Marlena Fejzo, PhD, an Associate Researcher at UCLA and USC talks about extreme morning sickness and the genes that are believed to cause it.
Interview conducted by Ivanhoe Broadcast News in April 2018.
Tell me about what you have discovered with the genes and extreme morning sickness?
Dr. Fejzo: We have found that there are two genes linked to extreme nausea and vomiting in pregnancy and normal nausea and vomiting in pregnancy. The extreme form is called hyperemesis gravidarum (HG). It affects about two percent of pregnant women. And what we found was that in those women, they have a variation around these two genes that code for proteins and are turned on in the placenta. And when they get expressed by the placenta those proteins then can get into the maternal bloodstream and into the brain and cause nausea and vomiting.
And that’s what makes you super sick?
Dr. Fejzo: We believe that what makes some women so sick is that they have levels of these proteins that are abnormally high.
Until now, pregnant women just had to grin and bear it even when it was terrible like that.
Dr. Fejzo: Yes, they still have to grin and bear it but finally we have some answers. We can start to look at therapies that will target these proteins and hopefully lower them safely in pregnancy so that we can have medications that work to treat nausea and vomiting in pregnancy.
So medications are not working now?
Dr. Fejzo: For normal nausea, some of them are okay. But for extreme nausea and vomiting, the most effective one in our studies is ondansetron or Zofran. It was developed to treat nausea and vomiting from chemotherapy. And it’s really only effective in about half of the women that have severe nausea and vomiting in pregnancy.
Let’s talk about safe, current treatments. You had just mentioned Zofran.
Dr. Fejzo: Zofran is currently the most effective treatment but it is only effective in about half of the women in our study.
What happens in the other half?
Dr. Fejzo: There are a few other medications they can try, but they are less likely to work. They should get hydration through IV fluids if they are dehydrated. In extreme cases, they’ll need tube feeding because if they can’t keep food down and they’re actively losing weight, especially into the second trimester of pregnancy, then they need to be supplemented with nutrition.
So the nausea and vomiting can last not just for the first trimester but all the way through the pregnancy?
Dr. Fejzo: Yeah, as many as twenty percent of women have it the entire nine months.
How were you guys able to pinpoint these two genes?
Dr. Fejzo: Many years ago, I talked to the personal genetics company, 23andMe, and they have survey data on their participants. I asked them if they could add questions related to nausea and vomiting in pregnancy, and that paid off. We have partnered to analyze the data. By last year they had over fifty thousand women that had reported on their levels of nausea and vomiting in pregnancy. We compared the genetic variation in women with no nausea and vomiting to women with very severe nausea and vomiting or hyperemesis gravidarum. And what we found was that the women with hyperemesis had a difference in their DNA around these two genes: GDF15 and IGFBP7.
The DNA information came from 23andMe?
Dr. Fejzo: Yes. They found the linkage to these two genes and then, over the years, I have collected over 1300 women. So I tested the 23andMe findings in my participants and confirmed that these two genes are indeed linked to hyperemesis gravidarum.
You said something about estrogen and something else, what is that?
Dr. Fejzo: The leading theory before this discovery was hCG, the pregnancy hormone that they use in pregnancy tests to show if you’re pregnant. Its levels rise early in pregnanc, so they thought that this was the cause of hyperemesis. But we found no evidence to support that.
Now you take this information and I’m sure there are a whole lot of pregnant women asking now what?
Dr. Fejzo: Yeah. A genetic study doesn’t prove causality so the next step is to prove that these genes code for proteins that then cause the disease. I’ve already started to do that and I’ve shown that the proteins are abnormally high in women hospitalized for hyperemesis gravidarum. Normal women have, at twelve weeks, about ten nanograms of the GDF15 hormone per ml of their blood. Women with hyperemesis have on average of fifteen nanograms per ml. So women with HG have significantly higher levels in their blood. GDF15 then goes to the brain and signals this loss of appetite and nausea and vomiting in extreme cases. There’s quite a bit of evidence now that it is a cause of hyperemesis gravidarum. The next step would be to make a medication that would lower the levels.
Could that be tricky because women are pregnant?
Dr. Fejzo: That is the question: is it going to be safe in pregnancy? So we’ll have to try it out and see. My thinking is that if we can make a medication where we can control the levels so that it doesn’t go down all the way but goes down to the normal level of ten nanograms per ml in the blood at twelve weeks, then it should be safe. But we’ll have to try it out and see.
