Dr Marlena Fejzo's research showed some people had predisposition to GDF15 sensitivity, which determined how sick they would get during pregnancy. Photo: 123RF
Dr Marlena Fejzo, like many women, suffered extreme morning sickness during her first pregnancy.
And when the symptoms returned during her second, escalating to the point she could do nothing but lay flat out on her back, she sought medical help - but her doctor brushed off her symptoms, claiming many women play it up for attention or sympathy.
Fejzo miscarried, her body too frail from the unrelenting sickness to support a baby.
So the faculty researcher in the Center for Genetic Epidemiology at the University of Southern California set out to use her own experience and her expertise to solve the problem - one many doctors appeared not to believe was even real.
"My doctor, he told me that he thought I was trying to get attention from my parents, who were taking care of me," Fejzo told Nine to Noon on Tuesday.
"I could not get out of bed… I became too weak to even speak, so I had to use a buzzer to signal to my parents - who had just retired, thankfully - and were able to take care of me, even though that wasn't what they had planned to do with their retirement.
"But I needed to use a buzzer to buzz them to come when I needed a bedpan change, or needed a medication change, because I could not even sit up or get up to use the bathroom for a shower, brush my teeth, nothing. I just had to lie completely flat every second of every waking moment, trying not to go into this spiral of endless vomiting. So it really was torture and I was so weak.
"But my doctor… he thought that I just, you know, wanted attention from my parents, which was ridiculous because the last thing you want is to have your father changing your bedpan. It got so bad."
Geneticist Marlena Fejzo lost her baby to severe morning sickness, so she discovered the cause
Fejzo spent weeks in this state. By the time she was put on a feeding tube, it was too late to save her baby.
"I could not eat, drink or move without violently vomiting, so I just had to lay completely flat for weeks and weeks and I could not eat or drink anything.
"I had IV fluids… and eventually my doctor put me on seven different medications at once, but nothing worked to help me to be able to eat or drink. And then eventually I ended up losing the baby in the second trimester."
She decided to put her education and training to good use, and figure out what was happening to women who experienced hyperemesis gravidarum (HG) - extreme morning sickness - and if there was a cause, get that knowledge through to those working on the frontlines of women's healthcare
"When I looked into what was done, there was basically hardly any good research done on hyperemesis… We really need a new education of doctors so that they know, just because you don't know what the cause of the disease is - and it's a woman's disease, and a women's disease in pregnancy - does not mean that we're faking our symptoms or exaggerating them."
Her first suspicion was that something genetic was behind the illness - but her mother had "four easy pregnancies", and genes could also be passed down from fathers who obviously would never experience HG.
"So the first thing I did was to do a familial aggregation study, which is to see if it does run in families. And I did - I found there was a 17-fold increase risk of having it if your sister had it. And so then I knew that there was likely a genetic component, and started using that approach to try to figure out what was causing it."
Photo: Christina Gandolfo
She spent years looking into it, with willing participants hard to come by. The turning point came in 2010 after her brother bought her a 23andMe genetic testing kit for her birthday.
"I saw what they were doing - which was really brilliant - which was asking their customers if they were interested in participating in surveys that they could link to their genetic data. And so I asked them if they would include questions about nausea and vomiting and hyperemesis in their surveys, and they did.
"And so by 2016, I had partnered with them and they had participants that were then scanned for over 15 million variants. And they had about 50,000 participants that had not had an experience of having HG and about 1300 that did have HG.
"And they compared them, the genetics of each of those, and found that the greatest genetic risk factor was in this gene that codes for this hormone called GDF15."
The gene was IGFBP7, "an insulin growth factor binding protein gene".
"[IGFBP7 is] the same gene that [causes] the octopus starves to death after it lays its eggs and dies - and it is the same gene in humans and octopus that leads to that maternal death spiral in the octopus.
"So, it seems that these genes evolved a long time ago to give some type of advantage to females to not eat in pregnancy or gestation."
That particular evolution might not be so useful now, she said, but it is still there, causing some mothers to be predisposed to extreme morning sickness. Not eating can have long-term effects for both mother and baby, she said.
For babies, it was "smaller brains and neurodevelopmental delay and other disorders as well, increased risk of respiratory disorders and cardiac disorders and even childhood cancer". And for mothers, the risks of HG include postpartum depression and suicidal ideation.
She said the research showed some people had predisposition to GDF15 sensitivity, which determined how sick they would get during pregnancy.
"To our surprise, this nausea and vomiting hormone, it is actually lower in patients that have this gene mutation or variation prior to pregnancy, and so they are hypersensitive to it during pregnancy. So, it's having a lower level of this hormone before pregnancy that makes you so sensitive during pregnancy and then if this hormone is made by the foetus.
"It also depends on how much the foetus makes, which is also based on the genetics of the foetus. So there is this interaction between the maternal level prior to pregnancy, which is in part defined by her genetics, as well as the baby and the genetics of the baby that will determine how high the level is during pregnancy.
"And so it's that combination that is going to determine how sick you are during pregnancy - from having no nausea and vomiting to having very severe nausea and vomiting, like I had in my case."
Despite her breakthroughs, Fejzo has struggled to get funding for the work.
"It's been very hard. It really has been frustrating. I have to say I wrote six grants this year and they were all denied, and it's not because I'm a bad writer… I think women's health has not been valued, and so that is changing of late and I think things will get better.
"But in addition to that, I think part of it is that because there are so few researchers on this that you, when you have people reviewing grants, they don't know about it. And people tend to be interested and fund the things that they know about and understand.
"And so, with me being one of the only people working on it, it's difficult to get people to review the grounds that understand what I'm writing and have interest in what I'm writing and will, you know, support it and say 'this is really important' as opposed to maybe things that they are used to working on and more interested in."
She is trying to raise money for trials on potential treatments. One would be to increase the levels of GDF15 before pregnancy, to get a mother's body used to it.
"I want to use the cheap medication metformin because that raises GDF15 levels, we know, and it's already used prior to pregnancy to increase fertility in patients with polycystic ovarian syndrome…
"And then the other strategy is to lower the levels or lower the signalling of GDF15 during pregnancy, and there are companies that have developed ways to do that with antibodies that block that hormone or block its receptor… We're actually fortunate because that same hormone causes the weight loss associated with cancer, as well as nausea and vomiting associated with chemotherapy, so, there are companies that are developing those drugs for those indications.
"They are not very interested in using them for testing on pregnant women, but I'm trying my best to encourage them to do so. And there is one company that announced that it is trying to go forward with testing its drug in pregnant women."
She was currently working with Harmonia Healthcare, supporting women with so-called obscure health conditions that were often overlooked or undiagnosed, including HG.
"The first place we opened our clinic in New Jersey and we have two more opening in the fall on the east coast, which I'm really excited about and these will set up the infrastructure for those clinical trials.
"But right now, they are already helping people to get better care because right now, at least in the United States people go to the emergency room for treatment and they have to sit there feeling extremely ill in a waiting room for hours and hours, just to get fluids and then they get sent home and end up coming right back again.
"So, the Harmonia Healthcare centres will really change the way that we have care in the United States and hopefully around the world. We hope to expand care and then set up the infrastructure for these clinical trials to occur once they get up and running."