Situación nutricional y acciones implementadas en niños internados en salas de cuidados intermedios y moderados de un hospital pediátrico de alta complejidad de la ciudad de Buenos Aires / Nutritional status and actions implemented in children admitted to intermediate and moderate care wards of a tertiary-care pediatric hospital in the city of Buenos Aires

Introducción: La malnutrición es un estado de deficiencia o exceso de nutrientes que provoca efectos nocivos y puede alterar el crecimiento aumentando la morbi-mortalidad. Materiales y métodos: estudio retrospectivo, descriptivo. Incluyó niños/as de 1-18 años hospitalizados entre 2016-2018. Se obtuvieron datos de caracterización de la muestra y antropométricos. La herramienta de tamizaje nutricional pediátrico (HTNP) se utilizó para detectar riesgo nutricional y en este subgrupo se analizó: variación de peso, intervención nutricional, complicaciones infecciosas y estadía hospitalaria. El análisis de variables se realizó con SPSS Statistics 20. Resultados: Se evaluaron 745 pacientes, 373 niñas (50,1%). Mediana de edad 7,3 años. Estancia hospitalaria media de 4 días (1-123). Se observó 5,9% emaciados, 56,4% eutróficos, 16,8% sobrepeso y 20,9% obesidad. Con baja talla 13%. Se detectó riesgo nutricional con HTNP en 50,7% de los ingresos. Las patologías de base más frecuentes fueron cardiopatías y neoplasias. En pacientes con riesgo nutricional: estadía hospitalaria media de 5 días, 13,5% cursó con infecciones intrahospitalarias, 68% mantuvo o aumentó de peso durante la internación, 13,5% requirió apoyo nutricional (más utilizado el gavage en 59%). Conclusiones: El niño hospitalizado se encuentra en una situación de vulnerabilidad, por lo que el tamizaje y evaluación nutricional resultan acciones claves para prevenir el deterioro nutricional. En los niños con malnutrición las acciones llevadas a cabo por el Nutricionista Clínico como integrante del equipo de atención, revisten un rol clave para promover y garantizar el derecho de los pacientes a la alimentación adecuada y así mejorar su condición nutricional. (AU)

Introduction: Malnutrition is a state of nutrient deficiency or excess that causes harmful effects and can alter growth increasing morbidity and mortality. Materials and methods: retrospective, descriptive study. Children aged 1-18 years admitted to the hospital between 2016-2018 were included. Sample characterization and anthropometric data were collected. The pediatric nutritional screening tool (PNST) was used to identify nutritional risk and in this subgroup we analyzed: weight variation, nutritional intervention, infectious complications, and length of hospital stay. The analysis of variables was performed with SPSS Statistics 20. Results: 745 patients were evaluated, 373 were girls (50.1%). Median age was 7.3 years. Mean hospital stay was 4 days (1- 123). Among the patients, 5.9% were emaciated, 56.4% eutrophic, 16.8% overweight, and 20.9% obese. Thirteen percent of the patients had short stature. Nutritional risk was detected using HTNP in 50.7% of the admitted patients. The most frequent underlying diseases were heart disease and cancer. In patients at nutritional risk: mean hospital stay was 5 days, 13.5% had hospital-acquired infections, 68% maintained or gained weight during the hospital stay, 13.5% required nutritional support (gavage was the most frequently used in 59%). Conclusions: Hospitalized children are in a vulnerable situation, therefore nutritional screening and evaluation are key actions to prevent nutritional deterioration. In children with malnutrition, the Clinical Nutritionist, as a member of the health care team, plays a key role in promoting and guaranteeing the right of patients to adequate food and thus improve their nutritional condition (AU)

Nutritional Approach to Prevention and Treatment of Cardiovascular Disease in Childhood.

