1. When Simple and Natural Gets Complicated Failure to Thrive

2. “I’m a Failure to Mother” Be careful of pejorative language – Parental Deprivation Syndrome (1960) Primary need is to instill confidence in the family

3. “I’m a Failure to Mother” “Growth Deficiency” Weight based assessment Insufficient growth velocity Weight Height Head Circumference Organic/Inorganic

4. Start at the Beginning Uteroplacental Insufficiency Maternal Hypertension Diabetes Mellitus Renal Disease Collagen Vascular Disease Genetics Parental - Age Fetal – Trisomy, Russell-Silver Syndrome Maternal Nutrition - time dependant, relatively resistant

5. Start at the Beginning 40% of Growth Deficient infants are born with birth weights of less than 2500 grams (5 pounds 8 ounces)

6. Start at the Beginning During fetal period, endocrine system has little impact on growth. Pituitary aplasia, congenital hypopituitarism or growth hormone insensitivity will have NORMAL weight at birth

7. Normal Growth Variation More than half of newborns experience an upward shift of growth during the first 3 months 30% of normal babies experience a downward shift between the ages of 3 and 18 months Children reach genetic length by 2 years Many children have significant weight decrease around between 9 and 15 months

8. Timing of Abnormality Severe Anatomic Abnormality Infection – GBS, TORCH Breast Feeding Dysfunction Cardiac Anomaly Cystic Fibrosis Milder Anatomic Abnormality Severe Reflux Protein Sensitivity Deprivation Chronic Reflux Inappropriate Diet Heavy Metal Poisoning Birth1 week2-4 weeks 1 month 6 months 9 months 1 year

9. Causes of Failure to Thrive Inadequate Input Excessive Output Increased Utilization

10. Humans are a Closed Energy System text CALORIES IN - METABOLIC USE - CALORIES LOST/ NOT USED = ZERO

11. Causes of Failure to Thrive Inadequate Input Excessive Output Increased Utilization

12. Inadequate Input 1. INSUFFICIENT NUTRITION OFFERED 2. MATERNAL/CHILD AXIS DYSFUNCTION 3. PSYCHOSOCIAL DYSFUNCTION 4. SEVERE GASTROESOPHAGEAL REFLUX / VOMITING 5. MECHANICAL PROBLEMS 6. SUCKING OR SWALLOW DYSFUNCTION

13. Inadequate Input INSUFFICIENT NUTRITION OFFERED Maternal Medical Stress Anti-histamines Narcotics/Alcohol Inappropriate or incorrectly constituted formula Displacement of nutritious offering by poor nutritional component Vitamin deficiency Lead (5-35 mcg/dL) potentiated by poor Calcium and Vitamin D

14. Inadequate Input MATERNAL/CHILD AXIS DYSFUNCTION Inappropriate knowledge of infant/child diet Sub-optimal feeding technique Maternal depression Poor bonding (NICU, illness, maternal aversion, abuse)

15. Inadequate Input PSYCHOSOCIAL DYSFUNCTION 25% of children in Tennessee live below the poverty level In Chattanooga 80% of African-American children are born to single mothers (poor social network)

16. Inadequate Input PSYCHOSOCIAL DYSFUNCTION Marital stress Domestic violence Parental employment Children of mother’s under 18 have poorer growth and twice as likely to be abused Number and age of siblings/health of others in the family Homelessness or home instability/unstable transportation

17. Inadequate Input SEVERE GASTROESOPHAGEAL REFLUX Poor intake Pain feedback loop VOMITING Infectious gastroenteritis/post-vial ileus Chronic pyelonephritis Increased intracranial pressure Cyclic vomiting Poorly controlled Abdominal migraines Adrenal insufficiency Ipecac

18. Inadequate Input MECHANICAL PROBLEMS Cleft palette Micognathia or Macroglosia Tight labial frenulum Nasal obstruction Intestinal Obstruction (Volvulus, Intusception, Hirschsprung’s, Pyloric Stenosis) Chronic constipation Adenoidal hypertrophy Dental lesions

