Nutritional safety and suitability of a specific protein hydrolysate derived from a whey protein concentrate and used in an infant formula and follow-on formula manufactured from hydrolysed protein by FrieslandCampina Nederland B.V.

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from a whey protein concentrate and used in an infant and follow-on formula manufactured by FrieslandCampina Nederland B.V., which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.4 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to a growth equivalent to a formula manufactured from intact cow's milk protein with a protein content of 2.1 g/100 kcal. Data on gastrointestinal tolerance of the formula did not raise any concerns. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. Given that it is consumed with complementary foods and the protein source is nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.4 g/100 kcal protein and complies with the compositional criteria of Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by HIPP-Werk Georg Hipp OHG (dossier submitted by meyer.science GmbH).

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in infant and follow-on formula by HIPP-Werk Georg Hipp OHG. The dossier that was submitted to the European Commission aimed at requesting an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 1.9 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to growth equivalent to a formula manufactured from intact cow's milk protein with the same protein content. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 1.9 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

Scientific and technical guidance for the preparation and presentation of a dossier for evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates (Revision 1).

[Table: see text] Following a request from the European Commission, EFSA was asked to provide scientific and technical guidance for the preparation and presentation of a dossierfor evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow-on formulae manufactured from protein hydrolysates with respect to the nutritional safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specificdossiers, and in the light of applicable Unionguidelines and legislation. The guidance was adopted by the Panel on Dietetic Products, Nutrition and Allergies on 5 April 2017.Upon request from the European Commission in 2020, it has been revised to inform food business operators of the new provisions in the pre-submission phase and in the procedure set out in the General Food Law, as amended by the Transparency Regulation. This revised guidance applies to all dossiers submitted as of 27 March 2021 and shall be consulted for the preparation of dossiers intended to be submitted from that date onwards. For dossiers submitted prior to 27 March 2021, the previous guidance, published in May 2017 remains applicable.

Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by Danone Trading ELN B.V.

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in an infant and follow-on formula by Danone Trading ELN B.V, which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.3 g/100 kcal and consumed as the sole source of nutrition by infants for 3.5 months led to growth equivalent to a formula manufactured from intact cow's milk protein (2 g protein/100 kcal). No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.3 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

Guidance for the Conduct and Reporting of Clinical Trials of Breast Milk Substitutes.

Importance: Breast milk substitutes (BMS) are important nutritional products evaluated in clinical trials. Concerns have been raised about the risk of bias in BMS trials, the reliability of claims that arise from such trials, and the potential for BMS trials to undermine breastfeeding in trial participants. Existing clinical trial guidance does not fully address issues specific to BMS trials. Objectives: To establish new methodological criteria to guide the design, conduct, analysis, and reporting of BMS trials and to support clinical trialists designing and undertaking BMS trials, editors and peer reviewers assessing trial reports for publication, and regulators evaluating the safety, nutritional adequacy, and efficacy of BMS products. Design, Setting, and Participants: A modified Delphi method was conducted, involving 3 rounds of anonymous questionnaires and a face-to-face consensus meeting between January 1 and October 24, 2018. Participants were 23 experts in BMS trials, BMS regulation, trial methods, breastfeeding support, infant feeding research, and medical publishing, and were affiliated with institutions across Europe, North America, and Australasia. Guidance development was supported by an industry consultation, analysis of methodological issues in a sample of published BMS trials, and consultations with BMS trial participants and a research ethics committee. Results: An initial 73 criteria, derived from the literature, were sent to the experts. The final consensus guidance contains 54 essential criteria and 4 recommended criteria. An 18-point checklist summarizes the criteria that are specific to BMS trials. Key themes emphasized in the guidance are research integrity and transparency of reporting, supporting breastfeeding in trial participants, accurate description of trial interventions, and use of valid and meaningful outcome measures. Conclusions and Relevance: Implementation of this guidance should enhance the quality and validity of BMS trials, protect BMS trial participants, and better inform the infant nutrition community about BMS products.

