Primary Infection Routes of Neonatal Sepsis After Birth

Newborns are particularly vulnerable to sepsis, a life-threatening systemic infection that can rapidly progress to organ dysfunction and shock. The primary route of infection in neonatal sepsis—especially in the early-onset form occurring within the first 72 hours of life—is vertical transmission from mother to infant. This typically occurs via ascending infection, where pathogens colonizing the maternal genital tract (such as *Streptococcus agalactiae* [Group B Streptococcus], *Escherichia coli*, or *Listeria monocytogenes*) ascend through the cervix into the amniotic cavity, leading to chorioamnionitis and subsequent fetal exposure during labor or delivery.

In contrast, late-onset neonatal sepsis—defined as onset after 72 hours of age—is more commonly associated with horizontal transmission: acquisition of pathogens from the healthcare environment, caregivers, or medical devices. Key risk factors include prolonged hospitalization, invasive procedures (e.g., endotracheal intubation, central venous catheterization), and prolonged use of broad-spectrum antibiotics, which disrupt normal microbial colonization and promote opportunistic infections by organisms such as coagulase-negative staphylococci, *Staphylococcus aureus*, or multidrug-resistant Gram-negative bacilli.

Importantly, prematurity and low birth weight significantly increase susceptibility to both early- and late-onset sepsis due to immature innate and adaptive immune responses, including deficient neutrophil function, reduced complement activity, and impaired barrier integrity of skin and mucosal surfaces.