Failure to Thrive Ipoh DR16_7_22(1).pptx

Growth faltering

1. Failure to Thrive (Growth Faltering) Professor Dr Lee Way Seah Senior Professor, Faculty of Medicine & Health Sciences University Tunku A bdul Rahman, B andar Sg. Long, Selangor; Honorary Professor, Department of Paediatrics Faculty of Medicine, University Malaya

2. Lecture Outline Definitions Prevalence and Burden of failure to thrive Factors affecting Growth Phases of Growth Bone Growth Catch-up growth

3. Growth & D evelopment in Children & A dolescents Physical growth: increase in size Development: growth in function & capability Genetic, nutritional, environmental factors. Optimal growth occurs when a child is provided with a nurturing environment and adequate nutritional needs. Toddler 1–3 years Childhood 3–11 years Adolescence 12–18 years Adulthood >18 years

4. Growth Faltering (previously known as failure to thrive) Growth faltering: slower rate of weight or height gain in childhood than expected for a child’s age & gender. Previously known as ‘failure to thrive’, ‘failure’ sounds alarming to parents. Inadequate intake Malabsorption Increased metabolism Causes of Growth Faltering Recommended thresholds of concern for growth faltering in infants & children: A fall across ≥ 1 weight centile if birthweight < 9 th centile A fall across ≥ 2 weight centile if birthweight between 9 th - 91 st centiles A fall across ≥ 3 weight centile if birthweight > 91 st centile When current weight is < 2 nd centile for age, whatever the birthweight *Based on WHO growth charts

5. Common Terms Normal Adequate weight- & height-for-age Wasted Low weight-for-height Can be rapidly corrected with nutritional therapy Stunted Low height-for-age Cannot be rapidly corrected with nutritional therapy Underweight Low weight-for-age Can be due to wasting or stunting Normal height-for-age

6. Determinants of Growth in Childhood Growth: a complex physiological process Genetic > 200 genes identified in genome-wide association studies Determines only 10% of the variation in adult height Lango Allen et al. Nature 2010 Environmental factors Nutrition Hygiene and sanitation Recurrent infections Access to healthcare Major determinants of growth in the first 2 y

7. Factors Affecting Childhood Growth Genetic effect on height is relatively weak during infancy & early childhood Nutrition: strongest environmental factor affecting growth Maternal nutritional status Child’s feeding practices Three strands of malnutrition Undernutrition Stunting, wasting, underweight Hidden hunger Deficiencies of essential vitamins and minerals Overweight / Obesity Abnormal or excessive fat accumulation Malnutrition: Lack of proper nutrition Inadequate intake Not having the right nutrients Malabsorption

8. Nutrition: Important Determinant of Growth in Infancy & Early Childhood Growth during infancy is most strongly influenced by nutrition Formon SJ . Nutrition of Normal Infants. St. Louis, Mosby 1993 % of energy consumed used for growth in different ages

9. Consequences of Malnutrition (failure to thrive) Physiological effects Socio-economic effects Impaired muscle function Body utilizes energy reserves from muscles, adipose tissue, bones, loss of functional capacity Increased cardiac issues Cardiomyopathy, arrhythmia , heart failure Altered gastrointestinal function Changes in intestinal architecture & permeability ⇒ susceptible to diarrhoea Delayed wound healing and impaired immunity Impaired intestinal barrier function, higher risk of infectious diseases Lower educational outcomes Shorter formal education due to poorer cognitive development, affecting learning ability & performance in school Lower productivity and earning potential Lower levels of education, reducing strength of workforce Increased armed conflict Growing evidence shows poor economic and health status (malnutrition) is associated with higher rates of armed conflict

10. Global Burden of Undernutrition Globally, ~ 8.8% of the world’s population are malnourished ~ 580 million children < 5y affected 1 in 3 children is not growing well 1 in 2 children experience hidden hunger 45% of deaths among children are linked to undernutrition Children < 5 y affected by malnutrition

11. Burden of Undernutrition in SE Asia & Malaysia WHO 2025 Global Nutrition Targets for children < 5 y: 40% reduction in stunting No increase in overweight Reduce and maintain childhood wasting < 5%. Malaysia: no progress over the years towards these targets. 7.2% overweight 8.4% wasted 25.8% stunted Malnutrition in Southeast Asia Prevalence of malnutrition in children < 5 y in Malaysia

12. Environmental Factors Affecting Growth: Physical Activity Benefits of physical activity on growth in children & adolescents Increases bone mass Physical exercise helps increase bone mass, reduces the risk of osteoporosis fractures throughout life. Increases muscle mass Physical activity helps strengthen muscles, persist into adult life. Higher self-esteem, reduced anxiety Physical activity associated with higher self-esteem and overall better mental health in children and adolescents. N o evidence of impaired height growth caused by strength and resistance exercises in children & adolescents.

