Pyridostigmine-induced microcephaly

Pyridostigmine (PYD), a cholinesterase inhibitor and the drug of choice for myasthenia gravis (MG), has been used safely in pregnant myasthenic patients for more than 50 years. Although it has not been associated with teratogenic effects in humans, PYD can produce growth retardation in rat pups.1 It passes readily into the fetal circulation. PYD levels in infants of myasthenic mothers were 85 to 90% of maternal plasma concentrations, whereas levels in the amniotic fluid were even higher.2 This makes the dosing of PYD a critical issue for the fetus. We present the findings of an infant with respiratory distress and microcephaly who was exposed to more than four times the recommended dose of PYD during gestation. The patient’s mother is a 24-year-old primigravida woman who was diagnosed with MG at 10 years of age. She had undergone thymectomy and received multiple courses of plasmapheresis. Her only medication during her pregnancy was PYD. Because her diplopia and ptosis did not improve, her dose of PYD was increased steadily to the point that she was taking five to 10 tablets (60 mg each) every 3 hours—an average of 1,500 to 3,000 g/day, or four to eight times the recommended daily dose. Despite little improvement, this dose was continued for the entire pregnancy. She had regular prenatal visits and denied smoking …