Hyperemesis gravidarum (HG), a severe form of nausea and vomiting of pregnancy (NVP) puts women at higher risk of significant cardiovascular events in the 3 decades after giving birth, according to a newly released Canadian study.  Women experiencing HG are almost 50% more likely to be hospitalized for cardiovascular events in the decades after delivery than those without hyperemesis, the large cohort study shows.

This risk was even higher among women with a history of pre-eclampsia, according to the study which followed more than 1.4 million women in Quebec from their first pregnancy for up to 30 years.  The results of the study, just published in the Journal of the American Heart Association, have prompted Canadian clinicians to call for guidelines to include HG as a pregnancy-related cardiovascular risk factor.

Prevalence of hyperemesis gravidarum

While NVP is a common condition affecting up to 70% of pregnant women (Fejzo MS et al., 2019), HG is generally considered to be the most serious expression of NVP and is reported in 0.3 to 10.8% of pregnant women (Jennings LK and Mahdy H. 2021).

HG goes beyond regular morning sickness in causing persistent nausea and vomiting during pregnancy.  Symptoms may lead to weight loss and dehydration and the condition has also been associated with other complications of pregnancy—namely, preeclampsia and eclampsia.

HG is diagnosed when nausea and vomiting are so severe that women are unable to eat and/or drink normally and have greatly limited daily activity.  This is frequently accompanied by weight loss and electrolyte disturbance which can carry significant risks to the longer-term health of both mother and offspring (Fejzo, 2019). Gazmararian and colleagues cite that HG is the leading cause of hospitalization in early pregnancy in the United States, and the second most common cause of pregnancy hospitalization overall (2002).  Treatment for HG is typically acute inpatient treatment comprised of fluid replacement and treatment of electrolyte imbalances.

Robust cohort followed for 30 years

To investigate the risk of future CVD in women with HG with or without preeclampsia, data of 1,413,166 pregnant women in Quebec between 1989 and 2021 was analyzed in this retrospective study.  All women were followed from their first pregnancy up to 3 decades later.

For purposes of their study, Auger and colleagues defined HG as extreme or excessive vomiting with onset before the 23rd week of gestation which required hospitalization or treatment during pregnancy, as gleaned from ICD codes in hospital records.

Based on their analysis, 1.2% of the women experienced HG alone, 4.9% suffered preeclampsia alone, and 0.08% experienced both conditions during pregnancy.

Hospitalization 3.5 times more likely

The authors found that the incidence of CVD was 17.7 per 100 women among those who had HG only while pregnant with adjusted hazard ratio (aHR) of 1.46, 28.2 per 100 women among those with preeclampsia only (aHR 2.58), and 30.9 per 100 women in those with both conditions (aHR 3.54).  Among women who had neither HG nor pre-eclampsia, the incidence of CVD was 14.0 per 100 women.

Women who experienced both the conditions during pregnancy were 3.5 times more likely to be hospitalized because of cardiac causes with a hazard ratio (HR) of 3.54.  The risk of hospitalization was more than doubled among women with pre-eclampsia with HR of 2.58, whereas in those with hyperemesis only, the HR was 1.46.  A strong association with valvular heart disease (HR, 3.38), heart failure (HR 3.43), and cardiomyopathy (HR 4.17) was noted in the group experiencing both HG and preeclampsia.

Study subjects who experienced HG were typically socioeconomically disadvantaged, and those with both hyperemesis and preeclampsia were disproportionately more likely to have an underlying comorbidity, multiple birth, and fetal congenital anomalies compared with women who experienced neither condition.

Despite attempts at statistical adjustment to balance study groups, the researchers noted, residual confounding could not be ruled out due to the study’s observational design.  Further, the authors acknowledged the possibility of miscoding in their hospital records and allowed they could not account for the effects of any medications taken by study participants.  Women who had CVD diagnosed and treated in the outpatient setting would have also been missed by the investigators, they stated.

Clinical implications and future directions

“Compared with no hyperemesis, women who had hyperemesis gravidarum during pregnancy were more likely to develop cardiocirculatory disorders such as pulmonary embolism and hypertension,” reported Nathalie Auger, MD, MSc, of the Quebec public health department in Montreal, one of one of the study’s authors.  “Hyperemesis gravidarum was also associated with an increased risk of nonischemic disorders such as valve disease and heart failure, but not myocardial infarction, stroke, or other ischemic heart disease.”

“While it remains to be determined whether each disorder has separate effects, adding hyperemesis gravidarum as a pregnancy-related risk factor in cardiovascular guidelines may be merited at this point,” the authors suggested.  “Women with hyperemesis gravidarum, especially hyperemesis combined with preeclampsia, may benefit from closer monitoring in the years following pregnancy to prevent adverse cardiovascular events.”

Towards intervention—but by whom?

With this new knowledge of HG’s association with long-term cardiovascular outcomes, interventions related to screening, monitoring, and coaching might be warranted soon after an affected pregnancy, some women’s health experts propose.

“To take advantage of the warning provided by pregnancy complications such as hyperemesis, preeclampsia, and placental disorders, we need systems in place to intervene as early as possible, preferably in the immediate postpartum period when the focus on pregnancy-associated pathology and maternal health and well-being has not yet waned,” urged Heather Boyd, PhD, of Statens Serum Institut in Copenhagen, Denmark, in an editorial accompanying the study’s publication.

Practically speaking, however, this will require some combination of resources, strong advocacy, and a clear demonstration of benefits, Boyd suggested.

“Who should be responsible for the postpartum follow-up of women who have had pregnancy complications remains unclear,” she wrote.  “Many medical societies, covering specialties including obstetrics, general practice, and cardiology, are currently discussing how to handle the so-called fourth trimester and postpartum monitoring of at-risk groups, as well as patient transitions between specialties.”

“The study and its results raise several points that are highly relevant at a time when researchers and clinicians from a broad swathe of specialties are trying to translate the links between pregnancy complications and later CVD into recommendations for postpartum monitoring and interventions,” according to Boyd.

In the interim, given the data revealed to date, “hyperemesis gravidarum may be considered as a novel pregnancy-related risk cardiovascular factor” in cardiovascular guidelines especially for cardiovascular disease of nonischemic origin, according to the authors.  These women, those with coexisting HG and preeclampsia in particular, merit close monitoring over the years to prevent cardiovascular events and should also be encouraged to lead a heart-friendly lifestyle following childbirth.

The complete study article, “Risk of Cardiovascular Disease in Women with a History of Hyperemesis Gravidarum, With and Without Preeclampsia,” can be found here.

The contents of this feature are not provided or reviewed by NPWH.