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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD065823-05
Application #
8676836
Study Section
Special Emphasis Panel (ZRG1-BBBP-N (05))
Program Officer
Ilekis, John V
Project Start
2010-08-10
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
$390,936
Indirect Cost
$120,633
Name
University of California Irvine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Sandman, Curt A; Head, Kevin; Muftuler, L Tugan et al. (2014) Shape of the basal ganglia in preadolescent children is associated with cognitive performance. Neuroimage 99:93-102
Davis, Elysia Poggi; Pfaff, Donald (2014) Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder. Psychoneuroendocrinology 49:11-25
Sandman, Curt A; Glynn, Laura M; Davis, Elysia Poggi (2013) Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res 75:327-35
Davis, Elysia Poggi; Sandman, Curt A; Buss, Claudia et al. (2013) Fetal glucocorticoid exposure is associated with preadolescent brain development. Biol Psychiatry 74:647-55