Inflammation and neurohormonal activation

The Fontan circulation may lead to a chronic systemic inflammatory state, even in those considered stable, promoting the secretion of pro-inflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor (TNF-α), growth/differentiation factor-15 (GDF-15), and beta-2 macroglobulin (B2M)). ^{Reference Shiina, Nagao, Shimomiya and Inai37–Reference Shiina, Murakami and Matsumoto39} With worsening of clinical status, this inflammatory state worsens further impacting energy metabolism and body composition. ^{Reference Shiina, Nagao, Shimomiya and Inai37} Neurohormonal activation associated with Fontan physiology is likely to lead to changes in skeletal muscle protein synthesis or breakdown.

Gastrointestinal system, metabolomics, and the gut microbiome

Fontan physiology is characterised by chronically elevated systemic venous pressure, which consequently leads to a passive increase in portal venous pressure and lymphatic dysfunction, which may alter gastrointestinal tract absorption and result in the loss of nutrients (i.e., protein, vitamin D, calcium). ^{Reference Rychik, Atz and Celermajer7,Reference Cordina, O’Meagher and Gould18,Reference RochéRodríguez and DiNardo40} Very little is known about the gut microbiome and metabolomic profile of people living with a Fontan physiology, both of which are likely to be abnormal, particularly if absorption is altered. Research investigating the gut microbiome in people with conditions, such as cystic fibrosis and heart failure, has consistently demonstrated abnormalities compared to the general population. ^{Reference van Dorst, Tam and Ooi41,Reference Linz and Schnabel42} Preliminary research in adults with a Fontan circulation has noted alterations in amino acid metabolism, phospholipid metabolism, and the tricarboxylic cycle. ^{Reference Motoki, Motoki and Utsumi43–Reference Michel, Dubowy and Zlamy45} Together, the gut microbiome and metabolites play an important role in ensuring essential functions are performed including the production of vitamins and amino acids, regulation of the immune system, and maintaining the epithelial barrier of the gastrointestinal system. ^{Reference Ahmed, Roy, Khan, Septer and Umar46,Reference Clemente, Manasson and Scher47} Over the course of a person’s life, environmental factors of diet and medication usage have a role in influencing the composition of the gut microbiome. ^{Reference van Dorst, Tam and Ooi41} Imbalances or disruptions to the gut microbiome at any life stage are known to influence metabolism, immunity, nutrition, and physiology. ^{Reference van Dorst, Tam and Ooi41,Reference Linz and Schnabel42}

Fontan-associated myopenia

While reductions in skeletal muscle (also known as fat-free mass) are prevalent in those with complex CHD, limited data have suggested that the deficiencies are more pronounced in the setting of a Fontan circulation, particularly in the lower half of the body. ^{Reference Tran, D’Ambrosio and Verrall8,Reference Cao, Tran and Briody9,Reference Shiina, Murakami and Matsumoto39,Reference Sandberg, Johansson and Christersson51–Reference Hansson, Sandberg and Ohlund53} A study by Powell and colleagues observed a 14% increase in adiposity and a 15% decrease in lean muscle mass in adolescents with a Fontan circulation when compared to those with complex CHD. ^{Reference Powell, Wittekind and Alsaied20} In the setting of Fontan physiology, this is especially concerning because the skeletal muscle in the lower limbs acts as a peripheral muscle pump contributing to venous return and cardiac filling. ^{Reference Ritmeester, Veger and van der Ven13,Reference Cordina, O’Meagher and Gould18} Fat-free mass loss is more severe in people who experience long-term complications associated with their Fontan circulation such as plastic bronchitis, protein-losing enteropathy, and circulatory failure. ^{Reference Powell, Wittekind and Alsaied20} The reduction in skeletal muscle mass is more accurately described by the term myopenia (Fontan-associated myopenia) rather than sarcopenia. ^{Reference Tran, D’Ambrosio and Verrall8,Reference Cao, Tran and Briody9} . Although their diagnostic criteria are similar, sarcopenia is characterised by a progressive muscle loss associated with ageing, in contrast to myopenia that may, at least in part, be developmental or “intrinsic.” ^{Reference Tran, D’Ambrosio and Verrall8,Reference Cao, Tran and Briody9,23,Reference Shiina, Nagao, Shimomiya and Inai37,Reference Shaw50,Reference Sandberg, Johansson and Christersson51,Reference Maurer and Tutarel54–Reference Cruz-Jentoft, Baeyens and Bauer57}

