Cumulative Physiologic Dysfunction and Pregnancy: Biological Mechanisms of Neighborhood Deprivation on Birth Outcomes

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Public Health Sciences, 2015.Background: The association between psychosocial stress and adverse birth outcomes is well established but poorly understood. Specifically, exposure to chronic stress through adverse neighborhood environmental conditions has been moderately but consistently shown to be associated with poor birth outcomes, but the biological mechanisms underpinning the association have not been well studied. During gestation, the maternal stress response may signal a stressful intrauterine environment, which has been demonstrated to affect organ maturation and early parturition. Allostatic load is a conceptual framework for physiological dysfunction arising from exposure to chronic stress and refers to the cumulative, physiological toll imposed on the body from the ongoing activation of the stress response. It is reflected in dysfunction spanning multiple physiologic systems; as a composite measure, allostatic load has been operationalized in the literature to encompass neuroendocrine, hormonal, inflammatory, and metabolic/cardiovascular domains. Cumulative physiologic dysfunction has been theoretically applied to pregnant populations to explain adverse birth outcomes, but as of yet, remains untested. Objectives: The propose of the study was to examine if physiologic mechanisms of chronic psychosocial stress arising from the neighborhood environment may explain adverse birth outcomes in women without identified clinical risk factors. The objective was to characterize a measure of cumulative physiologic dysfunction among a sample of pregnant women using biomarker and biometric components and to examine its associations with gestational age and birth weight using allostatic load as a guiding framework. It was of particular interest to understand the biological mechanisms of neighborhood deprivation on birth outcomes and what additional factors may moderate the effects of deprivation and cumulative physiologic dysfunction on birth weight. Results: Among the pregnant women sampled, cumulative physiologic dysfunction (CPD) scores ranged from 0-6, out of a total of 8 parameters. The mean was 2.09 with a standard deviation of 1.42. The interquartile range was 2.0, and the 75% percentile of the sample had a CPD score of 3.0 or higher. Physiologic dysfunction was not statistically associated with either birth weight or gestational age in the pregnant sample. Neighborhood deprivation was significantly inversely associated with birth weight in the crude analysis (p=0.0287). However, the coefficient for neighborhood deprivation became attenuated and lost significance after adjustment for race and income in both the OLS and MLM models for birth weight with CPD. In the formal test for mediation using Sobel’s Rule for assessing effect decomposition, the mediated path for CPD was not significantly different from zero (p-value=0.4483), suggesting other variables such as race and income may mediate the relationship. Women with major depression, had on average, a reduction in birth weight of 562.44 grams compared to women who were not depressed (p=0.0921). When CPD was added to the multivariable model, there was an small attenuation of the β-coefficient for depression, suggesting it may partially mediated the association between depression and birth weight although the coefficient for depression was further attenuated when race, smoking, and maternal age were added to the model. Conclusion: In this sample of pregnant women, cumulative physiologic dysfunction did not appear to be associated with birth weight or gestational age. Furthermore, it was not a mediator of the effect of neighborhood deprivation on birth weight. Further refinement of a CPD score for pregnancy is needed, taking into consideration both the component parameters and clinical and pre-clinical cut-points for risk scoring