Results of clinical trials of a specialized product for enteral nutrition: Nutrigen Low Fat

Abstract

BACKGROUND: Hereditary disorders of fatty acid oxidation are a group of fermentopathies caused by biallelic mutations in genes encoding enzymes of the mitochondrial β-oxidation cascade of fatty acids. Mitochondrial fatty acid oxidation deficiency is a genetically heterogeneous group of diseases in humans caused by defects in mitochondrial fatty acid β-oxidation. A common characteristic of all mitochondrial fatty acid β-oxidation disorders is hypoketotic hypoglycemia, resulting from an increased dependence on glucose oxidation and an inability to synthesize ketone bodies from fatty acids. The clinical manifestations of diseases in this group are highly variable. Patients with a defect in the oxidation of long-chain fatty acids are at risk of developing cardiac and skeletal muscle abnormalities, including cardiomyopathy and arrhythmias, which can progress to early death, as well as rhabdomyolysis and exercise intolerance. The optimal composition of Nutrigen Low Fat enteral mixture allows its use in children with intestinal dysfunction and metabolic disorders as a component of nutritional support or the sole source of nutrition.

AIMS: To study the clinical evidence on intestinal insufficiency syndrome in critically ill children, to assess the role of enteral nutrition in intestinal dysfunction prevention and treatment in critically ill patients in the pediatric intensive care unit, and to perform clinical monitoring of young children with inborn errors of fatty acid oxidation.

MATERIALS AND METHODS: Twelve children aged 3 months to 7 years with digestive dysfunction took part in the study. The study duration was 3 weeks. During the intervention, children received the product Nutrigen Low Fat in accordance with their age and individual nutritional needs. Throughout the study, the children’s nutritional status and the dynamics of digestive dysfunction were taken into account. A clinical trial of the dry complete enteral product Nutrigen Low Fat took place from May to August of 2021. A clinical trial of the product was conducted against a background of generally accepted medical treatment in accordance with the character of the disease. The study design was an observational, longitudinal cohort study.

RESULTS: The dynamics of objective clinical and laboratory data, as well as subjective patient characteristics, indicated an improvement in well-being, physical development, and positive dynamics of blood parameters. The product Nutrigen Low Fat meets the hygienic requirements for the composition and quality of pediatric medical nutrition products and has good organoleptic characteristics. It should be noted that Nutrigen Low Fat is convenient to use because it allows individual selection of the dilution and dosage in accordance with the child’s age and clinical status, has a high biological value (contains easily absorbed fat, with 84% medium-chain triglycerides, and easily digestible milk protein comprised of 60% whey). The product’s gluten-free formula is another advantage.

CONCLUSIONS: All of the above allows us to recommend the use of a complete product, Nutrigen Low Fat, as a supplement to the diet or as the sole source of nutrition. It can be used for oral nutrition (sipping) or tube feeding from birth in children with acute surgical and therapeutic diseases, as well as orphan inborn errors, including fatty acid oxidation errors, with maldigestion and malabsorption syndrome, intoxication, and malnutrition.

Keywords

children / orphan diseases / intestinal dysfunction / metabolic errors / enteral nutrition / Nutrigen Low Fat

References

[1] Novikov PV. The problem of rare (orphan) diseases in the Russian Federation: medical and regulatory aspects of its solution. Therapeutic Archive. 2014;86(12):3–12. (In Russ).

[2] Новиков П.В. Проблема редких (орфанных) заболеваний в Российской Федерации: медицинские и нормативно-правовые аспекты ее решения // Терапевтический архив. 2014. Т. 86, № 12. С. 3–12.

[3] Volgina SY, Nikolaeva EA, Sokolov AA, et al. Problems of children with rare diseases: ethical, social, psychological and medical aspects. Russ Bulletin Perinatology Pediatrics. 2019;64(5): 149–154. (In Russ). doi: 10.21508/1027-4065-2019-64-5-149-154

[4] Волгина С.Я., Николаева Е.А., Соколов А.А., и др. Проблемы детей с редкими болезнями: этические, социальные, психологические и медицинские аспекты // Российский вестник перинатологии и педиатрии. 2019. Т. 64, № 5. С. 149–154. doi: 10.21508/1027-4065-2019-64-5-149-154

[5] Gaiduk AY, Vlasov YV, Zakharova EY. Actual problems of providing medical care to patients with orphan diseases in the Russian Federation. Medical Genetics. 2020;19(11):13–20. (In Russ). doi: 10.25557/2073-7998.2020.11.13-20

[6] Гайдук А.Я., Власов Я.В., Захарова Е.Ю. Актуальные проблемы оказания медицинской помощи пациентам с орфанными заболеваниями в Российской Федерации // Медицинская генетика. 2020. Т. 19, № 11. С. 13–20. doi: 10.25557/2073-7998.2020.11.13-20

