7 MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH NATIONAL INSTITUTE OF NUTRITION PHAM THI THU THE EFFECTS OF LACTOBACILLUS CASEI SHIROTA ON THE NUTRITIONAL STATUS, DIGESTIVE AND ACUTE RESPIRATO[.]
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH NATIONAL INSTITUTE OF NUTRITION -PHAM THI THU THE EFFECTS OF LACTOBACILLUS CASEI SHIROTA ON THE NUTRITIONAL STATUS, DIGESTIVE AND ACUTE RESPIRATORY INFECTIONS IN CHILDREN 3-5 YEARS OF AGE IN COMMUNES, THANH HOA PROVINCE Major: Nutrition Code: 9720401 THE ABSTRACT OF THESIS HA NOI – 2022 THE WORK HAS BEEN COMPLETED AT NATIONAL INSTITUTE OF NUTRITION Supervisors: Assoc.Prof Dr Nguyen Ngoc Sang Assoc.Prof Dr Truong Tuyet Mai Reviewer 1: Reviewer 2: Reviewer 3: The dissertation is presented at the National Institute of Nutrition -level Dissertation Assessment Council Time: date .month year 2022 The dissertation can be found at: - The library of National - The library of National institute of Nutrition LIST OF THE WORKS OF THE AUTHOR Pham Thi Thu, Truong Tuyet Mai, Nguyen Ngoc Sang, Hoang Thi Hang (2021) Evaluating the effectiveness of supplementing Lactobacillus casei Shirota (LcS) on children 3-5 years of age with functional constipation in communes, Thanh Hoa province Journal of Vietnamese Medicine, 509(2): 170-175 Pham Thi Thu, Truong Tuyet Mai, Nguyen Ngoc Sang, Tran Thi Thu Trang (2022) Nutritional status and some related factors in children 3-5 years of age in communes, Thanh Hoa province in 2017 Vietnam Medical Journal, 514(2): 230-234 Truong Tuyet Mai, Pham Thi Thu, Hoang Thi Hang, Tran Thi Thu Trang, Shintaro Yui, Akira Shigehisa, Vu Thuy Tien, Truong Viet Dung, Phan Bich Nga, Nguyen Trong Hung, Le Danh Tuyen (2020) Efficacy of probiotics on digestive disorders and acute respiratory infections: a controlled clinical trial in young Vietnamese children European Journal of Clinical Nutrition https://doi.org/10.1038/s41430-020-00754-9 INTRODUCTION The malnutrition is a serious public health problem globally, mainly occurring in Africa and Asia Malnutrition in children under years old not only slows physical and intellectual development, but also increases the risk of acute respiratory infections, diarrhea or constipation for a long time, forming a pathological spiral, affecting the children's growth and development, even leading to death One of the methods to support the treatment of constipation, diarrhea, strengthen the body's resistance and bring lasting effects is the use of probiotics Lactobacillus casei Shirota (LcS) is a strain of beneficial bacteria that has been studied and used in Japan since 1935 LcS has been studied for its effects in relation to immunity and digestion In Vietnam, there are currently no studies evaluating the effectiveness of Lactobacillus casei Shirota on nutritional status, digestive health and ARI in children 3-5 years of age Therefore, we conducted a research with objectives: To describe the nutrition situation, digestion and acute respiratory infection in children 3-5 years of age in communes of Thanh Hoa province, 2017 To evaluate of the effectiveness of Lactobacillus casei Shirota supplementation on the incidence of constipation, diarrhea and acute respiratory infections in children 3-5 years of age in communes of Thanh Hoa province To evaluate of the effectiveness of Lactobacillus casei Shirota supplementation on improving constipation and nutritional status in children 3-5 years of age with functional constipation in communes of Thanh Hoa province New contributions of doctoral thesis: This is the first work in the country that has identified the nutritional status, digestion and acute respiratory infections in children 3-5 years of age in communes of Thanh Hoa province in 2017 with the percentage of underweight, stunting and waisting is 11.2%, 15.7% and 2.0% The study demonstrated the effectiveness of Lactobacillus casei Shirota on the incidence of constipation in children 3-5 years of age after 12 weeks of intervention, in the intervention group the incidence of constipation was significantly lower than the control group (1.3% vs 10.4%) The results of the study also showed the effectiveness of Lactobacillus casei Shirota in improving constipation in children 3-5 years of age with functional constipation The dissertation structure: The dissertation has 120 pages with the structure as follows: the introduction and objectives: pages; overview (literature review): 32 pages; methods: 21 pages; results: 