“Failure to Thrive”

1. “Failure to Thrive” Suzanne Swanson Mendez, MD August 31, 2012

2. Defining FTT • “Growth Deficiency” • Crossing 2 major percentile lines or a term child less than 5th percentile on growth chart • A child under 6 months who has not grown for 2 months • A child over 6 months has not grown for 3 months • http://www.mashby.com/images/posts/skinny_kid.gif

3. Types of Growth Deficiency

4. Type 1A: Inadequate intake • Incorrect preparation of formula: too dilute or too concentrated • Breastfeeding difficulties • Unsuitable feeding habits for age: excessive juices, food fads, poor transition to food (6-12 months) • Behavioral problems affecting eating • Poverty and food shortages • Disturbed parent-child relationship: neglect or hypervigiliance • Mechanical feeding difficulties: oromotor dysfunction, congenital anomalies, severe reflux, CNS damage

5. Type 1B: Inadequate absorption of calories • Celiac disease • Cystic fibrosis • Cow’s milk protein allergy • Vitamin or mineral deficiencies (acrodermatitis enteropathica, scurvy) • Biliary atresia or liver disease • Short gut syndrome

6. Type 1C: Increased metabolism • Hyperthyroidism • Hypoxemia • Chronic lung disease • Congenital heart defect • Severe obstructive sleep apnea • Chronic disease • HIV/Immunodeficiency • Renal disease • Malignancy

7. Type 1D: Defective utilization of calories • Genetic abnormalities (Trisomy 13, 18, 21) • Congenital infections • Metabolic disorders (storage diseases, amino acid disorders)

8. Case One • CJ, an 8-month-old male presents for WCC • Last seen at 6 months with poor weight gain, increased calorie formula recommended • Plotting his weight, you notice that he has crossed from the 95th percentile (at 2 months of age) to the 5th percentile now • What would you do?

9. Workup • History and physical will identify etiology in most cases • What do you want to know? • Pregnancy/birth history: • IUGR, congenital infections, risk factors for HIV, prenatal care and labs • Gestational age at birth, size at birth (SGA?) • Newborn screen • What does the newborn screen include in D.C.? • When is it done?

10. History and Physical • Diet/Feeding history: • How much does the baby eat? How is formula mixed? (What? When? Where? With whom? How?) • Food battles • Stooling/Voiding patterns • Vomiting or signs of reflux after feeds? • PMH: Hospitalizations, Recurrent infections? • Growth curve:growth velocity is most important and can point out when failure began. • Medications/Herbs/Supplements

11. More History • Allergies • Environmental and Toxin Exposures • Social History: risks for feeding problems • Family History: includes parental heights • Developmental History • Review of Systems

12. Expected Feeding and Voiding Patterns

13. Signs of successful breastfeeding 1) Weight gain; no more than 10% loss from BW in 1st week 2) Baby calm, relaxed after feed; no more hunger cues 3) Feeds 8-12 times/day 4) Swallowing may be heard 5) Steady rhythmic motion in cheeks 6) >6 soaking wet (or heavy) diapers/day 7) Stools change to yellow by 7th day of life, at least 1-2 stools/day until 5-6 weeks of age 8) Breasts feel softer/emptier after feed • At 4-6 weeks, may pull away if flow decreases---> compress to increase flow; not a sign of less milk

14. Further workup of Growth Deficiency • From the mother in Case One: • Prenatal/birth history: Had regular prenatal care, prenatal labs normal, HIV negative; Born by NSVD at 39 wks, home with mom on DOL 2. NB screen normal. • Nutrition/Feeding history: • For first 2 months, breastfed only and did well (95th%) • Then started refusing to eat, breastfed at night only for 5 min q2hrs. Often vomited during feedings when upset. • Started on 24kcal formula during day at 6 months by pediatrician due to poor wt gain but often refused to drink. • Does not seem to like any pureed foods: turns head away.

15. Feeding and Voiding • Feeding history: No difficulties with swallowing, no diaphoresis or tiring with feeds, but vomiting has become a daily event--mom blames his “temper” • Voiding/stooling patterns: • 3 wet diapers/day; • Stools every 3-4 days • No steatorrhea or blood/mucus noted in stools • Stools are yellow to green and soft, usually large amounts

16. Constipation • Is this baby constipated? • Infrequent stooling does not necessarily mean constipation nor does straining • Worry about constipation if: • Pain or crying during passage of BM • Unable to pass BM after straining/pushing over 10 minutes • No BM after more than 3 days (except if breastfed and over 1 month--may have 5-6 days btwn stools)

17. How much does this baby weigh? For an estimate of average for age: Newborn: 3.2 kg Ages 3-12 months [for weight in kg]: Age (in months) + 9 2 But in an emergency, use the color-coded tape!

