Background

  • Infection of the newborn due to group B Streptococcus (GBS) (Streptococcus agalactiae, a gram-positive Diplococcus), is acquired from colonized birth canal or after rupture of membranes
  • Colonization with GBS is asymptomatic, therefore screening is important to reduce incidence of early-onset GBS sepsis

Pathogenesis

  • Early-onset GBS-related sepsis
    • Occurs within first week of life; most have signs of infection within 12-24 hours
    • 10%-30% of pregnant women are colonized; 50% of women who are colonized with GBS will transmit GBS to newborn from vagina to amniotic fluid during labor resulting in:
      • Aspiration into lungs
      • Colonization of skin/mucous membranes of newborn
      • Intrauterine infection and possibly stillbirth/advanced infection at delivery
    • Clinical presentation
      • Involvement with skin/soft tissue, cardiovascular, urinary, ocular, gastrointestinal systems
      • Meningitis
      • Nonfocal bacteremia and sepsis (most common)
      • Pneumonia
    • Highest mortality reported among preterm Black infants
    • Without intervention, 1%-2% of infants born to colonized mothers develop early-onset disease
    • There has been about an 80% reduction in incidence of early-onset neonatal GBS sepsis reported in US since implementation of intrapartum antibiotic prophylaxis (IAP) guidelines
    • Despite universal prenatal screening, GBS reported to cause 19.9% of neonatal deaths among preterm neonates


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  • Late-onset GBS-related sepsis
    • Occurs from age 1 week to 90 days
    • Sources include:
      • Mother (in utero/skin contact or via breast milk)
      • Nosocomial infection
    • Clinical features
      • Meningitis (25%)
      • Rarely septic arthritis, osteomyelitis
      • Sepsis
    • National guidelines for preventative measures reported to have no effect on late-onset disease

Risk Factors

  • Risk factors for early-onset disease include:
    • ≥ 5 vaginal exams during labor
    • Chorioamnionitis
    • GBS bacteriuria
    • Intrapartum maternal fever
    • Low maternal GBS antibody levels
    • Maternal Black race
    • Maternal vaginal colonization/previous delivery of infant with GBS
    • Prematurity; gestational age <37 weeks and very low birth weight
    • Prolonged rupture of membranes
    • Use of intrauterine fetal monitoring devices
    • Young maternal age
  • Risk factors for late-onset disease include
    • Maternal Black race
    • Maternal GBS vaginal colonization
    • Prematurity

Screening

Prenatal Screening

  • Urine GBS screening
    • GBS bacteriuria during pregnancy represents heavy colonization and indicates need for IAP
    • GBS concentrations
      •  ≥ 105 colony-forming units (CFU)/mL requires acute treatment in addition to IAP at birth
      • < 105 CFU/mL does not require maternal antepartum antibiotic therapy but is an indication for IAP at birth
  • Universal vaginal-rectal GBS screening culture in late gestation (between 36 and 37 weeks gestation)

Intrapartum Screening

  • If preterm premature rupture of membranes (PPROM) or preterm labor, consider culture-based screening for vaginal and rectal GBS colonization and initiation of prophylactic antibiotics
    • If entering into labor, continue antibiotics until birth
    • If not entering labor
      • Continue IV antibiotics for 48 hours
      • Obtain GBS culture
        • If positive/result unavailable with onset of labor, provide IAP
        • If negative, do not give IAP
    • Consider rapid polymerase chain reaction (PCR) assay as alternative or be obtained at time of presentation in labor for those who have unknown/unavailable GBS screening results

Antibiotic Prophylaxis

  • IAP ideally should start ≥ 4 hours before delivery/obstetric procedures for:
    • GBS bacteriuria at any time during pregnancy
    • Prior infant with GBS/known GBS in prior pregnancy
    • Positive GBS vaginal-rectal culture obtained ≥ 36 weeks gestation during current pregnancy unless a cesarean birth is performed before labor onset with intact amniotic membranes
    • Unknown GBS status at labor onset and any of following:
      • Membrane rupture ≥ 18 hours duration
      • Maternal intrapartum temperature is 100.4° F
      • Positive nucleic acid amplification test (NAAT)
      • Negative NAAT test but < 37 weeks gestation and any above risk factors develop
    • Preterm labor < 37 weeks gestation, then:
      • If preterm labor progresses, continue IAP during labor
      • If preterm birth is not imminent, discontinue IAP
      • If preterm GBS culture positive/results unknown at labor onset, provide IAP whenever labor occurs 
    • Threatened preterm delivery, then:
      • If preterm labor progresses, IAP continued until birth
      • If preterm birth not imminent, continue IAP for 48 hours and obtain GBS culture (if positive, provide IAP when labor occurs)
  • Medications used for IAP include:
  • Prophylactic antibiotics not indicated for:
    • Planned cesarean delivery before labor onset with intact membranes regardless of GBS colonization status/gestational age
    • Negative vaginal/rectal GBS culture obtained ≥ 36 weeks of gestation during current pregnancy, regardless of intrapartum risk factors
    • GBS colonization or GBS bacteriuria during previous pregnancy unless colonization status in current pregnancy is unknown at labor onset at term

