Genes Predicting Severe Pregnancy Nausea and Vomiting Identified

CLACKAMAS, Ore., May 6, 2022 /PRNewswire/ -- Most pregnancies are affected by nausea and vomiting, but some people develop very severe symptoms and are diagnosed with Hyperemesis Gravidarum (HG). HG can be a form of starvation in pregnancy that harms both mother and baby. Some mothers terminate wanted pregnancies and many decide not to have any more children. One of the most common questions patients ask me is "what are the chances I will have this again in my next pregnancy," says Kimber MacGibbon, RN, Executive Director of the Hyperemesis Education and Research (HER) Foundation (https://www.hyperemesis.org/). "We now have information to help us answer that question."

The HER Foundation and the University of Southern California have identified risk genotypes associated with recurrence risk for HG. In the study presented at the American College of Obstetrics and Gynecology (ACOG) in San Diego, CA, the researchers compared genotypes at the genetic risk locus PGR-TRPC6 in 125 patients who had HG in both their first and second pregnancy to 26 patients who only had HG in their first pregnancy, but not their second. The study identified a genotype that was 9-times more common in patients that did not have a recurrence. In the future, patients may be able to test for this genotype and if they have it, know that they are less likely to have HG again in their next pregnancy. "This may help patients with their family planning, which is of critical importance to people with HG," says Marlena Fejzo, PhD, geneticist and coauthor of the study.

In a second study presented at ACOG, the researchers identified mutations in families affected by HG. In this study, using whole-exome sequencing, the researchers sequenced the DNA from 16 families with 3 or more family members who had HG. Affected patients in two families had mutations within or near the RET gene, which is the co-receptor for the nausea and vomiting hormone GDF15. "Some of the patients in the 2 families reported losing 30 pounds in their pregnancies due to severe nausea and vomiting," said Dr. Fejzo, "and now we have identified a possible biological explanation for their extreme symptoms." In February, the team published a study confirming GDF15 is the greatest genetic risk factor for HG https://www.hyperemesis.org/news/2022_bjog/. At ACOG, they present for the first time that not only GDF15, but its co-receptor RET, may also play a role in causing the disease.

HG patients have increased risk of suicidal ideation, PTSD, electrolyte disturbances, and nutritional deficiencies that can lead to cardiac arrest and maternal brain damage. Babies have increased risk of preterm birth and abnormal brain development resulting in an increased risk of neurodevelopmental delay and autism spectrum disorder. Current antiemetic treatments are not always effective, so novel approaches are needed.

Medications to block the GDF15-GFRAL-RET pathway are currently in clinical trials to treat loss of appetite in cancer cachexia and may lead to novel treatments for HG. These studies also have implications for genetic testing and counseling of patients with HG.

For more information contact:
Marlena Fejzo, PhD, [email protected]
Kimber MacGiboon, HER Foundation Executive Director, [email protected]
703-399-1272

SOURCE HER Foundation