title: Diuretic exposure in premature infants from 1997 to 2011.
abstract: OBJECTIVE
  Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia. We examined their use and safety in this group.
  
  
  METHODS
  Retrospective cohort study of infants < 32 weeks gestation and < 1,500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997 to 2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and fraction of inspired oxygen on the first day of each course of diuretic use were identified.
  
  
  RESULTS
  About 37% (39,357/107,542) infants were exposed to at least one diuretic; furosemide was the most commonly used (93% with ≥ 1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. About 74% patients were exposed to one diuretic at a time, 19% to two diuretics simultaneously, and 6% to three diuretics simultaneously. The most common combination was furosemide/spironolactone, followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants were not receiving mechanical ventilation on the first day of each new course of furosemide (47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%). Any adverse event occurred on 42 per 1,000 infant-days for any diuretic and 35 per 1,000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1,000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia.
  
  
  CONCLUSIONS
  Despite no Food and Drug Administration (FDA) indication and little safety data, over one-third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support.
authors.affiliation: Division of Neonatal-Perinatal Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Laughon
authors.affiliation: Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kim
authors.initials: K
authors.lastname: Chantala
authors.affiliation: Division of Neonatal-Perinatal Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Sofia
authors.initials: S
authors.lastname: Aliaga
authors.affiliation: Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Herring
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hornik
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Pediatrix Medical Group, Greenville, Sunrise, Florida.
authors.forename: Reese H
authors.initials: RH
authors.lastname: Clark
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
mesh_terms: D000086:Acetazolamide / Q000627:therapeutic use; D000584:Amiloride / Q000627:therapeutic use; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000517:prevention & control*; D002740:Chlorothiazide / Q000627:therapeutic use; D015331:Cohort Studies; D003981:Diazoxide / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004976:Ethacrynic Acid / Q000627:therapeutic use; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D008788:Metolazone / Q000627:therapeutic use; D056687:Off-Label Use; D012121:Respiration, Artificial / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D013148:Spironolactone / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000453:epidemiology*
chemical_list: D004232:Diuretics; D006852:Hydrochlorothiazide; D013148:Spironolactone; D008353:Mannitol; D002740:Chlorothiazide; D000584:Amiloride; D005665:Furosemide; D004976:Ethacrynic Acid; D000086:Acetazolamide; D003981:Diazoxide; D008788:Metolazone