NEONATAL HYPOCALCEMIC SEIZURES IN TWO SIBLINGS EXPOSED TO TOPIRAMATE IN UTERO

Objectives: To report neonatal hypocalcemic seizures in siblings exposed to topiramate in utero.

Methods: Case report and review of the literature.

Results: Two full term siblings (born 14 months apart) developed seizures within the first postnatal week. Their mother took topiramate during both pregnancies. She had previously delivered a healthy boy when taking valproic acid. Calcium levels were low at 6.8 and 5.7mg/dl and phosphorous levels high at 11.5 and 10.7mg/dl, when the infants presented with seizures at day 3 and 7 after birth, respectively. Parathyroid hormone (PTH) was inappropriately normal. They had no conditions associated with early-onset hypocalcemia, such as hypoxia-ischemia, intracranial hemorrhage, or infection. Conditions associated with neonatal parathyroid deficiency, including maternal hyperparathyroidism, maternal or neonatal vitamin D deficiency, and DiGeorge syndrome, were ruled out. Protein kinases A and C regulate PTH secretion via the calcium sensing receptor. Blockade of these kinases has been shown in vitro to decrease PTH secretion. Topiramate affects voltage-dependent sodium and calcium channels, GABA-A receptors, and glutamate receptors, all of which are regulated by protein kinases A and C. It has been postulated that topiramate may prevent protein kinase A from phosphorylating these targets. If topiramate has similar effects in parathyroid cells, it may decrease PTH secretion and result in hypocalcemia.

Conclusion: We suggest that exposure to topiramate in utero induced functional hypoparathyroidism and subsequent hypocalcemic seizures in two siblings via effects on protein kinase signaling. Neonates exposed to topiramate in utero should be monitored for hypocalcemia and seizures.