Hiệu quả can thiệp dinh dưỡng cho trẻ 1236 tháng tuổi biếng ăn sau sử dụng kháng sinh tại khoa nhi Bệnh viện đa khoa tỉnh Bắc Ninh ttta

1
MINISTRY
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


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THIS 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
Reviewer 1:

Reviewer 2:
Reviewer 3:

The thesis will be evaluated by the PhD. evaluation committee at
the Institute of Nutrition,
At the time…….h, date ………….month……..years 2019

The thesis can be found at:
- The National Library
- Library of the National Institute of Nutrition


1
INTRODUCTION
Anorexia is a common symptom in children, widely
distributed to different ages in different pathologies. The data from
Vietnam and other countries indicate that anorexia occurred in about
20-50% of children aged 6-36 months.
Anorexia will lead to adverse consequences for the child's
development such as malabsorption of nutrients in the digestive tract,
growth retardation in weight and height, micronutrient deficiency, and
immunodeficiency. The diarrhea and respiratory infections are two
manning infectious diseases in children under 5 years old. The using
antibiotics too widely, often unnecessarily, especially buying
antibiotics without a doctor's prescription are the causes of the
increasing resistance to bacteria. T1he antibiotics can disrupt the
intestinal microflora, affecting the activity of digestive enzymes, in
which the digestive enzyme polysaccharide is most weakened,
followed by protein digesting enzymes. These eating disorders have
led to anorexia, malnutrition, and micronutrient deficiencies in

children.
Studies on evaluating anorexia, especially anorexia after using
antibiotics, as well as research on the production of specific nutritional
products 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.


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Objectives of the study
1. To describe the status of anorexia, nutritional status in children 1236 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 using
antibiotics, when using 2 nutritional products: MTH.VC (contains bioenzyme, probiotic, zinc, lysine, vitamin B1) and VC (containing zinc,
lysine, vitamin B1) in Pediatric Department, Bac Ninh General
Hospital.
3. To evaluate the changes in weight, gastrointestinal disorders
(microflora, stool excess) of the supplement of MTH.VC and VC
products for children from 12 to 36 months of age anorexia after using
antibiotics.
New contributions of the thesis:
As the first study in Vietnam to assess anorexia status among 12-36
months old children with a history of infection diseases using
antibiotics. 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

in

improving the nutritional status, reducing the risk of underweight and
anorexia; positive improve zinc status, anemia and digestive
microflora 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; Research
objectives: 1 page; Overview of documents: 38 pages; Subjects and
research methods: 26 pages; Research results: 33 pages; Discussion:


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30 pages; Conclusion: 2 pages; Recommendation: 1 page. The thesis
has 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 Association
DSM-5:
- Reduced energy consumption compared to Recommendation
Dietary Allowance leads to a significant reduction in body weight
compared to age, gender, growth retardation.
- Fear of gaining weight or becoming obese, despite being
underweight.
- Disorders of perception, evaluation of lean body weight, not
noticed the excessive impact of the current weight loss of the
body.
.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 to
pressure, with a long meal time (> 30 minutes).
1.1.2. Anorexia consequences
Lack of energy, growth retardation; Micronutrient deficiency (iron
deficiency, 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 countries
indicesan estimated about 5% of babies are born lazy feeding, but by
the age of 2-3 years olds, up to 30-40% anorexic. In Vietnam, some
surveys conducted in Hanoi, TP. Ho Chi Minh showed that anorexia in
children 1-6 years old ranged from 16.33% - 46.9%, with fluctuations
depending on the age group, the highest encounter rate at 12-24
months.


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1.1. 4. Anorexia after using antibiotics
With the increasing incidence of infectious diseases, along with the
abuse of antibiotics, causing digestive disorders, fatigue, anorexia in
children may be due to the following mechanisms: 1) Imbalance in
intestinal microflora; 2) Disorders of the nervous system endocrine
gastrointestinal 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 cooperation
between the physician and the child's parents, from antibiotic process
therapy 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 older

children, receiving supplemented food: Should eat soft foods, diverse
food, easy to digest, divided into small meals. How to change foods
and offer foods that your child seems to like more to encourage them to
eat more, stimulate appetite. How to eat when your child has a
digestive 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 intestinal
microflora, 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 the
mouth, stomach, pancreas and intestines. Each type of digestive
enzyme participates in specific functions and helps food digested to
the absorptional units then absorbed into the lymphatic system and
blood vessels, providing nutrients for all activities of the body.
- Use of probiotics: Their effects are restoring natural microorganisms
after antibiotic treatment, helping to balance intestinal microflora,
preventing diarrhea and improving anorexia status.
- Zinc supplement: Zinc is included in the composition of hundreds of
biological enzymes, with thousands of different functions in the human
body, taking part in structural functions for some enzymes. The role of
zinc in growth function , immune capacity ... of people are increasingly


