Understanding Failure to Thrive in Children

1. Chapter 2 Disorders of Growth

3. Failure to Thrive • Weight is the most common and simplest parameter to define FTT. • FTT describes retarded growth in height and weight, whereas short stature is diagnosed in comparison to a reference height-for-age or to one’s own height over time. • Besides growth deficit, FTT also results in alteration in immunity and dysfunction in intellect, development, and behavior. • FTT should never be considered as a primary disease. It is always a manifestation of an underlying cause which should be investigated thoroughly.

4. Diagnostic Criteria of Failure to Thrive 1. Weight-for-age below 5th percentile 2. Weight deceleration—Serial weight monitoring shows downward trend and has crossed two major growth percentiles (i.e., 75th percentile to below 25th percentile) in a short time. 3. Weight-for-age <75% of the median 4. Weight-for-length <75% of the median 5. Length-for-age <5th percentile 6. Body mass index <5th percentile

5. Systemic Complications of Failure to Thrive • Short-term: – Hypothermia – Hypoproteinemia – Predisposition to infections – Nutritional deficiencies and electrolyte imbalance • Long-term: – Neurocognitive delay – Behavioral problems – Short stature – Adult onset metabolic diseases

6. OrganicCauses of FTT

7. Causes of FTT

8. APPROACH TO DIAGNOSIS A child with FTT should have a detailed evaluation of the following aspects:  Dietary assessment  Medical assessment  Psychosocial assessment  Developmental assessment

9. History Taking in FTT • Ask the parents about the onset of growth failure to differentiate between congenital and acquired causes. • Ask for common symptoms of possible organic disorders. • Amount of food offered and consumed should be separately measured. • Feeding habits should be enquired for both home and outside home settings (day- care and school). • Sociocultural environment of the child should be assessed. • Family dynamics, parental education, employment, substance abuse, and cultural factors should also be assessed.

10. Psychosocial Assessment • Psychosocial assessment should include evaluation of socioeconomic status, family dysfunction, and feeding problems. • Assess for Child’s drive for autonomy, attention seeking, gaining independence, and expressing anger or dislike. • Assess for physical or mental abuse. • Developmental assessment should include assessment for developmental delay, and abnormalities of posture, tone, and attention and language domains. • Any delay in two or more domains is abnormal. Mild degree of motor delay is commonly seen in children with FTT due to poor skeletal mass and muscle tone.

11. Clinical Examination A thorough general and systemic examination should be done to search for:  Any clue to organic disorders (facial dysmorphism, neurocutaneous markers, and clubbing).  Physical abuse (fractures, bruises, hematomas, and cigarette marks).  Markers of severe malnutrition and associated deficiencies (loss of buccal fat, edema, mucositis, and corneal ulcers).  A detailed neurological and developmental assessment using appropriate tests.  Any abnormal behavioral pattern, response to external stimulus, etc.  Look for red flag signs.

12. Anthropometry • Obtain complete and accurate anthropometry. • Serially measured values rather than a single observation are mainstay for diagnosing FTT. • Anthropometry should be interpreted on age and gender specific population reference growth charts. • Separate charts for preterm babies should be used to monitor their growth during infancy.

13. RED FLAG SIGNS

14. Laboratory Evaluation The FTT is a clinical diagnosis and most children do not need investigations. Tests are of prime importance when an organic etiology is suspected or in the presence of a red flag sign.  Initial tests : Hemoglobin, blood counts, urea, electrolytes, creatinine, liver function tests, total proteins, antiendomysial bodies (to screen for celiac disease), and urinalysis.  Other tests: Sweat chloride test for cystic fibrosis, blood pH, anion gap, urine pH for renal tubular acidosis; and stool examination in children with diarrhea/ malabsorption.  Radiological assessment: For determining bone age.  A karyotype may be ordered in suspected chromosomal disorder.

