儿的生存可能会增加早产和发育障碍的风险，特别是在脆弱的胎儿。这是合理的，因为：（i）GC处理刺激胎盘CRH产生，导致CRH浓度增加1.5倍，持续至少一周（Korebrits等人，1998; Marinoni等人，1998），（ii）在此妊娠期升高的胎盘CRH与早产相关，并且可能是因果途径（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; Smith等人，2009）和（iii）产前暴露于升高的CRH与发育障碍相关（Sandman等人，1999; Davis等人，2005; Class等人，2008; 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，并鉴定最易受GC治疗产生的负面后果影响的胎儿。该应用将确定胎盘CRH对GC治疗的反应程度是否与出生结局和婴儿发育相关。将通过连续采集150例出现早产体征的单胎妊娠非裔美国人和高加索女性的母体血浆样本，确定胎盘对合成GC治疗的反应。将在糖皮质激素治疗前和治疗后一周内采集样本。在6个月和12个月时，将采用标准化实验室指标评价婴儿发育。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）婴儿生理应激反应增加，（iii）婴儿恐惧气质和（iv）婴儿精神和神经运动延迟。

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.