title: Relationship of salivary and plasma cortisol levels in preterm infants: results of a prospective observational study and systematic review of the literature.
abstract: OBJECTIVE
  (1) To investigate the relationship of salivary and plasma cortisol levels in preterm infants with a focus on the usability of salivary cortisol in diagnostic work-up of infants at risk of adrenal insufficiency. (2) To perform a systematic review addressing this question.
  
  
  METHODS
  Clinical study: We conducted a prospective observational single-center study in preterm infants. We analyzed plasma and saliva cortisol concentrations by enzyme immunoassay. Correlation analysis was used to determine the relation between salivary and plasma cortisol levels and the agreement of the measurement methods was analyzed according to Bland-Altman. Systematic review: A systematic literature search (PubMed and Embase) on the relationship of salivary and plasma cortisol levels in neonates was performed in November 2012.
  
  
  RESULTS
  Clinical study: We enrolled 58 preterm infants (median (interquartile range) gestational age at birth was 31.4 (28.1-32.7) weeks, birth weight 1,340 (974-1,745) g, respectively). Correlation analyses revealed a relationship of plasma cortisol and salivary cortisol levels. Rank correlation coefficient was 0.6. Estimating plasma cortisol levels based on measured salivary cortisol levels showed poor agreement of the two methods for determining plasma cortisol levels (direct and via salivary cortisol). Sensitivity and specificity of salivary cortisol for the detection of adrenal insufficiency were 0.66 and 0.62, respectively. Systematic review: Six studies in preterm infants and term neonates depicting the correlation of salivary and plasma cortisol were identified with a range of saliva-plasma correlation coefficients from 0.44 to 0.83.
  
  
  CONCLUSIONS
  Substitution of plasma cortisol by salivary cortisol determination cannot be recommended in preterm infants because of unsatisfactory agreement between methods.
authors.affiliation: Department of Neonatology, University Children's Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Maas
authors.forename: Christine
authors.initials: C
authors.lastname: Ringwald
authors.forename: Karin
authors.initials: K
authors.lastname: Weber
authors.forename: Corinna
authors.initials: C
authors.lastname: Engel
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight; D005260:Female; D005858:Germany; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006854:Hydrocortisone