Evaluation of maternal cortisol-to-highly sensitive C-reactive protein ratio and glucocorticoid receptor resistance at 11–14 weeks of pregnancy to predict pre-eclampsia

Abstract

Background: Preeclampsia (PE) is a disorder of pregnancy with a worldwide prevalence of about 5-8% and 4.6% in India. It is the second leading cause of direct maternal and foetal adverse outcomes, resulting in about 50,000-60,000 deaths annually worldwide. Cortisol is a stress hormone, that suppresses the immune system and inhibits the production of pro-inflammatory substances to reduce inflammation. During pregnancy cortisol levels raise to three-fold of nonpregnant level by the third trimester, it is due to changes in HPA axis regulation, raised oestrogen levels and raised maternal CRH levels through placental secretion. Aims: The objective of this study is to evaluate the cortisol (CORT)-to-highly sensitive C-reactive protein (HS-CRP) ratio and glucocorticoid receptor resistance (GCR) in early pregnancy to understand the pathophysiology of pre-eclampsia (PE) and to test whether these parameters have a role in the prediction of PE. CO + RT: HS-CRP ratio evaluates the interrelationship between the hypothalamic–pituitary–adrenal axis (HPA-axis) and the inflammatory response system. It is a new concept and an integrated approach to understand the pathophysiology of PE. Materials and Methods: In this prospective case–control study, we recruited 250 healthy pregnant women at 11–14 weeks of pregnancy and followed them. Those who developed PE after the 20th week according to the American College of Obstetricians and Gynecologists guidelines were considered study participants and the remaining served as controls. CORT was estimated through the ELISA method and HS-CRP was measured by autoanalyser through the turbidimetric method. The CORT-to-HS-CRP ratio was calculated manually. GCR was measured indirectly through leucocytes subsets, neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-monocyte ratio (NMR); individual leucocytes were obtained from complete blood counts. Data were analysed using the SPSS version 20, Pearson's correlation test was used to correlate the results and receiver operator characteristic (ROC) was used to test the predictive capacity of parameters. Results: Low CORT: HS-CRP was associated with PE, having a significance of P < 0.00, but it did not show any specificity and sensitivity under ROC. NLR and NMR were elevated in cases who developed PE, especially NMR with P < 0.008. NMR showed good specificity and sensitivity under ROC with the area under curve 0.74, cutoff value is 23. Conclusion: Low CORT: HS-CRP ratio has an association with PE, the uncontrolled inflammation during early pregnancy in pregnant women who were destined to develop PE. This is due to low-CORT secretion due to dysregulation of the HPA-axis. GCR also has an association with PE, but it was not fully clarified. HS-CRP and NMR can be used to screen in early pregnancy for the prediction of PE.