15. Approach to Child with FTT

16. Failure to Thrive: TREATMENT 1. Dietary management 2. Parental counseling and education 3. Medical management 4. Psychosocial management 5. Developmental management

17. Dietary Management Nutritional rehabilitation aims at ־ Achievement of ideal weight for height ־ Correction of nutritional deficits, ־ Allowing catch up growth, ־ Restoration of optimal body composition, and ־ Parental education regarding nutritional requirements and feeding of the child. Diet management of a child with FTT is similar to that of a child with severe acute malnutrition.

18. Parental Counseling and Education • Parents should be involved in feeding actively. They should be told about their child’s requirements and how they can be met. • They should be counseled about calorie content of different food items, how to make calorie rich, simple, and appealing preparations, right techniques of feeding, and how to inculcate good feeding habits in their children. • Misconceptions and food fads should be addressed carefully. • Counseling a parent/caregiver for need of their active participation in continued rehabilitation and psychosocial care is important.

19. Medical Management • Several medical issues may be identified in children with FTT which may be primary or secondary and require specialized interventions. • Special diets may be required lifelong, e.g., celiac disease or special enzyme supplements for cystic fibrosis. • Drugs may be required (e.g., for gastroesophageal reflux disease) or special training in neuromotor dysfunction (e.g., cerebral palsy).

20. Psychosocial Management • The psychosocial aspects differ widely and hence the management cannot be generalized. • A good rapport is essential for both diagnosing and managing such issues. • Behavioral modifications in feeding disorders, psychotherapy, and counseling are of tremendous help. • In cases where there is severe abuse, neglect, and maltreatment, hospitalization or foster homes may be essential.

21. Developmental Management • This is the most challenging aspect that requires long-term care. • Studies have shown that even after aggressive nutritional rehabilitation, minor deficits such as language skills, subnormal intelligence quotient (IQ) scores, and decreased head circumference, can be detected on follow-up. • Thus, the key to neurodevelopmental management lies in prevention of severe FTT, early recognition of the condition, and management, before a permanent brain deficit occurs.

22. Failure to Thrive: IN A NUTSHELL 1. Failure to thrive is a term to denote the overall nutritional status of a child with respect to less energy intake or more energy expenditure. 2. Weight for age remains the most common parameter to monitor growth. 3. Serial weight monitoring if showing downward trend and crossing two major growth percentiles defines FTT. 4. The approach to clinical diagnosis should include detailed history and examination clues of underlying organic causes. 5. The management should be based on nutritional rehabilitation, parental counseling, development supportive practices, and appropriate medical therapy, as appropriate.

23. Short Stature: DEFINITION • Height below minus 2 Z-score or below 3rd percentile. • Height below minus 3 Z-score or below the first percentile indicates severe short stature. • Growth velocity below 10th percentile over a year or crossing of two percentile lines between the age of 2 years and puberty are also indicative of growth failure. • Use gender specific growth reference charts/ values to interpret [(WHO) growth charts from 0 to 5 years of age, and Revised Indian Academy of Pediatrics (IAP) 2015 growth charts from 5 to 18 years of age.] Available from https://iapindia.org/iap-growth-charts/.

24. DETERMINANTS OF GROWTH 1. Genetic growth potential [midparental height (MPH)]: ₋ Height is dependent on age, gender, nutrition, genetics, ethnicity, and racial differences. ₋ Genetic potential is determined by their parents’ heights and is calculated as MPH. ₋ A child may remain short, if he is born to shorter parents and diagnosed as familial short stature. 2. Nutrition 3. Systemic disease 4. Socioeconomic and Environment issues

25. Midparental Height • Calculation of midparental height (MPH) - MPH (boy) = (Father’s height + Mother’s height + 13)/2, or = [(Father’s height + Mother’s height)/2] + 6.5 - MPH (girls) = (Father’s height + Mother’s height – 13)/2, or = [(Father’s height + Mother’s height)/2] – 6.5 • MPH is marked at gender appropriate chart at 18/20 years. • In normally growing child, height at any given age corresponds to lie within 2 standard deviations of the MPH when it is extrapolated till adult height on a growth chart (target height range).

