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Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study


M.E. Belderbos, MD, Wilhelmina Children’s Hospital, Room KE 04.133.1, PO Box 85090, 3508 AB Utrecht, The Netherlands.
Tel.: +31 88 7554091
Fax: +31 88 8222762


To cite this article: Belderbos ME, Houben ML, van Bleek GM, Schuijff L, van Uden NOP, Bloemen-Carlier EM, Kimpen JLL, Eijkemans MJC, Rovers M, Bont LJ. Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study. Pediatric Allergy Immunology 2012: 23: 65–74.


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.

Aims:  To determine the environmental determinants of neonatal TLR function.

Materials and 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.

Conclusion:  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.