MINISTRY OFEDUCATION & TRAINING MINISTRY OF HEALTH NATIONAL INSITUTE OF NUTRITION NGUYEN THI LUONG HANH EFFICACY OF NUTRITIONAL INTERVENTION FOR ANOREXIC CHILDREN AGED 12-36 MONTHS AFTER
Trang 1MINISTRY OF
EDUCATION & TRAINING MINISTRY OF HEALTH
NATIONAL INSITUTE OF NUTRITION
NGUYEN THI LUONG HANH
EFFICACY OF NUTRITIONAL INTERVENTION FOR ANOREXIC CHILDREN AGED 12-36 MONTHS AFTER USING ANTIBIOTICS IN PEDIATRICS DEPARTMENT OF
GENERAL HOSPITAL
IN BAC NINH PROVINCE
Specialize: Nutrition Code: 9720401
SUMMARY OF PhD THESIS ON NUTRITION
Hanoi - 2019
Trang 2THIS THESIS WAS COMPLETED AT THE INSTITUTE OF NUTRITION
Science Advisors:
1 Asc Prof Nguyen Thi Lam, MD, PhD
2 Asc Prof Truong Tuyet Mai, MD, PhD
At the time…….h, date ………….month…… years 2019
The thesis can be found at:
- The National Library
- Library of the National Institute of Nutrition
Trang 3Anorexia is a common symptom in children, widelydistributed to different ages in different pathologies The data fromVietnam and other countries indicate that anorexia occurred in about20-50% of children aged 6-36 months
Anorexia will lead to adverse consequences for the child'sdevelopment such as malabsorption of nutrients in the digestive tract,growth retardation in weight and height, micronutrient deficiency,and immunodeficiency The diarrhea and respiratory infections aretwo manning infectious diseases in children under 5 years old Theusing antibiotics too widely, often unnecessarily, especially buyingantibiotics without a doctor's prescription are the causes of theincreasing resistance to bacteria T1he antibiotics can disrupt theintestinal microflora, affecting the activity of digestive enzymes, inwhich the digestive enzyme polysaccharide is most weakened,followed by protein digesting enzymes These eating disorders haveled to anorexia, malnutrition, and micronutrient deficiencies inchildren
Studies on evaluating anorexia, especially anorexia after usingantibiotics, as well as research on the production of specific nutritionalproducts for this target group have not been paid attention For this
reason, the study on " Efficacy of nutritional intervention for Anorexic children aged 12-36 months after using antibiotics in Pediatric Department of General hospital in Bac Ninh province”was conducted.
Trang 4Objectives of the study
1 To describe the status of anorexia, nutritional status in children
12-36 months after using antibiotics in Pediatric Department, Bac Ninh
General Hospital
2 To compare the efficacy in improving anorexia, serum zinc,hemoglobin in children 12-36 months of anorexia after usingantibiotics, when using 2 nutritional products: MTH.VC (contains bio-enzyme, probiotic, zinc, lysine, vitamin B1) and VC (containing zinc,lysine, vitamin B1) in Pediatric Department, Bac Ninh GeneralHospital
3 To evaluate the changes in weight, gastrointestinal disorders(microflora, stool excess) of the supplement of MTH.VC and VCproducts for children from 12 to 36 months of age anorexia after usingantibiotics
New contributions of the thesis:
As the first study in Vietnam to assess anorexia status among 12-36months old children with a history of infection diseases usingantibiotics Given the prevalence of anorexia in this group of children,confirming whether antibiotic used is one of the causes, or co-factors,that contribute to anorexia in children Providing scientific evidence
on the effects of both MTH.VC and VC nutritional products inimproving the nutritional status, reducing the risk of underweight andanorexia; positive improve zinc status, anemia and digestivemicroflora balance in children after using antibiotics
The layout of the thesis: The thesis consists of 133 pages (excluding
references and appendices), of which: Introduction: 3 pages; Researchobjectives: 1 page; Overview of documents: 38 pages; Subjects andresearch methods: 26 pages; Research results: 33 pages; Discussion:
Trang 530 pages; Conclusion: 2 pages; Recommendation: 1 page The thesishas 29 tables, 5 figures, charts and 202 references.
