Prenatal Stress Tied to Higher Risk for Childhood Epilepsy

Persistent prenatal distress is associated with a significantly increased risk for epilepsy in offspring, a new study showed. 
Investigators emphasized that the risk was only slightly elevated, indicating that most infants born to mothers experiencing moderate stress will not develop epilepsy. 
The findings confirm more general reports of prenatal stress affecting the central nervous system of offspring, researchers noted, adding that both animal and human studies have shown that prenatal exposure to maternal anxiety or depression is associated with changes in fetal brain structure and function, especially in the prefrontal cortex, hippocampus, and amygdala. 
“Our study demonstrated that persistent moderate or higher levels of stress, defined as a K6 [Kessler Psychological Distress Scale] score of 5 or higher during both early and mid-to-late pregnancy, were associated with an increased risk of epilepsy in the offspring,” first author Yuto Arai, MD, professor of child neurology at Tottori University in Yonago, Japan, told Medscape Medical News. 
The findings were published online on November 13 in PLOS ONE. 
Ways to Ease Stress
Epilepsy onset in children under 3 years is associated with treatment resistance and developmental delays, so identifying and modifying risk factors is a priority, the investigators noted.
To learn more about the association between maternal stress and epilepsy in children, the researchers examined data from the Japan Environment and Children’s Study.
A total of 97,484 pregnant women were recruited from across the country from 2011 to 2014. Participants completed the six-item K6 questionnaire during the first (median, 15.1 weeks) and second halves (median, 27.4 weeks) of pregnancy. 
The K6 includes questions about feelings of nervousness, hopelessness, restlessness, worthlessness, or sadness during the past 30 days. Scores range from 1 to 24, with a cutoff score ≥ 5 indicating moderate psychological distress. 
Mothers were asked if their children had been diagnosed with epilepsy at 1, 2, and 3 years, but investigators did not have information about epilepsy type.
Participants were divided into six groups based on K6 scores of two ranges ( ≤ 4 and ≥ 5 ) during the first and second halves of pregnancy. Pregnant women with moderate stress as indicated by the K6 only accounted for 20% of the study population. 
The numbers of children diagnosed with epilepsy at the ages of 1, 2, and 3 years were 89 (0.1%), 129 (0.2%), and 149 (0.2%), respectively. 
After multivariable analysis, persistent moderate distress as demonstrated by maternal K6 scores ≥ 5 during both pregnancy time periods was significantly associated with an increased risk for epilepsy in children ages 1 (adjusted odds ratio [aOR], 1.7; P = .030), 2 (aOR, 1.7; P = .012), and 3 (aOR, 1.7; P = .012) years in multivariate logistic regression analyses. 
Notably, there was no significant association between epilepsy and maternal K6 scores of ≥ 5 when the first or second halves of pregnancy when analyzed separately. 
Investigators also found that nutrition with artificial milk at 1 month of age was associated with epilepsy risk at age 2 years (P = .022). Epilepsy risk was also higher at age 1 year in children with low birth weight (< 2500 g). Chromosomal abnormalities were associated with an increased risk for epilepsy in offspring at all ages studied. 
The authors noted that various therapies, such as yoga, music, Benson’s therapy, progressive muscle relaxation, deep breathing exercises, guided imagery, mindfulness, and hypnosis, have been effective in reducing maternal stress and anxiety and in easing depressive symptoms. 
Study limitations include unverified epilepsy diagnoses in offspring, which were provided by mothers, and a lack of information about epilepsy type. The authors also acknowledged that they could not rule out all confounding factors in the analyses. 
Take Maternal Stress Seriously
Reached for comment, Autumn Ivy, MD, assistant professor of neurology and developmental medicine at Kennedy Krieger Institute and Johns Hopkins Medicine, Baltimore, Maryland, said the study highlights the need for physicians to take women’s symptoms of depression or anxiety seriously during the peripartum period.
“This is a vulnerable population with hormonal changes and sleep deprivation influencing mood, and yes, levels of stress,” she told Medscape Medical News. 
In her own research where she has examined the link between stress and epilepsy, Ivy found that stress activates the hypothalamic-pituitary-adrenal axis, releasing glucocorticoids and other stress hormones. 
“Signaling of these stress mediators in specific brain regions may contribute to seizure activity in mouse models, so the relationship between maternal stress and epilepsy in offspring is reasonable to consider,” she said. Ivy added that more research to further understand potential mechanisms.
Future research, she said, should prospectively track specific types of epilepsy in offspring while using more than one measure of stress in mothers during pregnancy.
There was no targeted study funding. Arai and Ivy reported no relevant financial disclosures.
 
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