We have made incredible strides in science — we walked on the moon decades ago; we are talking about sending people to Mars. Yet women are still dying from nausea and vomiting of pregnancy (NVP). This condition in its most severe form, hyperemesis gravidarum (HG), is not merely an inconvenience of pregnancy; it has profound implications for maternal and child health.
HG is the second leading cause of pregnancy-related hospitalizations. It continues to lead to maternal and fetal deaths in the U.S., the U.K., and worldwide. Black and Asian women are disproportionately affected, and many patients suffer from PTSD, postpartum depression, and other lasting complications. The effects on children can be equally dire, with small but significant increased risks for preterm birth, neurodevelopmental delays, smaller brains, autism spectrum disorders, respiratory disorders, and even childhood cancer. These outcomes likely stem from the severe nutritional deficiencies experienced during HG pregnancies.
While 70% of pregnant people experience some form of morning sickness, HG affects 0.3% to 10.8% and can cause severe malnutrition, weight loss, and long-term complications. The economic burden alone is staggering, with billions lost annually in the U.S. due to missed work, hospitalizations, and inadequate treatment.
In 1999, I experienced HG firsthand. My symptoms were so severe that I could not eat, drink, or even move without violently vomiting. I was confined to lying completely still and endured weeks of relentless suffering. Despite being put on seven different medications and later a feeding tube, it was too late to save my pregnancy. The physical and emotional toll was worsened by my doctor’s dismissive claim that I was “exaggerating for attention.”
Once I recovered, I was determined to take action. Armed with a PhD in medical science from Harvard, where I had previously identified key genes associated with uterine fibroids, I decided to dedicate my career to understanding and combating HG.
My path to discovering the gene that causes HG
In 2003, I partnered with the HER Foundation, and we launched a large study of HG patients. We discovered that 26% of HG sufferers lose more than 15% of their pre-pregnancy weight and that 22% endure symptoms until delivery, essentially experiencing prolonged starvation in pregnancy. Our research also uncovered a 17-fold increased risk of HG among women with affected siblings, which spurred our genetic investigations.
I got very limited support for HG research, so I worked primarily on ovarian cancer while enrolling and collecting clinical data and DNA from pregnant people as a side project for over a decade. In the evenings and on Fridays, I scheduled calls and spoke to and enrolled potential participants from across the country. I listened to their experiences with HG, answered questions about the study, reminded them to sign and return consent forms and complete our survey for data collection, assembled, addressed, stamped and mailed saliva collection and return kits, and asked each participant to refer an unaffected friend to participate as a control. This was all done in order to collect enough affected and unaffected people to run our genetic and epidemiology studies. It was slow going, considering many were pregnant and ill, some even speaking to me from their hospital bed, some with newborns, small children, and irregular schedules. Understandably, they cancelled often, so it required patience and perseverance.
But in 2010, my brother gave me a 23andMe kit for my birthday, and a lightbulb went off when I saw the company’s brilliant model of allowing customers to opt in as research participants. Realizing this could be applied to HG, I contacted the 23andMe team to ask if they could add HG to their survey, and was delighted when they agreed. As I was unable to get funding to sequence the samples I collected, this alternative approach turned out to be extremely fruitful — by 2016, 23andMe had genotyped over 1,300 HG cases and over 15,000 unaffected women who had reported on their experiences with NVP.
The 23andMe cohort findings were confirmed in my study participants, and in 2018 we published our results, identifying both a gene for the nausea and vomiting hormone (GDF15) and a gene upregulated during initiation of the maternal death spiral in the octopus (IGFBP7/IMPL2) as major contributors to HG. Both genes are also associated with cachexia, known as wasting syndrome, which is the cause of death for 20% of cancer patients. Cachexia has similar symptoms to HG — loss of appetite, weight loss, and muscle wasting — and in 2019 we published our study showing that blood levels of both GDF15 and IGFBP7 were abnormally high in patients hospitalized with HG.
Following these publications, we partnered with the biotechnology company Regeneron and finally were able to get all of our DNA samples analyzed, which confirmed GDF15 as the greatest genetic risk factor for HG and also resulted in the identification of a rare mutation in GDF15 associated with HG, further providing strong evidence for causality.
However, not all patients who carried the mutation had HG in every pregnancy — for example, some people experienced HG in their first pregnancy but then nothing more than mild nausea in their second. To determine whether HG risk was determined by the genetics of the fetus, we sequenced the children of the mothers who had the rare GDF15 variant and found, surprisingly, that the mothers were less likely to have HG in pregnancies in which their child inherited the mutation. We then collaborated with endocrinologist Professor Sir Stephen O’Rahilly and an international team of researchers and discovered that the GDF15-predisposing variants are associated with lower blood levels of the nausea and vomiting hormone prior to pregnancy, resulting in increased sensitivity to the rapid rise of the hormone, which is made by the placenta in huge amounts during pregnancy. In other words, the severity of NVP is primarily determined by a combination of the amount of GDF15 one is exposed to prior to pregnancy and the amount produced by the fetal placenta during pregnancy.
Where do we go from here?
