Stunting is still a major problem in developing countries, including Indonesia, and has been associated with impaired development. Stunted children have also a higher risk of metabolic syndrome in adulthood. The gut microbiota, as a part of intestinal integrity, may promote intake of nutrient during childhood. Probiotics supplementation may optimize the balance of gut microbiota and further improve child growth during the window period. Furthermore, calcium could also improve child growth by increasing the resistance to intestinal infection. However, the long-term effects of gut microbiota optimization during childhood using probiotics and calcium on growth, development, and the metabolic condition has not widely studied.
This study was a 10-year follow-up study of randomized controlled trials of 6-month probiotics and calcium supplementation of Lactobacillus reuteri DSM 17938 or Lactobacillus casei CRL 431 in children aged 1-6 years (n=494) living in urban low socioeconomic communities of East Jakarta in 2007-2008. We re-enrolled the subjects to assess the long-term effects of probiotics and calcium supplementation on growth, development, and metabolic parameters at the age of 11-17 years. Healthy children (n = 238) were included in this follow-up study. Each subject previously assigned to one intervention group: low-lactose milk with a low calcium content (LC = 53), a regular calcium content (RC = 70), regular calcium with L. reuteri DSM 17938 (n = 55), and regular calcium with L. casei CRL 431 (n = 60). Anthropometric measurements were performed by measuring the weight and height of the subjects, and further combining the results to report BMI-for-age z-score. Height was also plotted to the chart of the World Health Organization (WHO) Child Growth Standards. Gut integrity was assessed with the lactulose-mannitol ratio using high-performance liquid chromatography (HPLC) method. Cognitive function, symptoms related to depression, behaviour, and serum brain-derived neurotrophic factors (BDNF) of the adolescents were evaluated used to investigate the effects of supplementation on development. We quantified lipid profile and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as metabolic parameters using the vein blood sample. The metabolic parameters were measured in at least three groups of intervention.
Study Type
OBSERVATIONAL
Enrollment
238
50 mg calcium/day
400 mg/day
regular calcium milk + probiotic
regular calcium milk + probiotic
Human Nutrition Research Center, Indonesian Medical Education Research Institute; and Department of Nutrition, Faculty of Medicine, Universitas Indonesia
Jakarta Pusat, DKI Jakarta, Indonesia
Child's linear growth the age of 11-17 years
Height-for-age z-score based on the WHO Child Growth Standards.
Time frame: January - March 2019
Child's height at the age of 11-17 years
Height in meters.
Time frame: January - March 2019
Child's weight at the age of 11-17 years
Weight in kilograms.
Time frame: January - March 2019
Child's nutritional status at the age of 11-17 years
BMI-for-age z-score based on the WHO Child Growth Standards. BMI was calculated from height and weight measurement.
Time frame: January - March 2019
Gut integrity at the age of 11-17 years
Lactulose-mannitol ratio was calculated by dividing percent excretion of lactulose with percent excretion of mannitol.
Time frame: January - March 2019
Cognitive function assessed using Raven's Progressive Matrices at the age of 11-17 years
Raven's Progressive Matrices (RPM) was administered by psychologists. Raw score of RPM was used to evaluate adolescents' cognition.
Time frame: January - March 2019
Symptoms related to depression assessed using Children Depression Inventory at the age of 11-17 years
Children Depression Inventory (CDI) was a self-assigned questionnaire and the total score of CDI with a range between 0 - 54 (lower, better) was used to evaluate the symptoms related to depression among adolescents.
Time frame: January - March 2019
Behaviour assessed using Strength and Difficulties Questionnaire at the age of 11-17 years
Strength and Difficulties Questionnaire (SDQ) was a self-assigned questionnaire and the total difficulties score of SDQ with a range between 0 - 50 (lower, better) was used to evaluate the behaviour among adolescents.
Time frame: January - March 2019
Serum BDNF at the age of 11-17 years
Serum BDNF in pg/ml was quantified using ELISA method
Time frame: January - March 2019
Triglyceride level at the age of 11-17 years
Triglyceride level in milligrams per decilitre.
Time frame: January - March 2019
High-density lipoprotein level at the age of 11-17 years
High-density lipoprotein level in milligrams per decilitre.
Time frame: January - March 2019
Low-density lipoprotein level at the age of 11-17 years
Low-density lipoprotein level in milligrams per decilitre.
Time frame: January - March 2019
Fasting insulin level at the age of 11-17 years
Fasting insulin level in μU per millilitre
Time frame: January - March 2019
Fasting glucose level at the age of 11-17 years
Fasting glucose level in milligrams per decilitre.
Time frame: January - March 2019
HOMA-IR at the age of 11-17 years
HOMA-IR was quantified by multiplying fasting insulin level with fasting glucose level.
Time frame: January - March 2019
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