Elaborarea unui ghid inovator de diagnostic al copilului obez prin evaluare genetică, antropometrică, de bioimpedanță și ecografic – cod PN-III-P4-ID-PCE-2016-0766, director proiect: prof. dr. Oana Mărginean
| Title project | “The development of an innovative diagnostic guide of obese child through genetics, anthropometric, bioimpedance and ultrasound assessment |
| The Name Program from PN III | Program 4 – Fundamental and Border Research” |
| Type of project | Research Projects Exploratory |
| Action | 1.1.4 Attracting staff with advanced skills from abroad |
| Code Project | PN-III-P4-ID-PCE-2016-0766, Acronim: ID-PedOb |
| Duration contract: | 30 months |
| Beneficiary | University of Medicine and Pharmacy Tirgu Mureş |
| Main objective | The main objective of the project is to design a new custom panel for SNP genotyping of obese children for an early diagnosis and prevention, in order to improve their quality of life. |
| Specific objectives: | SO1: Establishing correlations among a new custom panel for SNP genotyping of obese children with circulating adipokine levels, antropometric, bioimpedance and echografic changes in obese versus normoponderal children; SO2: Designing a protocol for diagnosis of obese children above the age of 5 years depending on genetic determinism, the child’s food decreased intake, a physical activity, and environment and life factor; SO3: Developing a healthy nutritional guide for obese children. |
| Start date | 12/07/2017 |
| Implementation period | 12.07.2017 – 31.12.2019 |
| Total budget value | 849.863,80lei |
| Activities chart | Detailed activities |
| 1. Establishing the children’s inclusion criteria in the study (study group and control group); Deliverable: lists of subjects (400 children: 200 obese children and 200 normoponderal children); informed consent charts; ethics committee approval; blood samples; Members in charge: MCO, MLE, AL, DD1; Month 1 | 1. Identification of children groups who will be divided further according to the BMI/ obese children and control groups |
| 2. Developing the informed consent charts that will be signed by the children’s parents | |
| 3. Obtaining the ethics committee approval | |
| 4. Taking blood samples for laboratory and genetic tests | |
| 2. Obtaining the data regarding the groups of 400 children included in the study through their complex assessment (food intake, anthropometric, paraclinical, through bioimpedance, ecography, complex genetic analysis); Deliverable: Food intake – caloric value, anthropometric evaluation, paraclinical and bioimpedance assessment, elastographic evaluation, analysis of the SNP genotyping involved in obesity for 400 children; Members in charge: MCO, BC, MV, MLE, DM, AL, OP; DD2; Material resources: Caliper, centimeter, pediometer and BIA equipment, ultrasound equipment with elastographic soft, already available; Financial resources for genetic and lab tests: 239.500 lei; Months 2-13 | 1. Assessment of food intake |
| 2. Anthropometric assessment: W (kg), H (cm), MUAC, TSF, BMI, | |
| 3. Paraclinical assessment: total proteins, albumins, lipid profile (cholesterol, TG), glycaemia, proteins, analysis of serum cytokines involved in obesity | |
| 4. The assessment of body mass through electrical bioimpedance (BIA) | |
| 5. Liver ultrasound assessment – elastography | |
| 6. The analysis of the SNP genotyping involved in obesity | |
| 7.The statistical processing of the previously obtained data, establishing certain correlations | |
| 3.The longitudinal assessment (at 6 months) of the 200 obese children included in the study (food intake, anthropometric, paraclinical, BIA, ecography); Deliverable: Food intake – caloric value, anthropometric evaluation, paraclinical assessment; preliminary data analysis, assessment of body fat and lean tissue, elastographic analysis – preliminary data. Members in charge: MCO, MLE, MLE, DM, AL, OP; DD2, Materials: Caliper, centimeter, pedometer, already available, ultrasound equipment with elastographic soft; Financial resources for lab tests: 40.500 lei Month 8-19; | 1. Assessment of food intake |
| 2. Anthropometric assessment: W (kg), H (cm), MUAC, TSF, BMI, | |
| 3. Paraclinical assessment: total proteins, albumins, lipid profile (cholesterol, TG), glycaemia, proteins, analysis of serum cytokines involved in obesity | |
