A New Standard for Infant Formulas

Standard for Infant Formulas

Parents should avoid infant formulas made from intact proteins, a Stanford researcher told doctors assembled at the annual meeting of the Pediatric Academic Societies.

"Standard intact cow's milk protein formulas cause allergies," said John A. Kerner, Jr., MD, who is director of the Nutrition Support Team, medical director of Children's Home Pharmacy at Lucille Packard Children's Hospital and professor of pediatrics at Stanford University. "Should we continue to increase risk using the current standard? Or should we change the standard?"

Kerner's questions came as the climax of an April 30 symposium in San Francisco sponsored by Baylor College of Medicine and supported by an educational grant from the Nestlé Nutrition Institute. The presentation began with Peyton A. Eggleston, MD, a professor of Pediatrics at Johns Hopkins University School of Medicine, who described evidence for the rise in the incidence of allergy-related diseases in the United States.

For example, in the National Health and Nutrition Examination Survey (NHANES) III, conducted between 1988 and 1994, almost 20 percent of 20-year-olds had positive skin tests for cat dander allergies, four times the percentage in NHANES II, which was conducted between 1976 and 1980. Rye grass allergies for this group doubled to about 30 percent. 1 Similarly, he said, the rate of asthma mortality in people aged 15 to 34 about doubled, from a low of fewer than 3 per million in 1975 to about 6 per million in 1999.2 "It's a worldwide trend," said Eggleston.

Eggleston listed six possible factors that contribute to allergic diseases: genetic predisposition, allergen exposure, viral infection, hygiene, pollutants and diet. Researchers are still puzzling out how these factors may be causing the upsurge in allergies.

One explanation could be a change in the types of allergens people encounter. "We have lots more wall-to-wall carpet, and we spend a lot more time indoors," Eggleston said. Pollutant exposure, on the other hand, has decreased in recent years.

Evidence has been mounting in favor of another explanation, the "hygiene hypothesis" which holds that our immune systems have been thrown off balance because we are living in a cleaner environment and suffering fewer childhood infections. During childhood, the immune system's development is affected by the antigens and allergens in the environment. Children exposed to enough antigens, such as viruses and bacteria, develop a more robust system of Th1 immune cells, which are less sensitive to allergens. Children whose immune systems are not challenged this way develop a greater reliance on Th2 immune cells, which are more sensitive to allergens.

A number of studies offer evidence in support of the hygiene hypothesis. One group of researchers reported that children without siblings and children who don't go to daycare appear more likely than other kids to develop allergies.3 Another found that children born in Mexico—where sanitation standards are lower—are less likely to develop allergies than children of Mexican heritage born in the United States.4

A Heavy Toll

Whatever is causing the increased incidence of allergies, they are taking a heavy toll, said the second speaker in the symposium, Mark Boguniewcz, MD, a professor in the division of pediatric allergy-immunology at the National Jewish Medical and Research Center and University of Colorado School of Medicine. Citing the American Academy of Allergy, Asthma and Immunology, he said that allergic diseases are the sixth leading cause of chronic disease in the United States, costing more than $18 billion annually.5

Atopic dermatitis can cause children to scratch themselves bloody and may keep them—and therefore their families—awake through the night. "I continue to see patients where that issue has never been addressed," he said. "When I bring it up, oftentimes moms will break down and cry."

Other forms of allergy can have severe effects, too. Food allergy is the most common cause of anaphylaxis, with one study finding that it results in around 120 deaths a year, Boguniewcz said.6 That causes a lot of anxiety for families of children with food allergies. "They worry more when they are out and about—certainly when they are in restaurants—than patients with diabetes," he said.7

Boguniewcz added that asthma remains the most common chronic disease among children, causing 658,000 emergency department visits per year, according to CDC figures. Finally, he said, allergic rhinoconjunctivitis can be extremely disruptive, affecting school attendance, relationships and emotional wellbeing.


Fortunately, parents and healthcare providers can prevent allergies by reducing children's exposure to allergens. Eggleston cited several studies showing that patients could improve their symptoms of asthma. For example, they could cover mattresses and pillow covers and wash bedding weekly to reduce exposure to dust mites.For infants at high risk of developing allergies, the American Academy of Pediatrics suggests that there is little evidence for delaying the introduction of solid foods beyond 4-6 months, and the current evidence does not support a major role of maternal dietary restrictions during pregnancy and lactation.9

Breast-feeding itself can also protect against allergies, said Kerner. Kerner, the final presenter at the symposium, presented data from several studies showing that human milk contains a wide range of ingredients believed to affect allergies. Some, such as traces of cow's milk or peanuts consumed by the mother, can have either protective or sensitizing effects, he said, citing recent research. Likewise, mothers pass down both protective and sensitizing cytokines and PUFAs. The immunoglobulin slgA and various polyamine and prebiotics, on the other hand, are only believed to protect infants.10

Whatever the ingredients responsible, feeding an infant with formula instead of human milk has a big influence in the organisms that live in an infant's intestines, Kerner said. For example, he cited several studies that found far more bifidobacteria in breast-fed infants.11