26. Nutrition • Babies with intrauterine growth retardation many catch-up or fail to achieve catch- up growth and do not attain normal height in childhood. • Deficiency of both macronutrients and micronutrients such as iron during growing years adversely impacts attainment of height. • Malnutrition has been reported as one of the most common causes of short stature. Systemic disease Chronic diseases, syndromic genetic disorders, diseases of musculoskeletal system, and those affecting the hypothalamic-pituitary axis [affecting growth hormone (GH), etc.], are other causes of short stature

27. Causes of Short Stature Normal variants • Familial short stature • Constitutional growth delay Pathological short stature • Malnutrition: Macronutrient or micronutrient deficiencies and small for gestational age • Chronic systemic diseases: – Gastrointestinal: Celiac disease and chronic liver disease – Cardiopulmonary: Acyanotic and cyanotic heart disease and congestive heart failure – Infections: Tuberculosis, giardiasis, and human immunodeficiency virus (HIV) – Renal: Chronic kidney disease, renal tubular acidosis, and chronic pyelonephritis – Hematological: Nutritional anemia, leukemia, and thalassemia – Pulmonary: Chronic asthma and bronchiectasis – Storage disorders: Mucopolysaccharidosis and glycogen storage disorders – Neurological: Cerebral palsy

28. • Metabolic bone disease—Rickets • Endocrine causes: – Hypothalamic-pituitary axis: Growth hormone deficiency, growth hormone receptor defect (Laron dwarfism) – Other endocrine organs: Hypothyroidism, Cushing syndrome, diabetes, and precocious puberty • Genetic syndromes: Turner syndrome, Prader–Willi syndrome, Russell–Silver syndrome, and Noonan syndrome • Skeletal dysplasia: Achondroplasia and osteogenesis imperfecta • Psychosocial dwarfism • Drugs: Systemic steroids and substance abuse

29. Disproportionate Short Stature • Occurs because of abnormal skeletal growth. • Either the limbs or the trunk is short. • Short limb dwarfism can be further classified into rhizomelic (shortening of proximal limb segment), mesomelic (shortening of middle segments), and acromelic (shortening of the distal segments) short stature. • In short limb dysplasia, e.g., achondroplasia (Fig. 2.1), chondrodysplasia, arm span is less than height and upper segment (US)/lower segment (LS) ratio is high.  In short trunk mucopolysaccharidosis, dysplasia, US/LS ratio is decreased, and arm span exceeds the height. anomalies, spondyloepiphyseal e.g.,

30. Proportionate Short Stature • This is more common, all the body proportions are equally shortened. • Occur secondary to constitutional delay in growth, chronic infections, malabsorption, congenital heart disease, renal failure, hypothyroidism which has disproportionate short stature. • A child with proportionate short stature may be thin or fat. Thin and short children usually have an underlying systemic disorder, while fat and short children are likely to have an endocrine etiology. or endocrine disorders, except

31. Constitutional Delay • This represents a group of children with delayed maturation but preserved growth potential. • This is particularly common in boys. • Family history of delayed puberty is common in father or elder brothers. • These children grow at a normal rate in childhood, show a late height spurt and pubertal onset, and continue to grow beyond the normal stage of growth to achieve a normal final adult height. • They have a mild delay in bone age. • Children with familial short stature on the other hand have normal bone age, normal pubertal onset, and usually end up short.

32. Other Causes of Short Stature 1. Malnutrition: • Most common pathological cause of short stature. • Growth failure is preceded by poor weight gain. This contrasts endocrine short stature where weight is usually normal. • Zinc deficiency is an important treatable cause. 2. Intrauterine growth retardation (IUGR): • Might be due to genetic disorders, intrauterine infections, maternal malnutrition, and placental disorders. • Most of these achieve catch-up growth in the first 2 years and have normal final height • Around 15%, fail to grow normally and have short stature. 3. Systemic disease: • Short stature occurs in all chronic systemic disorders and infections. • Celiac disease, renal failure, and renal tubular acidosis, are readily identified. • A few may be asymptomatic and missed Contd..

