Q&A: Misconceptions, risk factors, treatment for nausea, vomiting of pregnancy

Key takeaways:

• Women with severe nausea and vomiting of pregnancy or hyperemesis gravidarum symptoms should seek treatment.
• Familial hyperemesis gravidarum history increases nausea and vomiting of pregnancy risk.

Nausea and vomiting of pregnancy, commonly called morning sickness, is a complex condition that can occur at any time of the day and includes and combination of nausea, vomiting and retching.

“There’s really no one discrete definition of morning sickness, and morning sickness is kind of the ‘old school’ term, if you will,” Shannon M. Clark, MD, FACOG, professor, associate OB/GYN residency program director and levels of maternal care director at the University of Texas Medical Branch, told Healio. “It’s called nausea and vomiting of pregnancy now, because we know that the symptoms of morning sickness can occur at any time of the day. It’s not just in the morning.”

According to ACOG, the prevalence of nausea in pregnancy is 50% to 80% and 50% for vomiting and retching during pregnancy. Overall, studies have found that nausea and vomiting in pregnancy is associated with good pregnancy and fetal outcomes, Clark said, and some studies also demonstrated a reduced risk for pregnancy loss for women affected by nausea and vomiting of pregnancy.

Healio spoke with Clark about what nausea and vomiting in pregnancy is, risk factors for worse symptoms and adverse outcomes related to long-term morning sickness for pregnant women.

Healio: Are there any big misconceptions surrounding nausea and vomiting of pregnancy?

Clark: The first misconception would be that it only occurs in the morning. It doesn’t. It can be any combination of nausea, vomiting and retching at any time of the day. Some people have more nausea, some people have more vomiting, and some have both. The symptoms can vary. Just because someone’s nauseated all the time, but doesn’t have vomiting, doesn’t mean that they will be less affected. They could still be just as affected as someone who’s having multiple episodes of vomiting per day.

Another misconception is that it’s more associated with male fetuses when it’s [actually] more associated with female fetuses. People with female fetuses have a higher risk of hyperemesis gravidarum, and there is also a genetic component. If your mother had nausea and vomiting of pregnancy or hyperemesis gravidarum, or if you have a sister who was affected by it, you’re also more likely to have nausea and vomiting of pregnancy or hyperemesis gravidarum.

One of the biggest misconceptions about nausea and vomiting of pregnancy that has the most effect on the individual is that it’s expected that every pregnant person has it, that it’s just part of pregnancy and will go away after the first trimester, and that you’ve just got to stick through it. That’s not true.

People do not need to feel guilty if they want or need medications for treatment of their symptoms. It’s not something that you have to suffer through, especially if it’s affecting your quality of life and day-to-day living. Many times, family members or even health care professionals will say, “Oh, you’re pregnant. What do you expect?” And that’s not the attitude you should have because if people have significant symptoms, and they go undertreated or untreated, they are much more likely to be hospitalized with symptoms and much more likely to progress to hyperemesis gravidarum, which is the more severe form of nausea and vomiting of pregnancy.

There are many social media posts saying that if you have these symptoms, you’re more likely to have a healthy pregnancy. When you’re having these symptoms early in the first trimester, it could be because your estrogen level is increasing, as it should, but there are some studies like one in 2016 in JAMA that looked at whether or not having nausea and vomiting of pregnancy is associated with increased risk for pregnancy loss. Those researchers found that there was a lower risk for pregnancy loss when people had nausea and vomiting of pregnancy.

There are a couple things that are protective for nausea and vomiting of pregnancy, although we wouldn’t recommend them, and that would be alcohol use and cigarette smoking.

Healio: What are some risk factors that might cause worse nausea and vomiting of pregnancy?

Clark: For me, I had terrible migraines and motion sickness. Those are two things that will predispose someone to having nausea and vomiting of pregnancy or hyperemesis. Super tasters are also at increased risk, and those who can’t smell have a lower risk.