Coronary Heart Disease (CHD) is a major mortality and morbidity cause in adulthood worldwide. The atherosclerotic process starts even before birth, progresses through childhood and, if not stopped, eventually leads to CHD. Therefore, it is important to start prevention from the earliest stages of life. CHD prevention can be performed at different interventional stages: primordial prevention is aimed at preventing risk factors, primary prevention is aimed at early identification and treatment of risk factors, secondary prevention is aimed at reducing the risk of further events in those patients who have already experienced a CHD event. In this context, CHD risk stratification is of utmost importance, in order to tailor the preventive and therapeutic approach. Nutritional intervention is the milestone treatment in pediatric patients at increased CHD risk. According to the Developmental Origin of Health and Disease theory, the origins of lifestyle-related disease is formed in the so called "first thousand days" from conception, when an insult, either positive or negative, can cause life-lasting consequences. Nutrition is a positive epigenetic factor: an adequate nutritional intervention in a developmental critical period can change the outcome from childhood into adulthood.

[Evaluating malnutrition in pediatrics, a current challenge]. / Evaluando la desnutrición en pediatría, un reto vigente.

INTRODUCTION: Malnutrition in pediatric patients conditions their health/illness. Malnutrition in sick children further aggravates their baseline situation, and conditions their evolution and prognosis. Despite its relevance, it is not evaluated in many cases, nor is there a single definition that facilitates its diagnosis. The objective of this article is to establish the principal aspects to consider when evaluating malnutrition, and to highlight the importance of routine evaluation.

INTRODUCCIÓN: La desnutrición en el paciente pediátrico condiciona su salud/enfermedad. La desnutrición en el niño enfermo agrava aun más, si cabe, su situación de base y condiciona su evolución y pronóstico. A pesar de su relevancia, no se evalúa en muchos casos ni se tiene una única definición que facilite su diagnóstico. El objetivo de este artículo es establecer los aspectos prioritarios a la hora de evaluar la desnutrición y resaltar la importancia de hacerlo de forma rutinaria.

Comparing costs and cost-efficiency of platforms for micronutrient powder (MNP) delivery to children in rural Uganda.

Micronutrient powder (MNP) can reduce iron deficiency in young children, which has been well established in efficacy trials. However, the cost of different delivery platforms has not been determined. We calculated the cost and cost-efficiency of distributed MNP through community-based mechanisms and in health facilities in a primarily rural district in Uganda. An endline survey (n = 1072) identified reach and adherence. During the 9-month pilot, 37,458 (community platform) and 12,390 (facility platform) packets of MNP were distributed. Each packet consisted of 30 MNP sachets. In 2016, total costs were $277,082 (community platform, $0.24/sachet) and $221,568 (facility platform, $0.59/sachet). The cost per child reached was lower in the community platform ($53.24) than the facility platform ($65.97). The cost per child adhering to a protocol was $58.08 (community platform) and $72.69 (facility platform). The estimated cost of scaling up the community platform pilot to the district level over 3 years to cover approximately 17,890 children was $1.23 million (scale-up integrated into a partner agency program) to $1.62 million (government scale-up scenario). Unlike previous estimates, these included opportunity costs. Community-based MNP delivery costs were greater, yet more cost-efficient per child reached and adhering to protocol than facility-based delivery. However, total costs for untargeted MNP delivery under program settings are potentially prohibitive.

Effectiveness and cost-effectiveness of 4 supplementary foods for treating moderate acute malnutrition: results from a cluster-randomized intervention trial in Sierra Leone.

