What Causes Morning Sickness?

Nausea and vomiting is most common in the first trimester but can last until the baby is born, ranging from mild nausea to its most severe form, hyperemesis gravidarum, characterized by relentless vomiting that can lead to malnutrition, weight loss and electrolyte imbalance that endanger the health of both the mother and fetus. Hyperemesis gravidarum is one of the most common reasons for hospitalization in pregnancy, second only to preterm labor, and occurs in somewhere between 0.3 and 3 percent of pregnancies.

Marlena Fejzo, a geneticist at UCLA and the University of Southern California who studies hyperemesis gravidarum, had this severe form of the condition and, despite multiple medications, IV fluids and a feeding tube, miscarried at the beginning of the second trimester. One study led by Fejzo showed that hyperemesis runs in families, with sisters of women with the condition having a 17-fold increased risk of experiencing it themselves. Less severe nausea and vomiting has also been shown to be strongly heritable.

More recent research by Fejzo and colleagues has identified several genes that are associated with nausea and vomiting in pregnancy. One codes for a protein known as GDF15, which is produced in large quantities by the placenta in early pregnancy and has a receptor in an area of the brainstem linked to vomiting and reduced food intake. The protein appears to be found in higher concentrations in pregnant women with nausea and vomiting, making it a plausible candidate for causing the condition.

These recent discoveries also fit with an existing hypothesis that nausea and vomiting during pregnancy may be part of an evolutionary strategy to protect developing fetuses by reducing the chance that their mothers will consume foods containing toxins or pathogens during a critical time of organ development. “Maybe it’s an evolutionary trade-off that we keep a very, very low-risk diet in the first trimester of pregnancy,” said Dr. Stephen O’Rahilly, director of the metabolic diseases unit at the University of Cambridge. GDF15, he said, could be the “signal which says, ‘don’t eat much, lie in the corner, wait until this is over.'” Research also shows that women who experience nausea and vomiting in pregnancy have a lower risk of miscarriage.

“I think it’s appealing in terms of an explanation, and maybe it will lead to other therapeutic targets, which would be interesting,” said Dr. Hyagriv Simhan, professor of obstetrics and gynecology at the University of Pittsburgh School of Medicine, though he noted that other factors are likely to contribute. Indeed, another hypothesis is that human chorionic gonadotropin (hCG), a hormone produced by the placenta, causes nausea and vomiting, although Fejzo’s research and another recent study do not support this idea.

Both Fejzo and O’Rahilly are optimistic that a drug targeting GDF15 could be useful for treating hyperemesis but note that pharmaceutical companies are hesitant to test new drugs on pregnant women, a fear that can be traced back to the thalidomide disaster of the 1950s and ‘60s, when that drug was used to treat nausea and vomiting in pregnancy and resulted in children born with major limb abnormalities and other birth defects.

“After that, pregnant women were scared to try medications, and doctors were afraid of prescribing them, and drug companies were afraid of developing them,” Fejzo said. The “huge lawsuit culture” in the United States has further discouraged pharmaceutical investment, leaving most anti-nausea drugs without adequate testing or official approval for use in pregnant women, she said.

The American College of Obstetricians and Gynecologists recommends that pregnant women with nausea and vomiting first try diet and lifestyle changes. If these do not help, there are several safe pharmaceutical options, but they do not work for everyone.

“Understanding and treating it, at least preventing its more adverse consequences like hyperemesis, is intrinsically valuable, and we shouldn’t just write it off as just part of being pregnant,” Simhan said.