18. The First Year • Baby should regain BW by 2 weeks (earlier if formula fed) • Doubles BW by 4-5 months • Triples BW by 1 year, quadruples by 2 • Height does not double until 3-4 years • OFC reflects neuronal cell division from 0-6 months; later from neuronal cell growth and supporting tissue proliferation

19. Expected Growth

20. Growth history • BW 3.4kg (at 39 wks) • 6.8 kg at 2 months (95th percentile) • 7 kg at 6 months (10th percentile) • 7.1 kg at 8 months (5th percentile) • Height/OFC both near 50th percentile • http://www.keepkidshealthy.com/growthcharts/boysbirth.gif

21. History (continued) • PMH/PSH: No hospitalizations or surgeries, no recurrent infections, no risk factors for HIV, NB screen in Virginia was normal, AOM at 6 months. • Medications: none, no herbs, no supplements • Allergies: no known drug allergies, no known food allergies • ROS: no snoring/apnea noted, but not a good sleeper and mom thinks he cries a lot. No tachypnea, no choking or diaphoresis during feeds; otherwise unremarkable.

22. More History: • Developmentally, he “cruises” and says “mama” and “dada,” but has quite a temper according to mom. • Family history: mid-parental height is at 50th percentile (dad’s + mom’s height in cm +/- 13) div by 2 • Social history: • Father works as engineer, moved from China 2 years ago • First child; lives only with mom and dad now, but grandmother lived with family for child’s first 2 months then returned to Taiwan • Mom’s English skills very limited

23. Screening for social factors • No longer “organic” versus “nonorganic” FTT; many cases multifactorial • Caregiver depression/attachment disorder:can affect baby’s growth especially in the first 6 months • Anxiety disorder or separation/ individuation disorder:may affect baby’s growth from 6-12 months • Child abuse or neglect always a concern

24. Maternal depression • One of the most common complications of pregnancy • 10-20% of women experience depression during or within the first 12 months after pregnancy • Pediatrician often has more contact with mothers than their PCPs do yet less than 10% screen • 2 easy questions: • During the past month, have you been bothered by feeling down, depressed, or hopeless? • During the past month, have you been bothered by having little interest or pleasure in doing things? *Parents might respond better to paper questionnaire

25. Further social history • CJ’s mom does admit to feeling very isolated and screens + for anhedonia • Does not drive and is alone with infant in apartment all day • Nearest friends 30 miles away

26. Physical Exam • Physical exam: weight 7.1kg (5th percentile), height 69 cm (25th percentile), OFC 45 cm (50th percentile) • Fussy but consolable • Observed feeding: Mom offers bottle but baby gets irritable, refuses. Mom very anxious. • Description of formula mixing correct • Physical exam otherwise unremarkable

27. Nutrition * A prospective 3-day diet record is helpful in most cases of growth deficiency * In this case, baby refusing feeds and vomiting when upset were interfering with adequate caloric intake

28. Types of Growth Deficiency

29. Labs for Case One • Screening Hb, Pb levels normal for age • Confirm NB screen results • Other labs should be guided by detailed H&P • In CJ’s case, physical was unrevealing and history + observation suggests parent-child interaction problem • Later pH probe negative for GERD

30. Management • Depends on underlying cause • For CJ, counseling for mother was recommended • Increased social support • Vomiting improved with behavioral management, less force-feeding and decreased parental anxiety.

31. Case Two • AB, a 12-month-old infant, presents to Urgent Care for fever, ear pain • T 38 C, HR 130, RR 24, sat 100% RA • Wt 7.1 kg (at 3rd percentile for age) • History of fever for 2 days with cough for 1 wk • Mom also reports baby has had loose stools for “months” but no vomiting. • Stools are yellow to green without blood or mucus; occur 3-4 times/day. • Normal urine output with light yellow urine. • What else do you want to know?

32. History • PMH/PSH: Born at term, no problems with pregnancy, NB screen negative. BW 3.8kg. Multiple episodes of AOM, last 1 month ago. Also hospitalized 1x for bronchiolitis and once for pneumonia, no surgeries. • Medications: High-dose amox completed 2 1/2 weeks ago • Allergies: NKDA, no known food allergies • Family history: Mid-parental height at 75th%, mom has Type I diabetes

33. Further history • No growth chart available, but mom thinks child hasn’t gained wt in months: “much smaller than other kids her age.” • Nutrition history: breastfed until 2 months and then switched to formula and did well. At 4 months, rice cereal introduced, then pureed foods at 6 months. Now eats “everything”--all table foods.

