Hyperemesis gravidarum linked to mental health disorder risks

Researchers from King’s College London have identified that multiple neuropsychiatric and mental health outcomes are more likely in patients with hyperemesis gravidarum (HG), defined as excessive nausea and vomiting in pregnancy.¹

The association was identified in a retrospective cohort study of 476,857 pregnant women with an HG diagnosis, in which researchers evaluated neuropsychiatric and mental health outcomes in this population. Based on the results, 13 conditions had an over 50% increase in risk among women with HG.

“Whilst we already knew from previous research that women with HG are at an increased risk of anxiety, depression, and PTSD [post-traumatic stress disorder], our study not only confirmed these findings, but also demonstrated an increased risk of severe mental health conditions,” said Hamilton Morrin, MBBS, BSc(Hons), a doctoral fellow at King’s College London.

Key findings: elevated risks

Data were obtained from the TriNetX Global Collaborative Network, which compiled electronic health records from 18 countries. Twenty-four neuropsychiatric and mental health-related outcomes were assessed, with follow-up occurring for a year following HG diagnosis.

Postpartum psychosis and post-traumatic stress disorder were included in the conditions, with an increase in risk greater than 50% among patients with HG. Additionally, a 2-fold increased risk of Wernicke encephalopathy, defined as a neurological condition linked to vitamin B1 deficiency, was reported.

Other conditions with a more than doubled risk in patients with HG included refeeding syndrome, eating disorders, and depression. Postpartum depression was especially more likely, with a 2.7-fold increase in risk.

HG severity and mental health outcomes

Investigators also assessed whether classifying HG as mild HG or HG with metabolic disturbance would influence mental health outcomes, defining the latter condition as HG with carbohydrate depletion, dehydration, or electrolyte imbalance. Classifications were based on the International Classification of Diseases, Eleventh Revision, the latest version.

The risk of depression was significantly reduced in cases of HG with metabolic disturbance vs those of mild HG. According to investigators, this highlights the need for all women with HG to receive support and adequate mental health screening regardless of perceived severity.

According to Morrin, although HG severity determined by metabolic disturbances is effective for identifying patients needing physical health intervention, this method is not effective for determining when mental support is necessary. No correlations have been identified between HG severity and the impact on mental health.

Impact on patients

Up to 3.6% of pregnancies are impacted by HG, making it the most common cause of first-trimester hospitalization in pregnant patients. Most of these cases resolve in the second trimester, but patients with HG experience a long period of severe nausea and vomiting. This often causes them to lose weight and be dehydrated.

Alongside anxiety about leaving home and feelings of isolation, HG may lead to uncertainty among women about how the remainder of their pregnancy will progress. Therefore, over half of women with HG consider pregnancy termination.

“HG can be associated with severe psychiatric disorders that require urgent recognition and joined-up physical and mental health care from the very start of pregnancy,” said Thomas Pollak, PhD, a clinical reader and consultant neuropsychiatrist at King’s College London.

Genetic factors

Biological and socioeconomic factors have been linked to HG risk. However, findings from a 2024 study revealed that the hormone GDF-15 may also be a source of HG.² Samples of patients with HG showed genome-wide associations between the condition and common genetic variants around GDF-15.

A decline in HG risk was reported in patients with greater circulating GDF-15 levels before pregnancy, with an odds ratio of 0.70. This indicated potential for GDF-15 as a source of strategies for HG prevention and treatment.

References

1. Severe pregnancy sickness raises risk of mental health conditions by over 50%. News release. King’s College London. September 18, 2025. Accessed September 25, 2025. https://www.eurekalert.org/news-releases/1098520.
2. Fejzo M, Rocha N, Cimino I. et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. 2024;625;760-767. doi:10.1038/s41586-023-06921-9