A new study led by researchers at University of Iowa Health Care has revealed a significant association between high blood pressure during pregnancy (gestational hypertension) and an increased risk of seizures in children.
The study, published June 16 in the Journal of Clinical Investigation, used extensive clinical databases and innovative animal models to uncover this critical link. The findings also suggest that inflammation in the brain may play a role in connecting gestational hypertension to seizure risk and could potentially be targeted to prevent seizures in children exposed to hypertension in the womb.
Clinical data links seizure risk in children to hypertension in pregnancy
Gestational hypertension, a common condition affecting nearly 16% of pregnancies in the United States, has long been associated with various health complications for both mothers and their children. However, this new research provides the first large-scale evidence connecting gestational hypertension to heightened seizure risk in offspring.
"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," says Alex Bassuk, MD, PhD, professor and DEO of pediatrics at the University of Iowa and senior author on the study. "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."
The study analyzed data from the Epic Cosmos dataset, which includes over 246 million patient records from hospitals and clinics across the United States and Lebanon. The researchers found that children born to mothers with high blood pressure during pregnancy had significantly higher rates of seizures compared to those born to mothers with normal blood pressure. This association was further validated using smaller, richly annotated cohorts from the University of Iowa and Stanford University, as well as a large Taiwanese cohort.
Mouse models reveal potential role of neuroinflammation
To explore the underlying biological mechanisms linking high blood pressure in pregnancy to increased seizure risk in offspring, the researchers used two complementary mouse models of gestational hypertension. These models confirmed that exposure to gestational hypertension in the womb increased seizure sensitivity and death due to seizures in offspring. The mouse models also identified neuroinflammation as playing a significant role in the disease process, and highlighted sex-specific differences, with male offspring showing greater vulnerability to seizures.
"This study is unique because you have an association drawn from analyses of large clinical databases, but then we go on to prove the association with animal models," says Vinit Mahajan, MD, PhD, professor of ophthalmology at Stanford University, and a co-author on the study. "We were even able to reduce seizures in mice offspring with anti-inflammatory drugs based on what we learned from the model."
The team hopes the new understanding of the link between high blood pressure in pregnancy and pediatric seizures in offspring will open new avenues for research.
"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," says Baojian Xue, PhD, UI senior research scientist in pediatrics, and first author on the study.
The study was funded in part by grants from the National Institutes of Health, The Tross Family Epilepsy Fund, and Research to Prevent Blindness.