For anyone who’s had nausea or vomiting of pregnancy, we all have our triggers with smells and things that never bothered us before. The smell components and the taste component do have some association with how significant symptoms might be.

In addition, the following are risk factors for worse symptoms of nausea or vomiting of pregnancy or hyperemesis:

• history of hyperemesis gravidarum;
• nulliparity;
• young maternal age;
• female fetus;
• multiple gestations;
• maternal comorbid conditions, such as parathyroid dysfunction, thyroid disorders, type 1 diabetes, hypercholesterolemia, Helicobacter Pylori infection or migraine headaches with nausea;
• use of assisted reproductive technology; and
• underweight BMI.

Healio: Are there any special considerations for nausea and vomiting of pregnancy for women with preexisting type 1 or 2 diabetes or gestational diabetes?

Clark: For type 1 diabetes, especially if it’s been poorly controlled, people can have diabetic gastroparesis. It’s not necessarily that they have an increased risk for nausea and vomiting of pregnancy, but they might have more severe symptoms. If you go into a pregnancy with diabetic gastroparesis, and then you add nausea and vomiting of pregnancy on top of that, or hyperemesis, that’s going to be hard to manage. Diabetic gastroparesis occurs with poorly controlled diabetes. That’s why keeping your diabetes under control, even before pregnancy, is key.

Corticosteroids can help treat more refractory cases of hyperemesis. One of the side effects, especially for people with diabetes, is that it can elevate glucose levels. We have to take that into consideration before we give that medication to anyone with diabetes, especially type 1 diabetes.

Also, someone with type 1 diabetes who can’t eat or tolerate liquids, and who is not able to take their medication, is at increased risk for diabetic ketoacidosis. So, anyone with type 1 diabetes with nausea and vomiting of pregnancy or hyperemesis must be monitored very closely, because that can increase the risk of diabetic ketoacidosis.

Risks with type 2 diabetes are lower. If they’re not able to tolerate their medications or they can’t eat, it’s hard to control diabetes that way. You may not be eating, but the placenta is still there — you can still have some elevations in glucose. So, we’ve got to get symptoms under control so that we can manage the diabetes.

Healio: What are some adverse outcomes related to long-term nausea and vomiting of pregnancy?

Clark: The good thing is that most pregnancies affected by nausea and vomiting of pregnancy are not affected by any kind of adverse pregnancy outcome. However, there are rare cases where long-standing hyperemesis can cause pregnancy complications. Maternal weight gain, poor nutritional status and fetal growth can be affected after a prolonged period of time of poor nutrition and dehydration. So, if you have a patient who has severe nausea and vomiting of pregnancy or hyperemesis, and they’re having multiple hospitalizations, or they’re requiring other forms of nutrition through a tube or IV, we need to watch the fetal growth to make sure that the fetus is growing.

I see nausea and vomiting of pregnancy and hyperemesis a lot, but I’ve only seen a handful of cases where we can say that the fetal growth was likely affected due to a severe case of nausea and vomiting of pregnancy or hyperemesis. It’s something to keep in mind.

The other thing is that if you have a patient who is having multiple episodes of vomiting, we should be worried about vitamin and mineral deficiencies. The first significant concern is vitamin B1 deficiency, which can cause Wernicke’s encephalopathy. Whenever a patient comes in having a weight loss, electrolyte abnormalities or persistent nausea and vomiting, we need to treat them daily with and IV multivitamin until they’re able to have oral intake again.

In addition, esophageal tears, esophageal rupture, splenic avulsion, pneumothoraces, pneumomediastinum, rhabdomyolysis, osmotic demyelination syndrome, hepatic insufficiency, diaphragmatic tear, venous thrombosis and acute tubular necrosis are rare events but can happen in patients with persistent, severe vomiting. Patients with severe nausea and vomiting of pregnancy and hyperemesis can also experience psychosocial morbidities like a reduced quality of life and inability to perform activities of daily living, including parenting other children, which can lead to depression, anxiety and PTSD. Some patients end up terminating otherwise very wanted pregnancies due to severity of the condition.