19. Inadequate Input SUCKING OR SWALLOW DYSFUNCTION Neonatal Abstinence Syndrome CNS pathology (stroke, tumor, hydrocephalus) Genetics Syndromes (Trisomy) Cardiopulmonary Disease Neuromuscular weakness/tone Cerebral Palsy Anorexia of chromic infection, immune deficiency, lead Behavioral (apathy or rumination)

20. Causes of Failure to Thrive Inadequate Input Excessive Output Increased Utilization

21. CARDIAC DISEASE Congenital or Acquired SEPSIS CHRONIC RESPIRATORY INSUFFICIENCY Bronchopulmonary dysplasia Cystic fibrosis RENAL DISEASE partial posterior valves, severe reflux with UTI, Renal Tubular Acidosis HYPERTHYROIDISM

22. Increased Utilization CHRONIC/RECURRENT SYSTEMIC INFECTION UTI, Tuberculosis, TORCH HIV – degree of viremia correlates with poor growth MALIGNANCY INFLAMMATORY BOWEL DISEASE DIABETES MELLITUS CHRONIC SYSTEMIC DISEASE Juvenile Idiopathic Arthritis

23. Increased Utilization Metabolic Disease Inborn errors of metabolism (normal infant that deteriorates with lethargy, poor feeding, convulsions, vomiting) Storage diseases Hypercalcemia Adrenal insufficiency

24. Causes of Failure to Thrive Inadequate Input Excessive Output Increased Utilization

25. Excessive Output Biliary Atresia Necrotizing Enterocolitis or Short Bowel Syndrome Malabsorption Lactose intoleranceCystic fibrosis Cardiac diseaseInflammatory bowel disease Milk/food allergy or irritationParasites Cystic FibrosisCeliac Disease Infectious diarrhea Renal losses Fanconi SyndromeChronic renal insufficiency Vitamin D resistanceType I Diabetes Mellitus

26. Causes of Failure to Thrive Inadequate Input Excessive Output Increased Utilization

27. Isolated Linear Growth Deficiency Familial Intrinsic Short Stature Chromosomal Abnormality Trisomy 13, 18, 21 Chromosome 22 del Gonadal Dysgenesis (45, X) Skeletal Dysplasia Endocrine Dysfunction Pituitary Insufficiency Hypothyroidism GH deficiency/resistance Younger children Hypophosphatemic Rickets Older children Hypercortisolism Pseudohypo- parathyroidism Isolated Linear Growth Deficiency

28. Management Tips If clinically and socially stable, give yourself time and use frequent observational follow up Even if clear organic cause evident do not forget about psychosocial components – most organic causes have mixed non-organic component Be clear with family about seriousness of child’s status –insist they be seen –“Ring the Bell” - get all hands on deck

29. Management Tips Look the grandmothers in the eye, get them on your side, ask them what they think is wrong and give them jobs Ask all important members of the team for their assessment and theories on treatment Normalize familial expectations Access parental dietary attitudes –Unhealthy, sweet, hot/cold foods, fattening, food allergy

30. Management Tips Ask every time you meet with the family –Diet “What are you feeding the child?” –Caloric Intake “What exactly did your child eat in the last 24 hours?” –Eating Environment “How are you feeding the child?” –“What do you Think about your child’s feeding”

31. Expected Daily Weight Gain grams/day 0 to 3 months30 3 to 6 months18 6 to 9 months12 9 to 12 months 9 1 to 3 years 8 “Catch Up” weight gain is two to three times greater than average for age

32. Calculating Calorie Need Dietary Reference Intake (kcals/kg/day) 0 to 6 months108 6 to 12 months98 1 to 3 years102 “Catch Up” calorie calculation 150% DRI Alternative method (DRI x median weight for length)/actual weight

