In-Utero Exposure to High Blood Pressure During Pregnancy Linked With Increased Risk of Childhood Seizures

Gestational hypertension is associated with an increased risk of seizures in children exposed in utero, according to research published in The Journal of Clinical Investigation.

“Hypertensive disorders of pregnancy, including severe forms such as preeclampsia, are common conditions affecting nearly 16% of deliveries at US hospitals (during 2017–2019) and even more among minoritized populations,” wrote the study authors. “Exposure to these disorders in fetal life increased the risk for neurodevelopmental, psychiatric, and neurologic sequelae in some offspring.”

The researchers investigated whether there was an association between prenatal exposure to a hypertensive maternal environment and the incidence of childhood seizures using four complementary cohorts.

“We examined large national clinical databases as well as databases at the University of Iowa and Stanford University, and we even have international collaborations with database analysis from our collaborators in Taiwan,” said Alex Bassuk, MD, PhD, professor and DEO of pediatrics at the University of Iowa and senior author on the study in a news release from University of Iowa Health Care. “This was a real team effort spanning several countries and institutions, and involved multiple departments at the University of Iowa, including pediatrics, obstetrics and gynecology, and psychology.”

First, the investigators analyzed data from the Epic Cosmos dataset, which comprises electronic health records for over 246 million patients across more than 1,415 hospitals and 33,000 clinics in the US and Lebanon.

Among 7,257,078 children with birth parent data available, 229,357 children had a seizure diagnosis. They found significantly higher rates of seizures in children born to mothers with gestational diabetes (50 288/1 365 254 [3.68%]) than in children born to mothers with normal blood pressure (179 069/5 891 824 [3.04%]; odds ratio, 1.22; 95% confidence interval, 1.21-1.23; P<0.001). They also found that male children were overrepresented relative to female children among the seizure groups, regardless of maternal hypertension. Complementary analyses adjusting for covariates using the University of Iowa, Stanford University, and Taiwanese cohorts validated these findings.

The researchers then used two murine models of gestational hypertension to uncover the underlying biological mechanisms linking high blood pressure in pregnancy to increased seizure risk in offspring. They found that exposure to prenatal hypertension altered the expression of proinflammatory and microglial (resident immune cells of the central nervous system) genes in the brains of mouse offspring, suggesting neuroinflammation likely plays a significant role in the disease process. There were also sex-specific differences in the mice, with male offspring showing greater vulnerability to seizures. Furthermore, the researchers were able to reduce seizures in the mice offspring by administering anti-inflammatory drugs and those that deplete microglia.

“The connection between high blood pressure in pregnant moms and seizures in children from these pregnancies had been postulated before, but never examined on a large scale, and never modeled in an animal. With these new mouse models and this new connection between gestational hypertension and seizures, we can now perhaps come up with new childhood anti-seizure therapies,” said Baojian Xue, PhD, University of Iowa senior research scientist in pediatrics and first author on the study in the new release.

Disclosure(s):

The authors have declared that no conflict of interest exists.