Association Between Depression and the Risk of Hyperemesis Gravidarum: A Systematic Review and Meta-Analysis

Background: Hyperemesis gravidarum (HG) is a severe pregnancy-related condition that may be influenced by maternal psychological factors. This meta-analysis aimed to evaluate the association between maternal depression and the risk of HG and to explore whether this association varies by maternal or study characteristics. Methods: A systematic search was conducted in PubMed, Embase, and Web of Science databases up to May 2, 2025, to identify observational studies examining the association between depression, assessed either prior to or during pregnancy, and HG. Heterogeneity was evaluated using the Cochrane Q test and I 2 statistic. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model, incorporating the influence of heterogeneity. Subgroup analyses were conducted by maternal age, timing of depression assessment, diagnostic tools, timing of HG diagnosis, adjustment for gravidity or parity, and study quality. Results: Totally, 13 case-control studies involving 95,249 pregnant women were included. Maternal depression was associated with a significantly higher risk of HG (OR: 5.08, 95% CI: 2.71– 9.52; p < 0.001; I 2 = 93%). The association was stronger among women who were younger than 27 years (OR: 11.64) than in those who aged 27 years or older (OR: 2.86; p (for subgroup difference) = 0.02). Depression assessed at the time of HG diagnosis showed a stronger association (OR: 6.04) than when assessed before diagnosis (OR: 2.11; p (for subgroup difference) = 0.04). Studies using the Beck Depression Inventory or Edinburgh Postnatal Depression Scale reported stronger associations than those using the Hospital Anxiety and Depression Scale (p (for subgroup difference) = 0.009). Conclusion: Maternal depression is associated with the occurrence of HG; however, this association does not imply causation, and depressive symptoms may reflect the psychological impact of this severe condition. Keywords: hyperemesis gravidarum, pregnancy, depression, risk factor, meta-analysis