What is the differential diagnosis (ddx) for a baby who is failing to thrive?

Differential Diagnosis for Infant Failure to Thrive

The differential diagnosis for failure to thrive in infants should be systematically organized into inadequate caloric intake, inadequate caloric absorption, and increased metabolic demands, with gastrointestinal disorders (particularly gastroesophageal reflux and swallowing dysfunction) being the most common organic causes. 1, 2

Gastrointestinal Causes (Most Common Organic Etiology)

Feeding and Swallowing Disorders

• Swallowing dysfunction with oral-motor incoordination is nearly universal in certain conditions and causes aspiration risk 3, 2
• Oral aversion related to prolonged nasogastric tube use or repeated oral stimulation 3
• Gastroesophageal reflux disease (GERD) with vomiting and feeding irritability 3, 2, 4

Structural Abnormalities

• Esophageal atresia and tracheoesophageal fistula causing feeding difficulties 2
• Intestinal malrotation, intestinal atresia, and anal stenosis 2
• Hirschsprung disease leading to chronic constipation 2
• Diaphragmatic, umbilical, and inguinal hernias 2

Malabsorption Disorders

• Pancreatic insufficiency (cystic fibrosis, Shwachman-Diamond syndrome) presenting with normal birth weight followed by early growth failure 3, 2, 4
• Celiac disease and inflammatory bowel disease 2
• Food protein-induced enterocolitis syndrome (FPIES) with chronic vomiting and diarrhea 2
• Intestinal dysmotility causing severe constipation 3, 2

Cardiac Causes

• Left ventricular dysfunction causing pulmonary edema and increased work of breathing 2
• Congenital heart defects increasing metabolic demands 2
• Pulmonary hypertension from chronic hypoxemia 2

Pulmonary/Respiratory Causes

• Chronic lung disease of infancy/bronchopulmonary dysplasia with increased work of breathing 3, 2
• Chronic hypoxemia increasing metabolic demands 2
• Tracheomalacia and laryngeal anomalies 2
• Aspiration pneumonia from swallowing dysfunction 3, 2

Endocrine and Metabolic Causes

• Hypothyroidism affecting growth velocity 1, 2
• Growth hormone deficiency 3, 2
• Glycogen storage disease type I with recurrent hypoglycemia and hepatomegaly 2
• Hypocalcemia causing feeding difficulties and irritability 2

Renal/Genitourinary Causes

• Hydronephrosis and obstructive uropathy 2
• Vesicoureteral reflux 2
• Renal tubular disorders 3, 2
• Decreased renal function causing sodium/water retention 2

Neurologic Causes

• Global hypotonia causing feeding difficulties and decreased oral intake 2, 4
• Polymicrogyria and cerebellar abnormalities 2
• CNS dyscoordination affecting swallowing 2
• Developmental delay affecting feeding skills 2

Genetic and Chromosomal Disorders

• 22q11.2 deletion syndrome with feeding difficulties, cardiac defects, and hypocalcemia 2
• Cardio-facio-cutaneous syndrome with severe feeding problems and GERD in virtually all cases 3, 2
• Skeletal dysplasias requiring enteral nutrition in 50% of cases 3, 2
• Shwachman-Diamond syndrome with feeding difficulties in 48-73% of cases 3, 2

Hematologic and Infectious Causes

• Anemia reducing oxygen delivery and energy availability 2
• Chronic infection from immunodeficiency 2
• Neutropenia associated with pancreatic insufficiency syndromes 3

Nonorganic Causes

• Inadequate caloric provision from poverty or caregiver knowledge deficit 5, 6
• Neglect or emotional deprivation 5, 6
• Hypervigilance with inappropriate dietary restrictions 5

Critical Red Flags for Organic Etiology

The following features strongly suggest organic rather than nonorganic failure to thrive:

• Vomiting, diarrhea, or signs of malabsorption 2, 4
• Chronic respiratory symptoms including tachypnea, hypoxemia, or increased work of breathing 2
• Hepatomegaly with metabolic derangements 2
• Dysmorphic features suggesting genetic syndromes 2
• Disproportionate growth failure with weight affected more than height 4
• Irritability during feeding combined with vomiting episodes 4

Important Clinical Distinctions

Weight faltering before height faltering indicates acute malnutrition affecting weight first, which is characteristic of organic causes 4. In contrast, proportionate weight and height deficits suggest chronic malnutrition or genetic short stature 4.

Approximately 25% of normal infants shift to a lower growth percentile in the first two years and then follow that percentile—this should not be diagnosed as failure to thrive 5. Premature infants, those with intrauterine growth retardation, and infants with Down syndrome follow different growth patterns than term infants 5.

Multiple organ systems often interact to cause failure to thrive—for example, pulmonary disease causing cardiac dysfunction, which then causes renal fluid retention, all contributing to poor growth 2.