Sepsis in babies is caused by infections, most often bacterial, that enter the bloodstream and trigger a dangerous immune response. Two bacteria, Group B Streptococcus (GBS) and E. coli, account for 70% to 80% of all neonatal sepsis cases. How and when a baby gets infected depends largely on whether the infection happens around the time of birth or days to weeks later.
Early-Onset vs. Late-Onset Sepsis
Neonatal sepsis falls into two categories based on timing. Early-onset sepsis occurs within the first three days of life and accounts for the majority of confirmed cases, about 72.5% in one large international study. These infections are almost always passed from mother to baby during pregnancy or delivery. Late-onset sepsis develops after the first three days, sometimes weeks later, and is typically picked up from the baby’s environment, whether at home or in a hospital setting.
The distinction matters because the source of infection, the likely bacteria involved, and the approach to treatment differ between the two.
How Babies Get Infected During Birth
In early-onset sepsis, bacteria travel from the mother’s body to the baby. GBS is the most common culprit. About 25% of pregnant women carry GBS in the vaginal or rectal area without any symptoms. During labor, these bacteria can reach the baby through the birth canal or, in some cases, through infected amniotic fluid before delivery even begins.
E. coli is the second most common cause, and it follows the same general route. Listeria, a less frequent but serious pathogen, can cross the placenta during pregnancy if the mother becomes infected, often through contaminated food.
Several maternal conditions raise the risk of early-onset sepsis. These include:
- Inadequately treated GBS colonization: when a mother who carries GBS doesn’t receive antibiotics during labor
- Infection of the amniotic fluid: sometimes called chorioamnionitis, which exposes the baby to bacteria before birth
- Maternal fever above 100.4°F during labor
- Prolonged rupture of membranes: when the water breaks more than 18 hours before delivery
- Preterm labor: delivering before 37 weeks of gestation
Sources of Late-Onset Infection
Late-onset sepsis is a different story. Rather than coming from the mother, these infections are acquired from the surrounding environment. Babies in the neonatal intensive care unit (NICU) face the highest risk because they’re exposed to medical devices and handled frequently by multiple caregivers.
Staphylococcal bacteria cause 30% to 60% of late-onset cases, most often linked to central lines and other IV catheters that provide a direct entry point into the bloodstream. E. coli also plays a significant role in late-onset sepsis, particularly in extremely low birth weight infants. Contaminated feeding preparations have been tied to outbreaks of specific bacteria like Cronobacter sakazakii, and contaminated respiratory equipment has been linked to Pseudomonas infections.
Fungal infections, especially from Candida species, are an increasingly recognized cause of late-onset sepsis in very small premature babies. These infants often have extended hospital stays, multiple courses of antibiotics, and IV lines, all of which create opportunities for fungal organisms to take hold.
Why Premature Babies Are Especially Vulnerable
Prematurity is the single biggest risk factor for neonatal sepsis, and the reasons go well beyond a baby simply being small. Preterm infants have an immune system that is immature at nearly every level.
Their skin, the body’s first barrier against infection, is thinner and more permeable. Their lungs clear mucus and trapped pathogens less effectively. The immune cells responsible for detecting and killing bacteria, primarily neutrophils, are present in limited numbers, move sluggishly toward infection sites, and are less effective at destroying bacteria once they arrive. The cells responsible for coordinating longer-term immune responses are also impaired, with reduced ability to mount the type of inflammatory reaction needed to contain an infection.
Antibodies add another layer of vulnerability. Babies receive protective antibodies from their mothers through the placenta, but most of this transfer happens in the final weeks of pregnancy. A baby born at 28 weeks has significantly lower antibody levels than one born at 40 weeks. Premature infants also have lower levels of complement proteins, a set of molecules that help immune cells identify and destroy bacteria. The result is an immune system that struggles at every step, from detecting invaders to eliminating them.
How Sepsis Is Detected in Newborns
Sepsis in newborns can be difficult to spot because the symptoms overlap with many other conditions. Warning signs include temperature instability (running too hot or too cold), lethargy or poor feeding, rapid or labored breathing, and a generally “off” appearance that experienced nurses and parents often describe as the baby just not looking right.
Diagnosing sepsis with certainty is challenging. A blood culture, where a sample of the baby’s blood is tested for bacterial growth, remains the gold standard but takes time. Common blood markers like C-reactive protein (CRP) don’t rise until 12 to 24 hours after an infection begins, meaning early results can be falsely reassuring. White blood cell counts and related measures perform poorly at distinguishing sepsis from non-infectious conditions. Because no single test catches every case, doctors typically start antibiotics when sepsis is suspected and adjust treatment once culture results come back, usually within 24 to 48 hours.
How GBS Screening Helps Prevent Sepsis
The most effective prevention strategy targets the most common cause. The American College of Obstetricians and Gynecologists recommends that all pregnant women be screened for GBS between 36 and 37 weeks of pregnancy using a vaginal and rectal swab. Women who test positive receive antibiotics through an IV during labor, which dramatically reduces the chance of passing the bacteria to the baby.
This universal screening approach has significantly reduced the rate of early-onset GBS disease. However, it has had no effect on late-onset GBS sepsis, which supports the understanding that later infections come from environmental sources rather than the birth process. For late-onset prevention in hospitals, the focus shifts to strict hand hygiene, careful management of IV lines and catheters, and infection control protocols in the NICU.