Trimethoprim-Sulfamethoxazole
TMP-SMX (Co-trimoxazole) is a folate antagonist with trimester-dependent risks. Trimethoprim inhibits dihydrofolate reductase, potentially impairing folate metabolism in early embryogenesis — associated with NTDs and cardiovascular defects in some studies. Sulfamethoxazole at term can displace bilirubin from albumin causing neonatal jaundice and theoretical kernicterus risk. Despite this, it remains essential for treating Pneumocystis jirovecii pneumonia (PCP), Toxoplasma gondii, and certain MDR UTIs. Supplementation with folic acid 5 mg/day is recommended if used in T1.