30 pages; discussion: 31 pages; conclusions and recommendations: pages The dissertation has 37 tables, figures, and 181 references Chapter I: OVERVIEW 1.1 The nutritional status, digestive and acute respiratory infections Malnutrition remains a major public health concern for children under years old in many low- and middle-income countries as it remains the leading cause of death among children in many countries The according to the WHO report 2020, about 144 million children under years old are stunted, 47 million children are wasting and 14.3 million children are severely malnourished Malnutrition remains a significant public health problem in Vietnam According to the survey results on the nutritional status of children, the rate of underweight malnutrition in Vietnam has decreased but is still high The direct cause of malnutrition is believed to be children's lack of food, improper eating, and disease of infections (diarrhea and ARI), prolonged constipation can all lead to malnutrition and vice versa Malnutrition makes children susceptible to infections and this vicious cycle continues without appropriate intervention or management Diarrhea and ARI are among the top 10 causes of hospitalization and death in children under years old, while constipation is a common and challenging problem in children, with serious implications affect children's emotions, psychology and quality of life, accounting for nearly 1-4% of school-age children 1.2 The role of probiotics in gastrointestinal and immune health Probiotics help supplement beneficial bacteria to create a balance of bacteria in the digestive system, helping digestion better Probitotic competes with harmful bacteria in the colon, creating a membrane that prevents bacteria, fungi and viruses from penetrating, protecting the body's digestive system against pathogenic bacteria The presence of a healthy and diverse gut microbiota is critical to achieving or maintaining a normal bowel function, which can significantly reduce intestinal transit time and increase bowel frequency and improve stool consistency Therefore, probiotics can be considered as natural and safe agents for the relief of functional constipation in adults and children Probiotics are considered safe for the prevention and treatment of antibiotic-associated diarrhea and infectious diarrhea The mechanism of action is a combination of direct competition with pathogenic bacteria in the intestine and stimulation of local immunity Daily supplementation of LcS-containing beverages may play a role in the prevention of acute diarrhea and may reduce acute respiratory infections and disease severity in preschool-aged children 1.3 The intervention studies on the effect of Lactobacillus casei Shirota supplementation on nutritional status, gastrointestinal and acute respiratory infections The numerous studies have shown that supplementation with Lactobacillus casei Shirota significantly reduces the length of stool retention in the intestines, increases the frequency of bowel movements, and improves stool consistency Therefore, probiotics can be considered as natural and safe agents for the relief of functional constipation in adults and children Probiotics have been extensively studied in recent years for the prevention and treatment of diarrhea, especially in children Effect of intervention with Lactobacillus casei Shirota on the incidence of diarrhea depends on the subject and duration of the intervention The studies have shown that certain strains of probiotic bacteria can improve immune function by increasing IgA counts, increasing or improving phagocytosis, and increasing the proportion of T lymphocytes and natural killer cells Several studies indicate that Lactobacillus casei Shirota (LcS) is beneficial for immune status However, several studies have also shown that daily intake of fermented milk containing LcS has no statistically or clinically significant effect on protection against respiratory symptoms The research results show that the impact of probiotics on the growth of weight and height of children is not still consistent CHAPTER 2: METHODS 2.1 Study subjects, setting and study period - Criteria for selecting study subjects for objective 1,2: Children aged 35 years of age, attending preschool, parents or main caregivers of children who agree to participate in the study and not have mental illness, the child did not give up one of the study stages Criteria for selecting study