Intrapartum Rapid GBS Testing in Patients Presenting With Threatened Preterm Labor

Group B streptococcus (GBS) or Streptococcus agalactiae is a gram-positive bacterium that
colonizes 10-40% of maternal gastrointestinal and urogenital tract sites. Maternal
colonization remains the primary risk factor and the leading cause of early onset GBS disease
in infants in the United States. Transmission of GBS to the neonate in early onset GBS cases
occurs at the time of labor and delivery, with a transmission rate of 52.5% if no intrapartum
antibiotics are used. Of those neonates, 1-2% term infants and 8% of preterm infants will
develop early onset disease.

The Centers for Disease Control (CDC) recommends universal screening at 35-37 weeks via
culture of the vagina and rectum. If this is performed ≤5 weeks before delivery, it has a
sensitivity of 85% and a negative predictive value of 95-98%. There is a downside to
screening remote from delivery however; vaginal GBS colonization fluctuates in the same woman
over time, thus rendering possibly inaccurate GBS results. It has been reported that at least
10% of antenatal GBS negative women turned positive at the time of labor. This may suggest
that screening at the time of delivery is a more accurate method of predicting actual GBS
colonization status. In fact, a majority of neonatal GBS sepsis occurs in infants born to
mothers with a negative antepartum screening culture.

Currently, a standard GBS culture may take up to 3 days to obtain results. A rapid diagnostic
test has more recently been studied as a possible method of GBS screening - real-time
polymerase chain reaction (RT-PCR). Prior studies of RT-PCR, specifically the Cepheid
GeneXpert GBS assay used at Miller's Children's and Women's Hospital, have reported
sensitivity from 85-98.5% and specificity of 96-99.6% using data from term gestations. The
CDC currently permits the use of RT-PCR as a rapid screening test for those with unknown
status at term.

Several reports demonstrate that RT-PCR is a rapid, more sensitive method than standard
culture for determining the intrapartum GBS colonization status. Some studies have also
demonstrated the ability of RT-PCR to identify patients who would otherwise be missed by
traditional GBS culture. A study by Mueller et al demonstrated that out of 64 patients with
positive RT-PCR results, 10 were actually negative on culture. A cost-effectiveness analysis
has demonstrated that PCR intrapartum screening strategy is not any less cost-effective than
traditional culture and confers a significant decrease in early onset GBS disease in term
gestations.

Preterm infants suffer the highest rate of mortality from GBS infection, with up to 30%
mortality in those < 33 weeks affected by GBS sepsis. Identifying GBS colonization is thus
imperative in the 7-11% of all pregnancies affected by preterm labor, given that they will
not have undergone universal screening yet (which typically occurs at 35-37 weeks). While the
CDC recommends giving antibiotics to patients with unknown GBS status at substantial risk for
preterm delivery, implementation of this recommendation is poor.

Advantages of the RT-PCR are that its results will come back much more rapidly than the
standard culture and may assist in management of these critical patients, 75 min vs 3 days,
respectively. Accurate screening for GBS in a rapid fashion, especially in preterm infants,
where the risk of GBS infection is most serious, can potentially allow antibiotics to be used
appropriately.

The investigators seek to evaluate the utility of RT-PCR for screening of GBS in women at
risk of preterm labor with an unknown GBS status. The investigators also aim to identify the
ability of RT-PCR to identify GBS colonization in patients who would have otherwise been
missed by culture.

Inclusion Criteria:

- Age ≥ 18 years

- Pregnant women presenting for unplanned obstetrical care at a participating clinical
study site

- Gestational age between 21 6/7 and 36 6/7 weeks

- Subject has not participated in the study before

- Subject agrees to complete all aspects of the study and provide informed consent in
accordance with applicable regulations

- Signs and/or symptoms suggestive of preterm labor, whereby the managing clinician
suspects preterm labor

- Uterine contractions (with or without pain)

- Intermittent lower abdominal pain, dull backache, pelvic pressure

- Vaginal bleeding during the second and third trimester

- Menstrual-like intestinal cramping (with or without diarrhea)

- Change in vaginal discharge (amount, color, or consistency)

- Vague sense of discomfort characterized as "not feeling right"

- Change in cervical exam (cervical dilation, effacement, or consistency)

- Signs and symptoms necessitating preterm delivery (i.e abruption, preeclampsia,
hemolysis elevated liver enzymes, low platelet (HELLP) syndrome, ruptured membranes,
chorioamnionitis, fetal indications)

Exclusion Criteria:

- Exposure to antibiotics within 1 week prior to enrollment (15)

- Known GBS bacteriuria at the time of enrollment

- Prior history of neonatal GBS sepsis