Preeclampsia Linked to Autism, Developmental Delay

Megan Brooks

December 12, 2014

Fetal exposure to preeclampsia, and in particular, severe disease, may raise the risk for autism spectrum disorder (ASD) and developmental delay (DD), a large population-based study suggests.

Dr Cheryl Walker

Results from the Northern California–based Childhood Autism Risks from Genetics and the Environment (CHARGE) study show that exposure to preeclampsia in utero was associated with a greater than twofold increased risk for ASD and a greater than fivefold increased risk for DD, compared with no exposure.

"Since preeclampsia is more common in women who are obese or who have diabetes or chronic hypertension, our findings provide one more piece of evidence supporting efforts to encourage women to maximize their metabolic health through healthy diet and exercise behaviors and medical care prior to conception and throughout pregnancy," senior author Cheryl K. Walker, MD, of the University of California (UC), Davis, MIND Institute, in Sacramento, told Medscape Medical News.

"This is a tremendous public health imperative, as over half of pregnant women in the United States are overweight or obese," she said.

The study was published online December 8 in JAMA Pediatrics.

Possible Mechanisms

The analysis included 1061 children from singleton pregnancies, including 517 with ASD, 194 with DD, and 350 typically developing (TD) children.

Among the children with ASD, 7.7% had been exposed to preeclampsia, compared with 5.1% of children with DD and 3.7% TD children. After adjusting for maternal education, parity, and prepregnancy obesity, the adjusted odds ratio (aOR) for ASD with preeclampsia exposure was 2.36 (95% confidence interval [CI], 1.18 - 4.68).

When the analysis was limited to women with severe preeclampsia that was confirmed in medical records, the aOR was 2.29 (95% CI, 0.97 - 5.43) for ASD and 5.49 (95% CI, 2.06 - 14.64) for DD. "Preeclampsia was associated with DD primarily in severe presentations that involved placental insufficiency," the authors note.

"Preeclampsia may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms," they suggest.

Most prior studies of preeclampsia as a risk factor for autism have been small and have yielded "varying results," said Dr Walker. "The level of detail in the CHARGE study allowed us to comprehensively examine this topic."

"Although single studies cannot establish causality, the cumulative evidence supports efforts to reduce preeclampsia and diminish severity to improve neonatal outcomes," the authors write.

Optimizing metabolic health before and throughout gestation "may improve placental perfusion and should be investigated," they add.

"Maternal administration of low-dose aspirin has shown modest benefit, and use of statins shows promise given their ability to diminish angiogenic signaling, endothelial injury, oxidative stress, and inflammation pathways implicated in preeclampsia's pathogenesis. Finally, a deeper understanding of these complex etiologic pathways will be of clinical utility in managing pregnancies and timing the deliveries of women with preeclampsia," the authors conclude.

Interpret With Caution

Commenting on the study for Medscape Medical News, Max Wiznitzer, MD, associate professor of pediatrics and neurology at Case Western Reserve University and pediatric neurologist at Rainbow Babies and Children's Hospital in Cleveland, Ohio, urged caution in interpreting the data.

Dr Max Wiznitzer

"The 2.29 ASD risk has a CI of 0.97-5.43, therefore, not significant," he points out.

He also cautioned that the numbers are "too small to ascribe any causal association" and the "failure to include analysis of preterm births leads to loss of information."

D. Wiznitzer also questions why the "influence of DD is downplayed ― could this be the reason ASD is increased? Could the ASD finding just be due to the DD influence? Like the authors, I would be careful in the interpretation of any findings and their significance," he said.

The study was supported by the National Institute of Environmental Health Sciences, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, the US Environmental Protection Agency, and the UC Davis MIND Institute. Dr Walker has served on the speaker's bureau for Merck & Co. The original article includes a complete list of author disclosures.

JAMA Pediatr. Published online December 4, 2014. Abstract

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