EU LEGISLATION ON PRODUCTS USED IN THE MANAGEMENT OF INBORN ERRORS OF AMINO ACID METABOLISM
Food for special medical purposes (FSMP) is an important part of the restrictive diet used to manage inherited metabolic disorders (IMD). This article focuses on those FSMP used in the management of infants and children with inborn errors of amino acid metabolism (IEM).
These products are governed by legislation in the EU which has recently been updated, although there are remaining provisions within these rules that present issues for products such as protein substitutes (PS).
Initiation of a modified diet at diagnosis aims to ensure the best outcome for infants and children with IEM. Natural dietary protein is severely restricted and a PS is provided to meet essential requirements for protein and other nutrients in order to achieve acceptable metabolic control.
DIETARY MANAGEMENT IN EARLY INFANCY OF INBORN ERRORS OF AMINO ACID METABOLISM
In infancy, effective dietary management relies on a combination of restricted quantities of standard infant formula or breast milk and a specially adapted infant formula.
The specially adapted infant formulas for the management of IEM (which are categorised as FSMP) are based on amino acids rather than natural whole protein. To take phenylketonuria (PKU) as an example, the specially adapted formula contains no added phenylalanine, but provides the other essential and non-essential amino acids in combination with other nutrients to satisfy requirements. Dietary phenylalanine is restricted to 25% or less of normal intakes, and phenylalanine requirements are provided in the form of a standard infant formula or breast milk.
CHANGES TO EU LEGISLATION AFFECTING SPECIALLY ADAPTED INFANT FORMULAS FOR IEM
In the same way as standard infant formulas, the specially adapted infant formulas are governed by EU legislation. Updated EU legislation was introduced in February 2016, with transitional arrangements in place until February 2020, governing the labelling, promotion and essential composition of FSMP, infant formula and followon formula. There are two separate Regulations,1,2 which replace similar rules that had been in place in the EU.3,4 In terms of the energy and macronutrient content of FSMP for infants, the new EU Regulation2 requires that FSMP for infants should be based on the composition of standard infant formula,1 whilst taking into account any adaptations required for the intended use of the product. For standard infant formulas, the maximum limit for protein has been reduced, from 3g/100kcal to 2.5g/100kcal and to 2.8g/100kcal for infant formula based on soy/hydrolysed protein.
Protein requirements in IEM are typically higher than those for healthy infants. For example, recently published European clinical guidelines for the management of PKU,5 recommend that protein intake should supply the age-related safe levels of protein intake established by the World Health Organisation, with an additional 40% provided by L-amino acids. As a consequence, infant formula for the
management of IEM usually has a higher protein content to meet the increased needs of these infants. Under the provisions in the new EU legislation, an evidence based deviation from the compositional standard for infant formula would be accepted, as a higher protein content is necessary for the effective management of IEM in infancy.
In the updated EU legislation, no changes have been made to the energy (60-70 kcal/100ml), fat (4.4-6g.0/100kcal) or carbohydrate (9-14g /100kcal) compositional standards for infant formula. The standards for essential fatty acids have been amended and docosahexaenoic acid (DHA) must be added to all infant formulas including specially adapted infant formulas. Under the previous provisions, DHA could be added up to a maximum limit, but there was no minimum limit.
In common with the previous legislative provisions, the new rules have set compositional standards for vitamins and minerals. The updated minimum compositional standards for FSMP for infants are the same as those that apply to standard infant formula. The maximum compositional standards for many micronutrients are higher for FSMP for infants than for standard infant formula. This allows for the adaptation of products to address specific nutritional considerations for infants affected by the varying medical conditions for which FSMP are required.
DIETARY MANAGEMENT IN CHILDHOOD
Beyond infancy, children with IEM continue to require specially adapted products to meet their nutritional requirements in the form of a PS, typically fortified with a wide range of vitamins and minerals. The weaning phase and feeding children with IEM can be especially challenging as food and, in particular, PS refusal, is common and the restrictive feeding choices are often burdensome for anxious parents.6 Given that the diet for IEM excludes sources of animal protein and many other foods are restricted, many nutrients are in limited supply and patients rely on supplementary sources of nutrients provided by their PS to meet their nutritional requirements.
PROBLEMS FOR PS COMPLYING WITH THE COMPOSITIONAL STANDARDS
PS are FSMP and come under the same EU regulation as specially adapted infant formulas.2
These products are required to comply with a separate set of compositional standards for FSMP not intended for infants, with the caveat that compliance with the standards would not be required where the intended use of the product precludes this.
This category of FSMP includes products designed for the dietary management of a wide range of medical conditions, in some cases to meet nutritional requirements in full, or, as in the case of PS, designed to supplement the diet. In common with the standards for FSMP for infants, these compositional standards are based on the amounts of nutrients provided per unit of energy. Whilst this approach is logical for FSMP for infants and products such as oral nutrition supplements, it presents compliance issues for products such as PS, as recommendations for PS intakes are based on protein requirements rather than energy requirements.
In recent years, manufacturers have developed PS with reduced energy by decreasing the amount of carbohydrate these products contain amid growing concerns about the prevalence of obesity among patients. Most PS will provide quantities of many micronutrients in excess of the maximum compositional standards when assessed on the basis of the quantity of these micronutrients per 100kcal of the product.7 However, when the levels of micronutrients are assessed on the basis of protein requirements, as they are prescribed, the amounts provided by products should be nutritionally appropriate. This is an example of where the intended use of the product (to meet protein and micronutrient requirements) precludes compliance with compositional standards based on a product’s energy content. That said, it would seem to be a more sensible approach if the legislation made specific provision for these types of FSMP to ensure that products are safe and effective.7
Dietary management of IEM has been very successful in ensuring excellent outcomes for children affected by these conditions. In the UK, the new-born screening programme was extended in 2014 to include four new conditions (maple syrup urine disease, homocystinuria, glutaric acidurea Type 1, isovaleric acidaemia), allowing management of infants to commence in the first few weeks of life rather than following a period of acute illness, sometimes requiring intensive care.