These findings have exciting implications. We now know that maternal and fetal DNA both contribute to HG risk, providing a genetic explanation for why the condition can vary from one pregnancy to the next. Even more promising, our research has paved the way for potential preventive and therapeutic approaches. For example, we are investigating metformin as a treatment to modulate GDF15 levels before pregnancy, potentially reducing HG severity. Metformin increases GDF15 levels, so we believe we may be able to increase GDF15 prior to pregnancy to desensitize patients to it, similar to the approach to desensitize patients to allergens. Additionally, pharmaceutical companies are developing antibodies to block GDF15 signaling, offering hope for effective treatments in the future.
But science alone is not enough. Regulatory agencies are cautious about testing medications in pregnancy, leaving conditions like HG under-researched and poorly treated. This must change. Pregnant people deserve access to safe and effective therapies, and we need better training for obstetricians and emergency room doctors to recognize and treat HG.
Specialized treatment centers are a critical step forward. That is why I helped open the Harmonia Healthcare Center in Red Bank, N.J., which takes insurance and focuses on compassionate care for HG patients. There is also a clinic in Birmingham, Alabama, the HG and Morning Sickness Clinic. These centers not only provide lifesaving treatment but also serve as hubs for research and, in the future, clinical trials. They provide a solution to the current broken model where patients, pregnant and extremely ill, are waiting for hours in emergency rooms to get fluids, only to be sent home and have to return again. The HER foundation also has excellent resources for patients, providers, and their families, including a severity scoring tool (HELP score), a detailed treatment algorithm, online support groups led by trained personnel, a referral network of “HG-friendly” doctors by location, and so much more.
The lack of support for women’s health research has far-reaching consequences. HG is a glaring example of how gaps in knowledge and care perpetuate suffering. It should not have taken decades — and the loss of my own pregnancy — to make progress for this common and devastating condition. Moving forward, we need increased funding for women’s health, stronger support for female scientists, and systemic changes to prioritize maternal care.
We can and must do better. With continued research, advocacy, and collaboration, I am confident that we will one day cure HG, ensuring healthier futures for mothers, babies, and generations to come.
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This is so incredible – I had severe HG during my pregnancy and none of my providers warned me that it also comes with a higher risk of pre eclampsia, which I also had, leading to some pretty traumatic outcomes during labor and delivery. This was all a pretty heavily weighted factor in deciding, with my husband, that we won’t be having any other children. I just can’t handle the risk, mentally or physically. I truly hope more research like this gets out there and improves outcomes for people! It gives me so much hope!
I’m profoundly grateful for this research and the hope of better advocacy and outcomes. My mother had HG symptoms in all of her pregnancies and lost two pregnancies due to complications, one at 20 weeks. My sister and I both are thankful to each have carried a healthy daughter to term after having HG in our pregnancies as well. Perhaps with this work our daughters might have an entirely different experience of pregnancy without so much suffering and fear. I have infinite gratitude for Marlena and the HER foundation, thank you also to Emily for publishing on this topic 🙂
Wow, your advocacy is incredible and inspiring. Keep going, we are cheering you on!!
Thank you Marlena. This gives me so much hope and will change so many lives. I hope treatments are available in time for me to have a second. If not, then for my daughter so she never has to experience this. I’m so sorry for what you went through too.
I know someone recently diagnosed with HG. What is the best way to support them? How would you have liked to been supported?
This research is so exciting and promising. Thank you for shining a light on Marlena’s critical work.
What an amazing story of perseverance, strength and the power of science! You’re a hero!!!
This is amazing work–it is ludicrous to me that Prof. Fejzo is an Assistant professor and has not been promoted further. This further demonstrates how much research on pregnancy and women’s health is so undervalued. I hope her institution realizes how amazing she is ASAP!
I’m just one of the many, many people whose lives have been changed by the Morning Sickness Clinic in Birmingham, Alabama. After suffering through my first pregnancy, finding the clinic in my second pregnancy made it an entirely different experience for me and my baby. Incredibly grateful for your work (and in turn, for the clinic here.)
I completely agree- this is hero level medical work! I often felt so isolated with my Hg. No one could really understand unless they saw me lay on the couch in adult diapers bc I was dry heaving every 1-3 hours into disposable puke bags (bought in bulk on Amazon) so hard I’d pee myself. Well meaning people told me to eat ginger candies and eat smaller meals. Medical advice was completely disconnected from my reality. In the end, I was incapacitated till week 39 of my pregnancy when I was induced due to my daughter’s low weight. If it wasn’t for all the (eventual) medical interventions, including 2 daily oral anti nausea medications, a Zofran pump, and 5x week IVs, I’m not sure my daughter and I would have survived. If this was 100 years ago I don’t think we would have made it… I also identify with the dr not taking you seriously. I was too sick to work at 5 weeks and yet my original OBGYN refused to even see me for nausea till I “hit 8 weeks”. My advice, go to the HER Foundation, find a Dr who has knowledge and a background, and ask for support from your ‘village’. PS My daughter was absolutely worth the suffering.
Thank you so much for pushing for this important research! So grateful for people like you!
The HER foundation and the HG-knowledgeable doctor I found through them are the reason I have my daughter today. I had a termination scheduled for the same day I was able to have my first appointment with this doctor. He understood how sick I was when my regular OB/GYN had told me to sip ginger ale and eat crackers.
Thank you, Marlena, for turning your grief into action and change. I add your name to my list of heroes.