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concerned. Zinc play the improtant roles in energy metabolism and
celle/tissus developpment, in appetite and growth of the children .
- Lysine supplementation: Lyzine plays a key role in converting fatty
acids into energy. Lyzine helps children to increase appetite, increase
metabolism, absorb maximum nutrients. Lack of lyzine can cause

children to grow slowly, anorexia, easily lack of digestive enzymes and
hormones.
- Vitamin B1 supplement: involved in glucid metabolism, in the
process of transmitting nerve impulses such as acetylcholine or
thymidine triphosphate (TTP) in the transportation of sodium through
the nerve cell membrane and many other functions. Clinical signs of
B1 deficiency are also common, starting with anorexia and weight loss,
mental changes and muscle weakness.
Chapter 2
SUBJECTS AND METHODOLOGY
2.1. Research subjects
2.1.1. Criteria for subject selection
* For objective 1:
Children 12-36 months old, residing in 8 communes of Yen Phong
district, Bac Ninh province; have been examined and treated with
antibiotics at Bac Ninh hospital in the period from April 2015 to May
2016.
* 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 1
week to 1 month before selection time; existing the anorexia; have the
weight for/ age Z score(WAZ) from - <1SD to - 2SD; The parent of
the child agrees to participate in the study.
2.2.2. Exclusion criteria
For objective 1: Children are outside the age of 12-36 months; Children suffer from birth defects such as heart disease, cleft lip, cleft
palate ...
For objective 2 and 3: Have a WAZ outside - 2SD to -1SD; Having
acute infections, taking oral or injection antibiotics or stopping using


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antibiotics for more than 1 month; Children with birth defects such as
heart disease, cleft lip ...
2.2. Research location
Bac Ninh General Hospital; Yen Phong district Preventive Medicine
Center; Children have permanent address in 8 communes of Yen
Phong district, Bac Ninh province.
The analysis of fecal and biochemical samples have been done in
National Institute of Nutrition.
2.3. Implementing time: Total time for screening and intervention
were extended from April 2015 to June 2016; Analyze, process data
and 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 anorexia children
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% for
maximum sample; d: estimated error(= 0.052).The number of
samples counted was 356 children, an additional 3% of the reserve,
the number of samples to choose was 366 children.
2.5.2. For objective 2, 3:

 Compare the different
between 2 intervention
groupsat the end of the
intervention time.
.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


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group( 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(1Z (1-β) =1,28(β
α/2) = 1,96(α = 5%);
=90%); µ1 - µ2 : Diferents estimated between 2 groups at the end of
the study; δ: standar devariation of the average value.
Combining the indicators of anorexia children, the number of samples
for each intervention group, the 76 children / group were selected.
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, finished
antibiotics 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 age

groups for each selection.
At the baseline evaluation (D0), in addition to the general sample of
the screening, the child had a blood drawn for testing, given a stool
collection device, instructions on how to take and store stool, and take
care to return stool samples at the next day.
Children are scheduled to come back for re-examination at the
weekend day (Saturday and Sunday) of each week in the month to
identify anorexia and nutritional status.
At each visit, parents of the child are given the material for tools
sample and instructions on how to take stool, store stool and bring it to
the 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 same
packaging shape, are denoted by the groups AA, BB corresponding to
2 intervention groups:


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- 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 Bacillus
clausii 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…for
children.
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 research
design, site selection, daily sample selection for screening and
intervention study, evaluation at follow-up visits ... as well as being
responsible 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, research
subjects and selection criteria subjects, how to monitor the use of
research products, time of re-examination, how to collect data for
indicators, 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 basic
information about illnesses, taking children's products during study in
daily monitoring book. Teach mothers how to use the product package
by mixing it with cold or warm filtered water, how to mix the product
package into a bowl of porridge, milk for children. Instruct mothers on
how to collect and store stool for children on the first day of
examination 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 health
collaborators about the work. The distribution of research product
packages: collaborators directly distribute products weekly (on
Saturdays and Sundays), each child is given 1 bag of 14 packages of


