Iron and Prebiotics Fortification in Kenyan Infants
关键词
抽象
描述
Fifty infants per group will be enrolled (n=150) and randomly divided in three groups, from those identified in selected villages in the catchment area of the Kikoneni Health Clinic in southern coastal Kenya, about 2 hours south of Mombasa. All children whose caregivers agree to participate in the study will have their iron status assessed by measurement of hemoglobin (Hb), erythrocyte zinc protoporphyrin (ZPP), serum ferritin (SF) and serum transferrin receptor (TfR). Enrolled subjects will be randomized into three groups. Group 1 will receive the MNP alone, group 2 will receive an identical MNP with iron (2.5 mg Fe as NaFeEDTA and 2.5 mg as ferrous fumarate), and group 3 will receive the MNP with iron (2.5 mg Fe as NaFeEDTA and 2.5 mg as ferrous fumarate) and 7.5 mg of galactooligosaccharides as GOS-75. Each household will receive 2 kg of maize meal per week and the caregivers of the participating children will be shown how to prepare a maize porridge, which is the most widely-used local complementary food. This maize meal will be provided free-of-charge to all participating families. The caregiver will add one MNP sachet each day to a portion of maize porridge, and feed the entire portion to the infant. The Kikoneni Clinic will serve as the collection point for the MNPs, the monitoring center for surveillance of infant health, as well as the blood and stool collection point.
At baseline and at endpoint of the intervention (after 4 months), a blood sample will be collected from the infants for measurement of Hb, SF, TfR and ZPP to define anemia and iron status and C-reactive protein (CRP) to define systemic inflammation status. In addition, anti-measles Serum IgG will be measured, as infants receive their first measles vaccination at 9 months, following Kenyan Ministry of Health guidelines. At baseline, after 3 weeks and after 4 month, a stool sample will be collected from both the infant and his/her mother, for measurement of the gut microbiota and gut inflammation.The mothers will be trained to collect the stool samples at home in a provided container with a tight, screw-top lid, that includes an Anerocult® sachet to create an anaerobic environment. At these 3 timepoints (baseline, after 3 weeks and after 4 month) the mother will bring in the two stool samples of the same day, where they will be labeled and kept at 4°C. The samples will be then transferred to the central lab, filled in 2 ml Eppendorf tubes, labelled and frozen at -20°C.
In addition, compliance and morbidity will be assessed weekly during the distribution of the MNPs. The children will be checked and referred to the health center clinicians whenever indicated by the clinical history. In the case of fever, a rapid malaria test (RTD) kit will be performed according to local guidelines. If the test results positive, the child will be treated for presumptive malaria, mild malaria cases will be treated at Kikoneni clinic as per WHO Integrated management of childhood illness (IMCI) guidelines. Cases of diarrhea will be treated according to the local standard of care including oral rehydration salt and, if necessary, antibiotics. If deemed necessary by the Kikoneni clinical management, the study team will support the clinic in re stocking ORS, iron supplements and antimalaric drugs for the study duration.
Anthropometry (weight, height, age and sex) will be recorded at baseline and endpoint using standardized procedures to calculate the prevalence of child stunting. The measurements will be done twice and the average used for data analysis. The data analysis software WHO Anthro (WHO, Geneva Switzerland) will be used to calculate the prevalence of stunting among this infant population.
To investigate the effect of oral antibiotics on the infant gut microbiota we will select the first 12 infants of each of the three study groups that become ill during the study and receive broad-spectrum antibiotic treatment. We will also select 6 non-treated controls from each study group matched for sex and weeks of MNP consumption. A total of n=54 children will be included in this sub study and we will collect five additional stool samples from the selected children to determine the gut microbiota composition. The first stool sample will be collected before starting the antibiotic treatment (day 0). Thereafter, a stool sample will be collected at day 5, 10, 20 and 40. Stool samples will be collected as described above. Besides these additional stool samples the children continue the intervention according to the main protocol.
A breast milk sample will be collected from 90 mothers at two time points (week 3 and week 16). These samples will be analyzed for the concentration of human milk oligosaccharides, a potential source of natural prebiotics.
Three years after the end of the study, we would like to examine iron status and gut microbiota of these children and determine whether the differences observed after the intervention persist or if they all converge and have a similar microbiome profile. In addition, we will measure anti-measles serum IgG, as infants received their second measles vaccine at 18 months following Kenyan Ministry of Health guidelines.
