A preterm neonate was doing well initially until 6 days postpartum. At this time, the neonate exhibited increasing lethargy and poor feeding associated with temperature instability, hypotonia, and increasing periods of apnea. Which of the following is the most likely diagnosis?

• A. Phenylketonuria
• B. Bacterial sepsis
• C. Congenital syphilis
• D. Hepatitis B infection

Answer: (D)

Late-onset neonatal sepsis is the key idea. In a preterm newborn, infections acquired after birth can surface around day 6 with nonspecific but concerning signs such as lethargy, poor feeding, temperature instability, hypotonia, and apnea. The immature immune system of preterm infants makes them especially vulnerable to bacteremia and sepsis, and these systemic, neurologic, and respiratory findings fit an infectious process more than a metabolic or congenital infection.

Phenylketonuria typically presents later with developmental issues and signs related to high phenylalanine, not an acute septic-appearing illness in the first week. Congenital syphilis and Hepatitis B infection have other characteristic presentations (syphilis with rash, snuffles, hepatosplenomegaly; Hep B with jaundice and liver involvement) and do not usually present as an acute, septic-appearing deterioration this early in a preterm infant.

Therefore, bacterial sepsis best explains the clinical picture at this time.