3.1. Participants
Sixteen semi-structured interviews were carried out with parents/caregivers of children with PKU (8 females, 8 males), who had been diagnosed by newborn screening. All had transitioned from a second stage semi-solid weaning protein substitute to an age-appropriate liquid or powder protein substitute. Ten interviews were with the mother only, and six were joint interviews with both mother and father. Demographic information and clinical characteristics of children are presented in Table 2. The median blood phenylalanine concentrations of children remained within the reference ranges of 120–360 µmol/L (4): 12 months pre-protein substitute transition (median 215 µmol/L [range 110–340]), and 12 months post transition (median 240 µmol/L [range 130–390]).
Table 2. Demographic information and clinical characteristics of children with PKU.
Variable
|
Number of children (n=16)
|
Gender, n (%)
|
|
female
|
8 (50%)
|
male
|
8 (50%)
|
Child age, median (range)
|
|
at interview (years)
|
8 (5-11)
|
Birth order in the family, n (%)
|
|
first and only child
|
5 (31)
|
first born
|
4 (25)
|
second born
|
4 (25)
|
third born
|
2 (13)
|
fourth born
|
1 (6)
|
Blood phenylalanine levels in µmol/L, median (range)
|
|
12 months before the transition
|
215 (110-340)
|
12 months after the transition
|
240 (130-390)
|
Prescribed total protein intake, median (range)
|
|
total protein (g/day)
|
65 (49.0-83.0)
|
total protein (g/kg/day)
|
2.9 (1.8-3.6)
|
natural protein (g/day)
|
5.0 (3.0-20.0)
|
natural protein (g/kg/day)
|
0.2 (0.1-0.7)
|
protein equivalent intake from PS (g/day)
|
60.0 (45.0-80.0)
|
protein equivalent intake from PS (g/kg/day)
|
2.6 (1.7-3.3)
|
Abbreviations: n= number of patients; PS: protein substitute; g: gram; kg: kilogram.
3.2. Process of transitioning to third stage protein substitute
Table 3 describes the protein substitute transition process. All children (n=16) were taking semi-solid second stage protein substitutes before transitioning onto the third stage protein substitute. The majority (n=13, 81%) were transitioned to ready to drink liquid protein substitutes (e.g., PKU Cooler [Vitaflo International], PKU Air [Vitaflo International], PKU Lophlex [Nutricia]). One child (6%) was transitioned to cGMP powdered third stage protein substitute (PKU Sphere [Vitaflo International]), and n=2 (12%) a combination of a liquid and powdered third stage protein substitute (n=1 to PKU Cooler + PKU Sphere, and n=1 to PKU Air + PKU Express [Vitaflo International]).
The median age of commencement of the third stage protein substitute transition was 4.8 years (range 3.1-8.0 years). This process was started from 3 to 4 years of age in 31% (n=5/16), from 4 to 5 years in 25% (n=4/16), from 5 to 6 years in 38% (n=6), and at 8 years of age in 6% (n=1) of children. The time of transitioning to third stage protein substitute was commonly associated with nursery or school commencement. The median age of children fully transitioning to third stage protein substitute was 5.3 years (range 3.5-8.0).
In 56% (n=9/16) of children, the third stage liquid protein substitute was given in small volumes, gradually increased and offered in addition to usual protein substitute e.g., started at 10 ml/day and increased in 10 ml/daily increments at daily to weekly intervals until one full daily dose of protein substitute was established, and then it replaced a full dose of usual protein substitute. This was commonly conducted and supervised in nursery or school by teachers or teaching assistants. Of these children, the median duration of achieving one full dose of liquid protein substitute (around 90 ml) was 1 month (range 2 weeks to 4 months). In 13% (n=2/16) of children, the third stage liquid protein substitute immediately replaced one full dose of daily protein substitute. One child (patient 12) was reluctant to try the third stage protein substitute until aged 8 years and then transitioned immediately to the full dose, encouraged by her younger sister with PKU who had previously transitioned her protein substitute.