Fontan-associated myopenia is likely due to a myriad of factors, which are poorly characterised. These factors include, but are not limited to, physical inactivity, increased protein turnover in the myocardium and skeletal muscle, increased energy requirements of the peripheral pump with exercise, metabolic alteration of substrates (i.e., glucose, lipids, amino acids) secondary to body composition changes, inadequate dietary intake compared to nutritional requirements, malabsorption, nutrition-impact symptoms, feeding difficulties during childhood, and reduced appetite secondary to low levels of the appetite hormone ghrelin. ^{Reference Ritmeester, Veger and van der Ven13,Reference Ohuchi, Miyamoto and Yamamoto15,Reference Ohuchi, Negishi and Hayama16,Reference Cordina, O’Meagher and Gould18,Reference Powell, Wittekind and Alsaied20,Reference Shiina, Murakami and Matsumoto39,Reference Michel, Dubowy and Entenmann44,Reference Michel, Dubowy and Zlamy45,Reference Cordina and d’Udekem52,Reference Michel, Zlamy and Entenmann58–Reference O’Connell, Logsdon, Mitscher and Payne62} Potential mitigators of suboptimal body composition include amino acid supplementation, nutritional education, and exercise training, however, there is a lack of evidence on the therapeutic effectiveness except for isolated resistance training. ^{Reference Shiina, Nagao, Shimomiya and Inai37,Reference Cordina and d’Udekem52,Reference Collamati, Marzetti and Calvani63} In addition to reduced mass, the skeletal muscle may also be dysfunctional. Unsurprisingly, reduced muscle mass is associated with reduced strength. ^{Reference Tran, D’Ambrosio and Verrall8} There is also abnormal skeletal muscle oxygen uptake and autonomic dysfunction in the setting of Fontan physiology. ^{Reference Brassard, Bedard, Jobin, Rodes-Cabau and Poirier64,Reference Brassard, Poirier and Martin65} A study assessing skeletal muscle metabolism (phosphocreatine recovery) using magnetic resonance spectroscopy before, during, and after exercise in adults with a Fontan circulation demonstrated impairments in the aerobic capacity of skeletal muscle compared to controls. ^{Reference Cordina, O’Meagher and Gould18,Reference Bogdanis66}

Increased adiposity

In general, body mass index underestimates adiposity in people with a Fontan circulation as the increased fat mass is masked by reduced fat-free mass. ^{Reference Tran, D’Ambrosio and Verrall8,Reference Powell, Wittekind and Alsaied20,Reference Chung, Hong, Patterson, Petit and Ham49,Reference Martinez, Byku and Novak67–Reference Freud, Webster and Costello69} As health outcomes and survival continue to improve beyond the Fontan procedure, so does the prevalence of people with a Fontan circulation who are above a healthy weight range. ^{Reference Tran, D’Ambrosio and Verrall8,Reference Powell, Wittekind and Alsaied20,Reference Chung, Hong, Patterson, Petit and Ham49,Reference Martinez, Byku and Novak67–Reference Freud, Webster and Costello69} Research investigating the weight trajectories of people with a Fontan circulation has demonstrated that adolescence is often the period when weight gain occurs. ^{Reference Payne, Garden and d’Udekem48} Concerningly, adiposity tends to accumulate in the trunk or abdominal area. ^{Reference Cao, Tran and Briody9,Reference Hansson, Sandberg and Ohlund53,Reference Hansson, Lind, Öhlund, Wiklund and Rydberg70} Given this distribution tendency, there may be merit in measuring waist circumference across all ages to aid in monitoring for excess adiposity although this measurement will be confounded in the presence of ascites. ^{23,Reference Shaw50,Reference Hansson, Lind, Öhlund, Wiklund and Rydberg70–72} Ascites is likely to develop in 17% of those with a Fontan circulation as a subsequent complication of Fontan-associated liver disease. ^{Reference Wu, Kogon and Earing73} In broader populations, there is no consensus on the use of waist circumference or waist-to-height ratio within international guidelines. ^{Reference Lau, Douketis and Morrison71,72,74–Reference Hampl, Hassink and Skinner76} A limitation of this measurement is the absence of evidence determining an appropriate threshold associated with morbidity risk in children. ^{Reference Lau, Douketis and Morrison71,72,74–Reference Hampl, Hassink and Skinner76}

