(4 min read)
This blog was inspired by Episode 226 of The Science of Motherhood podcast. You can listen to the full episode here.
If you've ever been so sick in pregnancy that you couldn't keep water down, lost weight, or ended up in hospital on IV fluids, and then been told it was stress, anxiety, or that you just needed to eat some dry crackers, this one is for you.
Because the science has finally caught up with what women with hyperemesis gravidarum have been saying for decades.
First, let's get clear on what HG actually is
Most pregnancies come with nausea. Around 70 to 80% of pregnant women experience it in the first trimester, and for most, it passes. Uncomfortable, yes. But it responds to food and time.
Hyperemesis gravidarum, or HG, is something else entirely. It affects roughly one to two percent of pregnancies and involves persistent, relentless vomiting, weight loss of more than five percent of pre-pregnancy body weight, dehydration, electrolyte imbalances, and in many cases, hospitalisation. The word hyperemesis literally means excessive vomiting, but that label doesn't come close to capturing what women with HG actually live through.
For centuries, the medical establishment treated HG as a psychological disorder. A Freudian theory that persisted well into the 20th century suggested women with HG were subconsciously rejecting their pregnancy. That theory shaped how doctors spoke to patients, how women were dismissed in emergency departments, and how slowly the research moved. It did not, however, help anyone get better.
Where this research came from
A lot of the most important research in women's health starts personally. This did too.
A Harvard-trained geneticist developed severe HG in her second pregnancy. She was hospitalised, placed on a feeding tube, and despite everything, she lost the pregnancy. When she went looking for answers, she found almost nothing. The condition that had nearly killed her was barely studied, and the dominant explanation on offer was still psychological.
So she did what the best scientists do when the answer doesn't exist yet. She went and built it.
She partnered with the HER Foundation and began collecting DNA samples from women who had survived HG. Not dozens. Thousands. One of the largest patient-driven genetic databases for any pregnancy condition in the world, built one cheek swab at a time.
What the research found
In 2018, using a genome-wide association study, researchers identified two genes that stood out in HG patients. The most significant was GDF15, or growth differentiation factor 15, a hormone produced in very large quantities by the placenta during pregnancy. The placenta essentially becomes a GDF15 factory, ramping up production around that five to seven week mark when most women first feel pregnancy nausea. Suddenly there was a measurable, biological candidate. Not a feeling. A hormone with a name.
But if the placenta produces this hormone in every pregnancy, why do only some turn into HG?
The intuitive assumption was that women with HG must be producing too much GDF15. More hormone, more sickness. What the research found, in a 2023 paper published in Nature, was far more interesting.
The bigger predictor of who develops HG wasn't how much GDF15 a woman produced during pregnancy. It was what her GDF15 levels looked like before pregnancy. Women with HG tended to have unusually low baseline levels in their non-pregnant state. So when the placenta flooded their system with the hormone in early pregnancy, that spike was enormous relative to what their body had ever experienced. Minimal prior exposure. Minimal tolerance.
Think of it like caffeine. If you've never had coffee in your life and someone hands you three espressos, you're going to feel it intensely. But if you drink coffee every morning, three espressos on a Tuesday isn't going to move you much. GDF15 appears to work the same way. It's not just how much you have during pregnancy. It's how much of a change that represents from your normal baseline. Researchers call this the sensitivity hypothesis, and it reframes HG entirely.
What this means for treatment
Because HG is fundamentally a sensitivity problem, researchers are now exploring whether that gap can be closed before pregnancy even begins. The idea, called pre-pregnancy desensitisation, is that gently raising a high-risk woman's GDF15 levels before she conceives allows her body to adapt. Then when the placenta ramps up production in early pregnancy, that spike feels smaller and the nausea response is dampened.
A clinical trial is now underway using metformin, a well-studied diabetes medication that raises GDF15 levels as a known side effect, to test whether it could reduce the severity of HG in women with a previous history. Researchers are also working on drugs that could block the receptor in the brain stem that GDF15 binds to, potentially treating HG once it's already started.
The research space is moving faster than it ever has.
For every woman who was told it was in her head
HG is a measurable genetic and hormonal condition. It lives in a gene. It runs through a receptor. It was never a character flaw, and it was never in anyone's head.
If you've been through HG, or you're in it right now, the science sees you. The research is moving. And so much of it started because one woman lived through exactly what you're living through and refused to accept that there were no answers.
Disclaimer: The information presented by Fill Your Cup is not a substitute for independent professional advice. Nothing contained here is intended to be used as medical advice and it's not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice.
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