In some children (n=5/16, 31%), it took a substantial amount of time to fully transition to the full dose of third stage protein substitute (Table 3). One child (patient 7), who commenced on one daily dose of powdered third stage protein substitute at 5.4 years, fully transitioned to the prescribed dosage at 6.7 years of age. One patient (patient 15) transitioned to one daily dose of third stage liquid protein substitute at 4.3 years of age, refused more than one dose of liquid protein substitute, so the remaining doses were given as powdered third stage protein substitute, and by 6.9 years of age, he reached the full prescribed dosage of third stage protein substitute.
Some parents (n=4/16, 25%) reported fewer gastrointestinal problems and increased appetite after transitioning of their children to the third stage protein substitute. However, two parents (13%) reported poor tolerance such as gagging, and constipation related to third stage protein substitute.
Table 3. Third stage protein substitute transition history of children with PKU.
Patient No.
|
Gender
|
Type of second stage protein substitute
|
Type of third stage protein substitute
|
The age third stage protein substitute transition commenced (years)
|
The age third stage protein substitute transition finished
(years)
|
Duration
(months)
|
1
|
F
|
Semi-solid
|
Liquid
|
3.5
|
3.7
|
2
|
2
|
M
|
Semi-solid
|
Liquid
|
3.1
|
3.5
|
5
|
3
|
F
|
Semi-solid
|
Liquid
|
5.5
|
6.5
|
12
|
4
|
M
|
Semi-solid
|
Liquid
|
3.8
|
4.3
|
6
|
5
|
M
|
Semi-solid
|
Powder+Liquid†
|
5.2
|
6.6
|
17
|
6
|
M
|
Semi-solid
|
Liquid
|
5.3
|
5.3
|
0
|
7
|
F
|
Semi-solid
|
Powder
|
5.4
|
6.7
|
16
|
8
|
M
|
Semi-solid
|
Liquid
|
3.9
|
4.0
|
1
|
9
|
F
|
Semi-solid
|
Liquid
|
5.0
|
5.6
|
7
|
10
|
M
|
Semi-solid
|
Liquid
|
4.2
|
4.4
|
2
|
11
|
F
|
Semi-solid
|
Liquid
|
3.3
|
4.7
|
17
|
12
|
F
|
Semi-solid
|
Liquid
|
8.0
|
8.0
|
0
|
13
|
F
|
Semi-solid
|
Liquid
|
4.7
|
4.7
|
0
|
14
|
M
|
Semi-solid
|
Liquid
|
4.9
|
5.3
|
5
|
15
|
M
|
Semi-solid
|
Powder+Liquid‡
|
4.3
|
6.9
|
32
|
16
|
F
|
Semi-solid
|
Liquid
|
5.3
|
5.6
|
4
|
Abbreviations: M: Male; F: Female.
† Started transition onto cGMP powder and commenced on three doses of cGMP powder; the remainder were given as liquid protein substitute to ensure target blood phenylalanine levels were not exceeded.
‡ Started transition onto liquid, refused more than one dose of liquid so remaining doses were powdered protein substitutes concentrated in protein equivalent.
3.3. Qualitative Findings
Parents/caregivers reported a range of experiences about the protein substitute transition process and how this process could be improved. These findings were grouped into two broad categories: (1) facilitators and (2) barriers of the protein substitute transitioning process. Each category was subdivided into the following four groups of factors: (a) individual, (b) family/caregiver, (c) third stage protein substitute features, and (d) social/organizational. Figure 2 summarizes the perceived facilitators and barriers for each group. We also focused on parental suggestions on several strategies that could improve the protein substitute transition process.
3.3.1. Perceived facilitators during the transitioning to third stage protein substitute
Individual factors
Individual factors that successfully facilitated the protein substitute transition process included: (i) child motivation and (ii) poor experience with the second stage protein substitute. Some parents reported that their children showed signs of being willing to try third stage protein substitutes, and their desire for independence was an important motivator. ‘So a trigger here was growing independence and it was going to hinder her going away independently if she didn’t start taking…’ (P12, transitioning age 8.0 years).