Overfeeding and growth catch-up nutrition strategies

There are no specific nutritional guidelines that include recommendations for optimising growth catch-up in children with a Fontan circulation. General advice based on other populations suggests that optimal catch-up growth in children should promote a balanced accumulation of approximately 73% lean muscle mass and 27% fat mass to achieve weight and height gains, through dietary supplementation of energy and protein, which is appropriate for the child’s nutritional requirements for their age, sex, weight, and clinical condition. ^{23,Reference Shaw50} Without a nutritional target to promote catch-up growth, it is imperative that dietary intakes and anthropometric measurements are routinely monitored to ensure nutritional adequacy is achieved. ^{Reference Rychik, Goldberg and Rand10} However, this approach remains problematic because, without clear targets on the energy and protein to achieve optimal catch-up growth, it raises concerns about whether current nutrition provision strategies are fostering overfeeding. Overfeeding is shown to be associated with rapid weight gains, contributing to increased adiposity, and weights above their healthy range later in life. ^{23,Reference Shaw50,Reference Zheng, Lamb and Grimes101,Reference Ong, Kennedy and Castañeda-Gutiérrez102} Unfortunately, there is no evidence available to compare the dietary intake of children with a Fontan circulation to their energy requirements. In children with complex CHD, nutrition provision is often higher in energy and frequency in comparison to healthy controls matched for age, although still not adequate for estimated requirements for age-related growth. ^{Reference Hansson, Öhlund, Lind, Stecksén-Blicks and Rydberg103}

Energy requirements

Research on resting energy expenditure in people with a Fontan circulation across all ages is extremely limited and is focused on the early post-operative period. ^{Reference Mehta, Costello and Bechard105} In the setting of Fontan physiology, energy requirements may be altered secondary to malabsorptive losses, the presence of inflammation, surgical intervention, and cyanosis. ^{Reference Rychik, Atz and Celermajer7,Reference Ritmeester, Veger and van der Ven13,Reference Nydegger and Bines79,Reference Nydegger, Walsh, Penny, Henning and Bines106} Theories regarding the energy expenditure in people with a Fontan circulation are largely underpinned by evidence in children related to growth trajectories, catch-up growth, and body composition changes but of course, other factors are also likely to influence energy expenditure including gender, age, sex, age-appropriate growth, body weight, body composition, exercise, nutritional intake (including nutrition support), medical therapies, stress, pain, injury, trauma, infection, inflammation, illness severity, organ failure, and sympathetic nervous system activity. ^{23,Reference Westerterp30,Reference Preiser32,Reference Preiser, Ichai, Orban and Groeneveld33} There is contention within the literature regarding whether children with a Fontan circulation have higher energy requirements than their peers matched for age and sex or compared to those with CHD. There is no data on the estimated energy requirements or energy expenditure for adolescents or adults living with a Fontan circulation.

Malnutrition

Malnutrition is defined by the European Society for Clinical Nutrition and Metabolism consensus as a state resulting from lack of intake or uptake of nutrition that leads to altered body composition (decreased muscle mass) and body cell mass leading to diminished physical and mental function and impaired clinical outcomes from disease. ^{Reference Cederholm, Barazzoni and Austin107} Unintentional loss of weight, muscle mass, and adiposity are common characteristics of malnutrition for all, in addition to potential growth and development deficits in children. ^{23,Reference Cederholm, Barazzoni and Austin107} No specific malnutritional screening or assessment tools are validated in people living with CHD. Malnutrition is considered a significant health issue in Australia and internationally; up to 50% of hospitalised adult patients on admission and anywhere from 14 to 55% of children hospitalised in developed countries are found to experience malnutrition, but there remains uncertainty as to whether these figures are a true representation. ^{Reference Cass and Charlton108,Reference White, Dennis and Ramsey109} Limited studies exist on children with complex CHD; it is estimated that 33–52% of children experience malnutrition, particularly during infancy (1–2 years) when rates of surgical intervention are high. ^{Reference Herridge, Tedesco-Bruce, Gray and Floh78}