BACKGROUND: Moderate acute malnutrition (MAM) affects 33 million children annually. Investments in formulations of corn-soy blended flours and lipid-based nutrient supplements have effectively improved MAM recovery rates. Information costs and cost-effectiveness differences are still needed. OBJECTIVES: We assessed recovery and sustained recovery rates of MAM children receiving a supplementary food: ready-to-use supplementary food (RUSF), corn soy whey blend with fortified vegetable oil (CSWB w/oil), or Super Cereal Plus with amylase (SC + A) compared to Corn Soy Blend Plus with fortified vegetable oil (CSB+ w/oil). We also estimated differences in costs and cost effectiveness of each supplement. METHODS: In Sierra Leone, we randomly assigned 29 health centers to provide a supplement containing 550 kcal/d for ∼12 wk to 2691 children with MAM aged 6-59 mo. We calculated cost per enrollee, cost per child who recovered, and cost per child who sustained recovery each from 2 perspectives: program perspective and caregiver perspective, combined. RESULTS: Of 2653 MAM children (98.6%) with complete data, 1676 children (63%) recovered. There were no significant differences in the odds of recovery compared to CSB+ w/oil [0.83 (95% CI: 0.64-1.08) for CSWB w/oil, 1.01 (95% CI: 0.78-1.3) for SC + A, 1.05 (95% CI: 0.82-1.34) for RUSF]. The odds of sustaining recovery were significantly lower for RUSF (0.7; 95% CI 0.49-0.99) but not CSWB w/oil or SC + A [1.08 (95% CI: 0.73-1.6) and 0.96 (95% CI: 0.67-1.4), respectively] when compared to CSB+ w/oil. Costs per enrollee [US dollars (USD)/child] ranged from $105/child in RUSF to $112/child in SC + A and costs per recovered child (USD/child) ranged from $163/child in RUSF to $179/child in CSWB w/oil, with overlapping uncertainty ranges. Costs were highest per sustained recovery (USD/child), ranging from $214/child with the CSB+ w/oil to $226/child with the SC + A, with overlapping uncertainty ranges. CONCLUSIONS: The 4 supplements performed similarly across recovery (but not sustained recovery) and costed measures. Analyses of posttreatment outcomes are necessary to estimate the full cost of MAM treatment. This trial was registered at clinicaltrials.gov as NCT03146897.

Response to Malnutrition Treatment in Low Weight-for-Age Children: Secondary Analyses of Children 6-59 Months in the ComPAS Cluster Randomized Controlled Trial.

Weight-for-age z-score (WAZ) is not currently an admission criterion to therapeutic feeding programs, and children with low WAZ at high risk of mortality may not be admitted. We conducted a secondary analysis of RCT data to assess response to treatment according to WAZ and mid-upper arm circumference (MUAC) and type of feeding protocol given: a simplified, combined protocol for severe and moderate acute malnutrition (SAM and MAM) vs. standard care that treats SAM and MAM, separately. Children with a moderately low MUAC (11.5-12.5 cm) and a severely low WAZ (<-3) respond similarly to treatment in terms of both weight and MUAC gain on either 2092 kJ (500 kcal)/day of therapeutic or supplementary food. Children with a severely low MUAC (<11.5 cm), with/without a severely low WAZ (<-3), have similar recovery with the combined protocol or standard treatment, though WAZ gain may be slower in the combined protocol. A limitation is this analysis was not powered for these sub-groups specifically. Adding WAZ < -3 as an admission criterion for therapeutic feeding programs admitting children with MUAC and/or oedema may help programs target high-risk children who can benefit from treatment. Future work should evaluate the optimal treatment protocol for children with a MUAC < 11.5 and/or WAZ < -3.0.

Evaluando la desnutrición en pediatría, un reto vigente / Evaluating malnutrition in pediatrics, a current challenge

La desnutrición en el paciente pediátrico condiciona su salud/enfermedad. La desnutrición en el niño enfermo agrava aun más, si cabe, su situación de base y condiciona su evolución y pronóstico. A pesar de su relevancia, no se evalúa en muchos casos ni se tiene una única definición que facilite su diagnóstico. El objetivo de este artículo es establecer los aspectos prioritarios a la hora de evaluar la desnutrición y resaltar la importancia de hacerlo de forma rutinaria. (AU)