33. Basal Intake Rate for Protein 2.2 grams/kg per day

34. Other Considerations Calculated calorie requirements are estimates. Severe failure to thrive may require greater than 200kcal/kg Target calorie intake should be achieved over 5-7 days Malnutrition is usually associated with some degree of anorexia High calorie feedings are hyperosmolar and may lead to diarrhea or malabsorption Rapid refeeding may lead to hyperkalemia or hypophosphatemia

35. Vitamin and Mineral Supplementation ZINC –No reliable lab assessment –Baseline addition IRON –If Hemoglobin, Hematocrit or MCV labs indicate further work up add to diet

36. Feeding Strategy Start with small quantities and advancing as tolerated Pushing feeding further apart Assisted feeding to help caregiver recognizing and responding to cues of hunger and satiety, identify active feeding Monitoring latch quality and persistence of latch

37. Increasing Milk Caloric Content - INFANTS Breast Milk –22 kcal/oz: add ½ scoop of formula to 4 ½ ounces –24 kcal/oz: add 1 scoop of formula to 5 ounces Formula –22 kcal/oz: add 2 ½ scoops of formula to 4 ½ ounces of water –24 kcal/oz: add 3 scoops of formula to 5 ounces of water

38. Increasing Milk Caloric Content - CHILDREN Increase calorie content of foods child likes to eat –Adding rice cereal to pureed foods –Replacing milk with high calorie substitutes –Limiting low nutrition liquids –Adding cheese, butter, sour cream, peanut butter to fruits and vegetables –Total energy and protein is more important than variety

39. Increasing Milk Caloric Content - CHILDREN

40. Increasing Caloric Density of Foods for Toddlers

41. Other Recipes 8 ounces of whole milk plus 2 Tbsp nonfat dry milk powder = 24 calories/ounce 8 ounces of whole milk plus 3 Tbsp nonfat dry milk powder = 28 calories/ounce 1 cup of whole milk, 1 package of instant breakfast and 1 cup ice cream = 430 calories

42. Adequate Response With adequate caloric and protein intake, “Catch Up” growth is initiated in 2 to 14 days 4-9 months of accelerated growth must be maintained to restore a child’s weight to height “Catch Up” height may lag behind weight by several months

43. Medical Appetite Stimulation Cyprohepatidine has no proven long-term benefit Lemons PK, Dodge NN. Persistent failure-to-thrive: a case study. J Pediatr Health Care 1998; 12: 27.

44. Indications for Hospitalization Severe malnutrition Significant dehydration Serious medical problems Psychosocial risk to child Failure to respond to outpatient management Precise documentation of caloric intake Extreme parental impairment or anxiety Severely disrupted parent-child axis Family issues make outpatient therapy impractical

45. Supplement Oral Feedings Severe malnutrition that is not achieving adequate catch up in 4 to 6 weeks consider nasogastric feedings Discontinue when consistent weight gain has been shown for 4 to 6 months If weight gain remains inadequate after 3 to 4 months of nasogastric feeds gastrostomy tube may be appropriate

46. Frequent Follow Up Weekly follow up should continue until solid baseline growth is demonstrated Use ancilary team members for observation –Home health nurse –WIC –Dietitian

47. Refeeding Syndrome Sweatiness Hyperthermia Hepatomegaly – increased glycogen deposition Widening of the cranial sutures- brain growth faster than the skull Increased periods of sleep Fidgetiness or hyperactivity

48. Refeeding Syndrome Follow Potassium and Phosphorus in the acute period of reinstating nutrition Initial intracellular ion shifts my cause –Hypokalemia –Hypophosphotemia Can produce serious arrhythmias and muscle weakness

49. Can laboratory studies help diagnosis and management?

50. Not Usually Sills et al (1978) 2607 laboratory tests were undertaken for the entire study group of 185 children hospitalized for failure to thrive. Only 36 (1.4%) of tests were of positive diagnostic significance. All of them were in the 34 patients whose diagnosis was strongly suggested by history and examination. Homer et al (1981) 82 children hospitalized for failure to thrive. History and examination was most sensitive indicator of organic disease. Berwick et al (1982) 122 infants hospitalized for failure to thrive. Only 0.8% of tests were of positive diagnostic significance and 3.8% contributed to management. GI related labs were most helpful but indication for labs usually appearant in history and examination.

