British Journal of Nutrition

Human and Clinical Nutrition

Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial

Margriet van Stuijvenberga1 c1, Annemieke M. Eissesa1, Christoph Grübera1, Fabio Moscaa1, Sertac Arslanoglua1, Gaetano Chiricoa1, Christian P. Braeggera1, Josef Riedlera1, Günther Boehma1 and Pieter J. J. Sauera1

for the Multicenter Infection Prevention Study-1 (MIPS-1) Study Group

a1 Beatrix Children's Hospital, UMC Groningen, CA51, PO Box 30001, 9700 RB Groningen, The Netherlands


The objective of the present study was to assess the effect of adding specific prebiotics to standard formula feeding on the number of fever episodes in the first year of life. In the present randomised, double-blind, placebo-controlled trial in seven centres in five West European countries, 830 healthy term infants, without a first-degree family history of allergic disease, of mothers who indicated to give only formula feeding were randomised either to receive a standard non-hydrolysed cows' milk-based formula to which a mixture of specific oligosaccharides was added (prebiotics group (PG)), or to receive a similar formula without oligosaccharides (control group (CG)). A separate reference group consisted of 300 breast-fed infants. The primary outcome was the number of fever episodes prospectively documented by the parents. There was no difference in the number of fever episodes between the PG (median value 1·19; 25th–75th percentile 0·09–2·34) and CG (1·16; 25th–75th percentile 0·06–2·38). The median number of fever episodes in the separate breast-feeding reference group was 1·24 (25th–75th percentile 0·51–3·45). There was no effect of adding specific prebiotics to standard formula feeding in reducing the number of fever episodes in the present study.

(Received December 01 2010)

(Revised April 14 2011)

(Accepted June 05 2011)

(Online publication October 04 2011)


c1 Corresponding author: Dr M. van Stuijvenberg, fax +31 50 3614235, email


Abbreviations: BG, breast-feeding group; CG, control group; FAS, full-analysis set; HR, hazard ratio; PG, prebiotics group; PPS, per-protocol set