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Full-term infants whose mothers had preeclampsia during pregnancy were more likely to develop a range of neurologic diseases later on, according to a population-based cohort study in Norway.

These included attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, and intellectual disability, according to Bob Sun, MD, MA, of the University of Washington in Seattle, and colleagues.

The study, online in , also showed an apparent association between preeclampsia and cerebral palsy (aOR, 1.30, 95% CI 0.94-1.80).

"Preeclampsia is this giant question mark in medical research," study co-author Allen Wilcox, MD, PhD, of the National Institute of Environmental Health Sciences in Durham, North Carolina, told MedPage Today. "It's long been a fascinating enigma as to what causes it and what the effects are." Wilcox added that he was surprised to find such a broad range of neurologic outcomes related to preeclampsia.

But despite the wide scope of neurodevelopmental outcomes linked to preeclampsia, the increased risk was small, he said in an interview. "The outcomes are rare, the increase in risk is rare in absolute terms, and even in relative terms."

Ellie Ragsdale, MD, director of Fetal Intervention at University Hospitals in Cleveland, who was not involved in the study, said the research marks the first time preeclampsia has been linked to adverse neonatal outcomes when filtering out babies born preterm.

"I think the idea that even when we get patients to full term, we're still seeing neurodevelopmental complications for babies, just solely from having preeclampsia, was sort of an eye-opener for everyone," Ragsdale said in an interview with MedPage Today.

Sun and co-authors noted that preeclampsia, a disorder of abnormal placentation, dysregulated vasculature, and inflammation, affects 4% of pregnancies. The condition is a leading cause of maternal morbidity and mortality, and is associated with adverse outcomes such as stroke, renal failure, elevated liver enzyme levels, and seizures.

Also asked for his perspective, Joshua Mann, MD, MPH, chair of the Department of Preventive Medicine at the University of Mississippi Medical Center in Jackson, noted that from a public health standpoint, preeclampsia is a fairly common complication of pregnancy.

Mann, who has conducted previous research on preeclampsia and fetal outcomes in the U.S., told MedPage Today that understanding the risks of this complication may lead to better prevention and management.

For the study, Sun and colleagues investigated the association between preeclampsia and a range of neurodevelopmental disorders in offspring. The researchers said they limited the analysis to term births to reduce the influence of preterm birth as a mediator between preeclampsia and neurodevelopment.

The team analyzed all singleton births from 1999 to 2009 from the Medical Birth Registry of Norway, including all infants born at term, defined as at least 37 weeks gestation. In Norway, diagnostic criteria for preeclampsia included proteinuria and elevated blood pressure after 20 weeks gestation.

All study participants were followed until 2014, providing a minimum of 5 years of follow-up for offspring. The researchers obtained neurodevelopmental diagnosis codes from national insurance data, and linked the information by each person's unique Norwegian identification number.

The investigators assessed a range of neurological disorders, including cerebral palsy, ADHD, ASD, epilepsy, intellectual disability, and vision and hearing loss, and adjusted multivariable logistic analyses for participant age and sex, maternal age, parity, maternal marital status, and parental education levels and immigrant status.

Of the more than 980,500 live births, approximately 29,000 of the children (2.9%) were exposed to preeclampsia during pregnancy. About 270 of these cases progressed to eclampsia. The birth cohort was around 49% female, and mean gestational age was 39.8 weeks.

Among term births, babies exposed to preeclampsia had a slightly lower mean gestational age (39.3 vs 39.8 weeks), and on average had lower birthweights (3,463 vs 3,628 grams).

Even among milder forms of preeclampsia in term births, infants exposed to pre-eclamptic pregnancies had a higher likelihood of developing a range of neurologic disease, the researchers reported. After adjusting for confounders, the team found that babies exposed to preeclampsia had an increased risk of ADHD (aOR 1.18, 95% CI 1.05-1.33), ASD (aOR 1.29, 95% CI 1.08-1.54), epilepsy (aOR 1.50, 95% CI 1.16-1.93), and intellectual disability (aOR 1.50, 95% CI 1.13-1.97). The results also showed a slightly increased risk of vision or hearing loss (aOR 1.21, 95% CI 0.82-1.79).

Ragsdale added that she was interested in how generalizable the results would be in a more diverse population such as the U.S. "I think it would be fascinating to look at a study like this in a high-risk population," she said.

Sun and colleagues said they recognized that the study included the most severe cases of preeclampsia. In addition, the research was limited by the absence of information on the duration of intrauterine exposure to preeclampsia, and unmeasured confounding.

Wilcox said that while the risk of the adverse outcomes was small, the study may be a good start to understanding what it is about preeclampsia that might lead to neurodevelopmental disorders. "Maybe we can learn something important in the future about mechanisms of neurologic development, and come up with better preventative measures," he said.

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