Malnutrition in pediatric patients conditions their health/illness. Malnutrition in sick children further aggravates their baseline situation, and conditions their evolution and prognosis. Despite its relevance, it is not evaluated in many cases, nor is there a single definition that facilitates its diagnosis. The objective of this article is to establish the principal aspects to consider when evaluating malnutrition, and to highlight the importance of routine evaluation. (AU)

Adequacy of Nutrient Intakes of Severely and Acutely Malnourished Children Treated with Different Doses of Ready-To-Use Therapeutic Food in Burkina Faso.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are designed to cover the daily nutrient requirements of children with severe acute malnutrition (SAM). However, with the transfer of uncomplicated SAM care from the hospital environment to the community level, children will be able to consume complementary and family foods (CFF) in addition to RUTF, and this might decrease the quantity of RUTF needed for recovery. OBJECTIVES: Using an individually randomized clinical trial, we investigated the effects of a reduced RUTF dose on the daily energy and macronutrient intakes, the proportion of energy coming from CFF, and the mean probability of adequacy (MPA) of intake in 11 micronutrients of 516 children aged 6-59 mo who were treated for SAM in Burkina Faso. METHODS: The data were collected using a single 24-h multipass dietary recall, 1 mo after starting treatment, from December 2016 to August 2018, repeated on a subsample of 66 children. Differences between children receiving the reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by linear mixed models. RESULTS: Daily energy intake was lower (P < 0.01) in the intervention arm (mean ± SD 1321 ± 339 kcal) than in the control arm (1467 ± 319 kcal). CFF contributed to 40% of the daily energy intake in the intervention and 35% in the control arm. The MPA for 11 micronutrients was 0.89 ± 0.1 in the intervention arm and 0.95 ± 0.07 in the control arm (P = 0.06). CONCLUSIONS: Reducing the dose of RUTF during SAM treatment had a negative impact on daily energy intake of the children. Despite this, children covered their recommended energy intake. The energy intake coming from CFF was similar between arms, suggesting that children's feeding practices did not change due to the reduction in RUTF in this context. This trial was registered at the IRSCTN registry as ISRCTN50039021.

The Nutritional Impact of Milk Beverages in Reducing Nutrient Inadequacy among Children Aged One to Five Years in the Philippines: A Dietary Modelling Study.

Around half of Filipino children are not consuming any dairy products on a given day, which has shown to be associated with increased risk of inadequate nutrient intakes. The current study applies dietary modelling to assess the nutritional impact of meeting dairy recommendations in reducing nutrient inadequacy in children aged one to five years in the Philippines. Dietary intake data of Filipino children aged one to five years (n = 3864) were analyzed from the 8th National Nutrition Survey 2013. Children who did not meet national dairy recommendations were identified. Two scenarios were applied, based on two types of commonly consumed milk products by the survey participants. In scenario one, one serving of powdered milk was added to the diet of these children. In scenario two, one serving of a young children milk (YCM) or preschool children milk (PCM) was added to the diet of children aged one to two years and three to five years, respectively. Mean nutrient intakes and percentages of children with inadequate intakes were estimated before and after applying modelling scenarios. Scenario one demonstrated improvement in calcium, phosphorus, sodium, vitamin A and riboflavin intakes, while in scenario two, further improvement of intakes of a wider range of nutrients including iron, selenium, zinc, magnesium, potassium, vitamins C, D, E, thiamin, niacin, vitamins B6, and B12 was observed. In both scenarios, if all children would meet their dairy recommendations, theoretical reductions in population nutrient inadequacy would be observed for all micronutrients, for example, only 20% of children aged one to two years would be inadequate in vitamin A instead of the current 60%, iron inadequacy would see a 5% reduction, and approximately 10% reduction for calcium and 20% reduction for folate. The present study is the first to apply dietary modelling to assess the theoretical impact of meeting dairy recommendations on nutrient inadequacy in children in the Philippines. Dairy consumption should be encouraged as part of the strategy to reduce nutrient inadequacies. Calcium, iron, vitamins D, E, and folate are of concern in the Philippines as the level of inadequacies are extremely high in early years, YCM and PCM can help increase the intake of these nutrients.

