A novel quartile scoring-based methodology for assessing combinatorial association of prenatal cortisol and DHEA-S with birth outcome among pregnant women

Background and purpose: Changes in the adrenal gland secreted prenatal stress hormones affect birth outcome. Therefore, during pregnancy, regular monitoring of the levels of these hormones such as cortisol and dehydroepiandrosterone-sulfate (DHEA-S) through reference range or quartile scoring approach is essential. Cortisol and DHEA-S regulate each other during pregnancy. In addition, the salivary and circulatory counterparts of these hormones do not correlate with each other during pregnancy. Therefore, in addition to the individual hormonal analysis, there is a need for combinatorial analysis of these hormones from multiple biological sources to understand their role in pregnancy and poor birth outcome. Methods: A prospective study involving 789 pregnant women, in their first or second trimester was conducted in the tribal regions of Modasa and Bhiloda blocks of Aravalli district, Gujarat, India for a period of two years. Blood (plasma) and saliva samples were collected simultaneously, and enzyme-linked immunosorbent assay (ELISA) was performed to determine concentrations of cortisol and DHEA-S. Concentrations of individual hormones in plasma or saliva in the dataset were divided into quartile scores. Microsoft Excel formulae were used to generate combinations of these hormones in plasma and saliva. The strength of association of individual and combinatorial categories with birth outcome was evaluated through binary logistic regression analyses. Results: For each pregnant woman in the study, along with the individual profile of prenatal stress hormones in plasma or saliva, unique 4-component and 2-component combinatorial profiles were generated through quartile scoring approach. These profiles in the dataset were characterized and unique combinations significantly associated with adverse birth outcome or low birth weight outcome were identified. Study has presented benefits of combinatorial over conventional individual component analysis for predicting poor birth outcome. Conclusion: Combinatorial profiling of prenatal stress hormones in plasma and saliva offers a novel and insightful approach for developing models for prediction of poor birth outcome.