What is the differential diagnosis for a neonate presenting with excessive crying?

Differential Diagnosis for Excessive Crying in Early Neonates

Immediate Life-Threatening Causes to Exclude First

Begin by systematically excluding serious pathology, as 61% of infants presenting with acute unexplained excessive crying have serious underlying conditions. 1

Metabolic Emergencies (Check Immediately)

• Hypoglycemia - obtain serum glucose immediately as this causes provoked irritability and is easily reversible 2
• Hypocalcemia - check serum calcium, can cause provoked seizures and jitteriness 3
• Hypomagnesemia - obtain serum magnesium level 2

Cardiovascular Emergency

• Incomplete Kawasaki disease - particularly critical in infants <6 months who are at highest risk for coronary artery abnormalities; presents with prolonged fever and irritability 2

Trauma

• Fractures or abusive head trauma - this is the peak age (2-4 months) for abusive head trauma, with crying being the most common trigger 4, 2
• Physical examination must include palpation of all large bones and careful skin inspection underneath all clothing 1

Ocular Causes

• Corneal abrasion or foreign body - perform fluorescein staining of cornea and evert eyelids 1
• Complete retinal examination required 1

Gastrointestinal Emergencies

• Malrotation with intermittent volvulus - consider if bilious vomiting, abdominal distension, or tenderness present 4
• Intussusception - evaluate for gastrointestinal bleeding 4

Common Benign Causes (After Excluding Serious Pathology)

Infantile Colic (Most Common)

• Paroxysmal inconsolable crying >3 hours/day, >3 days/week, for >3 weeks in otherwise healthy infant ("Rule of Threes") 4
• Peaks at 6 weeks to 2-4 months of age, then improves 4
• Accounts for 10-20% of early pediatric visits but organic cause found in <5% 5, 6

Cow's Milk Protein Intolerance

• Presents with irritability, poor feeding, and intermittent symptoms 2
• Trial maternal dietary elimination (milk and eggs for 2-4 weeks) in breastfed infants 4
• Switch to extensively hydrolyzed formula in formula-fed infants 4

Gastroesophageal Reflux

• Most common cause of intermittent vomiting and irritability from birth 2
• Only likely if frequent vomiting occurs (approximately 5 times daily) 6
• Symptoms typically improve after 6 weeks as lower esophageal sphincter matures 2
• Do NOT prescribe proton pump inhibitors - they are ineffective and carry risks including pneumonia and gastroenteritis 4

Neonatal Drug Withdrawal

• Obtain comprehensive maternal drug history - withdrawal has increased 10-fold in recent years 3
• Opioids - cause withdrawal in 55-94% of exposed neonates 3
• SSRIs - present with tremors, irritability, jitteriness within hours to days, lasting 1-4 weeks 3
• Benzodiazepines - cause tremors and jitteriness with onset from hours to weeks, potentially lasting 1.5-9 months 3
• Cocaine/stimulants - produce neurobehavioral abnormalities including tremors and hyperactivity, typically on postnatal days 2-3 3

Physical Examination Essentials

The physical examination reveals the diagnosis in 41% of cases and provides diagnostic clues in another 13%. 1

Required Components

• Careful skin inspection underneath ALL clothing 1
• Palpation of all large bones 1
• Fluorescein staining of cornea 1
• Eversion of eyelids 1
• Rectal examination 1
• Retinal examination 1
• Thorough neurologic examination for focal findings, abnormal tone, or dysmorphic features 3
• Assessment for hepatosplenomegaly and abdominal tenderness or distension 4

Diagnostic Algorithm

Step 1: Assess Crying Pattern During Evaluation

If crying persists during initial examination, this predicts presence of serious cause; if crying ceases before or during assessment, serious cause is unlikely. 1

Step 2: Laboratory Testing (Selective)

• Urinalysis and urine culture are the only useful screening tests 1
• Serum glucose, calcium, and magnesium if metabolic derangement suspected 2, 3
• "Screening" laboratory tests beyond these are of little help 1

Step 3: Imaging (Only If Indicated)

• Abdominal imaging only if concerning gastrointestinal symptoms present 2
• Neuroimaging and EEG reserved for focal neurologic findings, seizure concern, or atypical features 3

Management of Benign Excessive Crying

First-Line Interventions

• Gentle motion and rhythmic movement to calm overstimulated infant 4
• White noise for consistent auditory input without overstimulation 4
• Avoid overstimulation from excessive tactile, visual, auditory, and kinesthetic stimuli 4
• Swaddled holding, pacifier, and kangaroo care 7

Parental Safety Counseling (Critical)

Explicitly counsel parents that it's safe to put the baby down in a safe place and take a break if overwhelmed - almost 6% of parents admit to smothering, slapping, or shaking their infant because of crying 4

Additional Interventions If First-Line Fails

• Lactobacillus reuteri (DSM 17938) may reduce crying by approximately 65 minutes per day in breastfed infants, though evidence is insufficient for routine use 4

Common Pitfalls to Avoid

• Never dismiss prolonged fever with irritability as viral illness without considering incomplete Kawasaki disease, especially in infants <6 months 2
• Never attribute all irritability to normal crying without excluding metabolic derangements 2
• Never prescribe proton pump inhibitors for uncomplicated reflux 2
• Never perform incomplete physical examination - 41% of diagnoses are made on physical exam alone 1