People with a Fontan circulation should be considered at high risk of malnutrition at any life stage. A retrospective study evaluating the prevalence of malnutrition in children who underwent Fontan surgery identified rates ranging from 6 to 16%, of moderate-severe malnutrition defined based on Z-scores of weight, height, and body mass index for age. ^{Reference Sekhon, Foshaug and Kantor110} More surprisingly, moderate-severe malnutrition was identified in 38% of participants at any point in the 10 years following their Fontan procedure. ^{Reference Sekhon, Foshaug and Kantor110} Several evidence-based nutrition guidelines are available to inform the management of malnutrition in population groups including cystic fibrosis and cancer. ^{Reference Saxby, Paintern and Kench111–Reference Muscaritoli, Arends and Bachmann113} Nutritional advice to manage malnutrition is generally consistent, focusing on nutrition interventions (i.e., nutrient-rich foods, oral nutrition support) and nutrition education. ^{Reference Saxby, Paintern and Kench111–Reference Muscaritoli, Arends and Bachmann113} Those with malnutrition are encouraged to eat small frequent meals (i.e., three main meals and three snacks) of nutrient-rich foods that are high in energy and protein. It is strongly emphasised that foods are chosen to optimise enjoyment and taste to encourage better oral intake. ^{Reference Saxby, Paintern and Kench111,Reference Kiss, Loeliger and Findlay112} Modifications are recommended in instances where a person is unable to meet their estimated energy and protein requirements. Additional nutrition provision is encouraged by 1) high-energy high-protein fortification to increase energy and protein intake without having to consume more food; or 2) oral nutrition supplements. ^{Reference Saxby, Paintern and Kench111–Reference Muscaritoli, Arends and Bachmann113} Given that children around the time of their Fontan surgery experience malnutrition and issues impacting their nutrition status, a pragmatic approach would be to supplement suboptimal intakes to mitigate nutritional risk deficits and their impact. ^{Reference Sekhon, Foshaug and Kantor110} The prevalence of, and contributors to, malnutrition amongst adolescents and adults with a Fontan circulation are not known.

Altered glucose metabolism

It is unclear whether increased abdominal adiposity in the setting of Fontan physiology increases the risk of metabolic syndrome, as established in the general population. ^{Reference Hansson, Sandberg and Ohlund53} Metabolic abnormalities of impaired glucose tolerance, insulin resistance, and diabetes mellitus are increasingly recognised as comorbidities associated with Fontan physiology. ^{Reference Ritmeester, Veger and van der Ven13,Reference Ohuchi, Miyamoto and Yamamoto15,Reference Ohuchi, Negishi and Hayama16} Although the pathophysiologic mechanisms explaining abnormalities in glucose metabolism are not fully understood, it has been postulated that it may be related to Fontan-associated liver disease or altered body composition and exacerbated by physical inactivity. ^{Reference Ritmeester, Veger and van der Ven13,Reference Ohuchi, Negishi and Hayama16} Decreased adiponectin, an insulin sensitivity biomarker, has been associated with increased adiposity in adults with a Fontan circulation and may reflect insulin resistance. ^{Reference Powell, Wittekind and Alsaied20,Reference Hivert, Sullivan and Fox114} The role of skeletal muscle mass in the development of pre-diabetes mellitus has been observed among groups with altered body composition (i.e., sarcopenia, elderly) who are shown to have an increased risk of insulin resistance or impaired glucose tolerance, and this phenomenon may occur in those with Fontan physiology. ^{Reference Srikanthan and Karlamangla26,Reference Sinacore and Gulve27,Reference Moon115} Limited studies have demonstrated that adults with a Fontan circulation have altered glucose metabolism with a reported average prevalence of up to 40% for impaired glucose tolerance and up to 5% for diabetes mellitus. ^{Reference Ohuchi, Miyamoto and Yamamoto15,Reference Ohuchi, Negishi and Hayama16} Although the prevalence of impaired glucose tolerance is relatively high in comparison to those without a Fontan circulation, interestingly the prevalence of diabetes mellitus is relatively low given it is estimated that 70% of people with pre-diabetes during their life will progress to type 2 diabetes. ^{Reference Ohuchi, Miyamoto and Yamamoto15,Reference Ohuchi, Negishi and Hayama16,Reference Tabák, Herder, Rathmann, Brunner and Kivimäki116,Reference Nathan, Davidson and DeFronzo117} More longitudinal studies are needed to determine the incidence of impaired glucose tolerance and diabetes mellitus within the ageing Fontan population. ^{Reference Ritmeester, Veger and van der Ven13,Reference Ohuchi, Negishi and Hayama16} The role of modifiable factors (i.e., dietary patterns, weight, physical activity) in altered glucose metabolism among people living with a Fontan circulation is not known but are likely contributors due to their well-recognised role in metabolic pathways.