subjects for objective 3: children selected from objective 2, diagnosed as functional constipation Exclusion criteria for objective 2;3: Children with severe malnutrition, severe diseases (acute respiratory infections, acute diarrhea ), children using probiotics out of the program, children with birth defects, chronic liver and kidney diseases , digest - Study setting: The cross-sectional study and intervention study in communes: Yen Thai commune, Dinh Thanh commune, Yen Dinh district (intervention group) and Van Thang commune, Cong Chinh commune, Nong Cong district (control group), Thanh Hoa province - Study period: Cross-sectional study from June 2017 to Augusst 2017; interventional study from November 2017 to January 2018, data entry and analyses, and complete the dissertation from February 2018 to December 2021 2.2 Study design: The study was divided into two phases - Phase 1: A cross-sectional descriptive study - Phase 2: A controlled community intervention study This study was conducted on two groups The control group is a group of children who eat normally at home and kindergarten, without using the supplement Lactobacillus casei Shirota for 12 weeks The intervention group is a group of children who eat normally at home and kindergarten, but was allowed to use box of products containing 6.5 billion Lactobacillus casei Shirota per day (65ml/box) x days per week x 12 weeks 2.3 Sample size - For objective 1: Cross-sectional descriptive study, the minimum sample size is 225 children/commune x communes=1020 children Actually studied 1136 children - For objective 2: A controlled community intervention study, the minimum sample size is 506 children/group x groups = 1012 children In fact, 1036 children were studied - For objective 3: A controlled community intervention study, the minimum sample size is 90 children/group In fact, 216 children were studied 2.4 Sampling method The purposely selected communes Yen Thai, Dinh Thanh, Yen Dinh district as the intervention group and communes Van Thang and Cong Chinh in Nong Cong district as the control group 12 Group Control group Intervention Group Probability of new cumulative constipation Week Figure 3.1 Kaplan–Meier chart of the cumulative incidence of constipation in the intervention and control groups The probability of cumulative constipation in intervention group was lower than the control group The mean time of children without incidence of constipation after 12 weeks intervention in intervention group was significantly greater than the control group (p=0.000) Table 3.4 The effectiveness of prevention to the cumulative incidence of constipation after 12 weeks of intervention Intervention group Indicators (n = 374) Cumulative incidence of 81 (21.7%) constipation No new cumulative 293 (78.3%) incidence of constipation Control group (n = 364) 157 (43.1%) 207 (56.9%) p 0.000 13 ARR% (95%CI) 0.214(0.148-0.280) NNT 4.656 (3.564-6.714) (ARR) Absolute risk reduction after 12 weeks intervention (NNT) Number needed to treat to reduce case after12 week intervention (p) χ2 test compare percentages of groups at the same time After 12 weeks of intervention, supplementing Lactobacillus casei Shirota reduced 21.4% of cumulative incidence of constipation There was a significant difference in the cumulative incidence of constipation between the two groups (p0.05) However, after stopping the intervention for weeks, the cumulative incidence of diarrhea in the intervention group was significantly lower than that the control group (p0.05) Table 3.6 The efficacy of Lactobacillus casei Shirota on the cumulative incidence of acute respiratory infection during the 12 weeks of intervention and after weeks of stopping the intervention Intervention group Control group (n = 510) (n = 493 ) Time (n) (%) (n) (%) p 15 T0-T4 T0-T8 T0-T12 T0-T16 57 100 132 138 14.5 25.5 33.7 35.2 59 107 141 175 15.9 28.9 38.1 47.3 0.615 0.328 0.227 0.001 (p)χ2 test compare percentages of groups at the same time The percentage of children with the cumulative incidence of ARI in the intervention group was lower than the control group after 4,8,12 weeks of intervention (p>0.05) However, after stopping the intervention for weeks, the cumulative incidence of ARI in the intervention group was significantly lower than that the control group (p0.05) However, after weeks stopping the intervention, the probability cumulative of ARI in intervention group was significantly lower than that the control group (p