Babies born to women who were overweight or obese in early pregnancy were more likely to develop childhood epilepsy, with the risk increasing steadily across the entire range of maternal body mass index (BMI), researchers found.
In a large population-based cohort of 1.4 million births in Sweden, the increase in epilepsy incidence ranged from 11% in children of overweight mothers to 82% in those of mothers with obesity grade III (BMI =40), compared with children of normal-weight mothers, Neda Razaz, PhD, of Karolinska University Hospital in Stockholm, and colleagues reported online in JAMA Neurology.
"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," the researchers wrote.
Noting that one in two pregnant women from developed countries are overweight or obese, "there are opportunities for prevention and treatment by obstetricians and neurologists," William Bell, MD, of Ohio State University Wexner Medical Center, agreed in an accompanying editorial.
"Prevention of overweight and obesity with caloric reduction and physical activity in pregnant women appears to be the safest alternative," wrote Bell, who was not involved in the study. He noted that research has suggested that pre-pregnancy gastric bypass surgery carried increased risks, while interventions such as use of insulin or metformin in gestational diabetes to limit weight gain during pregnancy, and 20 to 30 minutes of moderate physical activity of moderate intensity daily during pregnancy, were ineffective.
Obesity in pregnancy has been linked with systemic inflammation, altered endocrine responses, folic acid deficiency, and insulin resistance, which Razaz and colleagues noted have a potential role in epilepsy in offspring. However, the lone previous study of maternal obesity and epilepsy in offspring, which included 84,000 subjects and used a more restrictive definition of epilepsy, did not find a connection.
The retrospective study cohort from the Swedish Medical Birth Register included 1,421,551 (46% female) live singleton births at 22 or more completed gestational weeks between 1997 and 2011, of which 7,592 children (0.5%) were diagnosed with epilepsy through Dec. 31, 2012.
Researchers found the hazard ratio of epilepsy rose across the range of maternal BMI (P<0.001 for trend), controlling for potential confounders including maternal age, country of origin, educational level, cohabitation with partner, height, smoking, maternal epilepsy, and year of delivery:
Increased risk of childhood epilepsy was strongly associated with several asphyxia-related neonatal complications, including malformations of the nervous system (aHR 46.4, 95% CI 42.2-51.0), hypoxic ischemic encephalopathy (aHR 23.6, 95% CI 20.6-27.1), and neonatal convulsions (aHR 33.5, 95% CI 30.1-37.4), the researchers found.
Increased rates of epilepsy were also noted among children with neonatal hypoglycemia (aHR 2.10, 95%CI 1.90-2.33), respiratory distress syndrome (aHR, 2.43; 2.21-2.66), and neonatal jaundice (aHR 1.47, 95%CI 1.33-1.63).
Rates of epilepsy were increased in the presence of maternal epilepsy (aHR 4.40), and by complications during pregnancy (gestational diabetes, preeclampsia, infections, and chorioamnionitis), cesarean delivery, and birth trauma.
Gestational age also influenced rates of epilepsy, they found. Moderately preterm infants (32-36 weeks) had a 1.7-fold increased rate while extremely preterm (22-27 weeks) infants had an increase of almost 5-fold.
Limitations included the possibility of misclassified or underreported diagnoses - for instance, maternal epilepsy, maternal infections, and chorioamnionitis - and the possibility that epilepsy was due to both genetic and environmental factors, including smoking, alcohol and antiepileptic medication use, and the possibility that the latter contributed to increased risk of epilepsy in the offspring.
Indeed, Bell cited a study that found that women with epilepsy before pregnancy were more likely to be overweight and obese than women without epilepsy. Excess weight was more likely in women receiving the antiepileptic drugs valproate sodium or carbamazepine, and less likely in those taking lamotrigine.
More information is needed before management can be optimized, Bell concluded. "In particular, there needs to be a better assessment of the risk of childhood-onset epilepsy in the offspring of obese mothers with epilepsy; this will likely come from large, population-based cohort studies. for childhood epilepsy."
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