Reduced bone mineral density

Bone mineral density is frequently reduced in people with a Fontan circulation compared to the general population across all age groups but appears to be more common later in life. ^{Reference D’Ambrosio, Tran and Verrall19,Reference Avitabile, Goldberg and Zemel96,Reference Goldberg, Dodds and Avitabile118–Reference Diab, Godang and Müller122} The pathophysiology of these bone alterations remains undetermined but is likely multifactorial. Probable contributors include reduced physical inactivity, malabsorption, vitamin D deficiency, medications such as warfarin, skeletal muscle deficits, neurohormonal activation, protein-losing enteropathy, liver dysfunction, and haemodynamic alterations inherent to Fontan physiology such as high venous pressure, reduced blood flow, and cyanosis. ^{Reference Rychik, Atz and Celermajer7,Reference Ritmeester, Veger and van der Ven13,Reference D’Ambrosio, Tran and Verrall19,Reference Avitabile, Goldberg and Zemel96,Reference Diab, Godang and Müller122} In the general population, warfarin usage has been associated with reduced bone mineral density, although the dietary patterns of people using warfarin (i.e., low vitamin K intake) may also contribute. ^{Reference Signorelli, Scuto and Marino123,Reference Fawzy and Lip124} . Bone mineral density in children with a Fontan circulation has been observed to be lower in those on warfarin compared to aspirin, while in adults, the association is less clear. ^{Reference Attard, Monagle and d’Udekem17,Reference D’Ambrosio, Tran and Verrall19,Reference Bendaly, DiMeglio, Fadel and Hurwitz120} Skeletal muscle is also recognised as another important determinant of bone health outcomes during childhood, whereby increases in skeletal muscle mass from growth or physical activity have been shown to induce adaptive changes in bones in dimension and strength gains. ^{23,Reference Shaw50,Reference Avitabile, Goldberg and Zemel96} While bone mineral density deficits in children and adults with a Fontan circulation are reported, no studies to date have diagnosed osteoporosis in children, while conversely, one small cohort study reported osteoporosis in around 5% of younger adults (19–33 years). ^{Reference D’Ambrosio, Tran and Verrall19,Reference Avitabile, Goldberg and Zemel96,Reference Goldberg, Dodds and Avitabile118,Reference Bendaly, DiMeglio, Fadel and Hurwitz120,Reference Diab, Godang and Müller122} There is a paucity of evidence to inform dietary interventions and management strategies for bone health in people living with a Fontan circulation. In the wider population, it is recognised that weight-bearing exercise and nutrition are modifiable factors that can improve bone outcomes (i.e., bone mass development and maintenance) and prevent osteopenia and osteoporosis; addressing micronutrient deficiencies, particularly calcium and vitamin D, to support good bone health is warranted. ^{Reference Rychik, Goldberg and Rand10,23,Reference Berger, Shenkin and Schweinlin125}