34. Social and developmental history • Developmentally appropriate: sat at 6 months, first words at 8 months, now can walk with both hands held • Social history: • Parents separated 7 months ago; father no longer involved • Mom works part-time; estimates income at $20,000/year • Has neighbors who cares for child while she works • History of depression; denies feeling depressed currently but is very worried about her daughter

35. What next for AB? • More history? • Physical exam: wt 7.1 kg (3rd%), L 70 cm (10th%), and OFC 46 cm (50th%) What do these parameters suggest about her growth deficiency? • Can be Type I (chronic malnutrition) or Type II growth deficiency: • Familial short stature/Constitutional growth delay • Endocrinopathy • Skeletal dysplasias *Though her weight is still more affected than her height

36. Physical exam • Child is thin, but alert, interactive, in no distress • HEENT: Thin, wispy blonde hair; R TM reddened and retracted, L TM with typmanosclerosis; Tonsils 2+, no lymphadenopathy. • Heart exam normal • Lungs have transmitted upper airway sounds but good aeration. • Abdomen is soft but very full/ protuberant, no HSM • Tanner I GU, good femoral pulses • Extremities are thin but well-perfused; no signs of dehydration, no edema • Skin warm, pink, without rashes

37. Differential diagnosis? • Type I Growth Deficiency: • Inadequate caloric intake • Increased metabolism • Inadequate absorption • Defective utilization • Type II Growth Deficiency: since height is also affected (but still less so than weight) • Familial short stature • Constitutional growth delay • Skeletal dysplasias • Endocrinopathies

38. Workup • You send her home with a prospective 3-day food diary and Augmentin and a WIC referral • Encourage social support for mom • 3 meals/3 snacks on a daily schedule for child • Any labs?

39. Labs • CBC for anemia, malignancy, immunodeficiency • Electrolytes and UA for renal/metabolic disease • Albumin and LFTs for abdominal workup • Stool studies: wbc/rbc smear, O&P • Sweat chloride test • HIV, consider quantitative immunoglobulins

40. Lab Results • CBC shows normocytic anemia • Lytes, UA normal • Albumin low at 2.3 mg/dl • Stool studies negative for wbc, rbc, O&P • Sweat chloride normal • HIV negative • QuIg’s normal (including IgA)

41. Follow-up • Two weeks later, the child returns and mom seems happier, but AB has only gained 0.05 kg (about 3g/day) • How much should she be gaining? • Answer: about 8 g/day just for normal growth, not including catch-up • Nutrition diary reveals an intake of 800 kcal/day (about 85 kcal/kg of IDEAL body weight/day)--is this enough? • Answer: It might be enough for normal growth, but she will need more to catch up (up to 1.5 x more)

42. Differential diagnosis now • Type I growth deficiency: • Inadequate intake? Not according to food diary • Increased metabolism? Not HIV/renal disease, unlikely malignancy or CHD/CLD • Inadequate absorption? Could be celiac disease; unlikely CF (sweat Cl normal) or vitamin def. • Defective utilization? No signs of genetic abnormalities, congenital infections, or metabolic disorders • Type II growth deficiency less likely without family history, signs of endocrinopathy

43. Further work-up • Given her low albumin with normal kcal intake for age and chronic diarrhea, malabsorption is likely • Stool reducing subs/alpha-1-AT sent • Screening test for celiac disease: Anti-tissue transglutaminase Ab (IgA and IgG) also sent • TGA comes back +

44. Management • AB is switched to a gluten-free diet and starts to gain weight well • Small bowel biopsy confirms diagnosis • Height also improves • Pt continues to do well with close followup and social situation improves

45. Importance of treating Growth Deficiency • Early childhood is a key period for growth and development. • Often multifactorial in etiology • Children with “failure to thrive” are at risk for: • Behavioral problems • Developmental delay • Short stature • Prompt intervention and close follow-up needed to reverse FTT pattern and prevent associated problems

46. On the path to good health!

47. Bibliography • Behrman RE, “The First Year,” Nelson Textbook of Pediatrics, Chapter 10, 17th edition, 2004. • Brayden RM, Daley MF, Brown JM, “Ambulatory and Community Pediatrics: Growth Deficiency,” Current Pediatric Diagnosis & Treatment, 16th edition, 2003, p 239-240. • Gahagan, Sheila, “Failure to Thrive: A Consequence of Undernutrition,” Pediatrics in Review 2006;27:e1-e11. • Krebs NF, Hambidge KM, Primak LE, “Normal Childhood Nutrition & Its Disorders,” Current Pediatric Diagnosis & Treatment, 16th edition, 2003, p. 277-307. • Krugman S and Dubowitz H, “Failure to Thrive,” American Family Physician, 68:5, Sept. 2003. • LPCH Health Library: “Constipation.” Pediatric Housecall Online. Barton Schmidt, Updated Aug. 2002. http://www.lpch.org/HealthLibrary/ParentCareTopics/AbdomenGISymptoms/Constipation.html • Robertson J, Shilkofski N, Johns Hopkins Hospital, “Normal Nutrition and Growth,” Chapter 20, The Harriet Lane Handbook, 17th edition, August 2005.

