• Congenital heart disease
• Pyloric stenosis
• Gastrointestinal malformation (duodenal atresia, annular pancreas, volvulus)
• Short bowel syndrome
• Lymphangiectasia
• Superior mesenteric artery syndrome
• Gastroesophageal reflux
• Immunodeficiency disorders
• Hirschsprung disease

• Urinary tract infection
• Tuberculosis
• Stomatitis
• Osteomyelitis
• Human immunodeficiency virus
• Hepatitis
• Parasitic disease
• Gastroenteritis
• Pericarditis
• Histoplamosis
• Acute severe febrile illness (pyelonephritis, pneumonia, septic arthritis)

• Lead poisoning
• Mercury poisoning
• Vitamin A poisoning
• Chronic methylphenidate, dextroamphetamine, or valproic acid use
• Substance abuse, especially amphetamines and crack cocaine

• Chronic subdural hematomas

• Diencephalic syndrome
• Leukemia
• Lymphoma
• Pheochromocytoma
• Other neoplasms

• Diabetes mellitus
• Diabetes insipidus
• Hyperthyroidism
• Cystic fibrosis
• Schwachman syndrome
• Addison disease
• Hypercalcemia
• Congenital adrenal hyperplasia
• Lactose intolerance
• Renal tubular acidosis
• Chronic renal failure
• Hypopituitarism
• Inborn errors of metabolism
• Storage diseases
• Muscular dystrophy
• Lipodystrophy

• Inflammatory bowel disease
• Juvenile rheumatoid arthritis
• Systemic lupus erythematosus
• Sarcoidosis
• Pancreatitis
• Hepatitis
• Celiac disease (gluten enteropathy)

• Malnutrition
• Child abuse
• Post-operative
• Dieting
• Depression/affective disorders
• Anorexia nervosa
• Chronic congestive heart failure
• Chronic pulmonary disease
• Chronic renal disease
• Iron deficiency
• Zinc deficiency
• Cerebral palsy
• Post-infectious malabsorption
• Factitious (e.g., scale error)

Question: Is the weight loss real?
Significance: Scale error, different scales, different technique (e.g., clothed versus unclothed)

Question: What is the child’s diet?
Significance: A prospective 3-day dietary record can be very useful for demonstrating insufficient caloric intake.

Question: Less than 2 weeks of age?
Significance: Physiological weight loss, underfeeding, inappropriate feeding, inborn errors of metabolism, congenital heart disease, gastroesophageal reflux

Question: Less than 4 months?
Significance: Malnutrition, improper formula preparation, cystic fibrosis, gastroesophageal reflux, pyloric stenosis, congenital heart disease, congenital adrenal hyperplasia, inborn errors of metabolism

Question: 4 months to 8 years?
Significance: Chronic infection, cystic fibrosis, malabsorption, neglect/abuse, renal disease, liver disease, diabetes mellitus

Question: Older than 8 years?
Significance: Eating disorder, chronic infection, neoplasm, renal disease, liver disease, substance abuse, diabetes mellitus, inflammatory bowel disease, collagen vascular disease

Question: Cramping, bloating or abnormally greasy, voluminous stools?
Significance: Possible malabsorption

Question: Vomiting, especially projectile?
Significance: Suggestive of intestinal obstruction, G-E reflux, inborn errors of metabolism

Question: Polyuria, polydipsia and polyphagia?
Significance: Possible diabetes mellitus

Question: Headaches, especially early morning?
Significance: Possible increased intracranial pressure, CNS malignancy

Question: Maternal history of multiple miscarriages, neonatal deaths, or consanguinity?
Significance: Possible inborn error of metabolism

Question: History of severe infections, persistent candidal infections?
Significance: Immunodeficiency, congenital or acquired

Question: Fear of fatness, preoccupation with food, distorted body image, and/or amenorrhea?
Significance: Possible eating disorder

Question: Delayed puberty?
Significance: Suggests chronic severe weight loss, pituitary abnormalities, anorexia nervosa

Question: Foreign travel?
Significance: Possible chronic infection (e.g., tuberculosis, parasitic dissease)

Question: Tiring during feeding or difficulty feeding due to cough and dyspnea?
Significance: Suggests CHF in newborn/infant, hypothyroidism

Question: Increased appetite with weight loss?
Significance: Suggests hyperthyroidism, cystic fibrosis, pheochromocytoma

Question: Altered mental status, seizures, unusual body/fluid odors
Significance: Inborn error of metabolism

Finding: Clubbing
Significance: Suggests chronic cardiac, pulmonary, or intestinal disease

Finding: Significant abdominal distension
Significance: Suggests celiac disease

Finding: Hypothermia, bradycardia
Significance: Suggests anorexia nervosa, hypothyroidism