We have medications available, and we have safety data on a lot of these medications. So, if the patient is not able to maintain their weight or perform their activities of daily living because of their symptoms, we need to treat them. We shouldn’t just tell them, “You’ll get through it. Wait until you’re in a second trimester, you’ll be OK.” They shouldn’t wait. They should be treated because we don’t want either a progression to hyperemesis or some of these rarer adverse consequences to occur in these patients.

Healio: How severe can nausea and vomiting of pregnancy become? How is it treated?

Clark: Whenever we have a patient with nausea and vomiting of pregnancy, we should try conservative measures first unless they present to the ER already dehydrated. We have multiple oral medications that we can try, and if that doesn’t work, we could add another agent. Sometimes you have to change the medications because not all combinations of medications work for every patient.

For treatment of severe nausea and vomiting of pregnancy or hyperemesis, we start with GI rest with nothing by mouth. We thengive them the medications through the IV until they’re able to take oral medications.

The important thing to know is that when you have a patient who has been admitted for treatment of severe nausea and vomiting of pregnancy or hyperemesis, once they get to that oral medication or medications, they need to stay on that regimen after discharge even if they feel well. Many patients will get home, start to feel better and stop the medications. Please tell patients not to stop the medications! The medications are what’s making them feel better. I tell patients to stay on their medications for at least 2 to 4 weeks after discharge or until they’re out of the first trimester and then start to taper. They shouldn’t quit cold turkey because they’re very likely to bounce right back into the hospital. Education on discharge about how to take medications at home is key so these patients don’t relapse.

Healio: In a new study, published in Nature, researchers found that the effect of GDF15 levels were dependent on the woman’s sensitivity and exposure to GDF15 prior to pregnancy. What are the implications of this study?

Clark: The headlines a many of the media articles and posts is that we found the cause of hyperemesis. I think the cause is multifactorial and genetic, but it’s great that these association with the GDF15 hormone was found. It is a potential target for finding pharmacotherapies or other modalities of therapy for patients who suffer with nausea and vomiting of pregnancy and hyperemesis.

In that study, the first thing the researchers talk about are therapies that can target and block the rise of GDF15 in early pregnancy because that hormone does rise early in pregnancy. If we have a patient with a history of nausea and vomiting of pregnancy or hyperemesis in a prior pregnancy, a medication that can block that GDF15 increase could prevent recurrence in a subsequent pregnancy.

The other thing is that higher levels of GDF15 in the nonpregnant state appear to be protective against the development of nausea and vomiting of pregnancy and hyperemesis in subsequent pregnancies. For example, if you have a patient who, at baseline, has higher levels of GDF15 before they get pregnant, they’re less likely to have nausea and vomiting of pregnancy because they’ve been exposed to the GDF15 and they’re in a way desensitized to it. In patients with a history of nausea and vomiting of pregnancy, one of the targets of therapy could be to expose them to GDF15 when not pregnant, so that they become desensitized to it. Then, in the next pregnancy, they may not have the symptoms or might have less severe symptoms.

The last thing they talk about is metformin, which is a an oral hypoglycemic that is used to treat diabetes. We know that metformin in people who are not pregnant increases GDF15 levels at baseline. If you have a patient who’s had a history of hyperemesis or nausea and vomiting of pregnancy, treating them with metformin may help to boost the GDF15 levels and desensitize them before they get pregnant again.

While all these possibilities sound promising, we are still far from having any potential therapies that target GDF15.

For more information:

Shannon M. Clark, MD, MMS, FACOG, can be reached at shclark@utmb.edu.

References:

• Clark SM, et al. Obstet Gynecol. 2024;doi:10.1097/AOG.0000000000005518.
• Fejzo M, et al. Nature. 2023;doi:10.1038/s41586-023-06921-9.