Partially Hydrolyzed For Infants:

Which to choose and what is the long-term impact?

Julistio Djais
RSHS
Breastfeeding is the best way to provide
optimal nutrition for the healthy growth
and development of infants.

Encourage exclusive breastfeeding to

mother through education about the
benefit of breastmilk.
 Breast milk remains the standard for infant feeding.

For infants that cannot be breast-fed,

a continuous effort should be made to mimic
the effects of breast milk on the infant
as close as possible with infant formula.

Human Milk Represents the Gold Standard in Infant’s Nutrition

 The Important of Protein
Optimal growth, development, and functional maturation of the infant clearly depend
on the provision of an adequate intake and balance of more than 50 essential macro-
and micro-nutrients.

Of all these, protein is by far the most important determinant.

Protein in the diet provides the essential amino acids necessary for protein synthesis
and thus not only protein quantity but also quality is important.

Protein cannot be considered alone since there is a close interrelation between protein
and energy metabolism with reference to growth.
NIELS C. R. RAIHA, M.D., Ph.D.
University of Lund Department of Pediatrics
Malmo General Hospital, Sweden
Nestlé Nutrition Workshop Series 1994.
 Breastmilk vs Cows Milk
Concentration and Composition

1. Heine WE. Protein Metabolism during Infancy. Nestlé Nutrition Workshp Series. Vol 33. 1994.
2. Aminograms-Nestlé data on file, Nunspeet 2012.
3. Zhang Z et al., Nutrients. 2013;5(12):4800-21.
Ziegler et al 2002
 Breastmilk, Beyond Nutrition

several enzymes are actively taking

part in the digestion of human milk
proteins within the mammary gland,
including plasmin and/or trypsin,
elastase, cathepsin D, pepsin,
chymotrypsin, a glutamyl
endopeptidase-like enzyme, and
proline endopeptidase

Khaldi N, et al. Predicting the Important Enzymes in Human Breast Milk Digestion. J Agric Food Chem. 2014;62(29):7225-7232
 Human Milk Protein is Unique and Match Babies Needs

Newborns have lower protein digestion enzymes

Milk from healthy mothers contains
hundreds endogenous peptide. Stomach Low gastric acid production  higher pH1

Pepsin 5-fold lower concentration than adults1

Proteolytic enzyme
“In other words, the mother provides the
infant with not only dietary proteins but
also the means to digest them”3
Gastric acid secretion similar to adults by 6
months of age, when pepsin activity likely
becomes significant
Trypsin Lower concentration and activity than adults1
Chymotrypsin 10 – 16% of adult concentration1
Enterokinase 20% of the activity found in older children1

Referensi
1. Dallas et al, J Nutr Disord Ther 2012; 2. Hall, Textbook of Medical Physiology Sauwnders Elsevier 2011;
3.Dallas et al, J Mammary Gland Biol Neoplasia, 2015
… Where for Formula, there are few
types of protein
 What is Hydrolyzed Formula (HFs)
• Formulas contain cow milk proteins (CMPs) that are subjected to chemical and enzymatic hydrolysis to
reduce the molecular weight, the peptide size, and, consequently, the allergenicity of the proteins.
• The differentiation between eHFs and pHFs is by molecular weight profile and clinical demonstration of
reduced allergenicity.
• Whey or Casein are used for the hydrolysis process instead of whole CMP.

Cow’s milk based formulas with intact proteins 14 kD (α-lactabumin) to 67 kD (bovine serum albumin)

pHFs Oligopeptide  molecular weight generally <5 kD

(ranges between 3 and 10 kD)
18% peptide > 6 kD
eHFs >90% a molecular weight of < 3 kD
1 – 5% peptide > 3,5 kD
To be acts as an allergen Peptides to be in range 10-70 kD (mainly 10-40kD)

Vandenplas, 2014
pHFs were developed initially because of its reduced protein
allergenicity, which may decrease the occurrence of atopic diseases.
Middle East Consensus Statement on the Prevention, Diagnosis,
and Management of Cow’s Milk Protein Allergy

Vandenplas et al., Pediatr Gastroenterol Hepatol Nutr 2014 June 17(2):61-

pHF for normal growth &
development ?
Short- and long-term effects of feeding hydrolyzed protein infant
formulas on growth at 6 y of age: results from the German Infant
Nutritional Intervention (GINI) Study

