Objectives: Hyperemesis gravidarum is a severe form of nausea and vomiting during pregnancy sufficiently enough to produce weight loss greater than 5%, dehydration, ketosis, alkalosis, and hypokalemia. Several studies have investigated risk factors for hyperemesis gravidarum in Ethiopia, but the studies have reported conflicting results attributed to study design, lack of proper sample size, and the selection of variables. This study aimed to assess the determinants of hyperemesis gravidarum among pregnant women in public hospitals of Guji, West Guji, and Borana zones, Southern Ethiopia, 2022. Methods: An institutional-based case–control study design was conducted from April 15 to June 15, 2022 with a ratio of 1:2 (103 cases and 206 controls). Cases were all pregnant women admitted with a diagnosis of hyperemesis gravidarum by a clinician while controls were pregnant women who were visiting antenatal care services at the same time. Cases were selected consecutively until the required sample size is attained, while controls were selected by a simple random sampling technique. Data were collected using structured questionnaires with face-to-face interviews. The collected data were cleaned, coded, and entered into EpiData version 3.1, and then exported to SPSS version 25 for analysis. Frequency distribution for categorical variables, median, and interquartile range for continuous variables was computed. Backward stepwise logistic regression analyses were done. A significant association was declared with a 95% confidence interval at a p value less than 0.05. Results: Those mothers who had antenatal follow-up (adjusted odds ratio = 0.082, 95% confidence interval: 0.037–0.180), pregnancy with multiple gestations (adjusted odds ratio = 3.557, 95% confidence interval: 1.387–9.126), previous history of hyperemesis gravidarum (adjusted odds ratio = 6.66, 95% confidence interval: 2.57–17.26), family history of hyperemesis gravidarum (adjusted odds ratio = 2.067, 95% confidence interval: 1.067–4.015), and those women had exercised before pregnancy (adjusted odds ratio = 0.352, 95% confidence interval: 0.194–0.639) were determinants of hyperemesis gravidarum. Conclusion: Antenatal follow-up, number of the fetus, previous and family history of hyperemesis gravidarum, and exercise before pregnancy were significantly associated with outcome. Lifestyle modification, early treatment, and early ultrasound scans for pregnant women are crucial to reducing the burden of hyperemesis gravidarum.