| 4. The assessment of body mass through bioimpedance (BIA) | |
| 5. Liver ultrasound assessment – elastography | |
| 6.The statistical processing of the previously obtained data, establishing certain correlations | |
| 4.The longitudinal assessment (at 12 months) of the 200 obese children included in the study (food intake, anthropometric, paraclinical, BIA, ecography); Deliverable: Food intake – caloric value, anthropometric assessment, paraclinical assessment; preliminary data analysis, assessment of body fatty and lean tissue elastographic analysis – preliminary data, Members in charge: MCO, MLE, DM, AL, OP; DD2, Materials: Caliper, centimeter, pedometer, already available, ultrasound equipment with elastographic soft; Financial resources for lab tests: 40.500 lei; Month 14-25; | 1. Assessment of food intake |
| 2. Anthropometric evaluation: W (kg), H (cm), MUAC, TSF, BMI, | |
| 3. Paraclinical assessment: total proteins, albumins, lipid profile (cholesterol, TG), glycaemia, proteins, analysis of serum cytokines involved in obesity | |
| 4. The assessment of body mass through bioimpedance (BIA) | |
| 5. Liver ultrasound assessment – elastography | |
| 6. The statistical processing of the previously obtained data, establishing certain correlations | |
| 5.The identification of the relevant correlations between the obtained data Deliverable: scientific papers, presentations at scientific events according the analysis of the SNP genotyping involved in obesity between the two groups of children; Members in charge: all team; Materials: correlation software; Month: 26-30 | 1. The final statistical processing of the previously obtained data (data base created during the study). |
| 2. The comparison of the obtained data. | |
| 3. Establishing the obesity related gene correlations between mother and child; | |
| 4. Dissemination: publications and participation in scientific events: presentation of the preliminary and final research results of the project | |
| 6. Designing a algorithm/guide for diagnosis of obese children above the age of 5 years depending on genetic determinism, the child’s caloric intake, physical effort. Deliverable: algorithm/guide for diagnosis of obesity in children; Members in charge: MCO, MLE, BC. Materials: budget: 45.000 lei; Month: 26-30 | 1.A meeting of the team to write the protocol and planning tasks to team members |
| 2. Scientific documentation | |
| 3. Developing the algorithm/guide for diagnosis of obesity in children | |
| 4. Dissemination | |
| 4. Developing a healthy nutritional guide for obese children; Deliverable: nutritional guide; Members in charge: MC, MCO, MLE; Materials: subscription to scientific data base; Month 26-30 | 1. A meeting the team to write the healthy nutritional guide for obese children and planning tasks to team members; |
| 2. Scientific documentation; | |
| 3. Developing the healthy nutritional guide for obese children; | |
| 4.Dissemination |
BASED ON THE RESEARCH ACTIVITIES PERFORMED WITHIN THE PROJECT THE FOLLOWING SCIENTIFIC ARTICLES WERE ISSUED
1. Mărginean CO, Meliț LE, Săsăran VS, Mărginean CD, Mărginean MO, Diagnostic challenges of celiac disease in a young child, A case report and a review of the literature, Medicine, 2018, 97, 22, e10893(1-4), doi: 10.1097/MD.0000000000010893
https://journals.lww.com/md-journal/Fulltext/2018/06010/Diagnostic_challenges_of_celiac_disease_in_a_young.40.aspx
2. Mărginean CO, Meliţ LE, Horvath E, Gozar H, Chinceşan MI, Non-Hodgkin lymphoma, diagnostic, and prognostic particularities in children – a series of case reports and a review of the literature (CARE compliant), Medicine (Baltimore), 2018 Feb; 97(8): e9802. doi: 10.1097/MD.0000000000009802
3. Mărginean CO, Meliț LE, Gozat L, Mărginean CD, Mărginean MO. incomplete Refractory Kawasaki Disease in an Infant—A Case Report and a Review of the Literature, Frontiers in Pediatrics, 2018
https://www.frontiersin.org/articles/10.3389/fped.2018.00210/full
4. Mărginean CO, Meliț LE, Mărginean MO, Segmental Colitis Associated Diverticulosis—A Possible Diagnosis in Teenagers, Front Pediatr. 2018; 6: 168.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996823/
