Background
Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes.

Objective
To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high risk infants [ISRCTN65195597].

Methods
We conducted a parallel-group, multi-centre, randomised double-blind controlled trial of pHF-OS versus standard cow's milk formula. Infants with a family history of allergic disease were randomised (stratified by centre/maternal allergy) to active (n=432) or control (n=431) formula until 6 months age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomised at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomised, immune markers at 6 months, and adverse events.

Results
Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks age, versus 93/324 (28.7%) control (OR 0.98 95%CI 0.68, 1.40; P=0.90), and 107/347 (30.8%) pHF-OS versus 112/370 (30.3%) control in all infants randomised (OR 0.99 95%CI 0.71, 1.37; P=0.94). pHF-OS did not change most immune markers including total/specific IgE, however pHF-OS reduced cow's milk-specific IgG1 (p<0.0001), and increased regulatory T cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events.

Conclusion
pHF-OS does not prevent eczema in the first year in high risk infants. The immunological changes found require confirmation in a separate cohort.