Differential Diagnoses of Neonatal Leukocytosis

Infectious Causes

The American Academy of Pediatrics recommends that Group B Streptococcus (GBS) is the leading cause of early-onset neonatal sepsis, particularly in term infants born to mothers with chorioamnionitis 1, 2
Escherichia coli is the second most common pathogen, especially prevalent in preterm infants and cases with maternal chorioamnionitis 3
Candida species (particularly C. albicans and C. parapsilosis) cause invasive candidiasis in 3-10% of very low birth weight neonates, accompanied by thrombocytopenia and elevated C-reactive protein 4

Maternal chorioamnionitis significantly increases the risk of neonatal sepsis and associated leukocytosis, and all infants born to mothers with chorioamnionitis should undergo limited evaluation including CBC with differential and platelets 1, 2, 3

Birth stress, crying, and immediate postnatal adaptation can cause transient leukocytosis, which typically resolves within 24-48 hours without other signs of sepsis 1, 2, 5

Down syndrome-associated transient myeloproliferative disorder presents with leukocytosis in 5% of newborns with trisomy 21, characterized by GATA1 mutations, which usually resolve spontaneously 5

The American Academy of Pediatrics recommends a CBC with differential and platelet count at birth and repeated at 6-12 hours of life, and blood culture before antibiotic initiation is essential 1, 2, 6, 7
Do not delay antibiotics while awaiting culture results in symptomatic neonates; initiate ampicillin plus gentamicin immediately after obtaining cultures 3, 7