Impact of Treatment with RUTF on Plasma Lipid Profiles of Severely Malnourished Pakistani Children.

(1) Background: Little is known on impacts of ready-to-use therapeutic food (RUTF) treatment on lipid metabolism in children with severe acute malnutrition (SAM). (2) Methods: We analyzed glycerophospholipid fatty acids (FA) and polar lipids in plasma of 41 Pakistani children with SAM before and after 3 months of RUTF treatment using gas chromatography and flow-injection analysis tandem mass spectrometry, respectively. Statistical analysis was performed using univariate, multivariate tests and evaluated for the impact of age, sex, breastfeeding status, hemoglobin, and anthropometry. (3) Results: Essential fatty acid (EFA) depletion at baseline was corrected by RUTF treatment which increased EFA. In addition, long-chain polyunsaturated fatty acids (LC-PUFA) and the ratio of arachidonic acid (AA)/linoleic acid increased reflecting greater EFA conversion to LC-PUFA, whereas Mead acid/AA decreased. Among phospholipids, lysophosphatidylcholines (lyso.PC) were most impacted by treatment; in particular, saturated lyso.PC decreased. Higher child age and breastfeeding were associated with great decrease in total saturated FA (ΣSFA) and lesser decrease in monounsaturated FA and total phosphatidylcholines (ΣPC). Conclusions: RUTF treatment improves EFA deficiency in SAM, appears to enhance EFA conversion to biologically active LC-PUFA, and reduces lipolysis reflected in decreased ΣSFA and saturated lyso.PC. Child age and breastfeeding modify treatment-induced changes in ΣSFA and ΣPC.

Sensory evaluation and volatile compounds of an alternative ready-to-use therapeutic food for malnourished children.

Ready-to-use therapeutic foods (RUTFs) are special foods used to encourage rapid weight gain in 5-year-old malnourished children, avoiding hospitalization. The factors affecting sensory characteristics and acceptability of RUTFs have been not adequately described. The aim of this work was to evaluate both the sensory properties and volatile compounds of four alternative RUTFs, varying in soy and sorghum, icing sugar, and oil content. Nine nonoral sensory attributes were evaluated by nine selected and trained assessors. The perceived intensity of five oral sensory attributes and the overall liking were assessed by 100 adult consumers. The volatile compounds were extracted and concentrated by solid phase microextraction and analyzed by gas chromatography/mass spectrometry. RUTF formulations significantly differed for graininess between fingers (size of granules) (P = 0.007), viscosity (P = 0.013), adhesiveness to the spoon (P < 0.044), and meltability (P = 0.005), but in consumers' opinion, they differed only for difficulty in swallowing, intensity of global odor, flavor, and sweetness. A positive correlation between overall liking and sweetness was found. Volatile compounds arising from lipid oxidation (hexanal and octanoic acid) were positively correlated with global odor and flavor. These attributes negatively affected the overall liking and were mainly contained in one out of the four formulations. Sensory and instrumental characterization identified key attributes for this kind of food, such as difficulty in swallowing, global odor, and sweetness, suggesting how to formulate an alternative RUTF to be used for a future clinical trial on malnourished children. PRACTICAL APPLICATION: Starting from the world's need to fight child malnutrition, the present study tried to characterize alternative ready-to-use therapeutic foods (RUTFs), special foods used to encourage rapid weight gain in 5-year-old malnourished children, from several points of view, such as acceptability, stability, technological, and overall quality. Results obtained will be an aid to setup the technological conditions and scale-up parameters for local productions of RUTFs to be tested in real trials on malnourished children. Indeed, key sensory attributes that drive consumer acceptance for this special food, such as sweetness and difficulty in swallowing, came out from the present study.