9

products per week, with a dose of 2 packages / day for 3 weeks (21
days). Families will be issued an appointment for the coming weeks to
receive the product or review.
Supervisors also record the health status of children. When children
have clinical signs such as diarrhea, constipation, live feces,
infections, supervisors and collaborators come directly to check and
record 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; Taking
care 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 Hb
and 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 (3
ml) for Hb, Zn test. Take stool (about 5g) to identify microflora.
- At D35: Assessing nutritional status (weight); Anorexia;food
consumption 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, analysis
nutritional status by using the ENA smart software, using reference
standard of WHO 2006.
- Diagnosis of anorexia after using antibiotics based on 1 of 3 signs

lasting from 7 to 30 days: 1) Refuse to eat or keep food in the mouth
for a long time (>30 min); 2) Do not eat half of the child's quantity
food 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.


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- Ask the dietary consumption, using the recording method during
the last 24 hours, according to the survey training document of the
National Institute of Nutrition, Ministry of Health.
- Taking blood samples for Hb, Zn test: Taking blood for testing: all
subjects 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-index
automatic analyzer (Sysmex- XP 100). Anemia was determined
when Hb <110g / l.
+ Serum zinc was quantified by the Atomic
adsorptionSpectrometry (AAS) method. Zinc deficiency was
determinedwhen Zn <9.9 umol / l.
-Take stool samples to test the digestive microflora and residue
residues 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 is
70/30).
2.11. Data analysis: Children who consume the product reach> 90%
of the delivered packages (from 25/28 packages for 14 days and
38/42 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 evaluate
the efficacy of the intervention.
2.12. Ethics of research:Study proposal was proved by Ethics
CommitteeNo. 377 / VDD-QLKH of National Institute of Nutrition
before implementation.


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Chapter 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
Aged groups

Boys

1217months
n = 94
18(28,6)

Girls

15(48,4)

Total

33(35,1
0

+

1823months
n =110
20(29,9
)
20(46,5
)
40(36,4
)

24-29
months
n =69
21(63,6
)
19(52,8
)
40(58,0
)

30-36
months
n =85
23(48,9
)
25[65,8

)
48(56,5
)

12-36
months
n= 358
82(39,0
)
79(53,4
)
161(45)

p>0,05 between aged groups, sex, 2 test

Table 3.1 shows that the general prevalence of anorexia after using
antibiotic is 45%, including boys 39%, girls 53.4%. The rate of
anorexia tends to increase gradually with age: from 35% in the
younger group to 56.5% in the older group; There is a tendency for
girls to be more anorexic than boys in some age groups;although the
difference is not statistically significant (p> 0.05).
Table 3.2.Comparaison the nutritional status of children suffered
anorexia or no anorexia
Indices

No anorexia
n=197

Anorexian=161

p(t test)

Age (month)

22,33±6,77

24,96±7,06

<0,001

Weight (kg)

10,2±1,6

10,0±1,3

0,2020

Height (cm)

80,5±6,1

81,5±5,9

0,1183

-1,16±1,06
-1,54±1,08
-0,54±1,02

-1,53±0,49
-1,76±0,86
-0,86±0,67

<0,001
0,0366
<0,001

WAZ
HAZ
WHZ

Data = X±SD,a: t - test; b:Mann-Whitney test


12
Table 3.2 shows that the age of the anorexia group is larger in anorexic
group, but the weight and height do not have significant difference (p>
0.05) between the two groups of anorexic and non-anorexic children.
However, all three indicators of WAZ, HAZ, and WHZ were
significantly lower in the group of anorexic children compared to the
group of anorexic children, especially clearly with the two indicators
of WHZ and WAZ (p <0.001), as evidenced by the acute impact of
anorexia negatively affects a child's weight.
Figure 3.1. The rate (%) of anorexia after using antibiotics, according to maining diseases
58.5

