Ask An Expert Question: Are hyperemesis gravidarum (HG) and preeclampsia related?

Hyperemesis gravidarum (HG), is severe and persistent nausea and vomiting in pregnancy that, unlike morning sickness, can last until delivery. It is not well understood, but does seem to be related somehow to preeclampsia. This does not mean every woman with one illness will always develop the other - but that for some reason, women with one are more likely to also have the other.

In the largest population study to date there is a slightly higher risk to develop preeclampsia if you develop HG. Researchers looked at over 8 million pregnant women in England over 15 years and counted the rate of each pregnancy complication, finding that women with HG were slightly more likely to develop preeclampsia and almost twice as likely to experience eclamptic seizures as women without hyperemesis. The increase in absolute risk was not large; an increase in the odds of preeclampsia from 1.0 to 1.16 means that the frequency of preeclampsia rises from approximately 50 in every 1000 pregnant women to 58 in every 1000 pregnant women with hyperemesis. An increase in the odds of eclampsia from 1.0 to 1.84 means that the frequency of eclampsia rises from approximately 12 pregnant woman in 1000 to 22 women in every 1000 pregnant women with hyperemesis.

According to another large population study, hyperemesis that persists into the second trimester of pregnancy makes preterm preeclampsia more than twice as likely to occur. Looking at over 1 million pregnant women in Sweden over 12 years, adjusting for known/ potential confounders that could change the odds, and counting the rate of each pregnancy complication, researchers found that the rate of preterm preeclampsia increased from odds of 6 pregnant women in 1000 to 14 women in 1000 pregnant women with hyperemesis. One possible reason this connection exists may be that in both conditions, higher levels of cell-free fetal DNA are present in the mother’s body. During pregnancy, the placenta must successfully convince the mother’s body to tolerate it even though it is taking her resources to give to the developing fetus. In preeclampsia and hyperemesis gravidarum, that tolerance appears to partially break down, and the maternal immune system responds differently to the foreign placenta than it does in normal pregnancies. (One word researchers use to talk about this is “inflammation”, which is part of the maternal immune response. But inflammation also appears to be necessary for a normal pregnancy to occur; it is unusual inflammation that is related to these issues.) There are changes in serotonin levels in both conditions as well; women with hyperemesis have elevated blood levels of serotonin and women with preeclampsia have placentas that have more serotonin receptors than in normal pregnancy. These are changes that will be related to levels of sex-steroid hormones in pregnancy, like estrogen and progesterone, as well as to maternal anxiety. Since these factors are so central to normal pregnancy, it will take researchers more time to untangle how these relationships play out and what interventions could help to make our pregnancies more normal. Recent meta-analyses have also suggested that in both preeclampsia and hyperemesis gravidarum there is more frequent infection with a gut bacterium called h.pylori, although these findings are relatively new and will need to be confirmed. If you have nausea persisting into your second trimester (past 12 weeks of pregnancy) or changes in your anxiety (which can be related to serotonin levels), please talk to your care providers about these symptoms and ask if you should be more closely monitored for preeclampsia.