48. Bibliography (continued) • Save Babies Through Screening Foundation, “Disorders Screening for in State NBS Programs and Puerto Rico,” Updated June 18, 2006. http://www.savebabies.org/states/washingtonDC.php • “Food Stamp Program,” Food and Nutrtion Services Home Page, Last updated October 11, 2006. http://www.fns.usda.gov/fsp/faqs.htm#2 • Flora, B, “Breastfeeding Essentials: Is My Baby Getting Enough?” Last updated April 2003. http://breastfeeding.hypermart.net/enoughmilk.html • Johnson CP and Blasco PA, “Infant Growth and Development,” Pediatrics in Review. 18:7, July 1997. • “Women, Infants, and Children,” Food and Nutrition Service, USDA, Last updated June 20, 2005.http://www.fns.usda.gov/wic/

49. 1) 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC) 2) 3-OH 3-CH3 glutaric aciduria (HMG) 3) Argininosuccinic acidemia (ASA) 4) Beta-Ketothiolase deficiency (BKT) 5) Biotinidase deficiency (BIOT) 6) Carnitine uptake defect (CUD) 7) Citrullinemia (CIT) 8) Classical galactosemia (GALT) 9) Congenital adrenal hyperplasia (21-hydroxylase deficiency) (CAH) 10) Congenital hypothyroidism (CH) 11) Cystic fibrosis (CF) 12) Glutaric acidemia type I (GA 1) 13) Hb S/C disease (Hb S/C) 14) Hb S/ß-thalassemia (Hb S/ßTh) 15) Homocystinuria (due to CBS deficiency) (HCY) 16) Isovaleric acidemia (IVA) 17) Long-chain L-3-OH acyl-CoA dehydrogenase deficiency (LCHADD) 18) Maple syrup disease (MSUD) 19) Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) 20) Methylmalonic acidemia (Cbl A,B) (Cbl A, B) 21) Methylmalonic acidemia (mutase deficiency) (MUT) 22) Multiple carboxylase deficiency (MCD) 23) Phenylketonuria (PKU) 24) Propionic acidemia (PROP) 25) Sickle cell anemia (Hb SS disease) Hb (SS) 26) Trifunctional protein deficiency (TFP) 27) Tyrosinemia type I (TYR I) 28) Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) 29) 2-Methyl 3-hydroxy butyric aciduria (2M3HBA) 30) 2-Methylbutyryl-CoA dehydrogenase deficiency (2MBG) 31) 3-Methylglutaconic aciduria (3MGA) 32) Argininemia (ARG) 33) Biopterin cofactor biosynthesis, defects of (BIOPT BS) 34) Biopterin cofactor regeneration, defects of (BIOPT REG) 35) Carnitine palmitoyltransferase I deficiency (liver) (CPT IA) 36) Carnitine palmitoyltransferase II deficiency (CPT II) 37) Carnitine: acylcarnitine translocase deficiency (CACT) 38) Citrullinemia type II (CIT II) 39) Dienoyl-CoA reductase deficiency (DE RED) 40) Galactokinase deficiency (GALK) 41) Galactose epimerase deficiency (GALE) 42) Glutaric acidemia Type II (GA 2) 43) Hypermethioninemia (MET) 44) Hyperphenylalaninemia, benign (H-PHE) 45) Isobutyryl-CoA dehydrogenase deficiency(IBG) 46) Malonic acidemia (MAL) 47) Medium/short-chain L-3-OH acyl-CoA dehydrogenase deficiency (M/SCHADD) 48) Medium-chain ketoacyl-CoA thiolase deficiency (MCKAT) 49) Methylmalonic acidemia (Cbl C,D) (Cbl C,D) 50) Short-chain acyl-CoA dehydrogenase deficiency (SCADD) 51) Tyrosinemia type II (TYR II) 52) Tyrosinemia type III (TYR III) 53) Variant Hb-pathies (including HB E) (Var Hb) D.C. Newborn Screening