[7] Nechkin AV. Screening for hereditary diseases: a cursory look at the domestic and foreign experience of legal regulation. Russ Immunol J. 2019;13(2-2):1031–1033. (In Russ). doi: 10.31857/S102872210006482-5

[8] Нечкин А.В. Скрининг на наследственные заболевания: беглый взгляд на отечественный и зарубежный опыт правового регулирования // Российский иммунологический журнал. 2019. Т. 13, № 2-2. С. 1031–1033. doi: 10.31857/S102872210006482-5

[9] Zhilina SS, Kozhanova TV, Meshcheryakova TI, et al. Medical and genetic service in a multi-profile clinical center is an important stage in providing medical care to children with neuropsychiatric, oncological diseases and malformations of the craniofacial region. Quantum Satis. 2019;2(2-4):44–49. (In Russ).

[10] Жилина С.С., Кожанова Т.В., Мещерякова Т.И., и др. Медико-генетическая служба в многопрофильном клиническом центре ― важный этап оказания медицинской помощи детям с психоневрологическими, онкологическими заболеваниями и пороками развития черепно-лицевой области // Quantum Satis. 2019. Т. 2, № 2-4. С. 44–49.

[11] Gundorova P, Kuznetsova IA, Agladze D, et al. Molecular genetic study of phenylketonuria in patients from Georgia. Genetics. 2019;55(8):955–963. (In Russ). doi: 10.1134/S001667581908006X

[12] Гундорова П., Кузнецова И.А., Агладзе Д., и др. Молекулярно-генетическое исследование фенилкетонурии у пациентов Грузии // Генетика. 2019. Т. 55, № 8. С. 955–963. doi: 10.1134/S001667581908006X

[13] Kazanova AA. Genetic testing: monogenic and multifactorial diseases. Student Bulletin (Ural State Medical University). 2021;(20): 86–88. (In Russ).

[14] Козонова А.А. Генетическое тестирование: моногенные и мультифакториальные болезни // Студенческий вестник (Уральский государственный медицинский университет). 2021. № 20. С. 86–88.

[15] Wanders JA, Visser G, Ferdinandusse S, et al. Mitochondrial fatty acid oxidation disorders: laboratory diagnosis, pathogenesis, and the complicated route to treatment. J Lipid Atheroscler. 2020;9(3): 313–333. doi: 10.12997/jla.2020.9.3.313

[16] Wanders J.A., Visser G., Ferdinandusse S., et al. Mitochondrial fatty acid oxidation disorders: laboratory diagnosis, pathogenesis, and the complicated route to treatment // J Lipid Atheroscler. 2020. Vol. 9, N 3. Р. 313–333. doi: 10.12997/jla.2020.9.3.313

[17] Spiekerkoetter U. Mitochondrial fatty acid oxidation disorders: clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening. J Inherit Metab Dis. 2010;33(5): 527–532. doi: 10.1007/s10545-010-9090-x

[18] Spiekerkoetter U. Mitochondrial fatty acid oxidation disorders: clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening // J Inherit Metab Dis. 2010. Vol. 33, N 5. Р. 527–532. doi: 10.1007/s10545-010-9090-x

[19] Bonnet D, Martin D, de Lonlay P, et al. Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children. Circulation. 1999;100(22):2248–2253. doi: 10.1161/01.cir.100.22.2248

[20] Bonnet D., Martin D., de Lonlay P., et al. Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children // Circulation. 1999. Vol. 100, N 22. Р. 2248–2253. doi: 10.1161/01.cir.100.22.2248

[21] Baruteau J, Sachs P, Broué P, et al. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study from 187 patients. Complementary data. J Inherit Metab Dis. 2014;37(1):137–139. doi: 10.1007/s10545-013-9628-9

[22] Baruteau J., Sachs P., Broué P., et al. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study from 187 patients. Complementary data // J Inherit Metab Dis. 2014. Vol. 37, N 1. Р. 137–139. doi: 10.1007/s10545-013-9628-9

[23] Baruteau J, Sachs P, Broué P, et al. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients. J Inherit Metab Dis. 2013;36(5):795–803. doi: 10.1007/s10545-012-9542-6

[24] Baruteau J., Sachs P., Broué P., et al. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients // J Inherit Metab Dis. 2013. Vol. 36, N 5. Р. 795–803. doi: 10.1007/s10545-012-9542-6