5. CO Mărginean, LE Meliţ, M Dobreanu, MO Mărginean Type V hypertriglyceridemia in children, a therapeutic challenge in pediatrics: A case report and a review of the literature Medicine 96 (51)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758124/
BASED ON THE RESEARCH ACTIVITIES PERFORMED WITHIN THE PROJECT IN THE PERIOD 01.08.2018 - 31.12.2018, THE FOLLOWING SCIENTIFIC ARTICLES WERE ISSUED
1. Mărginean CO, Meliţ LE, Gozar H, Horvath E, Mărginean CD. Atypical onset of total colonic Hirschprung disease in a small female infant. Medicine 2018;97:38(e12315), http://dx.doi.org/10.1097/MD.0000000000012315, IF 2.028, ISSN0025-7974 https://www.frontiersin.org/articles/10.3389/fped.2018.00271/full
2. Mărginean CO, Meliţ LE, Gozar L, Mărginean CD, Mărginean MO. Incomplete Refractory Kawasaki Disease in an Infant—A Case Report and a Review of the Literature. Front Pediatr 2018;6:210. doi: 10.3389/fped.2018.00210, IF 2.335 https://www.frontiersin.org/articles/10.3389/fped.2018.00210/full
3. Mărginean CO, Meliț LE, Mărginean MO. Segmental colitis associated diverticulosis – A Possible Diagnosis in Teenagers. Front Pediatr 2018;6:168. doi: 10.3389/fped.2018.00168, IF 2.335 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996823/
4. Mărginean CO, Meliț LE, Săsăran VȘ, Mărginean CD, Mărginean MO. Diagnostic challenges of celiac disease in a young child. Medicine 2018;97:22(e10893), ISSN0025-7974, IF 2.028, http://dx.doi.org/10.1097/MD.0000000000010893
5. Mărginean CO, Meliț LE, Horvath E, Gozar H, Chinceșan MI. Non-Hodgkin lymphoma, diagnostic and prognostic particularities in children – a series of case reports and a review of the literature. Medicine 2018; 97:8(e9802), ISSN0025-7974, IF 2.028, http://dx.doi.org/10.1097/MD.0000000000009802
6. Mărginean CO, Meliț LE, Dobreanu M, Mărginean MO. Type V hypertriglyceridemia, a therapeutic challenge in pediatrics. Medicine 2017;96:51(e8864), ISSN 0025-7974, IF 1.803, http://dx.doi.org/10.1097/MD.0000000000008864
Between 01.01.2019 - 31.10.2019
We continued to enroll 250 children in the study, out of which 110 children with obesity, respectively 140 children who met criteria for setting up the control group. These children were examined clinically, paraclinically (liver samples, hemogram, lipid profile, blood sugar), fat mass analysis, lean, water, BMR by bioimpedance, 2D abdominal ultrasound, elastography and fibroscan.
– The database was created in Excel format and immunological tests were performed (interleukins and adipokines), respectively, all the reagents necessary for the genetic tests that were purchased were prepared (determining the panel of polymorphisms involved in obesity, in order to establish the relevant correlations between the data obtained.
– We have continued to purchase the reagents needed to carry out the project.
– Elastography and fibroscan examinations were performed in healthy children, in order to establish cut-off values for healthy liver elasticity, using the 2 methods, knowing that there are no such values yet reported in children (others 200 children divided into different age groups). Then, elastography examinations, respectively fibroscan, were performed in both overweight and obese children versus healthy children, to evaluate the degree of liver fibrosis in NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis).
– There were elaborated several articles that were published in international ISI journals, respectively the preliminary results obtained within the project were communicated, at the following scientific manifestations: National Pediatric Conference April 3-6, 2019, Bucharest, National Pediatrics Congress September 11-14, 2019, Cluj Napoca, Nutrition Conference Tg. Mures, May 2019 (Low-grade systemic inflammation and obesity), PAE 19-22 September 2019 Porto (abstract – The role of neutrophil to lymphocyte ratio and platelet to lymphocyte ration in children’s obesity).
– 1 researcher attended the European Pediatric Congress (EAP Porto) – Dr Mărginean Oana
– At the European Week of Gastroenterology (UEGW) Barcelona 2019, a scientific article was sent.
– At present, we have under evaluation (uploaded to different international ISI journals) 4 more articles, works that are elaborated after analyzing the preliminary results obtained from the project.
