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Hyperemesis gravidarum was associated with subsequent development of cardiovascular disease (CVD) years after pregnancy, a large cohort study found.

By following over 1.4 million women in Quebec from their first pregnancy up to three decades later, investigators showed that the incidence of CVD requiring hospitalization could be linked to extreme morning sickness during pregnancy, independent of preeclampsia:

• 17.7 per 100 women with hyperemesis gravidarum only (adjusted HR 1.46, 95% CI 1.38-1.54)

• 28.2 per 100 women with preeclampsia only (adjusted HR 2.58, 95% CI 2.51-2.64)

• 30.9 per 100 women with both exposures (adjusted HR 3.54, 95% CI 3.03-4.14)

• 14.0 per 100 women with neither exposure (reference)

"Compared with no hyperemesis, women who had hyperemesis gravidarum during pregnancy were more likely to develop cardiocirculatory disorders such as pulmonary embolism and hypertension. 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," reported Nathalie Auger, MD, MSc, of the Québec public health department in Montreal, and colleagues in the .

"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."

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

Treatment for hyperemesis gravidarum is typically limited to acute inpatient treatment comprising fluid replacement and treatment of electrolyte imbalances.

Now, with new knowledge of hyperemesis gravidarum's association with long-term cardiovascular outcomes, some might propose interventions -- related to screening, monitoring, and coaching, for example -- soon after an affected pregnancy.

"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.

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

"Furthermore, 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."

"We do not yet know whether adding information on pregnancy complications to prediction algorithms improves the prediction of nonischemic cardiac end points beyond what is possible based on conventional measures of CVD risk, nor do we know whether improving traditional risk factor profiles in these women reduces the risk of nonischemic CVD outcomes," the editorialist cautioned.

Nevertheless, she reasoned, any disturbance to "the finely tuned cardiometabolic balance that must be maintained for a successful pregnancy" could increase the risk of a pregnancy complication. Similarly, "any factor that prevents a woman's body from fully adapting to the demands of pregnancy," Boyd said, "will probably have consequences for long-term health as well."

"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.

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

The study authors relied on a provincial registry including over 1,413,166 women, of whom 1.2% had hyperemesis gravidarum alone, 4.9% preeclampsia alone, and 0.08% both conditions during pregnancy.

Whereas women with hyperemesis gravidarum were typically socioeconomically disadvantaged, women with both hyperemesis and preeclampsia were disproportionately more likely to have an underlying comorbidity, multiple birth, and fetal congenital anomalies compared with neither exposure.

Despite attempts at statistical adjustment to balance study groups, residual confounding may not be ruled out due to the study's observational design, the researchers said.

Additionally, the authors acknowledged the possibility of miscoding in their hospital records and said 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.

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