Other researchers have shown that these differences appear to affect the development of allergies. Allergic infants have less bifidobacteria and lactobacilli.12 Kerner cited research showing that these organisms may improve the integrity of the gut barrier, help develop tolerance, decrease Th2-type immunity and reduce pro-inflammatory mediators.13 Other researchers have found that supplementing with these organisms may actually reduce allergic reaction.14

These findings add to all the other evidence in favor of breast-feeding. But many mothers can't breast-feed or need to supplement their own milk with formula, and in these cases some healthcare providers have been uncertain which kind of formula to recommend, especially to families with a history of allergies. One common error is to suggest a formula made from intact soy protein. "There is no benefit to soy in allergy prevention," Kerner said. He cited the American Academy of Pediatrics statement, which only endorses soy for infants who have already developed certain types of allergies to cow's milk—and then only as one alternative.9

Another alternative is hydrolyzed protein formulas, that is formulas in which the peptides that hold amino acids together have been broken. The formulas vary depending on the type of protein used and the degree to which it is hydrolyzed. In 2003, a team of German researchers reported how they had tackled that question with a study on 2,252 children at high risk of developing allergies. Infants in the German Infant Nutritional Intervention (GINI) study were randomized into groups that supplemented their breast milk as needed with formula made from either intact cow's milk, partially hydrolyzed whey, extensively hydrolyzed whey or extensively hydrolyzed casein.

Among the infants who drank the intact cow's milk formula, 16 percent showed signs of allergic reaction within 12 months: dermatitis, urticaria or food allergy with manifestation in the gastrointestinal tract. By comparison, 11 percent of those infants who drank only breast milk for the first four months showed signs of allergy. Those who got partially hydrolyzed whey formula also had an 11 percent incidence of allergy. The incidence of allergic manifestation in the extensively hydrolyzed casein formula group was 9 percent, and in the extensively hydrolyzed whey group it was 14 percent. Probably because of its bitter taste, a significantly higher number of the families assigned to extensively hydrolyzed casein dropped out of the study.

The results don't completely fit the recommendations of the American Academy of Pediatrics, which last issued a clinical report in January of 2008. For infants at high risk for allergies who are not exclusively breast-fed, the academy suggests that there is modest evidence that the onset of atopic disease may be delayed or prevented by the use of hydrolyzed formulas compared with formula made with intact cow milk protein, particularly for atopic dermatitis.9

Kerner draws slightly different conclusions from the data. Based on the results of the GINI study and other research from the past six years, he argues that partially hydrolyzed whey and extensively hydrolyzed casein are equally beneficial in avoiding allergies. In his own review of the literature, he found that 16 out of 18 controlled trials on partially hydrolyzed whey demonstrated efficacy for allergy prevention. By comparison, six out of eight reports on extensively hydrolyzed casein found it effective, while extensively hydrolyzed whey wasn't found effective in the one study where it was investigated.15

Furthermore, Kerner said, it is difficult to determine which patients are at high risk of allergy. It's not practical to do laboratory testing on most infants, family history is not consistently obtained, and "more than 50 percent of children at risk for allergies do not have a family history of them."

Based on all these findings, Kerner gave these recommendations for infants not exclusively breast-feeding: 

  • If there is a positive family history for allergy, use either a partial whey hydrolysate or an extensive casein hydrolysate.
  • For routine infant feeding, use a partial whey hydrolysate and not an intact cow's milk-based formula.
  1. Arbes SJ Jr., et al. J Allergy Clin Immunol 2005; 116:377-383
  2. Mannino DM, et al. MMWR Surveil Summ. 1998:47(No. SS-1);1-27
  3. Ball TM, et al. N Engl J Med. 2000;343:538-543
  4. Eldeirawi K, et al. J Allergy Clin Immunol 2205; 116:42-48
  5. AAAI. The Allergy Report 2000. Volume 1: Overview of Allergic Diseases: Diagnosis, Management, and Barriers to Care
  6. Yocum MW, et al. J Allergy Clin Immunol. 1999,104:452-456
  7. Avery NJ, et al. Pediatr Allergy Immunol 2003;14:378-382
  8. Walshw MJ, Evans CC. QJM. 1986;58:199-215
  9. Greer FR et al. Pediatrics 2008; 121(1):183-91.
  10. Friedman NJ, Zeiger RS. In Leung DYM, et al, eds: Pediatric Allergy: Principles and Practice. St. Louis, Mo: CV Mosby; 2003:496
  11. Harmsen HJ, et al. J Pediatr Gastroenterol Nutr. 2000;30:61-67
  12. Bjorksten B, et al. Clin Exp Allergy. 1999;29:342-346
  13. Shida K, et al. Clin Exp Allergy. 2002;32:563-570
  14. Isolauri E, et al. Clin Exp Allergy. 2000;30:1604-1610
  15. Von Berg A, et al. J Allergy Clin Immunol. 2003:111;533-540

This article was prepared through a grant from Nestlé.


Article copyright © 2006 Decision News Media SAS, All Rights Reserved. This article first appeared on the FoodNavigator Web site as "Doctor warns against 'standard' infant formulas" (Laird Harrison, 5/12/2006). Thanks to Decision News Media and FoodNavigator for permission to reprint this article.

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