Dietary reference values for chloride.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) has derived dietary reference values (DRVs) for chloride. There are no appropriate biomarkers of chloride status, no balance studies and no adequate evidence on the relationship between chloride intake and health outcomes that can be used to set DRVs for chloride. There is a close relationship between sodium and chloride balances in the body. Sodium chloride is the main source of both electrolytes in European diets and similar urinary excretion levels of sodium and chloride (on a molar basis) are typically observed in Western populations. Hence, the Panel considered that reference values for chloride can be set at values equimolar to the reference values for sodium for all population groups, and are as follows: 1.7 g/day for children aged 1-3 years, 2.0 g/day for children aged 4-6 years, 2.6 g/day for children aged 7-10 years, 3.1 g/day for children aged 11-17 years and 3.1 g/day for adults including pregnant and lactating women. Consistent with the reference values for sodium, these levels of chloride intake are considered to be safe and adequate for the general EU population, under the consideration that the main dietary source of chloride intake is sodium chloride. For infants aged 7-11 months, an adequate intake of 0.3 g/day is set.

Dietary reference values for sodium.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) derived dietary reference values (DRVs) for sodium. Evidence from balance studies on sodium and on the relationship between sodium intake and health outcomes, in particular cardiovascular disease (CVD)-related endpoints and bone health, was reviewed. The data were not sufficient to enable an average requirement (AR) or population reference intake (PRI) to be derived. However, by integrating the available evidence and associated uncertainties, the Panel considers that a sodium intake of 2.0 g/day represents a level of sodium for which there is sufficient confidence in a reduced risk of CVD in the general adult population. In addition, a sodium intake of 2.0 g/day is likely to allow most of the general adult population to maintain sodium balance. Therefore, the Panel considers that 2.0 g sodium/day is a safe and adequate intake for the general EU population of adults. The same value applies to pregnant and lactating women. Sodium intakes that are considered safe and adequate for children are extrapolated from the value for adults, adjusting for their respective energy requirement and including a growth factor, and are as follows: 1.1 g/day for children aged 1-3 years, 1.3 g/day for children aged 4-6 years, 1.7 g/day for children aged 7-10 years and 2.0 g/day for children aged 11-17 years, respectively. For infants aged 7-11 months, an Adequate Intake (AI) of 0.2 g/day is proposed based on upwards extrapolation of the estimated sodium intake in exclusively breast-fed infants aged 0-6 months.

Appropriate age range for introduction of complementary feeding into an infant's diet.

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) revised its 2009 Opinion on the appropriate age for introduction of complementary feeding of infants. This age has been evaluated considering the effects on health outcomes, nutritional aspects and infant development, and depends on the individual's characteristics and development. As long as foods have an age-appropriate texture, are nutritionally appropriate and prepared following good hygiene practices, there is no convincing evidence that at any age investigated in the included studies (< 1 to < 6 months), the introduction of complementary foods (CFs) is associated with adverse health effects or benefits (except for infants at risk of iron depletion). For nutritional reasons, the majority of infants need CFs from around 6 months of age. Infants at risk of iron depletion (exclusively breastfed infants born to mothers with low iron status, or with early umbilical cord clamping (< 1 min after birth), or born preterm, or born small-for-gestational age or with high growth velocity) may benefit from earlier introduction of CFs that are a source of iron. The earliest developmental skills relevant for consuming pureed CFs can be observed between 3 and 4 months of age. Skills for consuming finger foods can be observed in some infants at 4 months, but more commonly at 5-7 months. The fact that an infant may be ready from a neurodevelopmental perspective to progress to a more diversified diet before 6 months of age does not imply that there is a need to introduce CFs. There is no reason to postpone the introduction of potentially allergenic foods (egg, cereals, fish and peanut) to a later age than that of other CFs as far as the risk of developing atopic diseases is concerned. Regarding the risk of coeliac disease, gluten can be introduced with other CFs.

Update of the tolerable upper intake level for vitamin D for infants.

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants (≤ 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta-regression analysis of collected data, to derive a dose-response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 µg/day for infants aged up to 6 months and set a UL of 35 µg/day for infants 6-12 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 µg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 µg/100 kcal may lead some infants to receive an intake above the UL of 25 µg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4-12 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake.

Diet and Lifestyle Before and During Pregnancy - Practical Recommendations of the Germany-wide Healthy Start - Young Family Network.