What would be a potential time for the causality trial and to get into a drug trial?
Dr. Fejzo: It can take many years unfortunately. The fascinating thing is that this same protein, GDF15, which we found linked to HG is also the cause of cachexia, which is nausea and vomiting that actually kills twenty percent of cancer patients. Because of that finding, I know of several drug companies that are making a drug to treat cachexia so that will speed up the process. And then hopefully it will be prescribed off-label to test in pregnant women.
In trials, could you piggy back the HG on to the trials of cachexia?
Dr. Fejzo: Well no, they’ll have to be tested first in cancer patients and see if they’re safe in cancer patients. And then after that, if it turns out to be safe and effective in cancer patients, then we can move on to nausea and vomiting in pregnancy.
So in Jenny’s case was she one of the ones who responded to Zofran or did she have to just grin and bear it?
Dr. Fejzo: I haven’t talked to her. I know her doctor; you’ll have to ask her.
What haven’t I asked you that you want to make to say about this study?
Dr. Fejzo: The main thing is that I want pregnant women, doctors and caretakers to know that this is likely the cause of nausea, vomiting and hyperemesis gravidaram and I’m hoping that they stop treating women like it’s all in their head. And that the women should get the medical attention and treatment that they really desperately need. Also, women with HG who are unable to keep down prenatal vitamins should talk to their doctors about getting thiamin (vitamin B1) through IV or a shot. Low thiamin levels are associated with a rare but very serious neurological complication of HG.
And there’s a couple, Kate Middleton and Maria Shriver are some famous people who people can identify with this condition as well.
Dr. Fejzo: Yes, they had the condition too. Both were hospitalized for it. And it has been reported that the author, Charlotte Bronte, died from it. So it can happen to anybody, even a Princess.
Did you respond to Zofran or no?
Dr. Fejzo: It stopped me from vomiting but the nausea was still so bad that I could not eat or drink.
For the whole time?
Dr. Fejzo: Yeah, I lost the baby.
Do you mind talking a little bit about it. Did you know what it was?
Dr. Fejzo: No, in fact in my first pregnancy, I had it and I was never diagnosed. The second pregnancy when I got it in 1999 it was very severe. I couldn’t move without vomiting so I couldn’t even sit up. I just had to lay totally still staring at the wall. It was really a form of torture and I could not eat or drink. I ended up on a feeding tube but the baby died.
Associated with HG?
Dr. Fejzo: Yes.
So your work is potentially lifesaving.
Dr. Fejzo: Oh yeah, there have been women who have died in the United States in the last decade from this. It’s rare but maternal death does still occur. In addition to maternal mortality, there can be bad outcomes for the fetus too. Over 100 women in my study have terminated a wanted pregnancy specifically because of HG. In addition, there are increased risks of preterm birth and neurodevelopmental delay in children. Vitamin deficiencies during HG pregnancies can result in fetal death and abnormalities in children.
That’s serious.
Dr. Fejzo: It’s the second leading cause of hospitalization in pregnancy.
After gestational diabetes?
Dr. Fejzo: Preterm birth.
What are some things people might not know about normal morning sickness?
Dr. Fejzo: For normal morning sickness, making sure to have enough fluids is important. You can take Diclegis, which is a medication for normal morning sickness. It works in some people. It is basically a combination of Vitamin B6 and an antihistamine. And avoiding spicy or heavy foods and eating small and frequent meals is recommended.
At what stage do people need to go to the hospital for extreme morning sickness?
Dr. Fejzo: If women are rapidly losing weight, are continuously vomiting, have lost over five percent of their pre-pregnancy weight, or are dehydrated and unable to keep fluids down, then they need to go and get treatment. There’s a test to see if you’re dehydrated. If you think you might be dehydrated, you can pinch your skin- if it bounces back then you’re probably not dehydrated but if it slowly bounces back then you need to get fluid.
What other conditions have similar symptoms to morning sickness?
Dr. Fejzo: Like I said there’s cachexia which is nausea and vomiting in patients that are dying from cancer. And then just other forms of nausea and vomiting like food poisoning.
But would sea sickness or motion sickness be something like that too or no?
Dr. Fejzo: Sea sickness and motion sickness symptoms are similar to it. But I don’t know if they have the same biological cause, so I cannot predict whether a medication based on these findings would work for both HG and these other forms of nausea and vomiting. It is certainly possible.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Marlena Fejzo, PhD
310-383-3581
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