Pyridostigmine–induced microcephaly

To the Editor: Niesen and Shah describe an infant with microcephaly and a range of dysmorphic features whose mother had been treated with high doses of pyridostigmine bromide (PB).1 Although there is no question that PB was administered well beyond recommended doses, we believe the conclusion that pyridostigmine induced microcephaly be viewed with caution. As the authors point out in the text of their paper, this was an association of PB overuse and the infant’s congenital defects. Also, there is little support from this single report that toxicity is dose-dependent. There is scant evidence from animal studies to suggest that birth defects occur with PB exposure. Rats and rabbits administered 50 to 93 times the typical human dose of PB during pregnancy demonstrate no adverse effects on pregnancy, litter size, malformation rate, or fetal development.2 Injection of chick embryos with cholinesterase inhibitors, including PB, leads to abnormalities of the vertebral column and hypoplasia of leg muscles, but not the microcephaly observed in the infant in this case report.2 The authors cite the study of Levine and Parker3 that found rat pups exposed to PB had abnormal ossification of cervical vertebrae, but only at the highest doses tested. These authors conclude that the “slight increase in ossification …