The influence of nutrition on clinical outcomes in children with cancer.

Adequate and appropriate nutrition is essential for growth and development in children; all put at risk in those with cancer. Overnutrition and undernutrition at diagnosis raise the risk of increased morbidity and mortality during therapy and beyond. All treatment modalities can jeopardize nutritional status with potentially adverse effects on clinical outcomes. Accurate assessment of nutritional status and nutrient balance is essential, with remedial interventions delivered promptly when required. Children with cancer in low- and middle-income countries (LMICs) are especially disadvantaged with concomitant challenges in the provision of nutritional support. Cost-effective advances in the form of ready-to-use therapeutic foods (RUTF) may offer solutions. Studies in LMICs have defined a critical role for the gut microbiome in the causation of undernutrition in children and have demonstrated a beneficial effect of selected RUTF in redressing the imbalanced microbiota and improving nutritional status. Challenges in high-income countries relate both to concerns about the potential disadvantage of preexisting obesity in those newly diagnosed and to undernutrition identified at diagnosis and during treatment. Much remains to be understood but the prospects are bright for offsetting malnutrition in children with cancer, resulting in enhanced opportunity for healthy survival.

The relevance of nutrition to pediatric oncology: A cancer control perspective.

It is indisputable that adequate and appropriate nutrition is fundamental to the health, growth, and development of infants, children, and adolescents, including those with cancer. Nutrition has a role in most of the accepted components of the cancer control spectrum, from prevention through to palliation. The science of nutrigenomics, nutrigenetics, and bioactive foods (phytochemicals), and how nutrition affects cancer biology and cancer treatment, is growing. Nutritional epigenetics is giving us an understanding that there are possible primary prevention strategies for pediatric cancers, especially during conception and pregnancy, which need to be studied. Primary prevention of cancer in adults, such as colorectal cancer, should commence early in childhood, given the long gestation of nutritionally related cancers. Obesity avoidance is definitely a target for both pediatric and adult cancer prevention, commencing in childhood. There is now compelling evidence that the nutritional status of children with cancer, both overweight and underweight, does affect cancer outcomes. This is a potentially modifiable prognostic factor. Consistent longitudinal nutritional assessment of patients from diagnosis through treatment and long-term follow-up is required so that interventions can be implemented and evaluated. While improving, there remains a dearth of basic and clinical nutritional research in pediatric oncology. The perspective of evaluating nutrition as a cancer control factor is discussed in this article.

Clinical Outcome of Febrile Tanzanian Children with Severe Malnutrition Using Anthropometry in Comparison to Clinical Signs.

Children with malnutrition compared with those without are at higher risk of infection, with more severe outcomes. How clinicians assess nutritional risk factors in febrile children in primary care varies. We conducted a post hoc subgroup analysis of febrile children with severe malnutrition enrolled in a randomized, controlled trial in primary care centers in Tanzania. The clinical outcome of children with severe malnutrition defined by anthropometric measures and clinical signs was compared between two electronic clinical diagnostic algorithms: ePOCT, which uses weight-for-age and mid-upper arm circumference to identify and manage severe malnutrition, and ALMANACH, which uses the clinical signs of edema of both feet and visible severe wasting. Those identified as having severe malnutrition by the algorithms in each arm were prescribed antibiotics and referred to the hospital. From December 2014 to February 2016, 106 febrile children were enrolled and randomized in the parent study, and met the criteria to be included in the present analysis. ePOCT identified 56/57 children with severe malnutrition using anthropometric measures, whereas ALMANACH identified 2/49 children with severe malnutrition using clinical signs. The proportion of clinical failure, defined as the development of severe symptoms by day 7 or persisting symptoms at day 7 (per-protocol), was 1.8% (1/56) in the ePOCT arm versus 16.7% (8/48) in the Algorithm for the MANagement of Childhood illnesses arm (risk difference -14.9%, 95% CI -26.0%, -3.8%; risk ratio 0.11, 95% CI 0.01, 0.83). Using anthropometric measures to identify and manage febrile children with severe malnutrition may have resulted in better clinical outcomes than by using clinical signs alone.

