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Development of national consensus statements on food labelling interpretation and protein allocation in a low phenylalanine diet for PKU
Orphanet Journal of Rare Diseases volume 14, Article number: 2 (2019)
In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients.
In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added.
The statements incorporated controversial dietary topics including: a practical ‘scale’ for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU.
The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.
Phenylketonuria (PKU) is an inborn error of amino acid metabolism, due to deficiency or absence of the enzyme phenylalanine hydroxylase, leading to accumulation of blood and brain phenylalanine (Phe). Untreated, it will cause severe, irreversible neurological damage . Strict dietary management is the only available treatment option in the UK. The aim is to correct abnormal biochemistry by decreasing the Phe load on the affected pathway and supplementation with Phe -free L-amino acids or low Phe glycomacropeptide protein substitutes . The diet involves avoiding high protein foods (e.g. meat, fish, eggs, cheese, seeds, flour, bread and nuts), with strict control of moderate containing protein foods (e.g. cereals, potato, milk and some vegetables) to maintain blood Phe levels within target range [1, 3]. Several fruits and vegetables are low in Phe and are incorporated in the diet without limit . From weaning when solids are first introduced  and later with the ever growing convenience food market, patients with PKU and their caregivers need simple, consistent, easy-to-understand rules for calculating protein intake. A national dietetic re-appraisal of some of the practical dietary advice given to UK patients and families with PKU was necessary because of: the recent publication of European PKU guidelines identifying different criteria for the allocation of fruit and vegetables in a low Phe diet ; introduction of new species of fruits and vegetables; new European protein labelling legislation ; contradictory information available via social media; and increasing patient usage of manufactured foods.
The British Inherited Metabolic Diseases (BIMDG) Dietitians Group, using the Delphi method set out to agree a set of practical statements about the classifications of foods in a low Phe diet. The Delphi process is a tool used to gain a majority decision in a structured or systematic manor. It helps secure a collective view from a panel of experts about complex issues or problems where there is little or no definitive evidence [7, 8]. Experts respond to questionnaires over several rounds with a facilitator coordinating and summarising responses for feedback. Responses and feedback from each expert, guide the questions for further rounds. With each successive round the number of questions declines as the group moves toward consensus.
To develop consensus statements about the practical allocation of foods and interpretation of protein food labelling in a low Phe diet for the management of PKU in the UK using the Delphi method to generate consensus.
In November 2015, BIMDG dietitians convened to discuss the allocation of foods and interpretation of food labeling with the aim of developing consensus statements for PKU. A multiple-choice questionnaire, comprising 14 questions about dietary advice to UK patients or caregivers regarding the allocation of different foods (allowed without measurement, not allowed, or allowed as part of Phe exchanges) and interpretation of protein from food labels, was distributed to 70 BIMDG dietitians from 30 centres treating individuals with PKU. The results of this questionnaire identified 7 specific areas where dietetic practice was variable, leading to contradictory advice being issued to patients and caregivers. These 7 areas are identified in Table 1.
Following a round table discussion of these results at a BIMDG dietitians meeting, 16 consensus statements for the practical dietary management of PKU were put forward and agreed in Phase 1. In Phase 2 a further 6 statements, and in Phase 3 one final statement was proposed. The Delphi method was then used to gain consensus from the BIMDG dietitians about each of the statements. The lead author acted as facilitator.
The 23 consensus statements on practical dietary management were circulated to all BIMDG dietitians by email. A written response of agreement or disagreement with each statement was then returned to the facilitator for analysis. After each round of circulation, a telephone conference was held with the BIMDG dietitians to provide collective feedback and the draft consensus statements were further adapted. Modified statements were then recirculated to the BIMDG dietitians with additional questions until a majority decision (> 60%) was obtained on each statement. Dietitians were given 8 weeks to respond in each Delphi round.
Approval of the final consensus statements was sought and received by the UK National Society for PKU (NSPKU).
Phase 1: Round 1 of Delphi method
The 16 draft consensus statements on practical dietary management were prepared with accompanying notes explaining their rationale. They were then distributed for approval or non-approval of each statement to all BIMDG dietitians (73 dietitians: 43 paediatric practice, 20 adult practice and 10 caring for both adult and paediatric patients; from 30 inherited metabolic disorder [IMD] centres).
Replies were received from 40 dietitians (55% of BIMDG dietitians, from 23 centres, 77%) and results were distributed to all dietitians within 5 months of initial circulation. After the first round, there was majority consensus by paediatric dietitians (≥86%; n = 29) and dietitians working in adult practice (≥65%; n = 17) for all 16 statements. At a BIMDG dietitians group teleconference, minor modifications were made to a small number of the consensus statements and 14 of the 16 statements were formerly agreed by paediatric dietitians (Tables 2 and 3).