[25] Boese EA, Jain N, Jia Y, et al. Characterization of chorioretinopathy associated with mitochondrial trifunctional protein disorders: long-term follow-up of 21 cases. Ophthalmology. 2016;123(10): 2183–2195. doi: 10.1016/j.ophtha.2016.06.048

[26] Boese E.A., Jain N., Jia Y., et al. Characterization of chorioretinopathy associated with mitochondrial trifunctional protein disorders: long-term follow-up of 21 cases // Ophthalmology. 2016. Vol. 123, N 10. Р. 2183–2195. doi: 10.1016/j.ophtha.2016.06.048

[27] Van Rijt WJ, Ferdinandusse S, Giannopoulos P, et al. Prediction of disease severity in multiple acyl-CoA dehydrogenase deficiency: a retrospective and laboratory cohort study. J Inherit Metab Dis. 2019;42(5):878–889. doi: 10.1002/jimd.12147

[28] Van Rijt W.J., Ferdinandusse S., Giannopoulos P., et al. Prediction of disease severity in multiple acyl-CoA dehydrogenase deficiency: a retrospective and laboratory cohort study // J Inherit Metab Dis. 2019. Vol. 42, N 5. Р. 878–889. doi: 10.1002/jimd.12147

[29] O’Callaghan B, Bosch AM, Houlden H. An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency. J Inherit Metab Dis. 2019;42(4):598–607. doi: 10.1002/jimd.12053

[30] O’Callaghan B., Bosch A.M., Houlden H. An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency // J Inherit Metab Dis. 2019. Vol. 42, N 4. Р. 598–607. doi: 10.1002/jimd.12053

[31] Putina NY, Koinosov PG, Chiryatyeva TV, et al. Somatometric assessment of premature infants in the sensitive period of development. Med Sci Education Urals. 2021;22(3):76–81. (In Russ). doi: 10.36361/1814-8999-2021-22-3-76-81

[32] Путина Н.Ю., Койносов П.Г., Чирятьева Т.В., и др. Соматометрическая оценка недоношенных детей в сенситивный период развития // Медицинская наука и образование Урала. 2021. Т. 22, № 3. С. 76–81. doi: 10.36361/1814-8999-2021-22-3-76-81

[33] Amato V, Zurlo V. Rare orphan diseases in patients on home artificial nutrition. Nutrition. 2021;87-88(Suppl.):111329. doi: 10.1016/j.nut.2021.111329

[34] Amato V., Zurlo V. Rare orphan diseases in patients on home artificial nutrition // Nutrition. 2021. Vol. 87–88, Suppl. Р. 111329. doi: 10.1016/j.nut.2021.111329

[35] Volgina SY, Sokolov AA. An analysis of medical care services for children with rare diseases in the Russian Federation. Front Pharmacol. 2021;12:754073. doi: 10.3389/fphar.2021.754073

[36] Volgina S.Y., Sokolov A.A. An analysis of medical care services for children with rare diseases in the Russian Federation // Front Pharmacol. 2021. Vol. 12. Р. 754073. doi: 10.3389/fphar.2021.754073

[37] Hettiarachchi D, Lakmal K, Dissanayake VH. A concise review of ketogenic dietary interventions in the management of rare diseases. J Nutrition Metabolism. 2021:6685581. doi: 10.1155/2021/6685581

[38] Hettiarachchi D., Lakmal K., Dissanayake V.H. A concise review of ketogenic dietary interventions in the management of rare diseases // J Nutrition Metabolism. 2021. Р. 6685581. doi: 10.1155/2021/6685581

[39] American Gastroenterological Association medical position statement: guidelines for the evaluation of food allergies. Gastroenterology. 2001;120(4):1023–1025. doi: 10.1053/gast.2001.23417

[40] American Gastroenterological Association medical position statement: guidelines for the evaluation of food allergies // Gastroenterology. 2001. Vol. 120, N 4. Р. 1023–1025. doi: 10.1053/gast.2001.23417

[41] Boronat AC, Ferreira-Maia AP, Matijasevich A, Wang YP. Epidemiology of functional gastrointestinal disorders in children and adolescents: a systematic review. World J Gastroenterol. 2017; 23(21):3915–3927. doi: 10.3748/wjg.v23.i21.3915

[42] Boronat A.C., Ferreira-Maia A.P., Matijasevich A., Wang Y.P. Epidemiology of functional gastrointestinal disorders in children and adolescents: a systematic review // World J Gastroenterol. 2017. Vol. 23, N 21. P. 3915–3927. doi: 10.3748/wjg.v23.i21.3915

[43] Fernandes J, Saudubray JM, van den Berghe G, Walter JH, editors. Inborn Metabolic Diseases. 5th ed. Berlin, Heidelberg: Springer, 2012. 561 p. doi: 10.1007/978-3-540-28785-8

[44] Fernandes J., Saudubray J.M., van den Berghe G., Walter J.H., editors. Inborn Metabolic Diseases. 5th ed. Berlin, Heidelberg: Springer, 2012. 561 p. doi: 10.1007/978-3-540-28785-8.