Vitamin D deficiency

Vitamin D deficiency and secondary hyperparathyroidism are common in children and adults with a Fontan circulation and probably impact bone density. ^{Reference D’Ambrosio, Tran and Verrall19,Reference Avitabile, Goldberg and Zemel96,Reference Diab, Godang and Müller122} It is unclear why people with a Fontan circulation may be more susceptible to vitamin D deficiency. The prevalence of vitamin D deficiency (<50 nmol/L) among children with a Fontan circulation is estimated to be 20–25%. ^{Reference Hansson, Sandberg and Ohlund53,Reference Avitabile, Goldberg and Zemel96,Reference Avitabile, Leonard and Zemel97,Reference Sarafoglou, Petryk and Mishra119,Reference Diab, Godang and Müller122} Dietary data on vitamin D intake and levels in adults are lacking. One small cohort study in Australian adults (>16 years) with a Fontan circulation reported an average serum vitamin level of 66 nmol, with 24% of the cohort classified as deficient (<50 nmol/L). ^{Reference D’Ambrosio, Tran and Verrall19} Other Fontan-associated factors that warrant further investigation include the impact of Fontan-associated liver disease on vitamin D metabolism, altered absorption from the gut with increased portal pressure and lymphatic dysfunction, and microvascular fibrosis that may impact the conversion pathways in the skin. Individuals are encouraged to include foods that are high sources of calcium and vitamin D in their daily intake, with supplementation of these micronutrients if they are unable to meet their recommended dietary intake. ^{Reference Saxby, Paintern and Kench111,Reference Berger, Shenkin and Schweinlin125–129} In the general population, vitamin D supplementation in combination with calcium has been shown to be more effective for the promotion of bone mineral density than vitamin D alone. ^{Reference Saxby, Paintern and Kench111,Reference Berger, Shenkin and Schweinlin125–129} For those who are diagnosed with osteopenia or osteoporosis, the goals of nutrition interventions are to 1) achieve optimal growth in children and maintain weight within a healthy weight range for all ages which preserves muscle mass; 2) achieve the recommended dietary intake of calcium and vitamin D through supplementation; 3) engage in regular exercise which is appropriate to a person’s life stage and health needs; and 4) aim for serum vitamin D above >50 nmol/L. ^{Reference Saxby, Paintern and Kench111,Reference Berger, Shenkin and Schweinlin125–129}

Fontan-associated liver disease

The pathophysiology and nutritional management of Fontan-associated liver disease have been described in detail elsewhere. ^{Reference Gordon-Walker, Bove and Veldtman130,Reference Hilscher, Wells, Venkatesh, Cetta and Kamath131} Evidence is lagging to inform dietary management strategies for more advanced Fontan-associated liver disease. ^{Reference Rychik, Atz and Celermajer7,Reference Zentner, Celermajer and Gentles11,Reference Gordon-Walker, Bove and Veldtman130} Nutritional advice is generally based on recommendations from other liver diseases and suggests limiting hepatotoxins including alcohol and maintaining a healthy weight range through a balanced nutritious diet. ^{Reference Rychik, Atz and Celermajer7,Reference Zentner, Celermajer and Gentles11,Reference Gordon-Walker, Bove and Veldtman130} In general, cirrhosis has important implications for an individual’s nutrition status because energy and protein requirements are increased; secondary malnutrition is common and should be screened for routinely in nutrition assessments to ensure timely intervention to optimise body composition. ^{Reference Bischoff, Bernal and Dasarathy132} Evidence-based guidelines derived from general liver disease in adults recommend that individuals with cirrhosis eat small frequent meals, aiming for a meal pattern of 3–5 main meals per day and 1 carbohydrate snack late in the evening to minimise the overnight fasting period. Food choices should be high in energy and protein and low in salt aiming for an energy intake of 126–147 kJ/kg/day (30–35 kcal/kg/day) and a protein intake of 1.2–1.5 g/kg/day. ^{Reference Bischoff, Bernal and Dasarathy132} Modifications are recommended in instances of micronutrient deficiencies, ascites, obesity, or disease severity. Nutritional support via enteral or parenteral nutrition is only recommended when the individuals cannot tolerate food orally or cannot meet their nutritional targets from food alone. ^{Reference Bischoff, Bernal and Dasarathy132} Dietary advice for children is dependent on their clinical status, symptomology, and degree of liver dysfunction. ^{Reference Nightingale and Ng133}