33. 4. Chromosomal/genetic syndromes • Down syndrome and Turner syndrome 5. Endocrine causes • Disorders of the Growth • Hypothyroidism • Type 1 diabetes mellitus • Pseudohypoparathyroidism, and • Rickets are also associated with growth retardation.

34. Causes of Short Stature

35. EVALUATION • A child with height above –2 Z-score (third percentile) or growth velocity above 25th percentile (or at least 5 cm per year in prepubertal years) is essentially growing normal. Immediate evaluation is warranted, if height is below –3 Z-score (first percentile). Children with height Z-score between –2 and –3 should be followed up. Work-up is required if growth velocity is below 25th percentile. • • •

36. Clinical Clues for Short Stature

37. Step 1: History Taking • Perinatal history and birth weight should be recorded. • Nutritional assessment is crucial. • Family history of short stature or delayed puberty suggests familial short stature or constitutional short stature. • Features of chronic infections, malabsorption, raised intracranial tension, and cardiopulmonary disorders should be enquired. • Polyuria and polydipsia suggest diabetes insipidus, diabetes mellitus and/or renal tubular acidosis. • Constipation, delayed milestones, lethargy, and cold intolerance pinpoint hypothyroidism. • History of birth asphyxia, breech presentation, neonatal hypoglycemia, and prolonged jaundice are indicative of hypopituitarism.

38. Step 2: Growth Assessment • It involves comparison of height with population standards and parental height along with monitoring of longitudinal growth. • Growth velocity should be measured over at least 12 months. Growth velocity <6 cm/year from the age of 1–3 years, below 5 cm/year during prepubertal growth years is suggestive of growth retardation. • Midparental height should be plotted on the growth curve at around 18–20 years and the percentiles compared with current height percentiles. Plot this value of adult height prediction on the reference growth chart of height-for-age. The percentile line nearest to this point is known as the midparental 50th percentile. The child’s own percentile curve is expected to be between 10th and 90th percentiles (MPH ± 6.5 cm, target height range) on the MPH percentile chart. • Calculate the height age and BMI.

39. Step 3: Physical Examination • Reduced weight is suggestive of nutritional growth retardation (malnutrition, systemic illness, and malabsorption). • Increased upper segment to lower hypothyroidism, achondroplasia, and Turner syndrome. • Decreased upper segment to lower segment ratio is characteristic of Morquio syndrome and spondyloepiphyseal dysplasia. • Body proportions are normal in GHD. • Look for Specific features of GHD, hypothyroidism, and Turner syndrome. • Rickets and anemia should prompt evaluation for malnutrition, celiac disease, or renal failure. • Evaluate for dysmorphism, skeletal deformities, and sexual maturity rating. segment ratio is indicative of

40. Referral Criteria for Growth-related Problems • Severe short stature: Height <−3 Z-score. • Short stature: Height Z-score <−2.25 with poor growth. • Downward crossing of growth centiles. • Prepubertal growth velocity below 5 cm/year. • Difference between target height Z-score and current height Z-score >2 Children who are short and require referral should be offered further investigations

41. Step 4: Investigations Skeletal Age • Skeletal age or bone age (BA) is the first investigation to be ordered in a child with short stature. • It is estimated by evaluating the skeletal maturity of bones of the left hand and wrist using standard bone atlas (Greulich–Pyle atlas or Tanner–Whitehouse method). • Normally, the bone age matches the chronological age (CA) of the child. • In case the BA shows a delay of >2 standard deviations than the CA, it is called delayed BA as seen in pathological short stature. • BA can also help differentiate between familial short stature and constitutional delay in growth (CDG).

