Prebiotic-supplemented partially hydrolysed cow's milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial.
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.



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



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



Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (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.



pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.
Section of Paediatrics, Imperial College London, London, UK.|Imperial College Healthcare NHS Trust, London, UK.
R J
RJ
Boyle
Royal Children's Hospital Melbourne, Melbourne, Vic., Australia.|Murdoch Children's Research Institute, Melbourne, Vic., Australia.|University of Melbourne, Melbourne, Vic., Australia.
M L-K
ML
Tang
KK Women's and Children's Hospital, Singapore City, Singapore.
W C
WC
Chiang
KK Women's and Children's Hospital, Singapore City, Singapore.
M C
MC
Chua
Murdoch Children's Research Institute, Melbourne, Vic., Australia.|University of Melbourne, Melbourne, Vic., Australia.
I
I
Ismail
Nutricia Research, Utrecht, the Netherlands.|Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
A
A
Nauta
University College, Cork, Ireland.
J O B
JOB
Hourihane
Gold Coast Hospital, Gold Coast, Qld, Australia.
P
P
Smith
Women's and Children's Hospital, Adelaide, SA, Australia.
M
M
Gold
Sydney Children's Hospital, Sydney, NSW, Australia.
J
J
Ziegler
Royal Children's Hospital Brisbane, Brisbane, Qld, Australia.
J
J
Peake
Women's and Children's Hospital, Adelaide, SA, Australia.
P
P
Quinn
Poole Hospital NHS Foundation Trust, Poole, UK.
R
R
Rao
Salisbury Healthcare NHS Trust, Salisbury, UK.
N
N
Brown
Nutricia Research, Utrecht, the Netherlands.|Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
A
A
Rijnierse
Nutricia Research, Utrecht, the Netherlands.|Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
J
J
Garssen
Section of Paediatrics, Imperial College London, London, UK.|Imperial College Healthcare NHS Trust, London, UK.
J O
JO
Warner
D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D015415:Biomarkers; D002417:Cattle; D016207:Cytokines; D019587:Dietary Supplements; D004485:Eczema / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015994:Incidence; D007223:Infant; D041943:Infant Formula; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008892:Milk / Q000276:immunology*; D016269:Milk Hypersensitivity / Q000453:epidemiology / Q000517:prevention & control; D056692:Prebiotics / Q000008:administration & dosage*; D012307:Risk Factors
D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D056692:Prebiotics; D007073:Immunoglobulin E
eczema; hydrolysate; infant formula; oligosaccharides; randomized controlled trial