The association of high-dose pyridostigmine (PYD) during pregnancy with microcephaly and CNS injury in an infant is reported from the Children’s Hospital Los Angeles, CA. The mother was diagnosed with myasthenia gravis (MG) at 10 years of age, and had undergone thymectomy and plasmapheresis. PYD was the only medication during pregnancy, and the dose was increased steadily because of persistent diplopia and ptosis. The dose of 40 mg/kg day (average of 1500-3000 g/day) continued for the entire pregnancy was four to eight times the usual recommended amount. The infant delivered by cesarean section at 36 weeks because of fetal bradycardia weighed 1880 g (<2%) and the head circumference (HC) was 33.5 cm (10%). Apgars were 3 and 8. He was hypotonic with poor respiratory efforts and required intubation. A Tensilon test was positive for neonatal MG, and he was treated by exchange transfusion and IV immunoglobulin. He was weaned from the respirator at 3.5 months. At 3 months his HC was 37 cm (<5%), and at 5 months, it was 38 cm (<2%). He had dysmorphic facial features, short neck, broad chest, campylodactyly, bilateral cryptorchidism, and ankle clonus. MRI revealed mild ventriculomegaly. 
COMMENT. Pyridostigmine, a cholinesterase inhibitor, has been used safely in pregnant myasthenic patients in doses less than 600 mg/day. This is the first report of high-dose PYD being associated with microcephaly, growth retardation, and evidence of CNS damage in the infant. PYD passes readily into the fetal circulation, with concentrations amounting to 90% of the maternal plasma levels.