Chapter 1 OVERVIEW DOCUMENTS 1.1 Anorexia: diagnostic criteria, causes and consequences
1.1.1 Definition and criteria for anorexia diagnosis:
Classified by WHO 1993 and American Psychological AssociationDSM-5:
- Reduced energy consumption compared to RecommendationDietary Allowance leads to a significant reduction in body weightcompared to age, gender, growth retardation
- Fear of gaining weight or becoming obese, despite beingunderweight
- Disorders of perception, evaluation of lean body weight, notnoticed the excessive impact of the current weight loss of thebody
.Diagnosis of anorexia in Vietnam often relies on one of the
following three signs: 1) Refusing to eat or keep food in the mouth for
a long time; 2) Do not eat half of the child's food for age (by 1 day); 3)
Or the child eats> 1/2 the amount of food at one meal, but due topressure, with a long meal time (> 30 minutes)
1.1.2 Anorexia consequences
Lack of energy, growth retardation; Micronutrient deficiency (irondeficiency, zinc deficiency); Affect the psychology of the child
1.1.3 The situation of eating disorders and anorexia in children
The statistic data from United States and some developed countriesindicesan estimated about 5% of babies are born lazy feeding, but bythe age of 2-3 years olds, up to 30-40% anorexic In Vietnam, somesurveys conducted in Hanoi, TP Ho Chi Minh showed that anorexia inchildren 1-6 years old ranged from 16.33% - 46.9%, with fluctuationsdepending on the age group, the highest encounter rate at 12-24months
Trang 61.1 4 Anorexia after using antibiotics
With the increasing incidence of infectious diseases, along with theabuse of antibiotics, causing digestive disorders, fatigue, anorexia inchildren may be due to the following mechanisms: 1) Imbalance inintestinal microflora; 2) Disorders of the nervous system endocrinegastrointestinal tract; 3) Disorders of excretion of digestive enzymes;4) Loss or malabsorption of micronutrients
1.2 Solutions to prevent and treat anorexia after using antibiotics
1.2.1 Principle: The treatment process requires a close cooperationbetween the physician and the child's parents, from antibiotic processtherapy to other treatment with appropriate dietary changes
1.2.2 Direct or individual nutrition advice: Breastfeeding guidelines,about the importance of breast milk in the first 6 months For olderchildren, receiving supplemented food: Should eat soft foods, diversefood, easy to digest, divided into small meals How to change foodsand offer foods that your child seems to like more to encourage them
to eat more, stimulate appetite How to eat when your child has adigestive disorder in case of using antibiotics…
1.2.3 Nutritional supplements and some biological products
Because the use of antibiotics may have an impact on the intestinalmicroflora, digestive enzymes, zinc lead to digestive disorders,anorexia so it can be used: digestive enzymes, probiotics, zinc ,lysine, vitamin B1 for anorexia children
- Digestive enzymes: They are produced and start working from themouth, stomach, pancreas and intestines Each type of digestiveenzyme participates in specific functions and helps food digested tothe absorptional units then absorbed into the lymphatic system andblood vessels, providing nutrients for all activities of the body
- Use of probiotics: Their effects are restoring natural microorganismsafter antibiotic treatment, helping to balance intestinal microflora,preventing diarrhea and improving anorexia status
- Zinc supplement: Zinc is included in the composition of hundreds ofbiological enzymes, with thousands of different functions in the humanbody, taking part in structural functions for some enzymes The role ofzinc in growth function , immune capacity of people are increasingly
Trang 7concerned Zinc play the improtant roles in energy metabolism andcelle/tissus developpment, in appetite and growth of the children
- Lysine supplementation: Lyzine plays a key role in converting fattyacids into energy Lyzine helps children to increase appetite, increasemetabolism, absorb maximum nutrients Lack of lyzine can causechildren to grow slowly, anorexia, easily lack of digestive enzymes andhormones
- Vitamin B1 supplement: involved in glucid metabolism, in theprocess of transmitting nerve impulses such as acetylcholine orthymidine triphosphate (TTP) in the transportation of sodium throughthe nerve cell membrane and many other functions Clinical signs ofB1 deficiency are also common, starting with anorexia and weightloss, mental changes and muscle weakness
* For objective 2 and 3: Children 12-36 months of age who are from
the target of objective 1: have been treated with antibiotics, ending 1week to 1 month before selection time; existing the anorexia; have theweight for/ age Z score(WAZ) from - <1SD to - 2SD; The parent ofthe child agrees to participate in the study
2.2.2 Exclusion criteria
For objective 1: Children are outside the age of 1236 months;
-Children suffer from birth defects such as heart disease, cleft lip, cleftpalate
For objective 2 and 3: Have a WAZ outside - 2SD to -1SD; Having
acute infections, taking oral or injection antibiotics or stopping using
Trang 8antibiotics for more than 1 month; Children with birth defects such asheart disease, cleft lip
2.2 Research location
Bac Ninh General Hospital; Yen Phong district Preventive MedicineCenter; Children have permanent address in 8 communes of YenPhong district, Bac Ninh province
The analysis of fecal and biochemical samples have been done inNational Institute of Nutrition
2.3 Implementing time: Total time for screening and intervention
were extended from April 2015 to June 2016; Analyze, process dataand write reports in the period 6/2016-12/2018
2.4 Research design: Designed with 2 stages:
Phase I: Cross-sectional study describing and assessing anorexia and
nutrition in children after using antibiotics
Phase II: Double blind intervention study, comparing before and after
intervention to evaluate the efficacy of two types of products,comparing the efficacy between the two products for anorexiachildren after using antibiotics
2.5 Sample size
2.5.1 For objective 1:anorexia
prevalence after antibiotic
utilization:
n=sample size; Z(1- /2) = 1,96 (
= 5%); p: prevalence after antibiotics utilization, estimated 50% formaximum sample; d: estimated error(= 0.052).The number ofsamples counted was 356 children, an additional 3% of the reserve,the number of samples to choose was 366 children
.n=subject number for each group; Z(1-α/2) =1,96((α = 5%);Z (1-β) =1,28(β
=90%); p1:anorexia prevalence at the end of the study for VC
Trang 9group( 81%); p2: anorexia prevalence at the end of the study for MTH.