日期
最后验证: | 01/31/2020 |
首次提交: | 04/09/2014 |
提交的预估入学人数: | 04/15/2014 |
首次发布: | 04/20/2014 |
上次提交的更新: | 02/02/2020 |
最近更新发布: | 02/04/2020 |
实际学习开始日期: | 06/30/2014 |
预计主要完成日期: | 11/30/2015 |
预计完成日期: | 11/30/2015 |
状况或疾病
干预/治疗
Dietary Supplement: Fortified maize porridge
相
手臂组
臂 | 干预/治疗 |
---|---|
Active Comparator: Fortified maize porridge (MNP) The MNP contains 400 µg Vitamin A, 5 µg Vitamin D, 5 mg Tocopherol Equivalent, 0.5 mg Thiamine, 0.5 mg Riboflavin, 0.5 mg Vitamin B6 , 90 µg Folic Acid, 6 mg Niacin, 0.9 µg Vitamin B12, 30 mg Vitamin C, 0.56 mg Copper, 90 µg Iodine, 17 µg Selenium, 4.1 mg Zinc, 190 Phytase-units, maltodextrin carrier (added up to 11g) | |
Active Comparator: Fortified maize porridge (MNP+Fe) The MNP contains 400 µg Vitamin A, 5 µg Vitamin D, 5 mg Tocopherol Equivalent, 0.5 mg Thiamine, 0.5 mg Riboflavin, 0.5 mg Vitamin B6 , 90 µg Folic Acid, 6 mg Niacin, 0.9 µg Vitamin B12, 30 mg Vitamin C, 0.56 mg Copper, 90 µg Iodine, 17 µg Selenium, 4.1 mg Zinc, 190 Phytase-units, plus 2.5 mg Fe as ferrous fumarate and 2.5 mg Fe as NaFeEDTA, maltodextrin carrier (added up to 11g) | |
Active Comparator: Fortified maize porridge (MNP+Fe+GOS) The MNP contains 400 µg Vitamin A, 5 µg Vitamin D, 5 mg Tocopherol Equivalent, 0.5 mg Thiamine, 0.5 mg Riboflavin, 0.5 mg Vitamin B6 , 90 µg Folic Acid, 6 mg Niacin, 0.9 µg Vitamin B12, 30 mg Vitamin C, 0.56 mg Copper, 90 µg Iodine, 17 µg Selenium, 4.1 mg Zinc, 190 Phytase-units, 2.5 mg Fe as ferrous fumarate and 2.5 mg Fe as NaFeEDTA plus 7.5 g of galactooligosaccharides given as 10.5 g GOS-75, maltodextrin carrier (added up to 11g) |
资格标准
有资格学习的年龄 | 6 Months 至 6 Months |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: - Age of 6-10 months at baseline - Assessment of good health as assessed by professional staff at Kikoneni Health Clinic. - Willingness of their caregiver to provide informed consent Exclusion Criteria: - Hemoglobin <7g/dL; these participants will be referred for treatment at the local health clinic according to the guidelines of Kenya Ministry of Health. - Participants taking part in other studies requiring the drawing of blood. - Chronic or acute illness or other conditions that in the opinion of the PI or co-researchers would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol. - Not planning long-term residence in study site - Participants who are taking iron-containing food supplements or tablets/drops. |
结果
主要结果指标
1. The co-primary outcomes are the gut microbiome and gut inflammation [Change from baseline to 3 weeks and 16 weeks]
次要成果指标
1. Iron status and systemic inflammation [Change from baseline to endpoint (16 weeks)]
2. Anthropometry [Change from baseline to endpoint (16 weeks)]
3. Child to -mother transmission of gut microbiota [Change from baseline to 3 weeks and endpoint (16 weeks)]
4. Gut microbiota and gut inflammation during and after an oral antibiotic treatment [Change from baseline day 0 (prior to antibiotic administration) to day 5, 10, 20 and 40]
5. Morbidity [Weekly assessment from baseline to endpoint (16 weeks)]
其他成果措施
1. Human milk oligosaccharides in breast milk [Sampling time points at week 3 and week 16]
2. Long term gut microbiota composition [Change from endpoint to 3 years after study end]
3. Long term iron status and systemic inflammation [Change from endpoint to 3 years after study end]
4. Primary vaccine response [anti-measels serum IgG and avidity at age 12months (endpoint intervention)]
5. Secondary vaccine response [anti-measels serum IgG and avidity at 3 years after study end]