51. How can laboratory studies help? Infection or chronic inflammation Electrolyte irregularity and monitor for refeeding impact Iron deficiency Vitamin deficiency(B12 or folate) Nutritional status (albumin and prealbumin) Fat soluble vitamins (ADEK) Evaluate signs of specific disease –Cystic Fibrosis –Metabolic Disease

52. How can laboratory studies help? ELECTROLYTE IRREGULARITY AND MONITOR REFEEDING IMPACT Hypernatremic hypovolemia Poor fluid volume from feeding Hyponatremic Unmanageble free water volume RTA Hyperaldosteronism Hypomagnesium Stool loses Hypokalemia/Hypophosphatemia

53. How can laboratory studies help? IRON DEFICIENCY Most common nutritional deficiency in children Labs Mean Corpuscular Volume Serum Iron Plasma Ferritin sensitive but also an acute phase reactant Total Iron Binding Capacity, Transferrin Ususally associated with hypochromic, microcytic morphology

54. How can laboratory studies help? WATER SOLUBLE VITAMIN DEFICIENCY Macrocytic Anemia Serum B12 and Folate levels can be directly measured FAT SOLUBLE VITAMIN DEFICIENCY Vitamin A, E and 25-hydroxyvitamin D can be measured Prothrombin Time is a good proxy measure of Vitamin K

55. How can laboratory studies help? EVALUATING NUTRITIONAL STATUS Prealbumin Synthesized in liver Half-life 2 days Exquisitely sensitive to adequate levels of protein and energy intake Low levels in children <13, neonates <4 Albumin Synthesized in liver Half-life 14-20 days so reflect last three weeks of nutrition Be careful with large protein losses from circulation Ascites, Renal disease, GI losses

56. How can laboratory studies help? Cystic Fibrosis Stool for fecal fat or trypsinogen Other causes of malabsorption Stool for reducing substances (carbohydrate enzyme deficiencies) Celiac Disease Antibody Screening (Celiac Panel) Endocrine Dysfunction Growth hormone, IGF1, IGFBP3, TSH, free T4 Rule out if height above 50 th percentile

57. How can laboratory studies help? ZINC Serum Zinc level have a high degree of variation through the day Assume Zinc deficiency in malnutrition/growth failure

58. Long Term Considerations Systematic review of cohort studies shows Decreased IQ of questionable clinical significance Height and weight seem to be lower percentiles Psychomotor and educational outcomes seem to be lower than population norms

59. Child with no serious congenital anomaly or confirmed genetic disorder Greater than 5 organ symptoms involvement Multiple presentations to previous institutions for evaluation Long and convoluted history with multiple identifying features as treatment adherence failure leads to next subspecialty evaluation Refusing feeding team evaluation, home evaluation or changing/adding formula/supplement without medical consult History of maternal pregnancy complications Three of more parental-reported allergies Red Flags for Medical Child Abuse in Growth Deficiency

