We aimed to examine whether there is a statistical difference in maternal serum pepsinogen-1 (MSPG-1) between pregnant women with severe hyperemesis gravidarum (HG) and those with moderate HG managed without hospitalization and to explore an MSPG-1 threshold associated with hospitalization in pregnant women with HG. This prospective observational study was conducted in a tertiary referral hospital between August 31, 2024, and November 21, 2024. Singleton pregnancies hospitalized with severe nausea and vomiting in the first trimester and ketonuria in the urine spot test were considered severe HG. The control group comprised symptomatic pregnant women diagnosed with moderate HG who did not require hospitalization. The suitability of the MSPG-1 for hospitalization was determined by analyzing the Receiver Operating Characteristics Curve. MSPG-1 levels were significantly lower in pregnant women with severe HG than in pregnant women with moderate HG. The optimal MSPG-1 cut-off associated with hospitalization was ≤ 67.7 ng/mL (84% sensitivity and 66% specificity) for severe HG. Lower MSPG-1 levels were associated with more severe clinical presentation and hospitalization in HG patients. The optimal value for MSPG-1 (≤ 67.7 ng/mL) with a specificity of 66% and a sensitivity of 84% may serve as a potential cut-off value to support hospitalization decisions in patients with hyperemesis gravidarum. However, it should be noted that the design of the study, in which only one center is involved, requires external validation. The study is registered at www.clinicaltrails.gov registration number: NCT06581796; registration date: 30/August/2024.
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