Immuno-nutritional discordance: a novel composite index derived from pan-immune-inflammation value and micronutrient reserve (IN-Hg score) for predicting refractory hyperemesis gravidarum

Abstract

Hyperemesis gravidarum (HG) may exhibit a refractory course in some patients despite standard treatments. Validated biomarkers for the early identification of refractory HG are limited. This study aimed to evaluate the association and discriminative performance of the Immuno-Nutritional Hyperemesis Gravidarum (IN-Hg) score, a novel composite index derived from the pan-immune-inflammation value (PIV) and measured vitamin B12 and 25-hydroxyvitamin D concentrations, in refractory HG. This retrospective study included 281 pregnant women hospitalized with a diagnosis of HG. The cases were divided into two groups as non-refractory ( n  = 179) and refractory HG ( n  = 102). Demographic, clinical, hematological, biochemical, and micronutrient parameters were compared. Multivariable logistic regression analysis was performed to determine factors independently associated with refractory HG. The discriminative performance of the IN-Hg score was evaluated using ROC analysis. No significant differences were found between the groups in terms of maternal age, body mass index, and gestational week. The length of hospitalization and requirement for parenteral support were higher in the refractory HG group. White blood cell, neutrophil, platelet, and PIV values were significantly higher in the refractory HG group. In contrast, vitamin B12 and 25-hydroxyvitamin D concentrations were significantly lower. In multivariable logistic regression analysis, only the IN-Hg score remained independently associated with refractory HG (OR: 6.875, 95% CI: 2.901–16.290, p  < 0.001). The IN-Hg score demonstrated a high apparent discriminative performance for refractory HG in the same cohort in which it was developed (AUC: 0.998, 95% CI: 0.995–1.000). The IN-Hg score was associated with refractory HG and showed high apparent discrimination in this retrospective development cohort. The findings are consistent with the coexistence of higher inflammatory indices and lower measured micronutrient concentrations in refractory HG but do not establish a causal or pathophysiological relationship. External validation is required before the score can be considered for clinical use.