However, two of the statements generated considerable debate, so it was decided to further explore individual opinions on these 2 statements following additional investigation into the Phe content of the products. In addition, there was some disparity among dietitians working in adult practice in relation to maternal patients with PKU and Phe consumption from fruits and vegetables permitted without measurement. Consequently, it was decided that for round 2 of the Delphi process, paediatric dietitians and dietitians working in adult practice would separate to examine issues independently.
Phase 1: Round 2 of Delphi method
The remaining 2 ‘non-agreed’ draft consensus statements (statement 1: the upper protein content of soya sauces allowed as an exchange-free food; and statement 2: the allocation of fruits and vegetables containing Phe content from 76 to 99 mg per 100 g weight) were modified following examination of barriers to acceptance (Table 2). An in-depth investigation was conducted about the protein content of all commercial soya sauces available to purchase as well as issuing analysis about the Phe content of fruits and vegetables. These 2 consensus statements were then recirculated to the BIMDG dietitians; with 3 possible options for each statement.
Soya sauce was considered differently to other table top sauces. Its protein content is highly variable from < 0.5 g per 100 ml up to 15 g per 100 ml. Soya sauce option 1: protein ≤ 1 g per 100 ml is exchange-free, was consistent with the statement for wet cooking sauces but allowed very little brand choice; option 2: protein ≤ 1.5 g per 100 ml is exchange-free, allowed more choice but was inconsistent with statements for other foods; and option 3: up to 2 tablespoons per day of any soya sauce, allowed a wide choice of brands but could lead to a higher protein intake.
For fruit and vegetables with a Phe content between 76 to 99 mg per 100 g: option 1: count as part of the 50 mg Phe exchange system, considered that their uncontrolled consumption may increase dietary Phe intake considerably, but may be difficult to enforce in patients already established on dietary management who do not currently restrict their intake. Option 2: permit only one serving daily of any fruits and vegetables in this category, but calculate Phe intake from any additional servings of fruits and vegetables from this category, overcame some of the issues associated with option 1, but was complex for both dietitians and patients or caregivers. Option 3: permit 1 portion daily of any one of the fruits and vegetable in this category, was the existing guidance and whilst aiming to control overall intake, it did not consider increased opportunities for consumption of some of the more novel forms of these fruits and vegetables e.g. vegetable rice, vegetable pasta. An additional question was asked in this round (Table 2) about the acceptance of a standard exchange weight i.e. 60 g for fruits and vegetables with a Phe content between 76 and 100 mg per 100 g.
For BIMDG paediatric dietitians, option 2 for the soya sauce consensus statement received a majority response (67% of respondents; n = 24/36) and was agreed; but opinion was divided between the 3 options for the final consensus statement on fruits and vegetables containing Phe content from 76 to 99 mg per 100 g weight. However, there was consensus on the need for a standard exchange weight for these fruits and vegetables (Table 4). The dietitians working in adult practice continued to debate both questions but did not reach consensus at this round.
Phase 1: Round 3 of Delphi method
The remaining ‘non-agreed’ consensus statement concerning the allocation of fruits and vegetables was reissued with the 2-options scoring highest in the previous round. Option 1 statement was finally agreed by 64% (n = 25) of paediatric dietitians and endorsed at the dietitians BIMDG teleconference in February 2017.
In the final Delphi round, 75 % of dietitians working in adult practice (n = 15) agreed with the 16 consensus statements for adult patients following diet, concluding that consistency in dietary care in the transition from paediatric to adult services was important. However, 40% (n = 8) of dietitians working in adult practice proposed that separate maternal PKU consensus statements were required.
The initial consensus statements were endorsed by the UK National Society for PKU (NSPKU) in April 2017.
Phase 2: Round 1of Delphi method
Additional food items not covered by the initial statements were identified in the 6 months following completion of Phase 1, so 6 new statements on: low protein milks, soups, coconut desserts, coconut products, ice-cream and gelatine containing products, were distributed with accompanying notes. Replies were received from 25 dietitians (from 18 centres) and results were discussed at a BIMDG dietitians group teleconference in January 2018. There was majority consensus by dietitians (≥76%) for all but the low protein milks statement which it was agreed needed redefining (Table 2).
Phase 2: Round 2 of Delphi method
Two amended statements on plant milks and low protein milk replacements were sent out in February 2018 and results discussed and agreed at a teleconference in May 2018. There were 30 replies and 77% (n = 23) agreed with the plant milks statement and 80% (n = 24) with the low protein milk replacements statement (Table 2). Other low protein special foods were also discussed in detail and it was agreed that the initial statement in Phase 1 required elaboration due to significant protein containing ingredients in some products.