Diet and exercise before and during pregnancy affect the course of the pregnancy, the child's development and the short- and long-term health of mother and child. The Healthy Start - Young Family Network has updated the recommendations on nutrition in pregnancy that first appeared in 2012 and supplemented them with recommendations on a preconception lifestyle. The recommendations address body weight before conception, weight gain in pregnancy, energy and nutritional requirements and diet (including a vegetarian/vegan diet), the supplements folic acid/folate, iodine, iron and docosahexaenoic acid (DHA), protection against food-borne illnesses, physical activity before and during pregnancy, alcohol, smoking, caffeinated drinks, oral and dental hygiene and the use of medicinal products. Preparation for breast-feeding is recommended already during pregnancy. Vaccination recommendations for women planning a pregnancy are also included. These practical recommendations of the Germany-wide Healthy Start - Young Family Network are intended to assist all professional groups that counsel women and couples wishing to have children and during pregnancy with uniform, scientifically-based and practical information.

Scientific and technical guidance for the preparation and presentation of an application for authorisation of an infant and/or follow-on formula manufactured from protein hydrolysates.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to provide scientific and technical guidance for the preparation and presentation of applications for authorisation of infant and/or follow-on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow-on formulae manufactured from protein hydrolysates with respect to the safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specific applications for authorisation, and in the light of future Community guidelines and legislation. The NDA Panel endorsed a draft of this scientific opinion on 14 December 2016 for public consultation. The draft document has been revised and updated according to the comments received, where appropriate.

Scientific Opinion on the safety and suitability for use by infants of follow-on formulae with a protein content of at least 1.6 g/100 kcal.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on the safety and suitability for use by infants of follow-on formulae (FOF) based on cow's milk intact protein with a protein content of at least 1.6 g/100 kcal (rounded value) that meet otherwise the requirements of relevant EU legislation. If the formula under evaluation is considered to be safe and suitable for use by infants, the NDA Panel is also asked to advise on whether FOF based on goat's milk intact protein, soy protein isolates or protein hydrolysates are also safe and suitable for infants under the same conditions. The Panel concludes that the use of FOF with a protein content of at least 1.6 g/100 kcal from either intact cow's milk protein or intact goat's milk protein otherwise complying with the requirements of relevant EU legislation is safe and suitable for healthy infants living in Europe with an intake of complementary foods of a sufficient quality. This conclusion does not apply to infant formula (IF). The Panel also concludes that the safety and suitability of FOF with a protein content of at least 1.6 g/100 kcal manufactured from either protein hydrolysates or soy protein isolates cannot be established with the available data. The same conclusion applies to IF. The NDA Panel endorsed a draft of this scientific opinion on 14 December 2016 for public consultation. The draft document has been revised and updated according to the comments received, where appropriate.

Dietary reference values for vitamin K.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is suitable by itself to derive DRVs for vitamin K. Several health outcomes possibly associated with vitamin K intake were also considered but data could not be used to establish DRVs. The Panel considers that average requirements and population reference intakes for vitamin K cannot be derived for adults, infants and children, and therefore sets adequate intakes (AIs). The Panel considers that available evidence on occurrence, absorption, function and content in the body or organs of menaquinones is insufficient, and, therefore, sets AIs for phylloquinone only. Having assessed additional evidence available since 1993 in particular related to biomarkers, intake data and the factorial approach, which all are associated with considerable uncertainties, the Panel maintains the reference value proposed by the Scientific Committee for Food (SCF) in 1993. An AI of 1 µg phylloquinone/kg body weight per day is set for all age and sex population groups. Considering the respective reference body weights, AIs for phylloquinone are set at 70 µg/day for all adults including pregnant and lactating women, at 10 µg/day for infants aged 7-11 months, and between 12 µg/day for children aged 1-3 years and 65 µg/day for children aged 15-17 years.