Diagnosis of Early-Onset GBS in Newborn

  • Presentation of GBS disease at ≤ 7 days of life (usually within 24 hours) may include:
    • Involvement of skin/soft tissue, cardiovascular, urinary tract, ocular, gastrointestinal systems
    • Meningitis
    • Nonfocal bacteremia and sepsis (most common)
    • Pneumonia
  • Signs and symptoms of sepsis (typically within first 6 hours of life) may include:
    • Anuria
    • Cyanotic spells
    • Hypo/hyperglycemia
    • Hypothermia
    • Hypotonia
    • Lethargy/irritability
    • Petechiae/purpura
    • Respiratory distress/grunting (most common)
    • Unexplained jaundice
    • Vomiting/poor feeding
  • Diagnostic evaluation for sepsis includes
    • Blood culture
    • Complete blood count
    • Chest x-ray
    • Lumbar puncture
    • In certain situations, consider
      • Urine culture (if evaluation for GBS late-onset disease) 
      • Bone/joint fluid culture if bone/joint infection suspected
      • Cranial imaging to assess for ventriculitis or brain abscess
  • Confirmation of diagnosis
    • Invasive disease if GBS isolated in blood or CSF cultures (not surface cultures)
    • Colonization (not infection) supported by GBS in urine, saliva, gastric aspirate, umbilicus/groin, or external ear canal
  • Clinical observation for 36-48 hours recommended for healthy newborns if mother had indication for GBS prophylaxis and received ≥ 4 hours of intrapartum antibiotics

Secondary Prevention and Management of Early-Onset GBS Among Newborns

  • In infants at high risk of GBS sepsis, consider empiric treatment before GBS definitively diagnosed
  • Infants born ≥ 35 weeks gestation
    • If signs of neonatal sepsis, perform diagnostic workup and provide empiric antibiotics until culture results known
    • If maternal intrapartum temperature ≥ 38° C (≥ 100.4° F) or inadequate GBS intrapartum antibiotic prophylaxis (IAP), options include:
      • Perform diagnostic workup prior to initiation of empiric antibiotics
      • Serial physical exam and vital signs for 36-48 hours after birth
    • If healthy newborn whose mother had indication for IAP but received no IAP, observe for 36-48 hours after birth
    • If well-appearing newborn and mother received ≥ 4 hours of IAP, routine newborn care is recommended
  • Infants born ≤ 34 weeks gestation
    • Perform diagnostic workup and provide empiric antibiotics (penicillin G is preferred) in infant with any signs of sepsis or born in association with any of
      • Preterm labor
      • Prelabor rupture of membranes
      • Any concern for intraamniotic infection
      • Induction of labor with or without cervical ripening resulting in either vaginal or cesarean delivery and any of the following are present
        • Maternal indication for GBS IAP and inadequate GBS IAP given
        • Respiratory and/or cardiovascular instability
      • Birth by cesarean section with rupture of membranes at time of delivery and mother had indication for GBS IAP and adequate IAP was not given
    • Consider close observation for infants born by cesarean with rupture of membranes of at time delivery who appear well at birth

Differential Diagnosis

  • Other sources of early-onset neonatal sepsis include:
    • Bacteria, such as gram-positive cocci, gram-positive rods, and gram negative rods
    • Viruses (herpes simplex, Enterovirus, Parechovirus)
    • Fungi (primarily Candida albicans)
  • Other causes of neonatal meningitis include Escherichia coli, Listeria monocytogenes, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b
  • Other causes of respiratory distress:
    • Congenital heart disease
    • Persistent pulmonary hypertension of newborn
    • Respiratory distress syndrome (RDS) of the newborn
    • Transient tachypnea of the newborn (TTN)

Kendra Church, MS, PA-C, is a physician assistant at Dana-Faber Cancer Institute/Brigham & Women’s Hospital and is also an Associate Deputy Editor for DynaMed, an evidence-based point-of-care database.

Sources

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  2. Verani JR, Schrag SJ. Group B streptococcal disease in infants: progress in prevention and continued challengesClin Perinatol. 2010;37(2):375-392. doi:10.1016/j.clp.2010.02.002
  3. Koenig JM, Keenan WJ. Group B Streptococcus and early-onset sepsis in the era of maternal prophylaxisPediatr Clin North Am. 2009;56(3):689-708. doi:10.1016/j.pcl.2009.04.003
  4. Puopolo KM, Lynfield R, Cummings JJ; American Academy of Pediatrics, Committee on Fetus and Newborn, Committee on Infectious Diseases. Management of infants at risk for Group B streptococcal diseasePediatrics. 2019;144(2):e20191881. doi:10.1542/peds.2019-2350
  5. Prevention of Group B Streptococcal Early-Onset Disease in Newborns. ACOG Committee Opinion, Number 797. Obstet Gynecol. 2020;135(2):e51-e72. doi: 10.1097/AOG.0000000000003668