title: Breast-Milk Cortisol and Cortisone Concentrations Follow the Diurnal Rhythm of Maternal Hypothalamus-Pituitary-Adrenal Axis Activity.
abstract: BACKGROUND
  Very preterm infants often receive donor milk from mothers who deliver at term, but its composition differs from that of their own mother's milk. Because breast-milk glucocorticoids can support developing neonates, we explored concentration variability within and between mothers.
  
  
  OBJECTIVE
  We hypothesized that breast-milk glucocorticoid concentrations would be higher after very preterm delivery [gestational age (GA) <32 wk; study 1] and would follow the diurnal rhythm of maternal adrenocortical activity (study 2).
  
  
  METHODS
  Study 1 assessed differences in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio of mothers who delivered at (median) GA: 28.6 wk or at term weekly during the first month postpartum. Study 2 assessed variations in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio over 24 h, and tested Pearson correlations between milk and salivary concentrations in mothers who delivered at term (median GA: 38.9 wk) during week 4 postpartum. In these studies, foremilk glucocorticoids were measured by liquid chromatography-tandem mass spectrometry. Associations of milk cortisol, milk cortisone, and the milk cortisone-to-(cortisol+cortisone) ratio with prematurity (study 1) or collection time (study 2) were studied with longitudinal data analyses.
  
  
  RESULTS
  In study 1, giving birth to a very preterm infant was associated with reductions in milk cortisol and cortisone concentrations of 50% (β: 0.50; 95% CI: 0.26, 0.99; P = 0.05) and 53% (β: 0.53; 95% CI: 0.30, 0.93; P = 0.03), respectively, when adjusted for collection time. In study 2, concentrations of milk cortisol and cortisone were associated with collection time (both P < 0.01), peaking at ∼0700. Milk and salivary concentrations of cortisol (r = 0.92, P < 0.01) and cortisone (r = 0.93, P < 0.01) as well as the cortisone-to-(cortisol+cortisone) ratio (r = 0.64, P < 0.01) were correlated with one another.
  
  
  CONCLUSIONS
  Breast-milk glucocorticoid concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis activity and are lower in mothers who deliver very preterm.
authors.affiliation: Departments of Pediatrics and b.vandervoorn@vumc.nl.
authors.forename: Bibian
authors.identifier: http://orcid.org/0000-0003-1299-0067
authors.initials: B
authors.lastname: van der Voorn
authors.affiliation: Departments of Pediatrics and.
authors.forename: Marita
authors.initials: M
authors.lastname: de Waard
authors.affiliation: Departments of Pediatrics and.
authors.forename: Johannes B
authors.identifier: http://orcid.org/0000-0003-3960-1703
authors.initials: JB
authors.lastname: van Goudoever
authors.affiliation: Departments of Pediatrics and.
authors.forename: Joost
authors.initials: J
authors.lastname: Rotteveel
authors.affiliation: Clinical Chemistry, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Annemieke C
authors.identifier: http://orcid.org/0000-0002-6712-9955
authors.initials: AC
authors.lastname: Heijboer
authors.affiliation: Departments of Pediatrics and.
authors.forename: Martijn Jj
authors.initials: MJ
authors.lastname: Finken
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D003348:Cortisone / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000737:chemistry / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007231:Infant, Newborn; D008895:Milk, Human / Q000737:chemistry*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D047928:Premature Birth
chemical_list: D003348:Cortisone; D006854:Hydrocortisone
keywords: circadian pattern; glucocorticoids; mother’s milk; premature; very preterm