Phase 3: Round 1 of Delphi method
A statement regarding low protein special foods was distributed along with information on their content in May 2018. Results were conclusive and this along with Phase 2 statements were agreed at a BIMDG dietitians meeting in June 2018. A summary of all agreed guidelines was issued in July 2018 and endorsed by the NSPKU (Table 5).
National consensus statements on the practical interpretation of dietary management in PKU are central to ensuring consistent advice is given to all families and patients with PKU. We have systematic agreement on many basic dietary rules and definitions which have received united support from BIMDG dietitians. Using the Delphi method allowed all BIMDG dietitians to have the opportunity to give their opinion and influence several areas of dietary management in PKU where scientific evidence was unavailable to dictate practice. For most of the statements, clear consensus was reached in the first round of Delphi discussions, leaving only 4 controversial statements requiring more extensive discussion and negotiation. The process we have undertaken should lead to harmonization and consistency of dietetic practice in PKU with less confusion for professionals, patients and their families. Adoption of these consensus statements by the national patient’s society, NSPKU, will enable uniform written dietary information to be available for all patients. Further adaptation of these statements is necessary for maternal PKU, where dietary management practices are particularly rigorous. This exercise will be taken forward by the BIMDG dietitians working in adult practice.
The advantage of the Delphi method is that it involves the collective knowledge of a group of experts which is likely to be better than that of each individual; comparing, contrasting, challenging and complementing each other . The process is directed, impartial, helps engender group ownership, encourages consensus among individuals with diverse views and is an alternative to conventional meetings where strong personalities, status and group pressures can influence individual responses . It was clear that every opinion was valued and would be important in influencing the final decisions. Because this method is structured and focused, it can avoid much of the counterproductive digressions identifiable in face-to-face group discussions . Due to the combined contribution of all members, varying ideas and viewpoints were generated and these further directed later responses.
The Delphi Method did have some limitations. Being a qualitative method, it is considered subjective. However, in our consensus statements, only best practice opinion was available to support any of the specific decisions reached; when new scientific evidence is available these statements will be challenged. Also, 70 dietitians participated, which could be considered a limitation. However, the number of experts chosen was designed to be inclusive of all centres and dietitians in the UK who were members of the BIMDG dietitians group. Another drawback of the process was the tendency for participants to maintain the status quo rather than voting for change. For example, for two of the consensus statements, despite good initial agreement in round 1, further discussion identified the impracticality of the statements which prompted the generation of 3 possible options for round 2. A further limitation was the lack of response from some members. Unfortunately, this was unavoidable due to maternity leave, job changes and retirements occurring during the 18-month period of the project. Some dietetic non-responders were new to the IMD specialty or were from centres with fewer patients and or less clinical experience and may have been reluctant to respond due to uncertainty or a lack of definitive opinion. Despite some non-responding dietitians, most UK IMD centres were represented in each round.
In conclusion, this process of agreement between BIMDG dietitians across the UK will enable the introduction of consistent, easy-to-understand rules for calculating protein intake for professionals and patients with PKU. Both dietitians working in paediatric and adult services have endorsed these consensus statements which should contribute to a smooth transition between services, maintaining uniformity of information across all ages. Modification of the consensus statements may be warranted for maternal PKU patients requiring more rigorous dietary restriction. It will be important to perform an evaluation of the interpretation of these statements by dietitians and patients in clinical practice. Overall these consensus statements contribute to harmonising dietary advice offered to British PKU patients. Longitudinal monitoring of their application, acceptance and adherence by health professionals and patients or caregivers is essential.
British Inherited Metabolic Diseases Group
Inherited Metabolic Diseases
National Society for Phenylketonuria
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No funding was required as this project was conducted as part of routine service by all the dietitians involved.
Availability of data and materials
The supporting datasets analysed during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate
Consent for publication
AD – research funding from Vitaflo; financial support from Nutricia & Vitaflo to attend study days & conferences.
CE – honoraria & financial support from Vitaflo & Nutricia to attend study events and conferences.
SE - research funding from Nutricia; financial support from Nutricia & Vitaflo to attend study days & conferences.
SF – funding for conferences & study days from Nutricia & Vitaflo; advisory board participation for Nutricia & Biomarin.
SH - financial support from Nutricia & Vitaflo to attend study days & conferences.
AMac - research funding & honoraria from Nutricia, Vitaflo International & Merck Serono, Member of European Nutrition Expert Panel (Merck Serono international), member of Sapropterin Advisory Board (Merck Serono international), member of the Advisory Board Element (Danone-Nutricia).
CN - financial support from Nutricia & Vitaflo to attend study days & conferences.
LR – financial support from Nutricia & Vitaflo to attend study days & conferences.
RS - financial support from Nutricia & Vitaflo to attend study days & conferences.
KV – member of Nutricia Paediatric Metabolic Advisory Board.
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