42. Normal Variant Growth Patterns Familial short stature (FSS) • Seen as short stature in a child who is born to short parents, thereby implying the role of genetic potential for growth. • These children are short but their extrapolated height falls within the range of MPH. • General and systemic examination is normal. • They have normal skeletal maturation and thus their BA matches their CA. • However, as they are short, the HA is lesser than both CA and BA (BA = CA > HA). • This entity does not need any further investigation or treatment. • It is essential to reassure and monitor their growth annually.

43. Constitutional Delay in Growth and Puberty (CDGP) • These children have normal growth potential but show poor growth in late childhood. • The height velocity is normal. • There is usually associated delay in puberty which makes poor height more discernible in peripubertal years. • They need close monitoring of growth as they catch up subsequently on their height to attain final height within their MPH range. • Usually, there is history of similar delay in puberty in their parents. • These children have delayed BA which matches their HA. Both are less for their CA (HA = BA < CA).

44. FSS vs CDGP

45. Investigations in Pathological Short Stature First line tests: • Hemoglobin, blood counts, ESR—anemia, hematological disorders, chronic inflammatory diseases • Kidney function tests—chronic kidney disease • Liver function tests—chronic liver disease • Serum calcium, phosphorus—rickets • Thyroid function test—hypothyroidism • Serum transglutaminase—celiac disease • Urine routine examination—diabetes mellitus, nephrotic syndrome • Urine pH—renal tubular acidosis • Chest X-ray, including hand X-ray for bone age assessment • Karyotype (in girls)—Turner syndrome

46. Specific tests (done on case-to-case basis): • Infections—tuberculosis, HIV • Serum growth hormone (GH), IGF-1 levels and GH stimulation test—growth hormone deficiency (GHD) • Serum cortisol—Cushing syndrome • Skeletal survey—Skeletal dysplasia • Imaging of brain including pituitary fossa—GHD • Genetic mutations—POU1F1, PIT1, PROP1, HESX1, SHOX

47. Evaluate for Growth Hormone Deficiency • Evaluate for GHD after other common causes of growth retardation have been excluded. • These children generally have infantile facies (Fig. 2.3). • The extrapolated height falls significantly short of the respective MPH. • The skeletal maturation also shows a significant delay than their chronological age (BA < HA < CA). • Basal GH has no role in evaluating the GH–insulin-like growth factor (IGF) axis. • IGF-1 and its binding protein-3 (IGFBP-3) are screening tests for GHD. • Low levels of IGF-1 and IGF-BP3 should be followed by a GH stimulation test. • Stimulated GH levels below 10 ng/mL are suggestive of GHD.

49. Short Stature: TREATMENT Supportive therapy: • Treatment of underlying cause • Adequate nutrition intake: high protein and calorie diet. • Increase physical activity. • Iron, zinc, and vitamin deficiency should be corrected. Specific therapy: • Specific treatment is needed for hypothyroidism (thyroxine), celiac disease (gluten-free diet), and renal tubular acidosis (bicarbonate). • Testosterone (short course) should be given in boys with constitutional delay of puberty and growth. • Androgen, and anabolic steroids have been tried in genetic syndromes and skeletal dysplasia. • Recombinant GH therapy (SC daily) is effective in GH deficiency, Turner syndrome, chronic renal failure, SGA infants, Prader–Willi syndrome, and idiopathic short stature.

50. IN A NUTSHELL Short Stature 1. Correct measurement and interpretation of anthropometry is the most important step in assessment of short stature 2. Growth charts are the most important tool to interpret the growth patterns. Growth velocity is a better indicator than single-point value. 3. Systemic causes, familial short stature, and constitutional delay in growth are common causes of poor growth than endocrinal causes of short stature. 4. Assessment of growth should be in accordance with the pubertal growth pattern (in children of peripubertal age) and skeletal age (assessed on plain radiograph of left hand with wrist and fingers).