First prospective longitudinal study on weaning children with PKU

Weaning – the introduction of solid foods – can be challenging with healthy children. This is even more true for children with Phenylketonuria (PKU), a rare genetic metabolic condition.

However, until this point, no prospective studies have been conducted to identify any differences between weaning in children with PKU and children without PKU.

Weaning in PKU should follow the same introduction as with children without PKU. The aim of weaning is to transition from an exclusively liquid diet to a mixed diet incorporating a range of foods of varying tastes and textures, while helping the child develop skills to eat on his or her own. In children with PKU, the process can be more complex, as they require a weaning protein substitute suitable to replace their infant protein substitute. In addition, they must be introduced to both specialized low protein foods and low phenylalanine regular foods to meet energy requirements and support feeding development.

New prospective longitudinal PKU trial published


Prof. Dr. Anita MacDonald, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, UK: “The idea to do the research actually started many years ago. I saw so many young children struggling to take the full volume of a liquid protein substitute. In fact, the parents found this remarkably difficult. We changed practice to a spoonable semi solid alternative. Now we’d like to understand whether this method was associated with less or more problems with children with PKU and more specifically whether they experience any differences in growth, weight and body composition or in feeding patterns.”

“We need more than people’s opinion, we need guidelines and practical advice for parents with a child with PKU, based on longitudinal study results.” Prof. Dr. Anita MacDonald

Prof. Dr. Anita MacDonald continues: “The research is really quite important right now, as we have no evidence-based guidelines on how we should feed our young children with PKU. For the first time we have an evidence base. It’s important that we use this information to give good practical advice for our families in the future.”

This study has resulted in 2 publications in Nutrients:

–       Growth, protein, and energy intake in children with PKU taking a weaning protein substitute in the first 2 years of life: a case-control study.

–       How does feeding development and progression onto solid foods in PKU compare with non-PKU children during weaning?


In this longitudinal, prospective case-control study, 20 children with PKU were monitored as they transitioned to a semi-solid spoonable weaning protein substitute, together with 20 non-PKU controls who consumed normal weaning foods. Growth parameters (weight, length, head circumference, BMI), energy and macronutrient intake were measured monthly from weaning (4-6m) to 12m and at 15, 18 and 24m of age. Subjects completed a feeding development diary, capturing stages of feeding progression, motor skill development, feeding environment, gastrointestinal symptoms and, in the PKU group, usage of protein substitutes.


Prof. Dr. Anita MacDonald: “It is reassuring we’ve demonstrated that children with PKU who are given a spoonable weaning protein substitute grow at the same rate and have a similar feeding development to children without PKU.”

Study results demonstrate the PKU group that consumed the spoonable weaning protein substitute, shows growth patterns, and comparable energy intakes as their non PKU peers. Feeding development and progression in weaning children with PKU are surprisingly similar to that of control children, e.g. progression onto more textured foods, infant formula volume and gastrointestinal symptoms such as diarrhea, vomiting and constipation.

The PKU group experienced a comparable weaning process to the control group. Food texture progression, reduction in formula intake, self-feeding skills and gastrointestinal symptoms are developmentally equivalent by 2 years of age.

Differences between weaning in children with PKU and non PKU peers

Weaning PKU infants can be more challenging for parents as they need to ensure the right amount of protein delivery. Study results show that any differences with non PKU peers are likely associated with parental anxiety and a desire to feel in control of their child’s eating. This includes extended spoon-feeding, bottle feeding and separate mealtimes to the rest of the family; all of which may delay independent self-feeding. Challenges in acceptance of any kind of protein substitutes particularly occur between 9 and 18 months, at the time of teething and common childhood intercurrent infections. If parents are persistent these challenges are overcome. Retrospective data suggests that most refusal of weaning protein substitute is generally associated with normal weaning behaviour.

What’s next

Further longitudinal studies on growth and body composition, nutrient intake and dietary patterns beyond the weaning period are required to identify any changing trends over time and their eventual effect on long-term health outcomes. Parents of children with PKU require additional support in order to manage anxiety around mealtimes. Further study of how these anxieties compare with parents of non-PKU children would be beneficial to help parents with PKU children.

About PKU

Phenylketonuria (PKU) is a rare genetic metabolic condition. Those with PKU are missing the enzyme phenylalanine (phe) hydroxylase, which – if not treated – causes impaired brain development and function. Phenylalanine is found naturally in protein. People with PKU can prevent complications by avoiding protein-rich foods and following a special phe restricted diet that includes low-phe protein substitutes and specialized low protein foods and/ or by taking medications. To ensure optimal PKU management, patients’ dietary intake and nutritional status should be continuously monitored under the supervision of a doctor and a dietitian.