Peter Rzehak, Stefanie Sausenthaler, Sibylle Koletzko, Dietrich Reinhardt, Andrea von
Berg, Ursula Kra ̈mer, Dietrich Berdel, Christina Bollrath, Armin Gru ̈bl, Carl Peter
Bauer, H-Erich Wichmann, and Joachim Heinrich for the German Infant Nutritional
Intervention Study Group

Design: a prospective, randomized, double-blind trial

World Health Organization–standardized BMI trajectories for 1840 infants
(pHF-W; eHF-W; eHF-C; CMF; Breastfed)

Am J Clin Nutr 2009;89:1846–56.

solid blue line, pHF-W (partially hydrolyzed whey); solid green line, eHF-W (extensively hydrolyzed
whey);
solid red line, eHF-C (extensively hydrolyzed casein); solid yellow line, CMF (cow-milk formula);
gray line, BF (exclusively breastfed for 16 wk);
solid blue line, pHF-W (partially hydrolyzed whey); solid green line, eHF-W (extensively hydrolyzed
whey);
solid red line, eHF-C (extensively hydrolyzed casein); solid yellow line, CMF (cow-milk formula);
gray line, BF (exclusively breastfed for 16 wk);
solid blue line, pHF-W (partially hydrolyzed whey); solid green line, eHF-W (extensively hydrolyzed
whey);
solid red line, eHF-C (extensively hydrolyzed casein); solid yellow line, CMF (cow-milk formula);
gray line, BF (exclusively breastfed for 16 wk);
solid blue line, pHF-W (partially hydrolyzed whey); solid green line, eHF-W (extensively hydrolyzed
whey);
solid red line, eHF-C (extensively hydrolyzed casein); solid yellow line, CMF (cow-milk formula);
gray line, BF (exclusively breastfed for 16 wk);
Conclusions:

To our knowledge, this is the first randomized trial investigating

both short- and long-term effects of partially and extensively
hydrolyzed formula (pHF-W, eHF-W, eHF-C), CMF, and
breastfeeding on growth in one trial.

Feeding with eHF-C led to a transient lower weight gain in the

first year of life.

No long-term consequences of different formulas on BMI were

observed.
A perspective on partially hydrolyzed protein infant
formula in nonexclusively breastfed infants
Yvan Vandenplas1, Zakiudin Munasir2, Badriul Hegar2, Dewi Kumarawati3, Ahmad
Suryawan4, Muzal Kadim2, Julistio Djais5, Ray Wagiu Basrowi6, Deni Krisnamurti6
1KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussel, Belgium, 2Department of Child Health, Faculty of Medicine,
Universitas Indonesia, Jakarta, 3Department of Child Health, Udayana University Medical School/Sanglah Hospital, Denpasar,
4Department of Child Health, Medical School, Unviersity of Airlangga, Surabaya, 5Department of Child Health, Medical School,
University of Padjadjaran, Bandung, 6Nestle Nutrition Institute, Jakarta, Indonesia
Although CMA is common, the symptoms are nonspecific and is not often diagnosed
properly.

This will cause a burden on the infant and the parents; therefore prevention will be
beneficial.

One strategy in non breastfed infants is the use of partially hydrolyzed formula (pHF).

Most guidelines recommend pHFs to prevent allergic disease, mainly atopic dermatitis (AD),
and CMA in non breastfed infants at high risk.

Based on an epidemiological study, approximately half of the infants who developed

allergies are not part of the at risk group.

This is because the non at risk group is significantly larger than the at risk group and the
non at risk infants have approximately 15% risk of developing allergies.
Based on the available data, pHFW can be considered as an option in all non breast fed term
healthy infants regardless of their allergy risk status.

From a cost/benefit perspective, the use of pHF is more cost effective than the use of standard
CMF, especially in preventing AD.

vandenplas, nutrients 2017

Conclusions
Breastfeeding is the best feeding for infants.
In non breastfed infants, CMF provides adequate nutrition and supports normal growth and development.

A pHFW is a formula with proven efficacy in reducing AD and is recommended in some guidelines for high risk
infants to prevent the occurrence of atopic disease.

Since the number of infants who develop allergies is larger in the non at risk group than in the at risk group,
pHF should not be limited to the at risk group.

pHF W meets all nutritional requirements and can be considered as an alternative to CMF with intact protein for
all non breastfed infants.

The use of this formula was also proven to be cost effective in preventing AD compared with standard CMF.

No data suggest that pHF is potentially harmful for healthy term infants.

Therefore, the use of pHFW for non breastfed and non at risk infants could be considered regardless of the allergy
risk status.