This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prematurity has been described as the most significant problem in maternal-child health in the United States because it is the leading cause of inhant mortality and morbidity; its prevalence has not decreased over the last 40 years; and its etiology is unknown in a majority of cases (Creasy, 1994). In the emerging search for additional risk factors, prenatal stress has been identified as a variable of interest. There is a growing recognition, supported by the studies of the principal investigator (PI) and colleagues, that women who experience psychological and social adversity during pregnancy are at increased risk for preterm delivery, even after adjusting for the effects of established biomedical and sociodemographic risk factors (Wadhwa et al, 1993; Wadhwa et al, 1996; Wadhwa et al, 1997; Wadhwa et al, 1998a; Wadhwa et al, 1998b; Wadhwa et al, in press a; Wadhwa et al, in press b; Wadhwa et al, in press c; Sandman et al, 1999; Killingsworth-Rini et al, 1999; Dunkel-Schetter et al, 2000; Feldman et al, 2000; Glynn et al, 2001; Culhane et al, in press). This may be due to differences in the level and type of stress experienced, but mostly likely also varies across individuals. Although parameters such as the duration, frequency of exposure, and nature of the stress experienced are important in determining risks for adverse pregnancy outcomes, certainly not all women with high levels of prenatal stress deliver preterm. Clearly there are differences between individuals in their physiologic responsivity to stress, and the differences in these responses are belived to play a significant role in the impact of stress on biological outcomes such as gestational length. The objective of the present proposal is to examine the role of individual differences in women's biological responses to a mild behavioral challenge during pregnancy in outcomes related to the length of gestation. Our goal is to gain a better understanding of the specific factors that mediate an individual's propensity to respond to stress and how this response affects the observed relationshipo between prenatal stress and adverse pregnancy outcomes. The behavioral challenge is a standard operationalization of psychosocial challenge that evokes responses from the same physiologic systems that are involved when an individual experiences psychosocial stress. The responses of subjects undergoing this mild challenge are thus representative of their responses to psychosocial stress, yet the challenge, given in a controlled setting, is brief and the psychological and biological responses evoked in subjects is minimal. The primary study hypothesis is that greater maternal biological reactivity to a behavioral challenge (i.e., hyperreactivity) during pregnancy will significantly predict earlier delivery. Secondary study hypotheses are that the effects of maternal biological reactivity to challenge will be mediated via placental corticotropin-releasing hormone (CRH); that the magnitude of the maternal biological response to a behavioral challenge will decrease with advancing gestation; and that baseline hormonal levels, biomedical (obstetric) risk status, and maternal psychosocial factors will correlate significantly with measures of biological reactivity to challenge. To test these hypotheses, a prospective, longitudinal study is proposed over a three-year period in a sample of 200 women with a singleton intrauterine pregnancy. This study sample will be selected from clinical populations at low and high biomedical (obstetric) risk for pontaneous preterm birth, recruited before 10-12 weeks gestation, tested at two points in time in pregnancy, followed through delivery, and tested once in the post-partum period.
Specific Aim 1 : To quantify parameters of maternal physiological reactivity to a behavioral challenge paradigm.
Specific Aim 2 : To quantify changes in maternal physiological reactivity to a behavioral challenge over the course of gestation.
Specific Aim 3 : To assess the influence of maternal physiological reactivity to a behavioral challenge on pregnancy outcomes related to the length of gestation.
Specific Aim 4 : To quantify placental corticotropin-releasing hormone (CRH) activity over the course of gestation.
Specific Aim 5 : To examine the influence of baseline hormonal levels, biomedical (obstetric) risk and psychosocial factors on maternal physiological reactivity to a behavioral challenge.
Specific Aim 6 : To examine the combined effects of psychosocial environment, baseline physiological state, physiological reactivity to a behaviroal challenge, and biomedical/sociodemographic risk factors on pregnancy outcomes related to gestational length.
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