Children who struggled with the second stage protein substitute appeared willing to transition to the third stage protein substitute. ‘He was happy to try the -third stage protein substitute- because he didn’t like his -second stage protein substitute-.’ (P10, transitioning age 4.4 years). ‘I think it all went quite smoothly really with her… Because of her hate of the -second stage protein substitute- the change went quite smoothly.’ (P13, transitioning age 4.7 years).
Family/Caregiver factors
Family/caregiver factors that facilitated the protein substitute transition process included: (i) knowledge of the transition process, (ii) a role model (sibling/cousin/friend with PKU), and (iii) behavioral strategies. All parents/caregivers said they knew their child would eventually transition to third stage protein substitutes, which enabled them to prepare for the change. Many parents reported being given adequate information by their dietitian before the transitioning process. ‘We knew what was coming - we could prepare ourselves for a change but we did not have to start worrying about it too soon.’ (P4, transitioning age 4.3 years). ‘It’s something I learnt along the way because, like, our dietitian always mentioned it to us about once he goes to school he’ll have to start on changing to something more appropriate for his age.’ (P15, transitioning age 6.9 years).
Some of the children were influenced by an older sibling or cousin who had gone through the same process. ‘and because he’s got an older brother… he wants to be that step older all the time…’ (P2, transitioning age 3.5 years). ‘I think it made it easier from our point of view because we’ve got two elder kids in the house with PKU…so he’d seen his brother and sister have it…so he knew that it was something that he had to have.’ (P8, transitioning age 4.0 years).
Parents reported various behavioral strategies they used to facilitate the protein substitute transition process: encouragement and child rewards, a persistent and resolute approach, establishing a time routine and keeping a supply of the third stage protein substitute at home to get the child used to its appearance and taste from an early age. Parents often stated that encouraging their children by saying they were now a big boy or girl was helpful. Most parents reported offering rewards such as stickers, reward charts, or football cards to encourage the child for protein substitute change. Parents also used devices such as stopwatches and timers to help. Parents consistently emphasized that their children eventually adapted well to the change. ‘Yeah he got upset. Yeah he sort of resisted it. We just had to persevere with it…’ (P8, transitioning age 4.0 years). Parents reported that the slow transition and not forcing the child made the transition easier. They said that having a good routine helped so it became a regular part of a day. ‘We didn’t ever push him… any faster than he wanted to go… and I think, if we had done, he may well have pushed back and completely said no.’ (P2, transitioning age 3.5 years). Some parents reported that keeping third stage protein substitute samples at home helped their children become familiar with the products. ‘Having samples at house did help a bit because we kept trying him with it.’(P15, transitioning age 6.9 years).
Third stage protein substitute related factors
The third stage protein substitute related factors that facilitated the transition to a third stage protein substitute were: (i) ease of preparation, (ii) anticipation of increasing child independence, (iii) lower parent workload, (iv) improved tolerance, (v) attractive packaging, (vi) better taste and smell, and (vii) improved appetite.
Most parents reported that third stage liquid protein substitutes reduced parental workload, saved time, and were generally effortless to prepare. It was better when away from the home as there was no need to take scales, water, or spoons. ‘… it's easy when you are out and about that you can just, you know, shake it and open it …’ (P14, transitioning age 5.3 years).
Some parents were satisfied because third stage protein substitutes gave more independence to their children and they were less socially isolated at school. ‘Giving her more independence really, especially when she’s at school… She can get involved and her friends actually think it’s really cool they think she’s having a milkshake. So you know, she can sit in the class and have it, she doesn’t feel…different.’ (P7, transitioning age 6.7 years).
Parents also reported that the third stage protein substitute tasted and smelt better and had increased flavor options. Some parents also reported improved tolerance with fewer gastrointestinal problems and increased appetite. ‘I think one of the things that probably was a turning point on his liquid pouch was that he did start eating better. He has more of an appetite.’ (P6, transitioning age 5.3 years). ‘She’s got much less tummy ache on the third stage protein substitute.’ (P9, transitioning age 5.6 years).
