1. German Infant Nutrition Intervention Study

2. Summary
“…there is modest evidence that atopic dermatitis may be delayed or prevented by the use of extensively or partially hydrolyzed formulas, compared with cow milk formulas, in early childhood.”
“Comparative studies of the various hydrolyzed formulas have also indicated that not all formulas have the same protective benefit. Extensively hydrolyzed may be more effective than partially hydrolyzed in the prevention of atopic disease…The higher cost of hydrolyzed formulas must be considered in any decision-making process for their use.”
In January of 2008 the AAP published a Clinical Report focusing on allergy risk reduction. Though not a position statement, this clinical report replaces any previous positions and reports done by the Academy on allergy risk reduction.
Pediatrics 2008;121:

3. Role of Formula
“While some studies show a slightly more protective effect of certain extensively hydrolyzed formulas as compared to partially hydrolyzed whey-based formula, the clinical relevance of this small difference is uncertain at this time.”
Conclusion
“In summary, …for families with an infant at risk for atopic disease, exclusive breastfeeding for at least four months or the use of particular extensively or partially hydrolyzed infant formulas may prevent or delay several atopic diseases, when compared to using a whole cow’s milk or soy based formula.”
The same authors then published a shorter article based on the report in AAP News, also in January. The AAP News article actually uses more favorable language regarding partially hydrolyzed formulas and allergy risk reduction.
NESTLÉ® GOOD START® is the only partially hydrolyzed, 100% whey formula currently available in the US.
AAP News 2008;29:12

4. FACT
The use of certain hydrolyzed infant formulas, instead of intact cow protein formulas can reduce the incidence of atopic dermatitis in infants with a positive history of allergy

5. AAP Nutrition Handbook:
Countrywide
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AAP Nutrition Handbook:
Objections to pHF-W for allergy risk reduction
Composititional and functional differences between cow’s milk whey and human milk. (p. 69 under protein)
Evidence is “controversial” for recommending a partially hydrolyzed formula to reduce the risk of allergy. (p. 795)
Recently an INR was faced with an unexpected objection when discussing allergy with a physician. He pulled out the AAP Nutrition handbook and cited what he believed disqualified any claim of allergy risk reduction that we might make.
It is uncertain whether the MD discovered this information on his own or was led to it by our competition.
CMD 5

6. AAP Nutrition Handbook: Overcoming Objections
Countrywide
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AAP Nutrition Handbook: Overcoming Objections
The Handbook is five years behind on data
It does not include: GINI 3, 6, or the AAP Clinical Report on allergy risk reduction
Ex: Vitamin D – new recommendations are not included
Saying that partially hydrolyzed formulas may reduce the risk of allergy really is “controversial.”
Both MJ and PBM have partially hydrolyzed formulas that have NOT been proven to reduce the risk of allergy.
We have VERY strong evidence from numerous clinical trials and now GINI 6 that GS reduces the risk of allergy.
Use the “Curds” visual and “Protein Quality” pieces to show that whey is an excellent choice for formula.
We have VERY strong evidence from numerous clinical trials and now GINI 6 year results from the largest pediatric allergy prevention study ever done that our 100% whey, partially hydrolyzed formula does reduce the risk of allergy.
Again, the AAP can not endorse a product, so favoring a “100% whey, partially hydrolyzed formula” would be unethical since we are the only one on the market.
Review the curds picture and discuss the fact that bovine whey does not form the large, hard curds that bovine casein does. Review the protein quality piece pointing out that on every measure bovine whey is scores higher than bovine casein.
Also, point out that both cow’s milk casein and whey are highly antigenic to a newborn with an immature immune system. That is exactly why we hydrolyze the protein.
CMD 6

7. GINI – Key Points GINI I GINI 3 GINI 6
Countrywide
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GINI – Key Points
GINI I
The effect of hydrolyzed cow’s milk
formula for allergy prevention in the first year of life: The German Infant
Nutritional Intervention Study, a
randomized double-blind trial
GINI 3
GINI 6
I’m going to take just a moment to review the Key Findings in GINI 1, GINI 3 and GINI 6 – and then summarize them all in the new branded Allergy Leave Behind.
Certain hydrolyzed formulas reduce the incidence of atopic dermatitis but not that of asthma: Three-year results of the German Infant Nutritional Intervention Study
Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long term results from the German Infant Nutritional Intervention Study (GINI)
CMD 7