– We initiated the following activities: 5. The identification of the relevant correlations between the obtained data, 6. Designing an algorithm / guide for diagnosis of obese children above the age of 5 years depending on genetic determinism, the child’s caloric intake, physical effort and 7. Developing a healthy nutritional guide for obese children, activities that will be completed by the 30th month of the project.
ARTICLES PUBLISHED WITHIN THE PROJECT BETWEEN 01.01.2019 - 31.10.2019
Mărginean CO, Meliţ LE, Ghiga DV, Mărginean MO. Early inflammatory status related to pediatric obesity. Front Pediatr 2019;7:241. doi: 10.3389/fped.2019.00241, IF 2.349, https://www.frontiersin.org/articles/10.3389/fped.2019.00241/full
UPDATE DECEMBRIE 2019Between 01.01.2019 - 31.12.2019 the following activities were carried out within the project:
1. We continued to enroll 300 children in the study, out of which 125 children with obesity, respectively 175 children who met criteria for setting up the control group. These children were examined clinically, paraclinically (liver samples, hemogram, lipid profile, blood sugar), fat mass analysis, lean, water, BMR by bioimpedance, 2D abdominal ultrasound, elastography and fibroscan.
2. The Excel database was set up and immunological tests (interleukins and adipokines) were performed.
3. We continued to purchase reagents and equipment needed to carry out the project.
4. Elastography and fibroscan examinations were performed in healthy children, in order to establish cut-off values for healthy liver elasticity, using the 2 methods, knowing that there are no such values yet reported in children. (other 287 children divided by different age groups). Then, elastography examinations, respectively fibroscan, were performed in both overweight and obese children versus healthy children, to evaluate the degree of liver fibrosis in NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis).
5. There were elaborated several articles that were published in international ISI journals, respectively the preliminary results obtained within the project were communicated, at the following scientific manifestations: National Pediatric Conference April 3-6, 2019, Bucharest, National Congress of Pediatrics September 11-14, 2019, Cluj Napoca, Nutrition Conference Tg. Mures, May 2019 (Low-grade systemic inflammation and obesity), PAE 19-22 September 2019 Porto (abstract – The role of neutrophil to lymphocyte ratio and platelet to lymphocyte ration in children’s obesity).
6. 1 researcher: Dr Mărginean Oana attended the European Pediatric Congress (EAP Porto)
7. At the European Week of Gastroenterology (UEGW) Barcelona 2019, a scientific article was sent. At present we have under evaluation another article, work that is elaborated after analyzing the preliminary results obtained from the project. (Reference values of normal liver stiffness in healthy children by two methods: 2D shear wave and transient elastography, article uploaded to Scientific Reports – red tape)
8. In November 2019, we had two other articles accepted, one of which was the role of the Interleukins involved in obesity and one that evaluated by elastography and fibroscan liver fibrosis in obese children versus the control group.
9. Genetic analysis – Genotyping panel mononucleotide polymorphisms 64 Genetic determinations were also performed. The genotyping analysis was performed using the QuantStudio 12K Flex Real-Time PCR System realtime system provided with OpenArray type block that allows the analysis of dedicated plates.
10. Developing a guideline for good diagnostic practice and therapeutic behavior in obesity which can be useful for all pediatric doctors, but also for family doctors and for monitoring obesity cases in children.
11. In the following period from the data obtained as a result of genetic determinations in obese patients, we will develop scientific articles.
ARTICLES PUBLISHED WITHIN THE PROJECT BETWEEN 01.01.2018 - 31.12.2018
1. Mărginean CO, Meliț LE, Dobreanu M, Mărginean MO. Type V hypertriglyceridemia, a therapeutic challenge in pediatrics. Medicine 2017;96:51(e8864), ISSN 0025-7974, IF 1.803, http://dx.doi.org/10.1097/MD.0000000000008864
2. Mărginean CO, Meliț LE, Ghiga DV, Săsăran MO The assessment of liver fibrosis in children with obesity on two methods: transient and two dimensional shear wave elastography, Scientific Reports, 2019, in press, cu accept de publicare, IF 4,011, ISSN 2045-2322
3. Mărginean CO, Meliț LE, Huțanu A, Ghiga DV, Săsăran MO The adipokines and inflammatory status in the era of pediatric obesity, Cytokine 2020, 126: 154925, IF 3,078, ISSN 1043-4666 doi.org/10.1016/j.cyto.2019.154925