Finding: Tachycardia, resting
Significance: Hyperthyroidism, pheochromocytoma, anemia, acute weight loss

Finding: Orthostatic changes
Significance: Significant weight loss, possibly acute

Finding: Hypotension, resting
Significance: Addison disease, anorexia nervosa, significant acute dehydration

Finding: Visual field abnormalities
Significance: Suggests possible CNS malignancy

Finding: Swollen joint
Significance: Juvenile rheumatoid arthritis, inflammatory bowel disease

Finding: Muscle weakness
Significance: Connective tissue disorder, electrolyte abnormality, muscular dystrophy

Finding: Enlarged liver and/or spleen
Significance: Suggests malignancy, chronic infection, storage disease, inborn error of metabolism

Test: Complete blood count
Significance:

• Evidence of
  • Anemia—macrocytic associated with folate/B₁₂ deficiency, microcytic with iron deficiency or chronic infection
  • Polycythemia—suggestive of chronic pulmonary or cardiac disease
  • Neutropenia—suggestive of hematologic malignancy, Schwachman syndrome, immunodeficiency
  • Lymphopenia—suggestive of immunodeficiency
  • Eosinophilia—suggestive of parasitic disease
  • Leukocytosis—suggestive of infection
  • Thrombocytosis—suggestive of chronic infection, malignancy
  • Lymphoblasts—suggestive of leukemia

Test: ESR
Significance: May be elevated in inflammatory bowel disease, chronic infections, rheumatoid diseases

Test: Serum electrolytes
Significance: Abnormalities in dehydration, adrenal insufficiency (low Na, high K), renal disease, anorexia nervosa

Test: BUN, creatinine
Significance: Abnormal in renal disease, dehydration

Test: Stool for occult blood and pH, reducing substances (Clinitest)
Significance: Occult blood suggests inflammatory bowel disease; low pH and positive reducing substances suggest malabsorption

Test: Urinalysis
Significance: Hematuria and/or proteinuria suggest renal disease; glycosuria suggests diabetes mellitus; very low specific gravity suggests diabetes insipidus, chronic renal failure, hypercalcemia; pyuria suggests UTI; pH >6 suggests RTA (type I)

Test: Urine culture
Significance: Evaluation for UTI

Test: Serum protein levels
Significance: Very low levels imply impaired liver function, severe chronic weight loss or protein malabsorption

Test: Tuberculosis skin test
Significance: Possible chronic infection

Test: Liver function tests
Significance: Evaluation for hepatitis, chronic liver disease

Depending on age and clinical findings, other tests to consider include thyroid function tests, sweat test, tests for malabsorption (e.g., lactose breath test, stool fat, stool for trypsin), tests for metabolic disease (e.g., plasma ammonia, lactate, serum/urine amino acids, urine organic acids), imaging studies (e.g., CT, MRI, bone scan), immunologic studies.

• Significant dehydration: abnormal vital signs with orthostasis, decreased urine output, decreased skin turgor, delayed capillary refill (>3 seconds). Mandates cardiovascular support (intravenous hydration) and a more urgent diagnosis (e.g., inborn error of metabolism, obstructive GI disease, congenital adrenal hyperplasia, diabetic ketoacidosis).
• Abnormal mental status, significant lethargy: May be seen in severe dehydration, hypoadrenalism, hypoxic states, toxic ingestions, renal or respiratory failure, increased intracranial pressure, severe electrolyte abnormalities.
• Increasing vomiting in the setting of known weight loss in infants: High risk for dehydration, hypoglycemia, and electrolyte abnormalities. Need to evaluate for treatable conditions (e.g., obstructive GI disease, inborn errors of metabolism, congenital adrenal hyperplasia, congenital heart disease) in which a delay is life-threatening.
• Severe malnutrition (weight loss >20% of ideal body weight): high risk for metabolic derangements, including dysrythmias secondary to electrolyte abnormalities. Aggressive evaluation is warranted.

Q: How common is weight loss in the first 2 weeks of life?
A: Formula-fed babies may lose up to 7% of birth weight and breast-fed newborns up to 10% before regaining their birth weight by 2 weeks of age.

Issues for Referral

Weight loss is a diagnostic exigency—a cause must be found or the loss self-resolved. If a diagnosis is not uncovered in the setting of continued weight loss, referral to a pediatric diagnostic center is indicated.

Clinical Pearls

Kleinman RE, ed. Pediatric nutrition handbook, 4th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1998.

Maisels MJ, Gifford K. Breast-feeding, weight loss, and jaundice. J Pediatr, 1983;102:117–118.