Pregnancy: An increased risk of congenital malformations (neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, club foot) following maternal use of sulfamethoxazole and trimethoprim during pregnancy has been observed in some studies. Folic acid supplementation should be considered if used during the first trimester. Use during the first trimester should be limited to situations where no alternative therapies are available. Due to theoretical concerns that sulfonamides pass the placenta and may cause kernicterus in the newborn, alternatives can be considered at the time of delivery, though there have not been any cases reported with exposure in utero.

Breastfeeding: Sulfamethoxazole and trimethoprim are both present in breastmilk. A systematic review of the use of sulfonamides near term and during breastfeeding found no adverse reactions in infants. However, caution in jaundiced, ill, stressed or premature infants, because of the possible risk of bilirubin displacement and kernicterus (thought this has never been reported via breastmilk exposure). Breastfeeding is likely compatible in healthy, fullterm infants. Monitor for signs of jaundice. Sulfamethoxazole and trimethoprim should be avoided while breastfeeding a G6PD-deficient infant.