Severe nausea linked to pregnancy, birth complications in Stanford Medicine study

Pregnant women with a severe form of nausea face increased risks for several pregnancy and birth complications, according to a new Stanford Medicine study of 2.5 million California births.

The research was published June 16 in the American Journal of Epidemiology. It is the first large, U.S. population-based study of the dangers of severe pregnancy nausea and vomiting, a condition formally known as hyperemesis gravidarum, or HG.

While most pregnant women — 70% to 80% — experience some nausea, it usually leaves no lasting effects. In contrast, as the new research shows, HG puts a major strain on the 1% to 3% of the pregnancies affected.

“Hyperemesis gravidarum is not just bad morning sickness; it’s severe enough to cause dehydration and significant weight loss,” said lead study author Rebecca Gardner, a Stanford Medicine graduate student in epidemiology and clinical research.

The study’s senior authors are Julia Fridman Simard, ScD, associate professor of epidemiology and population health and of immunology and rheumatology, and Gary Shaw, DrPH, the Rosemarie Hess Professor and a professor of pediatrics.

The research team looked at complications in pregnancies in which the mother was hospitalized for HG, compared with pregnancies without such hospitalizations.

“We found hyperemesis gravidarum was linked to higher risk for preterm birth, anemia, smaller-than-expected babies, preeclampsia, gestational hypertension and placental abruption,” Gardner said. “Hospitalization for HG really does flag a pregnancy as being at higher risk for a range of serious complications.”

Struggling to get nourishment

Pregnant women with HG experience severe, sustained nausea and vomiting, often continuing throughout their pregnancies. They struggle to eat; stay hydrated; and absorb enough nutrients that play key roles in early pregnancy, such as folate. (Adequate folate intake reduces the risk of certain birth defects.) Women with HG can lose a lot of weight at a time when they should be gaining; one study found that about a quarter of HG patients lost more than 15% of their pre-pregnancy weight.

“We know from other studies that women with HG don’t get as many nutrients,” Gardner said. “This could impair placental development, which we think leads to higher risk for some of the outcomes we looked for, such as preeclampsia and babies being smaller than expected at birth.”

But previous studies examining potential links between HG and poor pregnancy outcomes had weaknesses, Gardner said: Many were small, and nearly all used data from European countries with populations that are less diverse than the U.S. population and that have medical systems structured differently from the U.S. system.

The study examined records for single-baby California births from 2007 to 2011. The researchers had access to demographic information about mothers, pre-pregnancy body mass index and census tract data that was used to calculate each patient’s level of social vulnerability. The researchers also had access to diagnostic codes from patients’ pregnancy and birth medical records.

Of the 2,476,492 births included in the final analysis, 53,681, or 2.2%, were to mothers with HG, meaning they received emergency department or hospital inpatient care for hyperemesis gravidarum.  

Compared with those who were never hospitalized for HG, women with HG had higher risk for preeclampsia, a pregnancy complication that can cause seizures if untreated; gestational hypertension, or high blood pressure in pregnancy; preterm birth, meaning delivery three or more weeks before the due date; babies that were small for their gestational age, meaning they had grown less than expected during fetal development; anemia, or low blood iron levels; and placental abruption, in which the placenta becomes partly or completely detached from the uterus before delivery.

The increase in relative risk for each complication varied. For instance, after adjusting for possible confounding factors, women with HG were about 18% more likely to have preeclampsia, about 25% more likely to deliver early, about 37% more likely to be anemic and about 14% more likely to experience a placental abruption than women without HG.

Women who were first hospitalized for HG during the second trimester of pregnancy were more likely to experience complications than those hospitalized during the first trimester, the study found.

A flag for closer monitoring

Guidelines from the American College of Obstetricians and Gynecologists for treating HG changed in 2018, after the data used for this study was collected, Gardner noted. The guidelines now encourage treating pregnancy nausea faster and more aggressively, and two medications are now approved by the U.S. Food and Drug Administration for nausea and vomiting in pregnancy. More research could help clarify the effects of these newer guidelines, Gardner said.

More research could also show whether HG should prompt physicians to offer additional preventive care, such as low-dose aspirin, which is already used to prevent preeclampsia in patients who are at risk for other reasons.

The research team hopes that its findings will motivate physicians and pregnant women to pay closer attention to HG.

“For physicians, I think this data means that pregnancies with HG hospitalization may warrant closer monitoring for certain complications,” Gardner said.

“Pregnant women need to know that most HG pregnancies still result in healthy outcomes for the mom and baby, but HG does need to be taken seriously,” she said. It’s important to advocate for yourself by asking your doctor if you need more monitoring or anti-nausea medication, Gardner said, adding, “This is not just something to push through.”

The research was funded by a grant from the National Heart, Lung, and Blood Institute (grant T32HL1513232.)

# # #

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.