Teratogen update: methylene blue.

Methylene blue (MB) is a cationic thiazine dye with the chemical name tetramethylthionine chloride. It has a characteristic deep blue color in the oxidized state, but the reduced form, leukomethylene blue (LMB), is colorless. Methylene blue has been widely used in a variety of clinical settings to identify anatomic (Manhes et al., ’94; Sills and Zinkham, ’94; Barber et al., ’95) and pathologic (Derom et al., ’93; Canto et al., ’96; Lee and Sharifi, ’96) structures and to treat methemoglobinemia (Curry, ’82; Ellis et al., ’95; Yang et al., ’95). It has also been used to inactivate viruses in fresh frozen plasma (Wieding et al., ’93), to treat chronic periodontitis (Gibson et al., ’94; Ower et al., ’95), to aid in the diagnosis of and targeted therapy for cancer (Orth et al., ’95; Link et al., ’96), and, experimentally, to treat septic shock (Schneider et al., ’92; Preiser et al., ’95; Brown et al., ’96; Driscoll et al., ’96). Intraamniotic injection of MB during obstetric procedures has been associated with serious adverse effects among newborns (Table 1). More recently, teratogenic effects have been reported following the injection of MB during midtrimester amniocentesis (Table 2). This article summarizes what is known about the biological actions of MB, the results of its use in obstetrics, and the evidence for its teratogenicity.