Dietary Reference Values for riboflavin.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for riboflavin. The Panel considers that the inflection point in the urinary riboflavin excretion curve in relation to riboflavin intake reflects body saturation and can be used as a biomarker of adequate riboflavin status. The Panel also considers that erythrocyte glutathione reductase activation coefficient is a useful biomarker, but has limitations. For adults, the Panel considers that average requirements (ARs) and population reference intakes (PRIs) can be determined from the weighted mean of riboflavin intake associated with the inflection point in the urinary riboflavin excretion curve reported in four intervention studies. PRIs are derived for adults and children assuming a coefficient of variation of 10%, in the absence of information on the variability in the requirement and to account for the potential effect of physical activity and the methylenetetrahydrofolate reductase 677TT genotype. For adults, the AR and PRI are set at 1.3 and 1.6 mg/day. For infants aged 7-11 months, an adequate intake of 0.4 mg/day is set by upward extrapolation from the riboflavin intake of exclusively breastfed infants aged 0-6 months. For children, ARs are derived by downward extrapolation from the adult AR, applying allometric scaling and growth factors and considering differences in reference body weight. For children of both sexes aged 1-17 years, ARs range between 0.5 and 1.4 mg/day, and PRIs between 0.6 and 1.6 mg/day. For pregnant or lactating women, additional requirements are considered, to account for fetal uptake and riboflavin accretion in the placenta during pregnancy or the losses through breast milk, and PRIs of 1.9 and 2.0 mg/day, respectively, are derived.

The timing of introduction of complementary foods and later health.

Complementary food is needed when human milk (or infant formula) alone is no longer sufficient for nutritional reasons. The timing of introduction needs to be determined on an individual basis although 6 months of exclusive breastfeeding can be recommended for most healthy term infants. Solid foods are intended to 'complement' ongoing breastfeeding with those dietary items whose intake has become marginal or insufficient. Both breastfeeding and complementary feeding can have direct or later consequences on health. Possible short-term health effects concern growth velocity and infections while possible long-term effects may relate to obesity, cardiovascular disease, autoimmunity (celiac disease and type 1 diabetes) and atopic disorders. For most of these it is impossible on the basis of the available evidence to conclude on the age when risks related to the start of complementary feeding are lowest or highest, with the possible exception of infections and early growth velocity. For undesirable health consequences, whilst potential mechanisms are recognized, the evidence from mostly observational studies is insufficient and requires more and prospective research. While the 6-month goal is desirable, introduction of suitable complementary food after 4 completed months with ongoing breastfeeding can be considered without adverse health consequences for infants living in affluent countries. Even less evidence on the consequences of the timing of complementary food introduction is available for formula-fed infants.

Growing-up milk: a necessity or marketing?

Growing-up milk (GUM) products intended for children between 1 and 3 years of age are increasingly being introduced into the diets of young children. Although not a necessity for adequate nutrition of that age group, they can compensate for nutritional deficiencies which may occur in the transition phase of infant nutrition to family food, particularly when bad dietary patterns prevail in the family. For that purpose, GUM should be composed to decrease the overall protein intake which tends to be higher than the reference values for that age. This can be achieved by diluting fat-reduced cow's milk to a protein level comparable to infant or follow-on formulae and by partially replacing cow's milk fat with appropriate vegetable oils to increase the content of essential fatty acids and possibly by adding long-chain polyunsaturated fatty acids, docosahexaenoic and arachidonic acids whilst preserving the content of some minerals (such as calcium and phosphorus) and vitamins (B2 and B12) well represented in cow's milk. The content of iron, iodine, zinc and the vitamins A and D should be the same as in a follow-on formula. Based on available evidence, GUM should not be promoted as a necessity in the nutrition of young children.

Critical appraisal of the assessment of benefits and risks for foods, 'BRAFO Consensus Working Group'.

BRAFO, Benefit-Risk Analysis for Foods, was a European Commission project funded within Framework Six as a Specific Support Action and coordinated by ILSI Europe. BRAFO developed a tiered methodology for assessing the benefits and risks of foods and food components, utilising a quantitative, common scale for health assessment in higher tiers. This manuscript reports on the implications of the experience gained during the development of the project for the further improvement of benefit-risk assessment methodology. It was concluded that the methodology proposed is applicable to a range of situations and that it does help in optimising resource utilisation through early identification of those benefit-risk questions where benefit clearly outweighs risk or vice versa. However, higher tier assessments are complex and demanding of time and resources, emphasising the need for prioritisation. Areas identified as requiring further development to improve the utility of benefit-risk assessment include health weights for different populations and endpoints where they do not currently exist, extrapolation of effects from studies in animals to humans, use of in vitro data in benefit-risk assessments, and biomarkers of early effect and how these would be used in a quantitative assessment.