VC group ( 55%)
Changes of the mean value before
and end of the intervention
n=number of the subjects /group; Z
2.6 Method and organization of sampling
2.6.1 Phase I: For investigate the rate of anorexia after using
antibiotics
• New selection: children who qualify for medical examination and
treatment at Bac Ninh province hospital, using antibiotics
• Selected through the archive file: eligible children from 8
communes, who have been treated with antibiotics, finishedantibiotics have been 1 week to 1 month up to the time of recruitment
2.6.2 Phase II: For Intervention study
When eligible, children were randomly selected and divided into one
of two groups, paying attention to similarities in WAZ score and agegroups for each selection
At the baseline evaluation (D0), in addition to the general sample ofthe screening, the child had a blood drawn for testing, given a stoolcollection device, instructions on how to take and store stool, and takecare to return stool samples at the next day
Children are scheduled to come back for re-examination at theweekend day (Saturday and Sunday) of each week in the month toidentify anorexia and nutritional status
At each visit, parents of the child are given the material for toolssample and instructions on how to take stool, store stool and bring it tothe examination area
2.7 Intervention products
Consists of 2 products, each of which is tested for 1 research group.The intervention products are packaged in 3g, have the samepackaging shape, are denoted by the groups AA, BB corresponding to
2 intervention groups:
Trang 10- MTH.VC group: each sachet contains zinc (4.1 mg), lysine (134
mg), B1 (0.5 mg), Amylase (390 UI / g), Protease (120 UI / g),Lipase (120 UI / g) , Probiotics (109 CFU / g per strain Bacillusclausii and B subtilis)
- VC group: each sachet contains zinc (4.1 mg), lysine (134 mg),
B1 (0.5 mg) like the MTH.VC group
These two types of products are formulated by the National Institute
of Nutrition, are manufactured in facilities that meet ISO standards,have been proven to ensure criteria on nutrition, food safety…forchildren
Children of each intervention group were instructed to use 2sachets /day (one in morning, and 1 pm afternoon), for 21 days consecutive,can be mixed with soups, porridge or mixed with water, milk to drink
2.8 Interventions organization and human resources
2.8.1 Training for staff involved in the study:
Human resources: PhD students are directly involved in researchdesign, site selection, daily sample selection for screening andintervention study, evaluation at follow-up visits as well as beingresponsible for conducting research organizations
Training for investigators of the National Institute of Nutrition,medical staff at the Pediatric clinic of Bac Ninh General Hospital,district and commune health center on research objectives, researchsubjects and selection criteria subjects, how to monitor the use ofresearch products, time of re-examination, how to collect data forindicators, blood collection techniques, stool collection
Training for mothers (caregivers), on the purpose, content of research,diet, how to care for children Instructions on how to identify basicinformation about illnesses, taking children's products during study indaily monitoring book Teach mothers how to use the product package
by mixing it with cold or warm filtered water, how to mix the productpackage into a bowl of porridge, milk for children Instruct mothers onhow to collect and store stool for children on the first day ofexamination as well as the re-evaluation days
2.8.2 Monitoring and supervision during the intervention
Researchers call daily or meet with commune and district healthcollaborators about the work The distribution of research productpackages: collaborators directly distribute products weekly (onSaturdays and Sundays), each child is given 1 bag of 14 packages of
Trang 11products per week, with a dose of 2 packages / day for 3 weeks (21days) Families will be issued an appointment for the coming weeks toreceive the product or review.
