title: Total bilirubin level in relation to excipients in parenteral morphine sulfate administered to seriously ill newborn infants.
abstract: We examined exposure to excipients in different morphine sulfate preparations in relation to maximum total bilirubin level during the first 5 days of life among 155 infants admitted to a newborn intensive care unit. Sixty-six (43%), 47 (30%), and 42 (27%) newborns were exposed to chlorobutanol, phenol and neither excipient, respectively. Mean maximum total bilirubin in the first 5 days of life among newborns not exposed to chlorobutanol or phenol was 10.8 mg/dL (184 mumol/L). After adjusting for birthweight, race, sex, and use of phototherapy, the maximum total bilirubin level among newborns exposed to phenol was 1.4 mg/dL (24 mumol/L) higher than the maximum level among newborns exposed to neither excipient (P < 0.05); the corresponding difference associated with chlorobutanol exposure was 1.6 mg/dL (27 mumol/L) (P < 0.02). Further adjustment for potential confounding by the major risk factors for hyperbilirubinaemia did not materially change the results. While unconfirmed, these findings support the growing concern that excipients added to parenteral medications may not be 'inactive' as is often assumed, and that the safety of such exposures in seriously ill newborn infants needs to be studied further.
authors.affiliation: Slone Epidemiology Unit, School of Public Health, Boston University School of Medicine 02146.
authors.forename: S M
authors.initials: SM
authors.lastname: Lesko
authors.forename: A A
authors.initials: AA
authors.lastname: Mitchell
mesh_terms: D001663:Bilirubin / Q000378:metabolism*; D001724:Birth Weight; D002724:Chlorobutanol / Q000009:adverse effects / Q000494:pharmacology; D005079:Excipients / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology*; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy*; D007263:Infusions, Parenteral; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D019800:Phenol; D010636:Phenols / Q000009:adverse effects / Q000494:pharmacology; D010789:Phototherapy; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D005079:Excipients; D010636:Phenols; D019800:Phenol; D009020:Morphine; D002724:Chlorobutanol; D001663:Bilirubin