Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children:A randomized controlled trial

(J Allergy Clin Immunol 2011;128:360-5.)

Sadudee Boonmee,MD

• Partially hydrolyzated whey formulas (pHWFs) have widely recommended to prevent the development of allergic disease in early childhood.

• Inexpensive formulas• Contain smaller , less immunogenic milk

protein – derived peptides reduced allergenicity

J Allergy Clin Immunol 2011;128:360-5

• Cochrane review found “ significant reduction in infant allergy compared pHWF with CMF “

• Publication Bias ???• Asymmetry in funnel plots• Small studies report stronger protective effectof pHWF than larger studies

• GINI studies reports that pHWF reduced the incidence of eczema in earlychild hood in a per protocal analysis but fails in ITT analysis

• Aim To determine the use of pHWF reduced the incidence of allergic manifestation (eczema,and food reaction ) up to age 2 years of age

Methods Inclusion criteria and Exclusion criteria

Between 1990-1994 at Mercy Maternity Hospital, Melbourne, Australia Mothers were invite to participate in a study of modification of infant diet on the risk of infant allery. Enrollment : unborn child had a first – degree relative with history of eczema, asthma, allergic rhinitis, or food allergy

J Allergy Clin Immunol 2011;128:360-5

Intervention

Soy - based formular (ProSobee ;Mead Johnson nutrition) 2 intervention

formulas

pHWFs ( NAN HA; Nestle)

CMF (NAN ; Nestle) Control

J Allergy Clin Immunol 2011;128:360-5

• Mother were encoraged to initiate and maintain breast-feeding for at least 6 months.

• Study formula were introduced only cessation or partial cessation or as breast milk substitute if breast – feeding was not intended .

J Allergy Clin Immunol 2011;128:360-5

Study design• Single blind Randomized control trial

(paticipant)• Idependent statistician random codes

allocation.• Code avialable to research staff • Staff were blind to allocated codes and group

allocated.• Mother & Baby pair allocated to the next

sequence number as enrolled J Allergy Clin Immunol 2011;128:360-5

Study design

• Cans of each formula were labeled • Parent informed of assigned formula only

child’s second birthday.

J Allergy Clin Immunol 2011;128:360-5

Study design

Rice cereal,pureed apple and pear from 4 months of age.

Vegetables and other fruit from 6 months of age.

Meat from 9 months of age.

Dairy products, egg, fish, peanut, and nuts avoided until 12 months of age

J Allergy Clin Immunol 2011;128:360-5

Outcome

• Primary outcome- Any allergic manifestation at first 2 years of life

• Secondary outcome - Sensitization to cow’s milk and any allergen- Childhood asthma, rhinitis, and eczema at ages 6 and 7 years

Outcome

SPT performed at 6, 12, and 24 months by research nurses with standard technique.

Allergen extracts used were cow’s milk, egg white, peanut, HDM, rye grass, and cat dander

J Allergy Clin Immunol 2011;128:360-5

J Allergy Clin Immunol 2011;128:360-5

• 18 telephone interview ( every 4 weeks until 64 weeks, then at 78 and 104 weeks)

Statistic methods

Primary analysis : ITT and compared risk of any allergic manifestation between the allocated formula groups by using simple proportions and χ 2 [ Odds ratio with 95% CI ]

Secondary analysis : outcome of sensitization to cow’s milk and any allergen and childhood asthma, rhinitis, and eczema at ages 6 and 7 years

J Allergy Clin Immunol 2011;128:360-5

Results

J Allergy Clin Immunol 2011;128:360-5

Baseline

Result

• 50% of infant received some of allocated formula by 4 month of age

• 16.5% never received allocated formula because of either continue BF or using nonallocated formula.

J Allergy Clin Immunol 2011;128:360-5

No differences in rates of exposure to allocated formula between groups

J Allergy Clin Immunol 2011;128:360-5

Result

• Majority of mothers fully adhered to study formula feeding protocol during first 6 months of life ( CMF 91.2%, pHWF 86.9%, Soy 87.4% )

J Allergy Clin Immunol 2011;128:360-5

Outcome

J Allergy Clin Immunol 2011;128:360-5

Secondary outcome in first 2 years

J Allergy Clin Immunol 2011;128:360-5

Outcome

J Allergy Clin Immunol 2011;128:360-5

Adjusted analysis

J Allergy Clin Immunol 2011;128:360-5

Interactions with family history of eczema

J Allergy Clin Immunol 2011;128:360-5

Per – protocal analysis

• None produced different findings from ITT analysis.

• Limiting analysis to children who compliant with the study feeding protocol did not alter the study conclusions (primary outcome OR, 1.20; 95% CI, 0.75-1.93, for pHWF

• Excluding infants exclusively breast-fed for more than 4 months did not alter the results OR, 1.22; 95% CI, 0.72-2.04, for pHWF

J Allergy Clin Immunol 2011;128:360-5

Per – protocal analysis

• Infants who had consumed some of the allocated formula OR, 1.16; 95% CI, 0.66-2.02

• consumed the allocated formula for at least 2 weeks during the first 4 months of life OR, 1.10; 95% CI, 0.59-2.04

Discussion

• This randomized controlled trial failed to show any beneficial effect of the pHWF for the prevention of any allergic disease outcome up to 7 years of age in high-risk children compared with a conventional cow’s milk–based formula.

J Allergy Clin Immunol 2011;128:360-5

Discussion

• An ITT analysis GINI study, also failedto demonstrate benefit of pHWF over conventional formulaFor allergic manifestations and eczema up to 12 mo, and childhood eczema, asthma, or allergic rhinitis at age 6 and 7 years

J allergy Clin Immunol 2008;121:1442-7

Conclusion

• There no evidence that introducing pHWF at the cessation of breast feeding reduced risk of allergic manifestation in high risk infant

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