Supervisors also record the health status of children When childrenhave clinical signs such as diarrhea, constipation, live feces,infections, supervisors and collaborators come directly to check andrecord to get accurate information and notify fellows to treatment
2.9 Evaluation and monitoring criteria
2.9.1 For objective 1:
The Anthropological and social indices, family background; Takingcare of children; Prevalence of diarrhea and respiratory diseases;Name of antibiotic used; Anorexia: anorexia rate by age, gender;Anthropology and nutritional characteristics
2.9.2 For objective 2,3:
- At D0: General information, internal examination, anthropometry,anorexia; food consumption in the last 24 hours; taking blood for Hband Zn tests; get stool to test digestive microflora
- At D14: Evaluation of nutritional status: weight; anorexia,
- At D21: Evaluation of nutritional status (weight, height); Anorexia;Consumption of food over the past 24 hours, Collect venous blood (3ml) for Hb, Zn test Take stool (about 5g) to identify microflora
- At D35: Assessing nutritional status (weight); Anorexia;foodconsumption in the last 24 hours
2.10 Data collection, classification and evaluation methods
- Family, illness, eating habits by interviewing the child's mother with
a set of pre-designed questionnaires
- Nutritional status: anthropometric data on weight, height, analysisnutritional status by using the ENA smart software, using referencestandard of WHO 2006
- Diagnosis of anorexia after using antibiotics based on 1 of 3 signslasting from 7 to 30 days: 1) Refuse to eat or keep food in the mouthfor a long time (>30 min); 2) Do not eat half of the child's quantityfood for age (by 1 day); 3) Or the child eats> 1/2 the amount of food
at one meal, but due to pressure and a long eating time (> 30 minutes)
- Other diseases: cardio and pulmonary examination, body
temperature, mucosal and dermatologic examinations, diarrhea,respiratory infections , and other medical history
Trang 12- Ask the dietary consumption, using the recording method duringthe last 24 hours, according to the survey training document of theNational Institute of Nutrition, Ministry of Health.
- Taking blood samples for Hb, Zn test: Taking blood for testing: allsubjects were taken 2 ml of venous blood in the morning on fasting
on the day of intervention (D0) and after 21 days (D21) intervened + Blood Hemoglobin measurement: using on 19-indexautomatic analyzer (Sysmex- XP 100) Anemia was determinedwhen Hb <110g / l
+ Serum zinc was quantified by the AtomicadsorptionSpectrometry (AAS) method Zinc deficiency wasdeterminedwhen Zn <9.9 umol / l
-Take stool samples to test the digestive microflora and residueresidues on the start days, 14 days and 21 days of intervention:Residue residues (fat, starch in the stool); The ratio of microflora(percentage of Gram (-) / Gram (+) bacteria in stool: normal is70/30)
2.11 Data analysis: Children who consume the product reach> 90%
of the delivered packages (from 25/28 packages for 14 days and38/42 packages for 21 days) to be included in the statistical efficacy
of the intervention Data were entered using EPIDATA software 3.1;ENA Smart; SPSS 20.0 The Absolute Risk Reduction (ARR)calculations, NNT (Number needed to treat) were used to evaluatethe efficacy of the intervention
2.12 Ethics of research:Study proposal was proved by Ethics
CommitteeNo 377 / VDD-QLKH of National Institute of Nutritionbefore implementation
Trang 13Chapter 3
RESULTS 3.1.Prevalence anorexia, their relationship characteristic of the children anorexia after usinng antibiotics
Table 3.1.Anorexie prevalence classify by aded, sex
18-n =110
24-29 months
n =69
30-36 months
n =85
12-36 months n= 358
)
21(63,6)
23(48,9)
82(39,0)
Girls 15(48,4) 20(46,5
)
19(52,8)
25[65,8)
79(53,4)
40(58,0)
48(56,5)
161(45)
+ p>0,05 between aged groups, sex, 2 test
Table 3.1 shows that the general prevalence of anorexia after usingantibiotic is 45%, including boys 39%, girls 53.4% The rate ofanorexia tends to increase gradually with age: from 35% in theyounger group to 56.5% in the older group; There is a tendency forgirls to be more anorexic than boys in some age groups;although thedifference is not statistically significant (p> 0.05)
Table 3.2.Comparaison the nutritional status of children suffered