New-Onset Epilepsy, Migraine Tied to Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy — gestational hypertension, preeclampsia, or eclampsia — were tied to an increased risk of new-onset neurologic disorders years after giving birth, Swedish registry data showed.

Women with these pregnancy complications had higher rates of developing a composite outcome that included new-onset epilepsy, migraine, and other disorders compared with women who had normotensive pregnancies, reported Therese Friis, MD, of Uppsala University in Sweden, and co-authors in JAMA Neurology.

Adjusted hazard ratios (HRs) for the composite outcome were:

• 1.27 (95% CI 1.12-1.45) for women with gestational hypertension
• 1.32 (95% CI 1.22-1.42) for women with preeclampsia
• 1.70 (95% CI 1.16-2.50) for women with eclampsia

The strongest tie was between eclampsia and future epilepsy: women with eclampsia had a fivefold increased risk of new-onset epilepsy (adjusted HR 5.31, 95% CI 2.85-9.89), the researchers said.

Future migraine risk rose for women with gestational hypertension (adjusted HR 1.39, 95% CI 1.19-1.63) or preeclampsia (adjusted HR 1.25, 95% CI 1.13-1.38). Preeclampsia also was associated with increased risks of new-onset headache and epilepsy.

In the U.S., CDC data suggest that hypertensive disorders affect nearly one in seven hospital deliveries. Women with these complications are at a significant risk for developing new cardiovascular disease.

“Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease,” Friis and colleagues wrote. “At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.”

Underlying mechanisms between eclampsia and new-onset epilepsy are unclear, Friis and co-authors noted. Two case series pointed to eclampsia as a potential risk factor for epilepsy, though both lacked a control group.

One previous publication on seizure disorders and eclampsia in Canada “reported similar results as our study,” the researchers pointed out. “While their definition of the outcome was more comprehensive, we chose to include only epilepsy, a well-defined disorder caused by unusual electric activity in the brain, which is most often diagnosed after two seizures. This stricter classification will avoid other causes of seizures, e.g., caused by mental stress or a physical condition.”

Friis and colleagues also said they may be the first to show relationships between gestational hypertension or preeclampsia and migraine onset. “The association between gestational hypertension and preeclampsia with migraine suggests that there might be a common underlying vascular component, which is plausible since preeclampsia is a risk factor for cardiovascular morbidity later in life,” they stated.

The researchers studied outpatient and hospital registry data for 648,385 primiparous women in Sweden who had singleton pregnancies from 2005 through 2018. Women with chronic hypertension or a prepregnancy neurologic disorder were not included in the study.

Follow-up started 42 days after delivery and continued until the first event, death, or until the study ended in 2019. Mean follow-up time was 7.7 years and included diagnoses of migraine, headache, epilepsy, sleep disorder, or mental fatigue. Diagnoses made in primary care were not included in the registry data.

Participants were age 28.5 years on average at the time of their first pregnancy. Overall, 11,133 women had gestational hypertension, 26,797 had preeclampsia, and 625 had eclampsia. Among women with preeclampsia, 5,778 had preterm birth.

Women with gestational hypertension and preeclampsia had about 1% incidence of a new-onset neurologic disorder 4 years after giving birth. That incidence was 2% for women with eclampsia. After that, the incidence for all exposure groups increased by almost 2% every 4 years.

Both women with preterm preeclampsia (adjusted HR 1.54, 95% CI 1.34-1.79) and women with term preeclampsia (adjusted HR 1.27, 95% CI 1.17-1.38) had a higher risk for new-onset neurologic disorders compared with normotensive women.

Hypertensive disorders of pregnancy were not tied to future increased risks of sleep disorder or mental fatigue, but sample sizes for those outcomes were small, the researchers acknowledged.

Overall study limitations included a lack of diagnoses from primary healthcare, which led to low absolute frequencies of many outcomes except epilepsy.

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