Serum Cortisol as an Independent Biomarker for Disease Severity and a Modifiable Factor in Nausea and Vomiting of Pregnancy: A Secondary Analysis of a Randomized Controlled Trial

Background: The pathophysiology of nausea and vomiting of pregnancy (NVP) remains incompletely elucidated. This study investigated whether serum cortisol level is associated with NVP severity, exploring its potential role as a biomarker. Methods: This secondary analysis used data from a randomized controlled trial involving 352 first-trimester women with moderate-to-severe NVP. Participants were stratified based on cortisol quartiles. Comprehensive data, including anthropometric, biochemical, and quality of life measures, were collected. Linear and logistic regression analyses assessed the associations between cortisol and clinical parameters and the risk of severe NVP. Receiver operating characteristic (ROC) analysis evaluated cortisol’s predictive performance. Changes in cortisol levels following treatment were also conducted. Results: Higher cortisol levels were independently associated with increased NVP severity, showing positive correlations with PUQE and VAS scores, alongside a significant association with impaired quality of life. Cortisol was positively correlated with liver enzymes, urea nitrogen, creatinine, free thyroid hormones, calcium, and magnesium, but inversely associated with chloride, potassium, and vitamin B1. Participants in the highest cortisol quartile had a significantly increased risk of severe NVP compared to the lowest quartile. ROC analysis indicated modest predictive value for severe NVP. Serum cortisol levels decreased significantly after treatment across all intervention groups. Subgroup analysis revealed that the positive association between cortisol and severe NVP was more significant in placebo subgroups than in doxylamine-pyridoxine subgroups. Conclusion: Elevated serum cortisol is independently associated with greater NVP severity and reduced quality of life. The observed decrease following effective intervention verifies cortisol as a promising biomarker reflective of disease severity and a potentially modifiable factor in the pathophysiology of NVP. Keywords: Nausea and vomiting of pregnancy; Cortisol; Severity; Biomarker; Stress Hormone