Nutrition and stunting

Question 1

The Karlberg ICP model for growth: what is driving growth in infants, children and adolescents?

Answer 1

• infants: insulin mediates IGF1 production
• children: GH mediates IGF1 production
• adolescents: GH and sex hormones influence IGF1 production
• in adults growth stops due to fusion of the growth plates (epiphysis)

Question 2

Description of infants versus older children growth patterns

Answer 2

• infants have saltatory growth, with stasis periods of 2-63 days. Growth and weight gain is coupled in the same week. They spend 90-95% of their time not growing
• children have stasis intervals of 15 days. Weight gain follows height. Greater GH is associated with greater height

Question 3

Model for growth: bone (including cellular basis), skeletal muscle, organ

Answer 3

• Bone growth: main driver. Occurs in the metaphysis (proliferation), causing the ends (epiphysis) to grow away from the middle. Bone growth is 70-90% genetically determined, but can be negatively influenced by environmental (infections, nutrition) in childhood, leg length is more adversely affected in this way.
• Skeletal muscle: growth determined by bone growth. Neighbouring bone growth causes the skeletal muscle to grow via the ‘passive stretch’ mechanism. Adequate nutrition and AA pool still needed for this process, as skeletal muscle grows, uses up the AA pool which drives increased appetite
• Visercal organ growth: principally driven by demand, i.e. food intake and metabolic work

Question 4

Human growth: nature versus nurture

Answer 4

• Nature: from GWAS and twin studies, we know that height is 70-90% heritable. 35% of variance can be explained with SNPs and epigenetic changes. Severe growth abnormalities may be due to mutations in IGF1
• Nurture: height is a good indicator of the nutritional status of a society. Countries such as Japan and South Korea have gained height over the last 100 years. Poor nutrition may impact leg length the most

Question 5

Growth faltering: definition of wasting and stunting

Answer 5

• wasting: where there is a low weight:height and low weight:age (2SD below average). They look visibly skinny. Global prevalence is 50 million.
• stunting: where there is a low height:age and weight:age. They are in proportion, but very small (2SD below average). Global prevalence is 160 million (25% of those <5 years are stunted). Common causes are infection/inflammation or poor nutrition

Question 6

The stunting syndrome: the cycle of stunting. How does it perpetuate?

Answer 6

• in pregnancy, poor diet and inflammation can lead to a low birth weight infant
• early weaning and recurrent infections leads to a stunted 2 year old
• poor diet and recurrent infections in childhood leads to a school aged child with stunted growth and poor performance
• the resulting adult will have a lower IQ, lower earning potential, and be more likely to have a stunted child themselves

Question 7

Causes of stunting

Answer 7

• Nutrition: can positively influence IGF1 production and factors which drive the growth plate. But too little, or deficiencies may negatively impact
• Infections/inflammation: drives FGF21, inflammatory cytokines and cortisol which negatively influence the growth plate. ‘Environmental enteropathy/environmental enteric dysfunction’ relates to poor sanitation/hygiene which can lead to malabsorption and stunting

Question 8

Type I and II nutrients and the growth plate

Answer 8

• Type I: have specific roles in pathways relating to growth with deficiency having characteristic signs. Examples: retinol (infection), folate/iron (anaemia)
• Type II: have less defined roles in pathway and are ubiquitous in function, with no deficiency signs. Examples: protein, zinc

Question 9

Protein as a driver for growth: type II nutrient

Answer 9

• in rat studies protein is independently associated with growth rather than energy
• mixed findings in humans, very rare to be deficient in protein (usually consume in excess). Stunting MAY occur

Question 10

Zinc as a driver for growth: type II nutrient

Answer 10

• Zinc is involved in growth factor signal transduction at the growth plate therefore deficiency may impact on height
• deficiency in rodents impairs IGF1 signalling
• 90% of free body zinc is held in muscle and bone
• in LMIC zinc deficiency is common due to diets which are predominately plant-based

Question 11

Iodine as a driver for growth: type I nutrient

Answer 11

• characteristic deficiency: cretinism
• onset is slow
• mediates height through GH which acts on IGF1

Question 12

Vitamin D, calcium, phosphorus and role in growth

Answer 12

• Vitamin D and Calcium are important for bone mineralisation= strength rather than length
• phosphorus deficiency also unlikely as most people massively over-consume phosphorus

Question 13

Foods which may impact linear growth: plant-based diets and milk

Answer 13

• plant-based diets: can be adequate as long as supplement with vitamin D, A, B12, protein pair and provide enough energy
• milk: independent driver for height as supported by epidemiological studies (tribes which are plant-based are short, Karamoja tribe which consumes milk and blood are very tall). May be due to bioactive factors, tryptophan/leucine (important for cellular growth), miRNA for growth, iodine source