13. Sleep Sleeps important in body’s homeostasis, affecting height & weight in children & adolescents. How does sleep affect height? Inadequate sleep impairs GH secretion, leading to a shorter stature. How does sleep affect weight? Appetite-regulating hormones (leptin, ghrelin, etc.) regulated by sleep. Sleep deprivation ↑ ghrelin levels & ↓ leptin levels, leading to increased hunger. Children & adolescents who are sleep deprived are 76% more likely to be overweight. Physiological secretion of hormones & inflammatory factors with a hypothetical sleep onset time of 9:00pm GH TH Leptin IL-6 Ghrelin IL-6 TNF Cortisol Insulin

14. Phases of Growth 2 phases of rapid growth (growth spurts), during infancy & adolescence . Distance & velocity curves of growth in a healthy human Dotted line – Girls; Solid line – Boys; I, infancy; C, childhood; J, juvenile; A, adolescence; M, mature adult Girls Boys Grows slower from birth – 7 m Grows faster from 7 m – 4 y Reaches puberty earlier (10–18 y) Grows faster from birth – 7 m Grows slower from 7 m – 4 y Reaches puberty later (12 – 21 y) Gender differences in growth

15. Bone Cells & Structure Cell type Function Location Osteogenic cell Progenitor stem cells, develop into osteoblasts Deep layers of the periosteum and the marrow Osteoblast Bone formation Growing portions of bone, including periosteum and endosteum Osteocyte Maintain mineral concentration of matrix Entrapped in matrix Osteoclast Bone resorption Bone surfaces and sites of old, injured or un-needed bone Bone cells Bone structure

16. Bone Growth: Hormones Hormones involved in oppositional bone growth during childhood & adolescence Hormones / growth factors Main effects on growth GH Stimulates hepatic IGF-1 & chondrogenesis in growth plate IGF-1 Stimulates uptake of amino acids from blood & chondrogenesis in growth plate Insulin Binds to the IGF-1 receptor, ⇧ growth velocity ⇧ free IGF-1 in the circulation Thyroid hormones Regulate bone turnover & bone mineral density Stimulate clonal expansion of chondrocyte progenitor cells Sex steroids (estrogen, testosterone) Regulate the secretion & effects of GH Affect chondrogenesis & growth plate fusion Leptin Regulates GH secretion & stimulates chondrogenesis locally in the growth plate

17. Bone Growth: Oppositional Growth In epiphyseal plate. Epiphyseal plate closes ~ 12–16 y in girls and 14–19 y in boys . Zone Description Reserve Quiescent chondrocytes Proliferative Rapid proliferation of chondrocytes; Cells orient themselves parallel to the growing bone in a columnar fashion Hypertrophic Chondrocytes stop proliferating, Begin to enlarge rapidly Calcification Chondrocytes undergo apoptosis, matrix begins to calcify Ossification Mature and terminally committed osteoblasts, helps laying down of mineralized bone Long bone

18. Bone Growth: Appositional Growth Appositional bone growth - determines bone strength throughout life, increasing in width of bone. Appositional growth continues after puberty. Osteoblasts add mineralized tissue at the periosteum Osteoclasts resorbs bone at the endosteum Yellow marrow moves in to fill the space in the medullary cavity Bone grows in width (this process is also known as modelling or remodeling) Appositional bone growth process Appositional bone growth

19. Inflammation & Nutrition Affecting Linear Growth Chronic inflammation leads to growth faltering due to high levels of inflammatory markers & cytokines inhibiting GH secretion & IGF-1 activity inhibiting chondrocyte differentiation, increase apoptosis at epiphyseal plate. Malnourished children have ⇩ levels of GH, IGF-1, insulin, leptin suppressing growth. Mechanisms of Growth restriction caused by chronic inflammation

20. Catch-up Growth Significant increase in growth velocity after transient growth inhibition. Type A – growth velocity up to 4x faster than usual, returns to normal growth trajectory rapidly Type B – growth velocity > chronological age, but not faster than bone age ~ 20% more nutrients required in moderately malnourished children for catch-up growth Early intervention maximises height potential. Growth trajectories

21. Nutritional Intervention for Catch-up Growth Nutritional Intervention: a set of planned actions to prevent malnutrition or improve nutrition state. Types Comments Nutritional counselling Simple, cheap, safe, widely available May not be very effective Depending on educational level & cultural practice of care-provider Oral nutritional supplement Liquid, semi-solids, or powders Provides both macro- and micronutrients Hospital or community setting to children unable to meet nutritional demands through oral diet alone Enteral feeding Feeding directly into the stomach or duodenum / jejunum (by-passing the mouth) using a feeding tube or stoma Parenteral nutrition Indicated in dysfunctional or inaccessible gut (short gut) Hospital setting

