This systematic review evaluated eight studies of methadone split-dosing during pregnancy, in which a daily dose is divided into two or more administrations rather than given once daily. The authors found that pregnancy-related changes in methadone metabolism can lower blood concentrations and require adjustments to maintain treatment. Across the included studies, split-dosing was associated with favorable maternal and neonatal outcomes, including measures of birthweight, preterm birth, fetal growth, and neonatal withdrawal. Because the evidence came from a small, varied group of studies, these associations should inform individualized clinical decisions rather than be treated as proof that split-dosing is superior for every patient.
