title: Potentially harmful excipients in neonatal medicines: a pan-European observational study.
abstract: OBJECTIVE
  We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure.
  
  
  METHODS
  All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis.
  
  
  RESULTS
  Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient.
  
  
  CONCLUSIONS
  European neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.
authors: Institute of Microbiology, Tartu University, Tartu, Tartumaa, Estonia Neonatal Unit, Tartu University Hospital, Childreńs Clinic, Tartu, Tartumaa, Estonia.
authors: Georgi
authors: http://orcid.org/0000-0002-3897-5482
authors: G
authors: Nellis
authors: Institute of Microbiology, Tartu University, Tartu, Tartumaa, Estonia Paediatric Intensive Care Unit, Tartu University Hospital, Clinic of Anaesthesiology and Intensive Care, Tartu, Tartumaa, Estonia.
authors: Tuuli
authors: T
authors: Metsvaht
authors: Neonatal Unit, Tartu University Hospital, Childreńs Clinic, Tartu, Tartumaa, Estonia.
authors: Heili
authors: H
authors: Varendi
authors: Department of Public Health, Tartu University, Tartu, Tartumaa, Estonia.
authors: Karolin
authors: K
authors: Toompere
authors: Institute of Microbiology, Tartu University, Tartu, Tartumaa, Estonia Pharmacy Department, Tartu University Hospital, Tartu, Tartumaa, Estonia.
authors: Jana
authors: J
authors: Lass
authors: Institute of Microbiology, Tartu University, Tartu, Tartumaa, Estonia.
authors: Inge
authors: I
authors: Mesek
authors: Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors: Anthony J
authors: AJ
authors: Nunn
authors: Neonatal Unit, Liverpool Women's Hospital, Liverpool, UK Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: Mark A
authors: MA
authors: Turner
authors: Institute of Microbiology, Tartu University, Tartu, Tartumaa, Estonia.
authors: Irja
authors: I
authors: Lutsar
mesh_terms: D004334:Drug Administration Schedule; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D057915:Drug Substitution; D004363:Drug Utilization / Q000706:statistics & numerical data; D005060:Europe; D005079:Excipients / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D005865:Gestational Age; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D012307:Risk Factors
chemical_list: D005079:Excipients
keywords: Neonatology; Pharmacology