60. References Berwick DM et al. Failure to Thrive: Diagnostic Yield of Hospitalization. Archives of Disease in Childhood. 1982; 57: 347-351. Bithoney WG, Dubowitz H, Egan H. Failure to thrive/growth deficiency. Pediatric Rev 1192; 13: 453. Ellerstein NS, Ostrov BE. Growth patterns in children hospitalized because of caloric-deprivation failure to thrive. Am J Dis Child 1985; 139: 164. Frank DA. Failure to thrive. In: The Zuckerman Parker Handbook of Developmental and Behavioral Pediatrics for Primary Care, 3 rd ed, Augustyn M, Zuckerman B, Caronna EB (Eds), Lippincott Williams & Wilkins, Philadelphia 2011. p.204. Frank D, Silva M, Needlman R. Failure to thrive: Mystery, myth and method. Contemp Pediatr 1993; 10: 114. Frank DA, Zeisel SH. Failure to thrive. Pediatr Clin North Am 1988; 35: 1187. National Research Council, Food and Nutrition Board. Recommended Daily Allowances. National Academy of Sciences, 10 th ed, National Academy Press, Washington, DC 1989. Goldbloom RB. Growth failure in infancy. Pediatr Rev 1987; 9: 57. Grey V, Landis L, Pall H, Drury D. Monitoring of 25-OH vitamin D levels in children with Cystic Fibrosis. J Pediatr Gastroenterol Nutr 2000; 30: 314. Haynes CF, Cutler C, Gray J, Kempe RS. Hospitalized cases of nonorganic failure to thrive: the scope of the problem and the short-term lay health visitor intervention. Child Abuse Negl 1984; 8: 229.

61. References Homer C. et al. Categorization of Etiology of Failure to Thrive. American Journal of the Diseases of Children. Sept 1981; 135: 848-851. Ingenbleek Y, Young V. Transthyretin (prealbumin) in health and disease: nutritional implications. Annu Rev Nutr 1994; 14: 495. Jafee AC. Failure to Thrive: Current Clinical Concepts. Pediatrics in Review 2011; 32: 100. Lemons PK, Dodge NN. Persistent failure-to-thrive: a case study. J Pediatr Health Care 1998; 12: 27. Mash C, Frazier T, Nowacki S, Worley S, Goldfarb J. Development of Risk-Stratification Tool for Medical Child Abuse in failure to Thrive. Pediatrics 2011; 128; e1467. Maggiono A, Lifshitz F. Nutritional management of failure to thrive. Pediatr Clin North Am 1995; 42: 791. MacLean WC Jr, Lopez de Romana G, Massa E, Graham GC. Nutritional management of chronic diarrhea and malnutrition: primary reliance on oral feeding. J Pediatr 1980; 97:316. Measurement of visceral protien status in assessing protein and energy malnutrition: standard of care. Prealbumin in Nutritional Care Consensus Group. Nutritional Care Consensus Group. Nutrition 1995; 11:169. Rudolf M, Logan S. What is the long term outcome for children who fail to thrive? A systematic review. Arch Dis Child 2005; 90: 925-931. Schmitt BD, Mauro RD. Nonorganic failure to thrive: an outpatient approach. Child Abuse Negl 1989; 13: 235.

62. References Seres DS. Surrogate nutritional markers, malnutrition and adequacy of nutrition suppot. Nutr Clin Pract 2005; 20: 308. Sills RH. Failure to Thrive. The Role of Clinical and Laboratory Evaluation. American Journal of Diseases of Children. Oct 1978; 132: 967-969. Smith DW, Truog W, Rogers JE, et al. Shifting linear growth during infancy: illustration of genetic factors in growth from fetal life through infancy. J Pediatr. 1976;89:225-230 Swartz I. Failure to Thrive: An Old Nemesis in the New Millenium. Pediatrics in Review 2000; 21: 257. Tougas L, et al. Dietary Manual, Department of Nutrition. Boston, MA: Children’s Hospital; 1991 Walravens PA, Hambridge KM, Koepfer DM. Zinc supplementation in infants with a nutritional pattern of failure to thrive: a double-blind, controlled study. Pediatrics 1989; 83: 532. Wright CM. Identification and management of failure to thrive: a community perspective. Arch Dis Child 2000; 82: 5. Zenel JA Jr. Failure to thrive: a general pediatrician’s perspective. Pediatr Rev 1997; 18: 371.