8. GINI I Conclusions:
“…our results clearly indicate that feeding a hydrolyzed formula instead of CMF as a supplement or substitute to breast milk during the first 4 months of life reduces the risk of AM during the first year of life. However, the different hydrolysates do not offer the same degree of prevention.”
“Our results confirm that allergy prevention in the first year of life in infants with a familial risk for atopy is possible by feeding hydrolyzed formulas instead of CMF as a supplement or substitute for breast milk.”
GINI 1 was one of the largest studies, not sponsored by industry, to first indicate that feeding a 100%Whey, Partially Hydrolyzed infant formula could offer primary prevention from AD in the first year of life.
Von Berg et al., 2003 J Allergy Clin Immunol 111(3):

9. GINI 3 Conclusions:
“Children who were supplemented with either eHF-C or pHF-W instead of normal CMF had AD significantly less often. The preventive effect developed in the first year and persisted into the third year, indicating real disease reduction rather than postponement of disease onset.”
“Considering the much higher cost of eHF-C compared with pHF-W, the cost/benefit ratio seems to be in favor of the pHF-W. However, the cost/benefit calculation may differ in certain subgroups.”
GINI 3 did prove that there was a protective benefit of PHF-W on AD until 3 years of age, but it also pointed out compliance and cost.
Von Berg et al., 2007 J Allergy Clin Immunol 119(3):

10. GINI 6 Conclusions:
“The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.”
“The results of the GINI study with a follow-up until 6 years of age revealed the important finding that nutritional intervention with hydrolyzed infant formulas in the first 4 months of life has a long-lasting preventive effect on atopic eczema in high-risk children.”
GINI 6 conclusion gave us stronger language than we’ve ever been able to use before.
Von Berg et al. J Allergy Clin Immunol 2008;121:

11. GINI 3: Cumulative Incidence of Atopic Dermatitis at 36 mos* * * *
The Key Point from the 3 year results from the GINI study: It indicated primary prevention of AD extended from 12 months to 36 months of life. * *
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2007 J Allergy Clin Immunol 119(3):

12. GINI 6: Cumulative Incidence of Atopic Dermatitis at 6 y* * * * *
The Key Point from the 3 year results from the GINI study: It indicated primary prevention of AD extended from 12 months to 36 months of life. *
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2007 J Allergy Clin Immunol 119(3):

13. GINI 1: Risk of AD at 12 Mos – Odds Ratio
1.0
0.81
19% risk reduction vs. CMF
CI ( ) *
0.56
44% risk reduction vs. CMF
CI ( )
The Key Points from GINI 1 were that it was the largest infant formula study that was double-blinded, prospective, and randomized --looking at infant nutrition and incidence of AD in the 1st year of life. The results were quite compelling. A 100% whey, phF used instead of a standard whole-protein formula, offers significant protection against allergic disease such as AD.
0.42 *
58% risk reduction vs. CMF
CI ( )
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2003 J Allergy Clin Immunol 111(3):

14. GINI 6: Risk of AD at 6 Years – Odds Ratio
1.0
0.64
0.55
36% risk reduction vs CMF
45% risk reduction vs CMF
0.74
26% risk reduction vs CMF
CI ( )
CI ( )
CI ( ) * * *
Key Points from the GINI 6 include: The intent to treat analysis was based on all 2,252 infants, and per protocol analysis was based on all 988 infants fed the fully or partially hydrolyzed study formulas that were compliant with the feeding recommendations. In the first 4 months of life, which was considered the study’s “strict intervention period”. Of the 988 infants included in the per protocol analysis at year 6, 39% (384) were diagnosed with an allergic manifestation and 26% (253) were diagnosed with atopic dermatitis.Significant risk reduction from birth to 6 years for atopic dermatitis: pHF-W (36%) and eHF-C (45%); all allergic manifestations: pHF-W (25%) and eHF-C (33%).
Extensively hydrolyzed whey formula (eHF-W) did not have an effect up to 3 years of age; however it did start to show an effect at 6 years of age with a risk reduction of 22% on all allergic manifestations and 26% risk reduction of AD. *
*p < 0.05 vs Intact Cow Milk
Von Berg et al., 2008 J Allergy Clin Immunol 121(6):