60
50

52.5

53.1

47.5
41.5

46.9
Anorexia
No Anorexia

40
30
20
10
0

Diges. Deseases

Res. Desease

Other desease

Figure 3.1 shows that among 80 children with gastrointestinal diseases
who use antibiotics, up to 52.5% have anorexia syndrome; Similarly,
with respiratory disease (n = 246) and other diseases (n = 32), up to
41.5% and 53.1% of children had anorexia; There was no significant
difference in the anorexia prevalence among antibiotics.
3.2. Effects of 2 interventions on the anorexia children
3.2.1.Effects on anorexia status and biochimie indicators

13
Table 3.3. Effects on the time for finishing a meal (minute)

Time

MTH.VC group
(n=74)

VC group

(n=72)

P
(t test)

D0

36,4±14,1

35,9±14,3

0,834

D14

27,1±14,8**

28,5±11,6**

0,546

D21

24,1±10,9***

25,9±11,1***

0,331

D35

20,3±10,5***

24,7±10,1***

0,012

X±SD;

++,

p<0,01;

+++

, p<0,001 vs. D0in same group, t paired test

Table 3.3 indicate the time for finishing a meal was significantly

reduced after the intervention in both groups, a significant reduction
was observed from time D14 (p <0.01) and further decreased to D 35 (p
<0.001) compared to the beginning. The MTH.VC intervention group
tended to eat faster than the VC intervention group, but the difference
was significant (p<0.05) observed only at D35.
Bảng 3.4.Efficacy of intervention in reduce the anorexia rate

Time
D0
D7
% reduced
D14
% reduced
D21
% reduced
D35
% reduced

MTH.VC group
(n=74)

N
74
59
38
22
15

%
100

79,7***
20,3
51,4***
48,6
29,7***
70,3
20,3***
79,7

VC group
(n=72)

n
72
68
58
44
32

***, p<0,001 vs. D0same group, 2 test

%
100
94,4NS
5,6
80,6***
19,4
61,1***
38,9
44,4***

55,6

P
0,0242
0,0051
0,0340
0,1706


14
Table 3.4 indicate that both groups had a significant effect on reducing
the anorexia rate by the time of intervention; The MTH.VC group fell
significantlybetter(p<0.05) than the VC group at most of the time.
Table 3.5. The specific effects of enzymes and probiotics to reduce
the risk of anorexia at times D7, D14, D21, D35
p
MTH.VC group
VC group
(2
Time
Evolution
test)
%
%
(n=74)
(n=72)
Cured
1 20,3
5
6,9

D7
5
0.0379
Still
5 79,7
67
93,1
anorexia
9
ARR
13,4
8
NNT
Cured
3 48,6
14
19,4
D14
6
<0,001
Still
3 51,4
58
80,6
anorexia
8
ARR
29,2
3
NNT

Cured
52
70,3
28
38,9
<0.001
Still
22
29,7
44
61,1
D21
anorexia
ARR
31,4
3
NNT
Cured
59
79,7
40
55,6
D35
0.0039
Still
15
20,3
32
41,4
anorexia

ARR
24,1
4
NNT
AAR: absolute risk reduction; NNT: number needed to treat

Table 3.5 indicate that at time D 7, group 1 reduced the risk of anorexia
by 13.4% and required 8 subjects to be treated to reduce 1 case; At
time D14, group 1 reduced the risk of anorexia by 29.2% and selected 3
subjects to be treated to reduce 1 case; By the time D 21 group 1


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reduces the risk of anorexia 31.4% and requires 3 subjects to be
treated to reduce 1 case; At the time of D 35 group 1, the risk of
anorexia was reduced by 24.1% and four subjects were treated to
reduce one case;
Table 3.6. Change of Hb (d/dL) & Zn(mcmol/L)concentration at D21supplement

MTH.VC
group (n=74)

Hb-D0

VC group
(n=72)

113,6 ± 8,8

p (t test)

114,1± 10,3
c+

Hb-D21

114,9 ± 9,3

Gain Hb(D21-D0)

1,29 ± 7,98

0,36 ± 8,35

0,4901

Zn-D0

8,5 ± 1,8

8,8 ± 1,7

0,3025

Zn-D21

10,6 ± 2,6

Gain Zn (D21-D0)
X± SD,

***

114,5±11,6

0,7527

c+

c***

c**

0,0761

1,13 ± 2,34

0,0102

9,9 ± 2,1

2,14 ± 2,35

0,8183

**

, p<0,001; , p<0,01 between D0& D21 ( t paired test)

