Hypertensive Disorders of Pregnancy Tied to Brain Injury, Growth Restrictions

Researchers at the Cincinnati Children’s Perinatal Institute have revealed the impact that maternal hypertension can have on brain injury and/or immaturity in very preterm infants.

Work led by Nehal Parikh, DO, MS, finds that maternal hypertension indirectly, via impaired intrauterine growth, and directly increases the risk for early brain injury and/or maturational delays in infants born at or before 32 weeks’ gestational age.

“Our goal was to clarify if hypertension during pregnancy is a bad thing for the baby’s brain development,” Parikh says.

The study, “Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at 32 Weeks’ Gestational Age,” was published in the Journal of Pediatrics in October 2024.

The next step is to identify prevention or treatment methods for maternal hypertension that can reduce the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Analyzing Cohort MRI Scans

Parikh’s team analyzed data from a cohort of 395 infants known as the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). One of the largest cohorts of its kind, Parikh recruited infants from neonatal intensive care units in five southwestern Ohio hospitals.

Each baby in the cohort underwent a 3T magnetic resonance imaging (MRI) scan after birth. Each scan was reviewed by a neuroradiologist and assigned a standardized rating called the Kidokoro global brain abnormality score.

Infants were classified by their exposure to hypertensive disorders of pregnancy (HDP) if the mother is diagnosed with chronic hypertension, gestational hypertension, preeclampsia or eclampsia. Among the cohort, 43% of infants were exposed to HDP.

Parikh and his team used adjusted multivariable regression and mediation analyses to tease out the direct effects of low blood flow between the mother and baby (caused by hypertension) and the indirect effects that fetal growth restriction has on the developing brain:

• HDP-exposed infants had 27% higher brain abnormality scores than those without HDP exposure.
• HDP-induced impaired intrauterine growth was a significant indirect contributor to brain abnormality scores (22%).

“This [information] is a good first step,” Parikh says.

As a neonatologist, Parikh is motivated to diagnose developmental disorders as early as possible, understand their underlying causes, and create interventions to deploy while infant brains retain their high neuroplasticity.

Ongoing Work to Intervene Early, Predict Outcomes

A key part of this work is identifying ways to predict outcomes early and intervene early to reduce or prevent brain abnormalities.

Shipra Jain, MD, the study’s first author, is further analyzing the data to understand how HDP affects placental insufficiency—the reduction of nutrients and oxygen delivered to the fetus.

“Hypertension is on the uptrend in pregnancy,” Jain says. “Many of these babies are small and do not grow.”

In the future, she plans to study the best way to promote growth after birth for these babies to overcome the brain abnormalities caused by HDP exposure.

“We want growth with better brain outcomes but, at the same time, we don’t want these babies to develop risk factors for obesity and other chronic health conditions,” Jain says.

Parikh expects ongoing insights as he and his team follow the cohort children until age 7 and beyond. He hopes to secure more funding to follow the group at age 12 and age 18. For example, he sees strong associations between HDP exposure and impacts on cognitive, language and motor development. Additional work could involve analysis of data provided by advanced quantified MRI biomarkers such as from diffusion MRI and resting state functional MRI.

“At each stage of development there are new challenges and life skills and tasks to manage,” Parikh says. “These brain abnormalities don’t always show up as functional problems until many years later.”

(Published February 2025)

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