22. Nutritional Supplement Promotes Catch-up Growth Nutritional supplements promotes catch-up growth in young children with faltered growth. Weight & height improved in 3 mths when children with picky eating given dietary counselling + lactose-free nutritional supplement (protein, carbohydrate and fat). Treatment group Dietary counselling + nutritional supplement (40 mL/kg/day) n=44 92 children in Taiwan & Philippines (<25 th percentile in wt -for- ht ) 3–5 y, picky eating Control group Dietary counselling only n=48 Followed up at day 30, 60, 90 Body weight, height, volume of formula intake and GI symptoms were assessed Alarcon PA, et al. Clin Pediatr 2003;42:209–217 .

23. Dietary counselling + nutritional supplement group: 50% faster height gain vs. control group. URTI significantly lower in the dietary counselling + nutritional supplement group. Intervention Day 30 Day 60 Day 90 Weight (kg) Dietary counselling 0.31 ± 0.40 0.44 ± 0.40 0.44 ± 0.41 Dietary counselling + supplement 0.54* ± 0.39 0.98* ± 0.58 1.18* ± 0.65 Height (cm) Dietary counselling 0.64 ± 0.76 1.15 ± 1.17 1.72 ± 1.12 Dietary counselling + supplement 1.12* ± 1.19 1.81* ± 1.24 2.66* ± 1.45 Weight and height changes *p<0.05 compared with control Percentage of URTI * *p<0.05 compared with control Nutritional Supplement Promotes Catch-up Growth Alarcon PA, et al. Clin Pediatr 2003;42:209–217 .

24. Nutritional Supplement Promotes Catch-up Growth Nutritional supplement did not interfere with normal food intake Promote nutritional adequacy and growth. Huynh DTT, et al. J Hum Nutr Diet 2015 Prospective Multicentre Single-arm Filipino children aged 3–4 y 5–25 th percentile in wt -for- ht N=200 Lactose free nutritional supplement twice daily (450 mL/day) Dietary counselling Weight, height, physical activity, appetite and dietary intakes using 24-hr food recalls Baseline Week 4 Week 8 Week 16 Week 24 Week 32 Week 40 Week 48

25. Nutritional Supplement Promotes Catch-up Growth Weight-for-height percentiles increased in first 4 w, remained significantly higher than baseline, relatively stable from week 8. Height-for-age percentiles increased steadily over time and became significantly higher than baseline from week 24 Appetite & physical activity scores at all post-baseline visits improved significantly from baseline. * * * * * * * *p<0.0001 compared with baseline * * * * * * * * * * * * Changes in weight-for-height, ht -for-age, appetite & physical activity

26. Adolescent phase the last opportunity for stunted individuals to reach optimal height. Catch-up Growth in Adolescence Ages 0–2 y & adolescent phase: 2 periods of growth spurts before reaching adult height 15–20% of final adult height 45% of final adult bone mass Adapted from Tanner JM. Nutr Rev 1981;39:43-55 Rogol AD, et al. Am J Clin Nutr 2000;72:521S-528S . Male Average peak velocity: 10.3 cm/y at age 14 y Female Average peak velocity: 9 cm/y at age 12 y

27. Inadequate Nutrient Intake in Adolescents is Common Protein 2.4% Vitamin C 57% Vitamin A 13% Vitamin D 99% Vitamin E 75% Calcium 89% Iron 47% Adolescents require up to 3x more key nutrients compared with toddlers Proportion of Malaysian adolescents (13–17 y) consume < 75% of RNI Adapted from MOH Malaysia. RNI 2017 Institute of Public Health, MOH Malaysia. Adolescent Nutrition Survey. 2017. X2.5 more X1.9 more X1.6 more X3 more X2.7 more X3 more RNI for toddlers 12 g per day 0.7 g per day 4.1 mg per day 80 mg per day 460 mg per day 15 µg per day 30.5 g per day 1.3 g per day 6.7 mg per day 240 mg per day 1,250 mg per day 45 µg per day RNI for adolescents

28. Summary Growth monitoring Adverse consequences of malnutrition: physiological, socio-economic Nutrition, physical activity, sleep affect growth 2 major growth spurts in life: infancy & adolescence. Epiphyseal plate closes ~ 12–16 y for girls and ~ 14–19 for boys Inflammation & malnutrition suppress bone growth. Catch-up growth requires at least 20% more nutrients to restore normal growth and development in moderately malnourished children. Nutrient supplementation helps with catch-up growth & improve immunity.