New findings may have an impact on reducing the epilepsy disease burden in future generations.
Dr Razaz is a postdoctoral fellow at the Reproductive Epidemiology Research Unit in the Department of Medicine at Karolinska Institutet in Stockholm, Sweden.
Increasingly, research is finding that the prenatal environment affects the offspring’s future health. Adding to this growing literature is a new study linking maternal obesity to an increased risk for epilepsy in children. Since obesity and body mass index (BMI) are modifiable risk factors, these findings may have an impact on reducing the epilepsy disease burden in future generations. Neurology Times is delighted to have lead author Neda Razaz, MPH, PhD, share study highlights and future clinical implications.
Neurology Times (NT): What led you to consider the role of maternal obesity in epilepsy? How might maternal weight cause epilepsy?
Dr Razaz: There is growing concern about what the long-term neurological effects are of prenatal exposure to maternal overweight and obesity. The etiology of epilepsy is poorly understood and in more than 60% of cases no definitive cause can be determined. The biological mechanisms by which maternal obesity might exert effect on neurodevelopment in offspring are not well established.
However, overweight and obesity in the mother increase risks for preterm birth and congenital malformations, which increase the risk for epilepsy and may lead to asphyxia as well as increased risk for brain injury. Maternal obesity might also affect neurodevelopment through obesity-induced inflammation.
NT: What were the findings of the study? How do the results compare to previous studies looking at similar issues?
Dr Razaz: Of the more than 1.4 million children born between 1997 and 2011, 7592 children (0.5%) received a diagnosis of epilepsy through 2012. The overall incidence of epilepsy in children (ages 28 days to 16 years) was 6.79 per 10,000 child-years.
The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women (BMI < 25) to 12.4 per 10,000 child-years among women with grade III obesity (BMI ≥ 40). The risk of epilepsy increased by 11% in children of overweight mothers (BMI 25 to < 30) compared with children of normal-weight mothers. Grade I obesity (BMI 30 to < 35) was associated with a 20% increased risk of epilepsy; grade II obesity (BMI 35 to < 40) was associated with a 30% increased risk; and grade III obesity was associated with an 82% increased risk.1
We are only aware of one previous study investigating this issue, in which no relation was found between maternal obesity and risk of childhood epilepsy.2 Reliance on a non-population-based data source (ie, Medicaid records) and use of a strict case ascertainment for diagnosis of epilepsy may have induced an underestimation of the risk of childhood epilepsy and contributed to the lack of association.
NT: What was the most important finding of the study?
Dr Razaz: We found that maternal overweight and obesity increased the risks of childhood epilepsy in a dose-response pattern. Our findings did not change substantially even after taking into account obesity-related pregnancy and neonatal complications, which suggests that overweight or obesity in a mother may play a critical role in fetal neurodevelopment. Other factors such as unmeasured genetic, lifestyle, and environmental influences that interact with obesity may also contribute to this association.
NT: What were the limitations of the study?
Dr Razaz: Limitations of the study include possible misclassification and underreporting in some of the data, as well as an acknowledgment that the cause of epilepsy may be multidimensional, with interaction between genetic and environmental factors.
Future studies might look at causality, underlying mechanisms, and effective interventions to reverse the epidemic of obesity in women of childbearing age.
NT: What can clinicians garner from this study?
Dr Razaz: Given that overweight and obesity are potentially modifiable risk factors, prevention of obesity in women of reproductive age may be an important public health strategy to reduce the incidence of epilepsy.
1. Razaz N, Tedroff K, Vallamor E, Cnattingius S. Maternal body mass index and perinatal risk factors for development of epilepsy. JAMA Neurol. 2017;74:668-676.
2. Pan C, Deroche CB, Mann JR, et al. Is prepregnancy obesity associated with risk of cerebral palsy and epilepsy in children? J Child Neurol. 2014;29:NP196-NP201.
For additional reading, see: Bell WL. Maternal obesity and epilepsy. JAMA Neurol. 2017. http://jamanetwork.com/journals/jamaneurology/article-abstract/2614286. Accessed June 20, 2017.