Nausea and Vomiting During Pregnancy Might Not Just Be Morning Sickness

Morning sickness is common in pregnancy, with up to 80% of pregnant women experiencing this symptom at some point, however, if the nausea and sickness is excessive and accompanied by an inability to keep food down, you might not be experiencing morning sickness.

Hyperemesis gravidarum (HG) is the medical name for this rare condition, and University of Southern California Researcher Marlena Fejzo, PhD has experienced it firsthand, tragically miscarrying as a result. Fejzo was part of a team that made the first link between a gene variant known as GDF15 and HG, and is working to bring attention to the disease and improve available diagnostics and treatment options.

Technology Networks had the pleasure of speaking with Fejzo to find out more about what women with HG currently face, the finding that HG may have a genetic cause and the possible future outcomes of this research.

Kate Robinson (KR): Can you tell us about your experience with HG and why research such as yours is so important?

Marlena Fejzo (MF): I had HG and was treated with 7 different medications, but nothing worked, and I couldn’t move without vomiting or keep anything down for 10 weeks. Every waking moment I had to lay completely still with extreme nausea. It was torture and ultimately, I was given total parenteral nutrition, but it was too late, and I lost the baby at 15 weeks’ gestation.

Ever since then I have been researching HG to try to find answers, so people don’t have to go through what I did. It’s been over 20 years and mothers and their babies are still suffering and even dying in the United States and around the world from HG. In addition, I and others have now shown that the saying “the baby gets everything it needs from mom” is false in the case of HG. A recent study found HG is associated with the highest risk (5-fold) of having a baby born small for gestational age – this is higher than exposure to cannabis, chronic hypertension, pre-gestational diabetes, preeclampsia, autoimmune disease, cocaine use, amphetamine use and tobacco use in pregnancy. HG is also associated with an increased risk for preterm birth, neurodevelopmental delay and autism spectrum disorder. Of note, HG has recently been shown to be associated with structural abnormalities of the brain. Adverse outcomes are not only limited to the offspring; mothers are at increased risk of suicidal ideation, post-traumatic stress and an array of long-term physical and social issues likely due to severe prolonged illness. Attention to this disease and progress are imperative.

KR: How is HG currently diagnosed and are there any treatment options available for the condition?

MF: HG is generally diagnosed as severe nausea and/or vomiting starting before 16 weeks gestational age, accompanied by an inability to eat and/or drink normally and inability to perform daily activities. It often leads to malnutrition, dehydration and weight loss. Treatment includes rehydration and prescription antiemetics. But current medications are not working well enough – the majority of patients do not gain any weight within two weeks of trying them. Importantly, patients who are unable to tolerate vitamins and are unable to eat properly should be administered thiamin to avoid a rare but serious complication of HG, Wernicke’s Encephalopathy (brain damage caused by thiamin deficiency). Patients and providers also need resources and support, many of which can be found on the HER Foundation website at www.hyperemesis.org.

KR: Can you talk us through how you discovered that variants and mutations of the GDF15 gene are linked to HG?

MF: In our study published in 2018, we partnered with a personal genetics company and performed a genome-wide association study comparing common genetic variants between 1,306 cases with HG and 15,756 controls. The greatest differences were found in variants around a gene that codes for a nausea and vomiting hormone called GDF15.

Recently, we performed a second genetic technique called whole-exome sequencing on a separate population of study participants, comparing common and rare variants within genes between 926 HG cases and 660 unaffected controls. In this study, the only gene that differed significantly between affected and unaffected individuals was GDF15. In addition, the only gene with a rare mutation in 10 or more people affected by HG was in GDF15. GDF15 is produced at high levels by the placenta in pregnancy and patients hospitalized with HG have significantly higher levels than pregnant patients with normal or no nausea and vomiting. This provides very strong evidence that GDF15 is involved in the etiology of HG. While other factors may contribute, I would argue that there is now stronger evidence for GDF15 causing HG than any other theory at this time.

KR: What implications do your findings have for individuals with HG?

MF: Patients are often dismissed or told that they are exaggerating symptoms, leading to undertreatment and pregnancy termination of wanted pregnancies. The immediate benefit of this research is that it provides clinicians and patients with an evidence-based cause of HG which validates the disease and will hopefully force providers and family members to take it more seriously. In the long run, it provides scientists and pharmaceutical companies with a novel pathway to pursue for prediction, diagnosis and treatment. Importantly, drugs targeting the GDF15 pathway are very effective in improving appetite and weight gain in animal models and are already in clinical trials in cancer patients. If safe, these new medications may benefit patients with HG, resulting in healthier mothers and babies.  

KR: How will the strengths and limitations of this study guide future HG research?

MF: Future research should focus on the GDF15 pathway, rather than continuing to waste resources on outdated theories such as the pregnancy hormone human chorionic gonadotropin (hCG) or psychological factors. In addition, our recent study included subsets of patients of African, admixed American and East Asian ancestries, and has provided preliminary evidence that the results may be generalizable, but larger studies in these populations are needed to prove this. There is still much to be done to understand how the GDF15 pathway works in pregnancy and what other factors may be involved. Hopefully the knowledge gained can be used to develop tools for prediction, diagnosis and more effective treatments.

Dr. Marlena Fejzo was talking to Kate Robinson, Editorial Assistant for Technology Networks.