Table 3.6 indicate that both groups tended to improve Hb levels at 21

days. Regarding serum zinc index: both groups increased significantly at
21 days of intervention compared to the intervention, MTH.VC
intervention group increased zinc concentration better than VC group (p
< 0.01).
Table 3.7.Efficacy of intervention on prevalence of anemia and zinc

deficiency at D21

D0
D21
% reduced
D0
D21

MTH.VC
group (n=74)
n
%
22
31,4
15
21,4 NS
10,0
55
78,6
22
31,4***

% reduced

45,4

Time
Anemia
Hb<110g/L
Zn
deficiency
<9,9μmol/L

***, p<0,001 between D0& D21

2

VC group
(n=72)
N
%
21
29,2
24
33,3 NS
-4.1
58
80,6
31
38,9***

p( 2
test)

0,8552
0,4885

37,5

test

Table 3.7 indicate that after 21 days of intervention, group 1
tended to reduce better than group 2 in terms of anemia and zinc


16
deficiency: Group 1 decreased 10% of anemia (p> 0.05), decreased
45.4% of deficiency rate. zinc (p <0.01); In group 2, anemia rate
increased by 4.1% (p> 0.05), zinc deficiency rate was reduced by
37.5% (p <0.01 compared to D0).
Bảng 3.8.Efficacy of enzyme & probioticin reducing the
anemia, risk and zinc deficiencyat D21time
Các chỉ
số

At D21
Cured

Anemia

Still
anemic
ARR
NNT

Cured

MTH.VC group
(n=74)
n
7

%
9,5

VC
group(n=
72)
n
%
0
0%

15

20,3

27

37,5

33

17,2
6

44,6

27

37,5

p( 2 test)

0,0062

Zn
deficien
cy

0,2170
Still ZnD
22
29,7
31 43,1
ARR
13,4
NNT
7
ZnD: zinc deficiency
AAR: absolute risk reduction; NNT: number needed to treat

Table 3.8 above shows that:
- About anemia: the MTH.VC group had a 17.2% risk of
anemia compared to the VC group; At the same time, the number of
patients who need treatment to cure anemia is 6 subjects;

- Zinc deficiency: MTH.VC group has reduced the risk of zinc
deficiency by 13,4% compared with VC group; At the same time, the
number of patients who need treatment to cure 1 case of zinc
deficiency is 7 subjects.


17
3.2.2.Efficacy of intervention on nutritional status, and digestive of
the subjects
Table 3.9.Weight & WAZ score of 2 groups during study

Indicator
Cân nặng
(kg)

WAZ

MTH.VC

VC

(n=74)

(n=72)

D0

10,06±1,36

10,03±1,29

0,9815

D14

10,30±1,37

10,20±1,26

0,2011

D21
D35

10,24±1,36
10,39±1,37

10,22±1,27
10,29±1,24

0,9270
0,6448

D0

-1,52 ±0,53

-1,44±0,67

0,4243

D14

-1,39 ±0,56

-1,36±0,72

0,7788

D21

-1,45 ±0,53

-1,37±0,74

0,4529

D35

-1,40 ±0,56

-1,39±0,72

0,9254

Time

P

Data = X±SD; ns, p>0,05 between the same time group,a: ANOVA repeted test

Table 3.9 shows that there was no significant difference in weight, as
did the Z score / age score between the 2 groups at the same time of
intervention. The average weight of the two research groups at D 14,
D21, and D35 time tended to be better than the D 0 time, but the
difference was not statistically significant (p> 0.05).


18
Table3.10.Effects of 2 products on the risk reduction of underweight and
stunting malnutrition at D21
p (2
MTH.VC
Malnutrition
At D21
VC group
test)
group
Risk
%
%
n = 35
Hết nguy cơ
45,
10
28,
0,2013
WAZ<-1,5
9
6

Còn nguy cơ 20
54,
25
71,
1
4
ARR
17,3
6
NNT
n = 23 %
n = 26
%
Hết nguy cơ
8
30,
6
26,
0,9660
8
1
HAZ<-1,5
Còn nguy cơ 18
69,
17
73,
2
9
ARR
4,7

2
NNT
AAR: absolute risk reduction; NNT: number needed to treat
n = 37
17

Table 3.10 shows that after 21 days of intervention, group 1 tended to
reduce better than group 2 in the risk of underweight and stunting,
although the difference was not statistically significant.
Table 3.11.Effects of bio-enzyme & probiotic on the perturbation rate of
digestive microflora at D14, D21