Social/Organizational factors
Social and organizational factors that facilitated the protein substitute transition process included: (i) dietetic plans and guidance, (ii) school and teacher support, (iii) PKU social events, and (iv) educational materials and written resources.
All parents expressed satisfaction with the plans and guidance provided by the dietetic team during the transition process. Keeping to the instructions given by their dietitian was critical and reduced parental stress. ‘We’ve always had great support. Yeah the dietitian was at the forefront of us changing.’ (P8, transitioning age 4.0 years).
Most parents valued the importance of school/nursery support. Despite parental concerns about handing over responsibility to school/nursery teachers, most teachers played an active role in the transition process. ‘It was his teacher. She did most of the hard work really.’ (P14, transitioning age 5.3 years). ‘They were really good with that at nursery. They did time her. So, I would get a record of that as well from them every day.’ (P1, transitioning age 3.7 years).
Seeing a range of products and observing other children while they took their protein substitute at PKU social events facilitated parents to prepare their children to transition. ‘It was a big thing seeing other older children taking the liquid pouches at the events… it really helped him.’ (P2, transitioning age 3.5 years).
Some parents mentioned that having a written individual health care plan for parents/caregivers and the nursery facilitated the transition. ‘We were really clear from the start because we kind of had a structure of how we were going to do it from start to finish and we knew the timescales.’ (P1, transitioning age 3.7 years).
3.3.2. Perceived barriers during the transitioning to third stage protein substitute
Individual factors
Individual factors that acted as barriers to protein substitute transition process included (i) aversion to new protein substitutes, (ii) poor child behaviour, and (iii) aged >5 years.
Many parents reported their child's aversion to new protein substitutes and preference for the old protein substitute as the main barrier. ‘It was more of a struggle and she was reluctant to try it.’ (P12, transitioning age 8.0 years). ‘He has never been happy to change substitute. He is always a bit “oh no”. He sticks to what he knows normally.’ (P6, transitioning age 5.3 years).
Parents described poor behaviors of their children as a barrier to the protein substitute transition process. These behaviors included: being stubborn or being quite definite in their views. ‘At the first start he was getting upset in that he wanted his old pouches back…and he was just “oh do I have to do this”.’ (P6, transitioning age 5.3 years).
Parents of children who transitioned to third stage protein substitutes aged >5 years reported experiencing more struggles. These children were often more attached to their second stage protein substitutes, resisted change, and needed effort and perseverance to change over to the third stage protein substitutes. ‘She got very attached to the second stage protein substitute so she got upset and refused to take the liquid for some time.’(P3, transitioning age 6.5 years).
Family/Caregiver factors
Family/caregiver factors that acted as barriers to the protein substitute transition process included (i) parental fear of change, (ii) loss of parental control, and (iii) time and persistence required.
Most parents felt anxious and worried about the transition due to the uncertainty of change. ‘I think any change makes you anxious, because it’s the unknown, and you have got control with what you have currently.’ (P2, transitioning age 3.5 years).
Many parents were concerned about losing control over protein substitute administration because the third stage liquid protein substitute offers independence to the child. Parents are worried about their child’s capacity to take protein substitutes on their own. ‘The one thing that we did find most difficult was the fact that she was then independent in taking it. We had no control over it.’ (P1, transitioning age 3.7 years).
Some parents reported feeling overwhelmed about the time and persistence required while incorporating the new protein substitute into their routine. ‘I think the thing that we found most hard is to stay positive as a parent and that because you are really…You need a lot of patience. it was a lot to be doing as well, the switching over and the remembering to do…’ (P1, transitioning age 3.7 years). ‘I think everybody would lose their rag a little bit cos sometimes it can be very hard and it’s when it’s 3 times a day or 4 times a day and its push push push push push. But you do not give up….’ (P11, transitioning age 4.7 years).
