There’s a lot we don’t know  about morning sickness.

And I don’t just mean why  it’s called morning sickness, when the urge to vomit can happen at any time of the day. I mostly mean why morning sickness  is a thing, like, biologically.

It affects so many pregnant  people…and the people in their lives… that we’ve already done a video that covered some of the potential causes. But that was—get ready for it—10 years ago,  and it turns out we were mere bit players. Since that video came out, the real  primary culprit has been found.

And if scientists can understand  its relationship to pregnancy, we may be able to stop a lot of unnecessary,  and sometimes life-threatening, barfing. [♪ INTRO] Since morning sickness is such a  misnomer, we’re going to stick to what researchers call it: nausea  and vomiting of pregnancy, or NVP. But whatever you choose to call it while  you or your partner is swearing off certain foods or hovering over the toilet  bowl, NVP affects about seven out of ten pregnant people, and it’s usually felt  in the first three months of pregnancy. But for some people, it’s even worse.

Like vomiting more than three  times a day, for all nine months. And in that case, we call it HG,  short for hyperemesis gravidarum. HG affects less than 3% of pregnant people, but more than 2%...which sounds like too much.

And many of those people need intravenous  fluids to replace nutrients they’ve lost. The side effects can be severe,  if not life-threatening, so scientists have spent decades  hunting for the best treatment options. For example, in the late 1950s and early 1960s, many doctors prescribed thalidomide  to treat both NVP and HG.

Unfortunately, that came with some  incredibly tragic consequences. And thankfully, these days we have safe  anti-nausea medications available, instead. They’re not a cure, though.

And to find one, researchers have to  understand exactly why NVP and HG exist at all. As we covered all those years ago,  there are a number of hypotheses… including the possibility that pregnant  people are just more sensitive to smells and tastes because that means they’re more  likely to detect and thus avoid spoiled food. Because spoiled food isn’t  exactly something a growing body… or the person growing that body…needs  to be dealing with right now.

But why does NVP happen to  some people and not others? Up until recently, the answer  was simply “We don’t know”. Then, scientists realized that  by looking at the biological, and more specifically genetic  differences between nauseated and non-nauseated pregnant people,  they could identify some answers.

The last time we covered NVP, aka  morning sickness, scientists thought that elevated levels of a hormone  called hCG, might be to blame. Hormones are proteins that the  body produces to send messages to various tissues throughout the body. Unfortunately, the data  haven’t really supported that.

There just isn’t conclusive evidence that hCG affects the amount of nausea  a person feels during pregnancy. But since that video came out, another  hormone has entered the arena as a major, if not the major cause of

NVP: Growth  differentiation factor 15, aka GDF15. GDF15 is found in everyone’s body, whether  you’re capable of getting pregnant or not. It’s part of your natural stress  response, and its abundance increases in a bunch of different situations, like  if you get exposed to something toxic. GDF15 does its job mostly by binding to a  specific kind of receptor in your brain, and issuing the order to your  body, “OK, time to throw up, now”.

In other words, it’s a  decent place to start looking if you want to identify causes of  nausea and vomiting during pregnancy. Thank you to Brilliant for  supporting this SciShow video! Brilliant is an online learning platform with thousands of lessons in  computer science, math, and science.

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Plus, you’ll get your first 30 days for free! So as early as 2000, researchers identified that people’s blood serum tended to have more elevated levels of GDF15 during pregnancy. But that only suggested there was a  correlation between GDF15 and NVP.

Not necessarily that the hormone caused it. Finally, in 2018, researchers  published a study that showed there was a genetic component to having  high GDF15 levels in pregnancy. And a follow-up study published  in 2022 looked at genomes from over 1,500 pregnant people…over  900 of which had to undergo treatment for HG, with the rest having either  normal NVP or no NVP symptoms.

The team was able to identify a few  mutated versions in the gene that codes for GDF15 that were associated with  the more severe HG condition. In other words, if you have  one of these mutations, you are more likely to have worse nausea  and vomiting during your pregnancy. So it appeared that GDF15 did seem  to play some kind of causal role.

And then, a paper published online in 2023 proposed how the problem of GDF15  is really one of sensitization. The idea is that, basically,  due to their genetics, some people have a very low baseline  amount of GDF15 in their body. But both a placenta and a  fetus make tons of GDF15, so if that person gets pregnant,  they experience a sudden, huge spike in GDF15 level that  leads to more severe nausea.

But, you might be thinking, “Why would the fetus be pumping out a hormone  that can make their parent sick for months?” Well, in addition to its role in  puking, GDF15 also suppresses certain immune signaling proteins, which do  basically what their name suggests. By releasing GDF15, a fetus ensures  that even though it’s a foreign body, its parent’s immune system won’t  panic and try to get rid of it. This is why experiencing NVP is correlated with  having a lower chance to lose the pregnancy.

To test their sensitization hypothesis,  the researchers injected non-pregnant mice with either a placebo or a  medium-level amount of GDF15. Not enough to induce nausea, but  enough to increase their baseline. Then, three days later, they  gave all of the mice an injection full of GDF15 and observed the results.

The mice that were first given the  placebo ate less and lost weight, consistent with symptoms of nausea. Meanwhile, the mice that had  been pre-treated with GDF15 didn’t have much of a response  to the second, larger dose. However, the team didn’t just look at mice.

They showed that if a human  fetus had a gene associated with producing less GDF15, their parent  experienced less nausea and puking. And they also found that people  who had higher levels of GDF15 before getting pregnant had  less nausea while pregnant. So it looks like NVP is a  side-effect of GDF15 levels spiking from really low to really high.

Not just being high. And the question of course, is can we use  this knowledge to help us prevent NVP? If having a higher level of GDF15 circulating  through your body really does help protect against NVP, then some  kind of graduated exposure to GDF15 pre-pregnancy could help desensitize  the people who are most at risk.

And scientists have already tested  ways to use GDF15 as a therapeutic for other conditions, so this could  merely be an extension of that research. Or maybe, a future drug  could prevent GDF15 molecules from doing their hormone job, like  by blocking them from interacting with the right receptors in your brain. In fact, some of these drugs  have made it to clinical trials, to see how they can manage  nausea in cancer patients.

However, a lot of experiments looking  into this line of drug development have only been done in mice. And mice don’t typically experience  GDF15 shifts during pregnancy, so more research is definitely needed. It’s going to be a while before  we start seeing commercials for an FDA-approved anti-morning sickness pill.

But the past few years suggest that  NVP is something you, or your partner, or anyone growing a mini-me inside  of them, doesn’t have to endure. They’ll just have to endure all the other side  effects that come with pregnancy, instead. [♪ OUTRO]