1. Neonatal Group B Streptococcal Infections
Perinatal CDC Prevention Guidelines
Priscilla Joe, MD

2. The Disease Leading cause of early-onset sepsis in US
Prior to intrapartum prophylaxis: 8,000 cases/year or 2/1000 live births
Reduced now to 1,600 cases/year or 0.6/1000 live births
Perinatal GBS disease burden
Neonatal illness/death, long-term disability
Maternal morbidity

3. Mother to Infant Transmission
GBS colonized mother
50%
50%
Non-colonized newborn
Colonized newborn
98% 2%
MATERNAL-TO-INFANT TRANSMISSION
Most group B streptococcal disease cases among newborns result from mother-to-infant transmission during labor and delivery.
Many women are asymptomatically colonized by group B streptococcus in the genital and gastrointestinal tracts.
Colonization is not altered by or dependent on pregnancy.
About half the infants born to colonized mothers are themselves colonized on the skin and mucosal surfaces as a result of passage through the birth canal or as a result of GBS ascending into the amniotic fluid.
The majority of colonized infants, 98%, are asymptomatic.
About 2% will develop early-onset disease, presenting with sepsis, pneumonia or meningitis in the first few days of life.
Early-onset sepsis, pneumonia, meningitis
Asymptomatic

4. Colonization Rates GBS Carriers
10% - 30% of women
Higher in African Americans and nonsmokers
Clinical signs not predictive
Dynamic condition
Risk factor for early-onset disease: GBS colonization at delivery
Prenatal cultures late in pregnancy predict delivery status

5. Additional Risk Factors for Early-Onset GBS Disease
Obstetric: prolonged rupture of membranes, preterm delivery, intrapartum fever
GBS bacteriuria
Previous infant with GBS disease
Demographic (African American, young age)
Immunologic (low antibody to GBS capsular polysaccharide)

6. Prevention of Perinatal GBS Disease
Intrapartum antibiotics
Highly effective at preventing early-onset disease in women at risk for transmission of GBS to their newborns
Challenge: How best to identify women at risk?

7. Rates of Early-Onset GBS Disease by Prenatal Colonization & Risk Factors
Col: prenatal vag/rect culture
RF: risk factors (gest. <37 wks, ROM >18 hr, fever > 37.5°C)
RATES OF EARLY-ONSET GBS DISEASE BY PRENATAL COLONIZATION & RISK FACTORS
A main consideration in development of prevention guidelines was characterizing which women were at risk for delivering infants with early-onset infection
This slide summarizes data from a prospective study conducted in the early 1980s by Boyer and Gotoff (published in Antibiotics and Chemotherapy in 1985) that assessed nearly 5300 infants born over a three-and-a-half year period, none of whom had received intrapartum antibiotics.
The cohort of deliveries was considered in terms of maternal prenatal colonization with group B streptococcus and the presence of an intrapartum risk factor, either pematurity, prolonged rupture of membranes, or intrapartum fever.
The attack rate was quite high among infants born to colonized mothers with one or more risk factors, 40.8 per 1000 births, or about 1 in 25 infants.
Infants born to colonized mothers without a risk factor had the next highest risk of early onset infants with an attack rate of 5.1 per 1000 births.
Infants born to mothers with risk factors who were not prenatally colonized and to mothers who were neither colonized nor had risk factors, had very low attack rates of 0.9 per 1000 births and 0.3 per 1000 births, respectively.
Boyer & Gotoff, Antibiot Chemother 1985.

8. First U.S. Consensus Recommendations (CDC '96, ACOG '96, AAP '97)
Screening-based approach:
35-37 wks culture, offer intrapartum antibiotic prophylaxis (IAP) to GBS carriers and to preterm unless neg. culture result available, or
Risk-based approach:
IAP to preterm, membrane rupture>18 hours, or intrapartum fever (T>38°C)
Both strategies also give IAP to women with GBS bacteriuria, or previous infant with GBS disease
FIRST U.S. CONSENSUS RECOMMENDATIONS (CDC ’96, ACOG ’96, AAP ’97)
In 1996 guidelines were issued by the Centers for Disease Control and Prevention, American College of Obstetricians and Gynecologists, and American Academy of Pediatrics.
These guidelines recommend health care providers and institutions choose between two alternative prevention strategies:
Screening-based approach
Pregnant women should be cultured between weeks
Intrapartum antibiotic prophylaxis (IAP) should be offered to women identified as GBS carriers and to women of unknown GBS status at the time of labor who are delivering preterm
Risk-based approach
IAP to preterm, membrane rupture from 18 hrs or more, or for an intrapartum fever of 100.4F or more (38C or more)
Both strategies also give IAP to women with GBS bacteriuria or previous infant with GBS disease

9. Why is screening more protective than the risk-based approach?
Broader coverage of at-risk population
Captures colonized women without obstetric risk factors (18% of all deliveries)
Antibiotic effectiveness in this cohort, based on birth survey data: 89% (64-97%)
Schrag et al, NEJM 2002, 347:233-9

10. Intrapartum Prophylaxis: Indications
Previous infant with invasive GBS disease
GBS bacteriuria during current pregnancy
Positive GBS screening culture during current pregnancy (unless a planned c-section, in the absence of labor or amniotic membrane rupture)
Unknown GBS status AND any of the following:
Delivery at < 37 weeks’ gestation
Amniotic membrane rupture >18 hours
Intrapartum temperature >38.0°C

11. Intrapartum Prophylaxis NOT Indicated
Prior pregnancy with a positive GBS screening culture (unless culture positive ALSO during current pregnancy)
Planned c-section performed in the absence of labor or membrane rupture (regardless of maternal GBS culture status)
Negative vaginal and rectal GBS screening culture during the current pregnancy, regardless of intrapartum risk factors

12. Maternal Antibiotic Prophylaxis
Dose given
Neonatal colonization
< 1 hr
46% similar to no treatment
2 to 4 hrs
2.9%
> 4 hrs
1.2%

13. Neonatal Management Algorithm

14. Neonatal Management Algorithm

15. Early Onset Disease Presentation within 1st 24 hrs, 0 - 6days
75% of cases of GBS disease
Vertical transmission
Sepsis 25-40%
Pneumonia 35-55%
Meningitis 5-10%
Mortality 5%; higher in preterm infants
Due to opsonin deficiency, limited maternal antibody transfer, limited maternal capsular antibody

16. Late Onset Disease 3-4 weeks after birth, range 7d-3mo
Term and preterm infants equally susceptible
Serotype III most common and predominant cause of meningitis
Bacteremia and meningitis
Osteomyelitis, septic arthritis, and cellulitis
Horizontal transmission (hospital, community, mother)
Incidence unchanged with intrapartum prophylaxis

17. Treatment of Asymptomatic Neonates
24-48 hr observation period for infants with pretreated mothers
Routine use of antibiotics in infants whose mothers received adequate treatment is not indicated

18. Diagnosis
Blood, CSF, ETT cxs
CBC
CRP
CXR

19. Treatment of GBS Disease
Ampicillin and Gentamicin
7-10 days for uncomplicated bacteremia
14 days for uncomplicated meningitis
21-28 days for meningitis complicated by abscesses, ventriculitis
4-6 weeks for osteomyelitis or endocarditis

20. References