Third stage protein substitute related factors
Third stage protein substitute related factors that acted as barriers during the transitioning process included (i) high product volume, (ii) different taste, smell and texture, and (iii) poor product tolerance.
Parents often reported that their child struggled to accept the prescribed volume of third-stage liquid protein substitute but also stated that their children became accustomed to the volume of liquid protein substitute over time, and it became less of an issue. ‘The volume was the problem and that’s what took us time.’ (P11, transitioning age 4.7 years). ‘He has a fairly big dose of protein substitute, he has got quite severe PKU so he has always struggled with the volume’ (P14, transitioning age 5.3 years).
Altough most children preferred the third stage protein substitute some children still struggled to take it due to the their different taste, smell, and texture. Parents frequently reported that their children were accustomed to the neutral taste of second stage protein substitute and found the flavoured taste of third stage protein substitute unpleasant. ‘It was introducing the taste because he was so used to the taste of the other product. He had taken this for ages and he is not adventurous with flavours. This was a big thing.’ (P4, transitioning age 4.3 years).
Some parents reported poor tolerance such as gagging, gastrointestinal problems, and constipation related to third stage protein substitute. One parent observed that drinking third stage protein substitutes fast triggered the gagging reflex in their child. ‘He gags, he still gags now. If he drinks it too fast.’ (P15, transitioning age 6.9 years).
Social/Organizational factors
Social/organizational factors that acted as barriers to the protein substitute transition process included (i) poor school communication, and (ii) peer bullying.
Overall, more parents expressed positive experiences with the school, but there were a small number of parents expressing dissatisfaction with the school's lack of feedback. ‘The feedback mechanism is important. Yes that’s where it is massively lacking with the school.’(P16, transitioning age 5.6 years).
Some parents identified child isolation or peer bullying as a particular concern. ‘Kids are laughing in school. They don’t understand what he is taking… and we don’t want kids laughing at him because of whatever he is drinking.’ (P5, transitioning age 6.6 years).
3.3.3. Parental suggestions to improve transitioning process
Parents gave several ideas that would improve the transition process. Many said that a child storybook with pictures explaining the protein substitute transition process would be beneficial. Some parents suggested creating storybooks with characters taking protein substitutes in different settings such as in school or on holidays. ‘… I think having a book aimed at their age group explaining what it is and that it's, you know, a big boy drink or a big girl drink… and they're gonna have to move on to it, I think that would be very good.’ (P14, transitioning age 5.3 years). Some parents stated seeing videos and short videoclips of children drinking protein substitute would be helpful. ‘All I can think is some recorded video which you can watch. Watching some kids taking it.’ (P5, transitioning age 6.6 years).
Some parents requested written instructions given to the school to facilitate the protein substitute transition process with formal feedback that would be helpful. ‘We expect teachers to report back on a daily basis.’ (P16, transitioning age 5.6 years). ‘Things like with sticky charts - it could be that the school ask us on a Monday morning about how they got on at a weekend at home…’ (P14, transitioning age 5.3 years).
Mothers were primarily responsible for the dietary treatment of their children, and they expressed their desire for more involvement of other family members e.g. fathers and grandparents, to share the workload. ‘Don’t always be the one to give it, let other people help you. So the pressure is not always on you.’ (P11, transitioning age 4.7 years).
Perceptions of parents on the variety of the third stage protein substitutes available differed. Some of them reported a good variety and suggested more options would cause difficulties. ‘I think it is better not to have too much choice sometimes. I think it would have caused confusion.’ (P2, transitioning age 3.5 years). ‘I think there was plenty choice and we tried him with all the different flavours and I don’t think having more flavours of different products would have helped him because he is not that adventurous.’ (P4, transitioning age 4.3 years). However, some parents expressed their wish to have more third-stage protein substitute options with different textures and flavours. ‘I would have liked more choices for my son to try’ (P10, transitioning age 4.4 years), ‘..it would have helped if we had more choices in flavours and textures.’ (P3, transitioning age 6.5 years).