Research protocol local ingredients-based supplementary food as an alternative to corn-soya blends plus for treating moderate acute malnutrition among children aged 6 to 59 months: a randomized controlled non-inferiority trial in Wolaita.

BACKGROUND: In Ethiopia, 12.5% of children below 5 years are wasted, and 9.7% are moderately wasted. The present strategy for the management of moderate acute malnutrition (MAM) is a supplementary feeding program; however, this is only provided to chronically food-insecure areas. This randomized controlled non-inferiority trial examines if Local ingredients-based supplement (LIBS) is as effective as corn-soya blends plus (CSB+) in treating moderate acute malnutrition among children aged 6-59 months. METHODS: A randomized controlled non-inferiority trial will be conducted with moderately wasted children aged 6 to 59 months in Wolaita, Ethiopia. The calculated sample size is 324 (i.e. with 162 children in each of two arms, to be assigned by randomization). The daily ration will be: 100 g of LIBS plus 25.2 g of sugar with 8 ml oil in the intervention group, and 150 g of CSB+ with 16 ml of oil in the control group. These interventions will be provided for a maximum period of 12 weeks, with follow-up performed on a weekly basis. Data analysis will be done using SPSS and STATA software. Both intention-to-treat and per protocol analyses will be done. Hazard ratio and Kaplan-Meier (log rank) curves of survival analysis will be done to predict the probability of recovery rate. Logistic regression will be used to test for interactions between independent and dependent variables. Analysis of variances, t-tests, fisher's exact test and chi-square tests will be used to assess baseline characteristics. CONCLUSIONS: This paper will introduce to the existing research locally available nutritious foods which have the potential to enhance recovery from moderate acute malnutrition and to reduce the burden of malnutrition. The perceptions of mothers on feeding children with local ingredient-based supplementary food to assist recovery from moderate acute malnutrition will be the focus of in a qualitative study to follow; this will provide a further contribution in an evolving area of research. TRIAL REGISTRATION: Pan-African Clinical Trial Registration number: PACTR201809662822990, retrospectively registered on 11/09/2018.

Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) - study protocol of an open-label trial to investigate the mechanisms underlying the effects of a few-foods diet on ADHD symptoms in children.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child's development. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Currently, treatment consists of behavioural and pharmacological therapy. However, ADHD medication is associated with several side effects, and concerns about long-term effects and efficacy exist. Therefore, there is considerable interest in the development of alternative treatment options. Double-blind research investigating the effects of a few-foods diet (FFD) has demonstrated a significant decrease in ADHD symptoms following an FFD. However, an FFD requires a considerable effort of both child and parents, limiting its applicability as a general ADHD treatment. To make FFD intervention less challenging or potentially obsolete, we need to understand how, and in which children, an FFD affects ADHD behaviour and, consequently, the child's well-being. We hypothesise that an FFD affects brain function, and that the nutritional impact on ADHD is effectuated by a complex interplay between the microbiota, gut and brain, that is, the microbiota-gut-brain axis. METHODS AND ANALYSIS: The Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) study is an open-label trial with researchers blinded to changes in ADHD symptoms during sample processing and initial data analyses. ETHICS AND DISSEMINATION: The Medical Research and Ethics Committee of Wageningen University has approved this study (NL63851.081.17, application 17/24). Results will be disseminated through peer-reviewed journal publications, conference presentations, (social) media and the BRAIN study website. A summary of the findings will be provided to the participants. TRIAL REGISTRATION NUMBER: NCT03440346. STUDY DATES: Collection of primary outcome data started in March 2018 and will be ongoing until 100 children have participated in the study. Sample data analysis will start after all samples have been collected.