Time

MTH.VC group
(n=68)

VC group
(n=68)

n

%

.n

%

D0
D14

% reduced

66
32

97,1
47,1***

67
51

98,5
75,0**

D21
% reduced

17

50,0
25,0***

23,5
45

72,1

**, p<0,01, ***, p<0,001 betwwen D0 vs D21 ,2 test

p( 2 test)

0,9692
0,0205

66,2***
32,4

0,0090


19
Table 3.11 indicate that both groups have a significant effect on
reducing the bacterial incidence (p <0.01 compared to D 0), group 1
has a 50% reduction (p <0.001) the rate of bacterial disorder at D 7, and
a 72.0% reduction Bacteria at D21; meanwhile the supplement group
2 decreased by 23.5% (p <0.01) at D7 and 32, 4% (p <0.001) at D21.
Table 3.12.Effects of bio-enzyme & probiotic on the risk of digestive
disorder microflora at D14, D21

Time

D14

Evolution
Cured
Still disorder
ARR
NNT

D21

Cured
Still disorder

MTH.VCgroup
(n=68)
%
n

VC group
(n= 68)
%
n

34

50,0

16

23,5

32

47,1

51

75,0

27,9
4
49
72,1

22

32,4

17

45

66,2

25,0

p ( 2
test)
0.0026

<0,00
1

ARR
41,2
2
NNT
AAR: absolute risk reduction; NNT: number needed to treat

Table 3.12 indicate that at the additional 14 days, the MTH.VC group
had a 27.9% lower risk of bacterial infection compared to the VC
group; At the same time, the number of patients who need treatment
for 1 case of bacterial disorder is 4 subjects. At the additional 21 days,
the MTH.VC group had a 41.2% reduction in the risk of bacterial
disorders compared with the VC group; At the same time, the number
of patients who need treatment for 1 case of bacterial disorder is 2
subjects.

DISCUSSION
This is the first Vietnamese study to evaluate anorexia among 12-36
months old children with a history of infection using antibiotics. The
results also determine that antibiotic use is one of the causes of
anorexia in children. The study showed that the children attending the
Bac Ninh General Clinic had a high rate of underweight malnutrition
(22.6%), stunting was 34.6%, and wasting was 7.0%, higher than that


20
of the national malnutrition prevalence. The first time the study
published data on anorexia in children after using antibiotics at a
provincial general clinic in the Red River Delta. The overall rate of
anorexia for children after using antibiotics was 45.0%, increasing
gradually from the group aged from the 12-17 month( 35.1%), then
the highest increase in the 24-29 month age group( 58%), and in the
30-36 month age(56.5%). The rate of anorexia among girls is
generally higher than that of boys (53.4% compared to 39.0%, p
<0.05).
The study also demonstrated that both groups of nutritional
supplements for anorexia children after using antibiotics, either

including multiple micronutrients in combination with enzymes and
probiotics (MTH.VC), or micronutrients alone (VC ), both have
positive significant effects on anorexia in these children, making them
more appetite, shortening the meal time; The amount of food
consumed as well as the nutritional value of the diet were significantly
increased within 3 weeks of using the product. This is one of the very
few studies in Vietnam conducted scientifically in the community,
which is seriously evaluated with reliable indicators on this issue.
Immediately after 14 days of using the product, the positive effects
were observed, then more clearlydifference by the 21st day
supplemented. However, the MTH.VC supplement group tended to
outperform the pure micronutrient supplement group. MTH.VC group
decreased by 20.3%, 48.6%, 70.3% and 79.7% at the time of D 7, D14,
D21, D35; while the VC group decreased by 5.6%, 19.4%, 38.9%,
55.6% at the respective time.
Our study also demonstrated the specific effect of enzyme and
probiotic supplementation on the risk or cure rate of these
diseasesthrough ARR and NNT index, by comparing MTH.VC group
(withenzyme, probiotics and micronutrients) with the VC group
(micronutrients only). The results showed that the MTH.VC group,
enzyme and probiotic supplementation were reduced by 13.4%,
29.2%, 31.4%, 24.1% of the risk of anorexia at times D 7, D14, D21 and
D35 days of supplement; the longer the treatment period, the higher the
chance of recovering the disease, the highest effect observed after 21
days of treatment. Similarly, the NNT at times also showed a gradual
reduction of D7 to D21 and maintained to D35, resulting in 8 subjects for
D7, 3 subjects for D14, 3 subjects for D21, and 4 objects for D 35. It is