17. Branded Allergy Leave Behind
Purpose
To Persuade healthcare professionals to recommend Nestle GOOD START Gentle Plus when formula is initiated for primary prevention of allergic manifestations.
Educate them on the latest research findings on allergy prevention, including GINI I, 3 and 6.
(basically –to prevent the problems associated with not breastfeeding)
If a partially hydrolyzed, 100% whey infant formula is given from the beginning, we can reduce the risk of developing atopic manifestations like atopic dermatitis.
Nutritional intervention with hydrolyzed infant formulas in the first 4 months of life has a long-lasting primary-preventive effect on atopic dermatitis in high-risk children. We can now see that there is not just a delay in the appearance of allergy, but that hydrolyzed formulas can truly reduce the risk of ever developing them.
The relative risk of AD up to 6 years is significantly reduced in partially hydrolyzed whey formula (pHF-W) (36%), extensively hydrolyzed whey formula (eHF-W) (26%) and extensively hydrolyzed casein (eHF-C) (45%) groups
“The data of the 6-year follow-up of the GINI study confirm a persistent preventive effect of eHF-C and pHF-W on AM and AD” (p. 1446, 2nd column, last paragraph)
The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.” (p. 1442,Abstract, Conclusion)
GOOD START uses 100% whey for its protein source and applies a unique [patented-delete b/c we are no longer patented] partial hydrolysis process to break the whey protein down into smaller peptides to help reduce allergic risk vs. intact cow’s milk whey and casein protein formula.
Cow casein-free to facilitate easy digestion.
Faster gastric emptying may help reduce the potential for reflux and spitting up.
Promotes soft stools similar to those of the breastfed infant.
DHA and ARA are at levels shown to support visual and cognitive development
Good Start formulas support healthy growth and development and are approved by the FDA.
When discussing Good Start benefits, we must be mindful that breast milk is the gold standard for growth and development, avoidance of allergy and digestive tolerance. We are simply trying to prevent the problems that may be associated with not breastfeeding

18. The GINI Timeline: A History of Clinical Efficacy
2008
Jan AAP: GINI citation in AAP Clinical Report
GINI 6: 6-year follow-up, 36% RR in AD in pHF-W. “Data confirms a long-term, allergy-prevention effect…”
2007
GINI 3: 3-year follow-up to GINI % RR using pHF-W for AD. Demonstrates real disease reduction
Today
INR Sales Force Grows! Speaker Programs spread the clinical message to HealthCare Professionals
2003
GINI 1: Largest Independent study conducted with focus on allergy reduction. INRs begin communicating a 44% RR in AD using pHF-W to MDs
2003 was an exciting time for INRs. The German Infant Nutritional Intervention Study was published in The Journal of Allergy and Clinical Immunology. We were able to bring a stronger clinical message and move from the “protein sensitization” discussion to “risk reduction of allergy manifestation”. Pediatricians responded positively to a study that was an independent, prospective, double-blind RCT. At the same time, the message was further validated by Osborn, et. al., 2003 published by The Cochrane Library.
In 2004, the INR sales force was expanded and MSU began to develop the Speakers Bureau. Speakers presented “ Pediatric Allergy: Prevalence and Prevention”. Later, a DVD featuring several presentations with Dr.Yinka Davies and Lynn Mattis, Clinical Nurse Specialist, was developed. This allowed INRs to bring an abbreviated allergy presentation discussing the GINI findings into the clinic or hospital setting. Again, the message was more powerful for physicians and nurses when presented by their peer group.
In 2007, GINI 3 was published, demonstrating that feeding a hydrolyzed formula vs intact cow milk formula in the first 4 months of age does have significant impact on the presence of allergic disease at 3 years of age. The preventive effect observed in the first year persisted into the 3rd year. This provided validation and continued to help tell the story of the benefit of feeding Good Start as a routine starter formula or supplement to BF.
In January of 2008, the American Academy of Pediatrics published the Clinical Report “Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants & Children: The Role of Maternal Dietary Restriction, Breastfeeding, Timing of Introduction of Solid Foods, and Hydrolyzed Formulas”. While not a strong endorsement of the role of
pHF-W in risk reduction of allergy, stronger verbiage was used, stating “modest evidence” of allergy risk reduction with hydrolyzed formulas. This report and the corresponding AAP News report provided additional talking points and validation on the subject.
Most recently, GINI 6 was published in True risk reduction of AD in the first 6 years of life in infants with a familial risk for atopy is possible when feeding a pHF-W in place of CMF. It is important to note that the studies – which were follow-up studies to the original study design – showed long-lasting primary-preventive effects. All were published in the Journal of Allergy and Clniical Immunology.
And the story continues….