Prenatal hypertension exposure linked to higher seizure risk in children
A new study reveals that children born to mothers with high blood pressure during pregnancy face a significantly increased risk of seizures, potentially because of brain inflammation.
Prenatal hypertension exposure linked to higher seizure risk in children | Image Credit: © vchalup - © vchalup - stock.adobe.com.
The odds of seizure are increased in children of mothers with high blood pressure during pregnancy, according to a recent study published in the Journal of Clinical Investigation on June 16, 2025.1
Maternal hypertension linked to increased seizure risk in offspring
Alongside highlighting this link, the data indicated that gestational hypertension may be connected to offspring seizure risk because of inflammation in the brain. This may be targeted to reduce seizure risk in children with prenatal exposure to hypertension.
"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,” said Vinit Mahajan, MD, PhD, professor of ophthalmology at Stanford University and study co-author. “We were even able to reduce seizures in mice offspring with anti-inflammatory drugs based on what we learned.”
Data sources and patient selection
The Epic Cosmos dataset was evaluated for human data, including vital signs, patient-generated health data, social determinants of health, and birth records. Patients recorded in the database between January 1, 2011, and December 31, 2023, and with more than 1 face-to-face encounter with a provider in any 2-year interval were included in the analysis.
International Classification of Diseases, Tenth Revision codes were used to identify maternal and child conditions, including maternal hypertension and child epilepsy and seizure. Relevant concomitant conditions included diabetes mellitus, obesity, and developmental delay.
Additional data was obtained from a case-control study and a validation cohort study. These studies used data from the Intergenerational Health Knowledgebase and the Stanford Electronic Health Records research database, respectively.
Defining hypertension and seizure
Maternal hypertension was the primary exposure. This was determined by the presence of preexisting hypertension complicating pregnancy, preexisting hypertension with preeclampsia, gestational hypertension without significant proteinuria, preeclampsia, unspecified maternal hypertension, essential hypertension, or secondary hypertension.
Child epilepsy and seizures were reported as the primary outcome. This was determined by at least 1 instance of epilepsy and recurrent seizures, convulsions not elsewhere classified, convulsions in the newborn, unspecified abnormal involuntary movements, or transient alteration of awareness when aged under 18 years.
This data was validated using animal studies with 80 female and 40 male mice. Offspring were euthanized when aged 10 to 12 weeks, after which brains were obtained for molecular and histologic analyses. Another experiment assessed the impact of antiinflammatory treatments on seizure risk in 7 groups of saline-treated dams.
Key results show elevated seizure risk
Of 7,257,078 children assessed in the Epic Cosmos database, 229,357 were diagnosed with seizures. Children with prenatal hypertension exposure had a seizure rate of 3.68%, vs 3.04% in those without prenatal hypertension exposure. This indicated an odds ratio (OR) of 1.22 for seizure in offspring of mothers with hypertension during pregnancy.
Investigators also noted higher rates of obesity and maternal diabetes in mothers with hypertension, as well as an increased prevalence of developmental delay among their children, at 43%, 20.4%, and 10.3%, respectively. In comparison, these rates were 16.3%, 8.4%, and 7.7%, respectively, in the normotensive group.
Similar results were reported in the case-control study and the validation cohort study, with an adjusted OR of 1.132 reported in the former for offspring seizure among mothers with hypertension in pregnancy and 1.36 in the latter. This association also remained present was analyzing a large international cohort, with an adjusted odds ratio of 1.17.
Animal models support this data
These findings were further validated in the animal models. Seizure grade and deaths were significantly increased following induced hypertension through angiotensin 2 infusion during pregnancy. However, this seizure response was prevented by depletion of microglia or antiinflammatory pentoxifylline using PLX5622, a CSF 1 receptor inhibitor.
These results highlighted an increased risk of seizures among children born to mothers with hypertension during pregnancy. Investigators concluded this risk may be reduced by interrupting inflammatory pathways.
“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, first author and senior research scientist in pediatrics at the University of Iowa.
References
- High blood pressure in pregnancy linked to increased risk of seizure in children. University of Iowa Health Care. June 16, 2025. Accessed June 17, 2025. https://www.eurekalert.org/news-releases/1087317?
- Xue B, Gumusoglu SB, Tiarks G, et al. Gestational hypertension increases risk of seizures in children and mice. Journal of Clinical Investigation. 2025. doi:10.1172/JCI183393