Protein-losing enteropathy

Previous reviews have described the pathophysiology and nutritional management of protein-losing enteropathy in Fontan physiology. ^{Reference Alsaied, Lubert and Goldberg134,Reference Barracano, Merola, Fusco, Scognamiglio and Sarubbi135} A collaborative individualised treatment approach is recommended, one first-step approach being dietary intervention, as no single treatment is recognised as the most effective in resolving protein-losing enteropathy. ^{Reference Zentner, Celermajer and Gentles11,Reference Alsaied, Lubert and Goldberg134} There is limited evidence from high-quality clinical trials evaluating the impact of dietary treatment of protein-losing enteropathy, therefore, nutrition targets for protein and fat within the literature are found to vary. Recommendations are to aim for less than 25 per cent of dietary fat energy (sourced from medium-chain triglycerides) and more than 2 g/kg of protein per day in both adults and children. ^{Reference Rychik, Goldberg and Rand10,Reference Zentner, Celermajer and Gentles11,23,Reference Shaw50,Reference Alsaied, Lubert and Goldberg134,Reference Barracano, Merola, Fusco, Scognamiglio and Sarubbi135} Nutrition targets don’t differ between children, adolescents, and adults as they are calculated based on individuals’ body weight or percentage of total energy consumption. Additional dietary support should be considered for those experiencing chronic diarrhoea with electrolytes and micronutrients including folate, iron, and fat-soluble vitamins. ^{Reference Zentner, Celermajer and Gentles11,23,Reference Alsaied, Lubert and Goldberg134,Reference Barracano, Merola, Fusco, Scognamiglio and Sarubbi135} This dietary approach is not long-term and is only recommended during periods of protein-losing enteropathy flares. ^{Reference Rychik, Goldberg and Rand10} In those whose protein-losing enteropathy is managed by diuretic therapy, particularly potassium-sparing diuretics, ensuring serum potassium levels are optimised, considering dietary potassium is important. ^{Reference Lamb, Kennedy and Raine136} In critical cases, where dietary intervention is unsuccessful, parenteral nutrition may be indicated. ^{Reference Shaw50}

General nutritional management in children living with a Fontan circulation

Paediatric nutritional guidelines are available to assist in informing the management of children with CHD broadly, however, the guidelines do not differentiate the type of cardiac surgery or severity of CHD. ^{Reference Mehta, Skillman and Irving138,Reference Tume, Valla and Joosten139} International guidelines recommend providing 35–55 kcals/kg/day (146–230 kJ/kg/day) of energy and 1.5 g/kg/day of protein post-operatively. ^{Reference Mehta, Skillman and Irving138,Reference Tume, Valla and Joosten139} While these nutritional recommendations are a broad target to ensure nutritional requirements are achieved, they do not reflect the variability in the nutritional needs of children with a Fontan circulation. ^{Reference Baldini, Librandi, D’Eusebio and Lezo77} At present, the goal for children with a Fontan circulation is to optimise nutrition to minimise the risk of malnutrition and meet increased energy requirements for age-related growth and development, catch-up growth, and metabolic response to surgery. ^{23,Reference Preiser, Ichai, Orban and Groeneveld33} Energy requirements are usually calculated using predictive equations or general population values, which are adjusted based on factors including growth, body composition, physical activity levels, and condition-related stress/injury factors. ^{23,Reference Baldini, Librandi, D’Eusebio and Lezo77} Nutritional assessments theoretically should prioritise measuring children’s energy expenditure using indirect calorimetry, if available, in combination with dietary intake assessments (i.e., 3-day food record or 7-day diet history) to ensure optimal nutrition is achieved until further research can establish nutritional targets. ^{Reference Rychik, Goldberg and Rand10,Reference Baldini, Librandi, D’Eusebio and Lezo77} Monitoring and assessments of growth, in terms of body composition and body mass index, are useful indicators to gauge if nutritional interventions are appropriate. ^{Reference Rychik, Goldberg and Rand10} Most children living with a Fontan circulation are encouraged to adopt healthy eating principles from national guidelines, including those of the World Health Organisation, with modifications made for any nutritional deficiencies or nutrition-related issues. ¹⁴⁰

General nutritional management for adults living with a Fontan circulation

The paucity of nutrition research means no evidence exists to develop specific dietary recommendations for people living with a Fontan circulation. Current nutritional advice for people living with Fontan circulation, without any comorbidities requiring nutrition management, is aligned with international and country-specific national health guidelines for general health promotion and chronic disease prevention. ^{Reference Rychik, Goldberg and Rand10} Malnutrition screening and nutritional assessments (including anthropometrics, biochemistry, clinic information, and dietary intake) are fundamental to inform nutritional management strategies, by identifying nutrition-related considerations and complications that can affect an individual’s nutritional status. ^{23,Reference Shaw50}