Investigation of Endoplasmic Reticulum Stress in Pregnant Women with Hyperemesis Gravidarum.

The role of the endoplasmic reticulum (ER) stress response in hyperemesis gravidarum (HG) remains incompletely understood. This study evaluated circulating PERK and ATF-4 levels and their associations with clinical and laboratory characteristics in HG. This prospective case-control study, conducted from August to November 2024, included 85 pregnant women with HG within the first 16 weeks of gestation and 85 healthy pregnant controls. Serum PERK and ATF-4 levels were measured using ELISA. Group comparisons, Spearman correlation analyses, and receiver operating characteristic (ROC) analysis were performed. Serum ATF-4 levels were significantly lower in the HG group than in controls [4.55 (0.82-42.86) vs. 6.16 (2.23-29.27) ng/mL; p = 0.002], whereas PERK levels did not differ between groups [3.73 (0.16-15.37) vs. 3.29 (0.67-19.36) ng/mL; p = 0.965]. Strong positive correlations were observed between ATF-4 and PERK in the HG group (ρ = 0.837), control group (ρ = 0.709), and overall study population (ρ = 0.765) (all p < 0.001). Within the HG group, ATF-4 levels did not differ significantly according to urinary ketone positivity (p = 0.282). ATF-4 showed limited discriminatory performance for HG (AUC = 0.638; p = 0.001; sensitivity 45.9%; specificity 77.6%). HG is associated with lower circulating ATF-4 levels without a corresponding change in PERK. These findings support further molecular and longitudinal investigation of the PERK-ATF-4 axis in HG.