title: Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study.
abstract: BACKGROUND
  Neonatal Toll-like receptor (TLR) responses are biased toward Th2-polarizing responses at birth and rapidly mature toward more balanced responses during the first month of life. Postnatal TLR maturation may be guided by environmental exposure.
  
  
  OBJECTIVE
  To determine the environmental determinants of neonatal TLR function.
  
  
  METHODS
  A prospective birth cohort study was performed in 291 healthy term neonates. Mode of delivery, breastfeeding, birth month, siblings, pets and parental smoking were analyzed in relation to neonatal innate immune parameters at the age of 1 month. Whole blood concentrations of innate immune cells were measured by flow cytometry. In vitro TLR-mediated cytokine production was determined by ELISA.
  
  
  RESULTS
  Breastfeeding was the major determinant of neonatal innate immunity, associated with 5 (31%) of neonatal innate immune parameters, of which the association with TLR7-mediated IL-10 production was most significant (76 pg/ml in breastfed neonates vs. 293 pg/ml in formula-fed neonates, p = 0.001). Of innate immune variables, TLR3-mediated IL-12p70 production was highly associated with environmental exposures (pets, breastfeeding and mode of delivery), whereas TLR9-mediated cytokine responses were not associated with any environmental factor.
  
  
  CONCLUSIONS
  Neonatal innate immune responses are differentially modulated by environmental exposure in the first month of life. The protective effect of breastfeeding against subsequent infections and atopy might be explained by its innate immune modulatory effects in the first month of life.
authors: Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands. m.belderbos@umcutrecht.nl
authors: M E
authors: ME
authors: Belderbos
authors: M L
authors: ML
authors: Houben
authors: G M
authors: GM
authors: van Bleek
authors: L
authors: L
authors: Schuijff
authors: N O P
authors: NO
authors: van Uden
authors: E M
authors: EM
authors: Bloemen-Carlier
authors: J L L
authors: JL
authors: Kimpen
authors: M J C
authors: MJ
authors: Eijkemans
authors: M
authors: M
authors: Rovers
authors: L J
authors: LJ
authors: Bont
mesh_terms: D016902:Air Pollution, Indoor / Q000009:adverse effects; D000485:Allergens / Q000009:adverse effects; D001942:Breast Feeding; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D061148:Hygiene Hypothesis; D006967:Hypersensitivity / Q000453:epidemiology / Q000276:immunology*; D007107:Immune System / Q000254:growth & development* / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D014028:Tobacco Smoke Pollution; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D016753:Interleukin-10; D018664:Interleukin-12