21

very important for planners to calculate the appropriate number of
patients who choose to be treated for a cure, as well as the duration
time they can be treated.
The study also showed the positive effects of both study groups
improve serum zinc and Hb levels, which was better in children with
initial anemia or zinc deficiency. The anthropometric indicators such
as weight and height gain, their Z-score also improved, but the
improvement did not reach statistical significance during 21 days of
intervention. After stopping the intervention within 14 days, some
positive effects remained, although there was a decrease compared to
that during the intervention.
The study also indicated that adding bio-enzymes and probiotics
combined with micronutrients to the product (MTH.VC group) was
better than the VC group (micronutrient alone) in some criteria such as
anorexia, anemia, intestinal microflora, all digestive disorders.
• Some limitations: the research did not use the placebo group,
because the study subjects had anorexia syndrome and the risk of
malnutrition; The during time of the study is difficult to take longer
due to the parents' reluctance to return to the hospital every week,
which leads to a less change in the anthropology; The diagnostic
criteria for anorexia have not been unified in Vietnam, especially for
young children.
CONCLUSSION
1. Nutritional and anorexia status of children after using
antibiotics on 358 children at Bac Ninh General Hospital in 2016:
• The prevalence of anorexia among Children aged 12-36 months after
using antibiotics is 45,0%, Specifically 39.0% in boys and 53.4%
girls. The rate of anorexia tends to increase with age, girls are more
anorexic than boys (53.4% compared to 39,0%).
• The prevalence of underweight children aged 12-36 months after

using antibiotics is 22.6%, stunting malnutrition is 34.6%, and wasting
malnutrition is 7.00%; The anorexic children have a higher prevalence
of malnutrition than children without anorexia.
2.The nutritional product containing digestive enzyme, probiotics
and micronutrient (MTH.VC) Has better effects on anorexia,


22
micronutrients than that of product
micronutrients (VC) In anorexic children:

contained

only

of

* Anorexia rates reduced significantly during the time of study,
especially in the MTH.VC group: reduced by 20.3%, 48.6%, 70.3%
and 79.7%, while the VC group reduced by 5.6%, 19.4%, 38.9%,
55.6%; Specific effects of enzymes and probiotic in MTH.VC product
decreased by 13.4%, 29.2%, 31.4% and 24.1% of the risk of anorexia
At time point of D7, D14, D21 and D35.
* Both zinc status and Anemia condition improved in both study
groups. At D21, MTH.VC group reduced by 10% of anemia and by
45.4% of zinc deficiency, while VC group increased 4.1% of anemia
and reduced by 37.5% of zinc deficiency. Specific effects of enzymes
and probiotic in MTH.VC product have contributed to a 17.2%
reduction in the risk of anemia, and a 13.4% reduction in the risk of
zinc deficiency.

3.The digestive disorders and microflora were significantly
improved after 21 days of intervention, especially in the MTH.VC
group; while the weight gain and WAZ- score tend to improve in
both product groups but not significantly different:
After 21 days using supplement, the MTH.VC group seems better than
group VC in terms of WAZ-score. The MTH.VC group reduced by
23.2% the risk of underweight, while the VC group reduced only the
risk by 13.9%. Specific effects of enzymes and probiotic in MTH.VC
product reduced by 17.3% of the the risk of underweight at D21
intervention.
* The intestinal microflora was significantly improved for both
supplement MTH.VC and VC products, although the MTH.VC group
had a significantly better effect than that of VC group. The MTH.VC
group reduced by 50,0% of the microflora disorder at D 14, and by
72,0% at D21; while the VC group decreased by 23.4% at D 14, and by
32.4% at D21 Specific effects of enzymes and probiotic in MTH.VC
product reduced by 27.9% (p <0.05) and by 41.2% (p <0.001) the risk
of microflora disorders at D14 and D21.


23

RECOMMANDATION
1. Early intervention for anorexia after using antibiotics is necessary
to restore the nutritional status of the children.
2. Both 2 supplement products, especially those with digestive
enzymes (enzymes + probiotics) and Micronutrients have a good
effects, can be applied in the prevention of malnutrition, anorexia
after using antibiotic.

__________________________________