[45] Iacobazzi V, Pasquali M, Singh R, et al. Response to therapy in carnitine / acylcarnitinetranslocase (CACT) deficiency due to a novel missense mutation. Am J Med Genet. 2004;126A(2):150–155. doi: 10.1002/ajmg.a.20573

[46] Iacobazzi V., Pasquali M., Singh R. et al. Response to therapy in carnitine / acylcarnitinetranslocase (CACT) deficiency due to a novel missense mutation // Am J Med Genet. 2004. Vol. 126A, N 2. Р. 150–155. doi: 10.1002/ajmg.a.20573

[47] Divarci E, Karapinar B, Yalaz M, et al. Incidence and prognosis of intraabdominal hypertension and abdominal compartment syndrome in children. J Pediatr Surg. 2016;51(3):503–507. doi: 10.1016/j.jpedsurg.2014.03.014

[48] Divarci E., Karapinar B., Yalaz M., et al. Incidence and prognosis of intraabdominal hypertension and abdominal compartment syndrome in children // J Pediatr Surg. 2016. Vol. 51, N 3. P. 503–507. doi: 10.1016/j.jpedsurg.2014.03.014

[49] Rohr F, van Calcar S. Genetic metabolic international guidelines for VLCADD, 2008 [Internet]. [cited 2021 Jul 15]. Available from: https://www.gmdi.org/Resources/Nutrition-Guidelines/VLCAD.

[50] Rohr F., van Calcar S. Genetic metabolic international guidelines for VLCADD, 2008 [Internet]. Режим доступа: https://www.gmdi.org/Resources/Nutrition-Guidelines/VLCAD. Дата обращения: 15.07.2021.

[51] Sopo M, Iacono D, Monigaa G, Giovannac M. Clinical management of food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol. 2014;14(3):240–245. doi: 10.1097/ACI.0000000000000058

[52] Sopo M., Iacono D., Monigaa G., Giovannac M. Clinical management of food protein-induced enterocolitis syndrome // Curr Opin Allergy Clin Immunol. 2014. Vol. 14, N 3. P. 240–245. doi: 10.1097/ACI.0000000000000058

[53] Spiekerkoetter U, Bastin J, Gillingham M, et al. Current issues regarding treatment of mitochondrial fatty acid oxidation disorders. J Inherit Metab Dis. 2010;33(5):555–561. doi: 10.1007/s10545-010-9188-1

[54] Spiekerkoetter U., Bastin J., Gillingham M., et al. Current issues regarding treatment of mitochondrial fatty acid oxidation disorders // J Inherit Metab Dis. 2010. Vol. 33, N 5. P. 555–561. doi: 10.1007/s10545-010-9188-1

[55] Tretyakov DS, Tretyakova EP, Shen NP. Intraabdominal pressure as an indicator of the severity of gastrointestinal insufficiency in children. Medicine: Theory Practice. 2018;3(4):185–190. (In Russ).

[56] Третьяков Д.С., Третьякова Е.П., Шень Н.П. Интраабдоминальное давление как показатель тяжести гастроинтестинальной недостаточности у детей // Медицина: теория и практика. 2018. Т. 3, № 4. С. 185–190.

[57] Tretyakova EP. Can intraabdominal pressure be used to assess gastrointestinal insufficiency in children? Eurasian Union of Scientists. 2019;(5):42–45. (In Russ). doi: 10.31618/ESU.2413-9335.2019.4.62

[58] Третьякова Е.П. Может ли интраабдоминальное давление использоваться для оценки гастроинтестинальной недостаточности у детей? // Евразийский союз ученых. 2019. № 5. С. 42–45. doi: 10.31618/ESU.2413-9335.2019.4.62

[59] Tretyakova EP, Shen NP, Suchkov DV. Assessment of readiness of children’s patients to increase the volume of enteral nutrition in gastrointestinal dysfunction. Medical Almanac. 2019;(5-6):36–38. (In Russ). doi: 10.21145/2499-9954-2019-5-36-38

[60] Третьякова Е.П., Шень Н.П., Сучков Д.В. Оценка готовности пациентов детского возраста к наращиванию объема энтерального питания при гастроинтестинальной дисфункции // Медицинский альманах. 2019. № 5-6. С. 36–38. doi: 10.21145/2499-9954-2019-5-36-38

RIGHTS & PERMISSIONS

Shen N.P., Tretiakova E.P.