What are the risk factors predisposing a newborn, especially those with premature birth, low birth weight, or exposure to maternal infection, to sepsis?

Risk Factors for Neonatal Sepsis

Newborns face potential sepsis primarily due to immature immune systems combined with exposure to maternal and environmental pathogens, with prematurity, low birth weight, and maternal infection representing the most critical predisposing factors. 1

Why Newborns Are Vulnerable to Sepsis

Immune System Immaturity

• Neonates, especially preterm infants, exhibit distinct rather than simply deficient immune function compared to older humans, with both innate and adaptive immune systems being underdeveloped 2
• The immature immune system cannot mount adequate responses to bacterial pathogens, making infection control particularly challenging 3, 4
• Multiple immune deficits specific to neonates increase their risk of death from sepsis compared to adults 4

Pathogen Exposure Pathways

• Early-onset sepsis (occurring within 72 hours to 7 days of birth) results from organisms acquired peripartum from the maternal genital tract, particularly Group B Streptococcus and enteric Gram-negative bacteria 1, 5
• Late-onset sepsis arises from pathogens acquired during hospitalization, with very low birth weight and early gestational age being strong risk factors 1
• Invasive life-saving medical interventions expose hospitalized neonates to serious nosocomial infections, particularly coagulase-negative staphylococci 3

Major Risk Factors for Neonatal Sepsis

Maternal Risk Factors

• Maternal Group B Streptococcus (GBS) colonization without adequate intrapartum antibiotic prophylaxis (IAP) is a primary risk factor 1
• Chorioamnionitis (clinical diagnosis by obstetric provider) is a significant risk factor for early-onset GBS sepsis, even in GBS-colonized women receiving IAP 1
• Maternal intrapartum fever ≥100.4°F (≥38.0°C) indicates possible chorioamnionitis and increases sepsis risk 1, 5
• GBS bacteriuria at any concentration during pregnancy indicates heavy genital tract colonization and requires intrapartum prophylaxis 1
• Previous infant with GBS disease mandates IAP for subsequent pregnancies 1

Intrapartum Risk Factors

• Prolonged rupture of membranes ≥18 hours before delivery significantly increases infection risk 1, 5
• Inadequate intrapartum antibiotic prophylaxis defined as less than 2-4 hours of appropriate antibiotics before delivery 1
• Preterm labor and premature rupture of membranes indicate high-risk delivery circumstances requiring empiric antibiotics 1, 6

Neonatal Risk Factors

• Prematurity (<37 weeks gestation, especially <35 weeks) represents the single greatest risk factor, with preterm infants at highest risk when delivered due to cervical insufficiency, preterm labor, or intra-amniotic infection 1, 3
• Low birth weight and very low birth weight are strong independent risk factors for late-onset sepsis 1
• Invasive medical interventions including central venous catheters, mechanical ventilation, and prolonged hospitalization expose infants to nosocomial pathogens 3

Geographic and Pathogen Considerations

Pathogen Distribution

• In high-income countries, Group B Streptococcus and E. coli are the predominant early-onset pathogens 5
• In low- and lower-middle-income countries, Gram-negative bacteria account for 60% of neonatal sepsis, with high rates of antimicrobial resistance against WHO-recommended empirical antibiotics 1
• E. coli infections show increasing ampicillin resistance, particularly in preterm and very low birth-weight infants 1

Racial Disparities

• Black infants have persistently higher incidence of early-onset GBS disease compared to white infants, even among both term and preterm populations 1
• This disparity has shown some reduction in recent surveillance data but remains clinically significant 1

Clinical Algorithm for Risk Assessment

For Term Infants (≥37 weeks)

• If maternal chorioamnionitis diagnosed: Perform limited evaluation (CBC, blood culture) and initiate empiric antibiotics regardless of IAP adequacy 1, 6
• If inadequate IAP (<4 hours) or maternal fever ≥100.4°F: Monitor clinically for 36-48 hours minimum 1
• If adequate IAP and no maternal fever: Routine care with 24-48 hours observation if other discharge criteria met 1
• If any clinical signs of sepsis: Full diagnostic evaluation including lumbar puncture (if stable) and immediate empiric antibiotics 1, 6

For Preterm Infants (<35 weeks)

• Highest risk (requiring empiric antibiotics): Those delivered for cervical insufficiency, preterm labor, premature rupture of membranes, intra-amniotic infection, or nonreassuring fetal status—even after adequate IAP 1
• Lower risk: Those delivered by cesarean without labor or membrane rupture for maternal/fetal indications (preeclampsia, fetal growth restriction) may be observed without empiric antibiotics if adequate IAP given 1

Critical Pitfalls to Avoid

• Do not delay antibiotic administration waiting for culture results when sepsis is suspected—empiric antimicrobials must be given within 1 hour of identifying severe sepsis 6
• Do not omit lumbar puncture in stable infants with suspected sepsis, as 15-38% of infants with early-onset meningitis have sterile blood cultures 1
• Do not use ceftriaxone in neonates with hyperbilirubinemia, as it displaces bilirubin from albumin and causes kernicterus—use cefotaxime instead 7, 6
• Do not continue antibiotics beyond 48 hours if blood cultures are negative and the infant remains asymptomatic, as prolonged empiric antibiotics increase risks of late-onset sepsis, necrotizing enterocolitis, and mortality 6
• Do not assume cesarean delivery eliminates risk if performed after labor onset or membrane rupture—GBS can cross intact membranes 1