Objective
We sought to evaluate an intrapartum nucleic acid amplification test (NAAT) for group B streptococcus (GBS).
Study Design
This was a prospective cohort study of 559 women comparing intrapartum GBS culture with antepartum culture and intrapartum NAAT.
Results
GBS prevalence was 19.5% by antepartum culture and 23.8% by intrapartum culture. Compared with intrapartum culture, antepartum culture had 69.2% sensitivity (60.6-76.9%) and 96.0% specificity (93.7-97.7%). The NAAT demonstrated sensitivity of 90.8% (84.6-95.2%), specificity of 97.6% (95.6-98.8%), and predictive values >92%. The incidence of discordant cultures was 10.4%. Of the women with negative antepartum and positive intrapartum cultures, only 1 (2.4%) received intrapartum antibiotics. Compared with white women, black ( P = .02) and Hispanic ( P = .02) women were more likely to have discordant cultures.
Conclusion
This intrapartum NAAT has excellent characteristics. It may be superior to antepartum culture for detecting intrapartum GBS–allowing more accurate management of laboring mothers and reducing neonatal GBS sepsis.
Although universal screening and intrapartum antibiotic prophylaxis have substantially decreased the incidence of group B streptococcus (GBS) disease in neonates, GBS remains a leading cause of neonatal morbidity and mortality in the United States. Administration of intrapartum antibiotics is based on maternal GBS colonization status as determined by culture-based screening performed at 35-37 weeks of gestation. The Centers for Disease Control and Prevention (CDC) recommends universal screening of pregnant women and specifies a culture procedure requiring incubation for up to 48 hours, which precludes intrapartum screening. The CDC guidelines indicate that a negative screening test becomes invalid after 5 weeks.
For Editors’ Commentary, see Table of Contents
GBS colonizes the gastrointestinal or genitourinary tracts in 15-35% of pregnant and nonpregnant women. Colonization can be chronic, transient, or intermittent. Therefore, the timing of GBS screening is important, and it is recommended that obstetricians screen women in the late third trimester to improve the likelihood that the antepartum culture reflects the true intrapartum colonization status. However, studies demonstrate that antepartum culture has sensitivity as low as 50% and positive predictive value <60%, as well as less than ideal specificity.
Despite compliance with universal screening, the majority (52.5-82.3%) of neonates developing GBS sepsis were born to women who screened negative in the late third trimester and thus did not receive antibiotic prophylaxis. This suggests that either the culture is insufficiently sensitive or the woman’s colonization status changes between screening and delivery.
Prior studies of rapid nucleic acid amplification tests (NAAT) for intrapartum detection of GBS suggest that intrapartum screening may more accurately reflect intrapartum GBS colonization. Accurate intrapartum testing could allow for more appropriate clinical management of mothers and newborns, including properly targeted intrapartum antibiotic prophylaxis for laboring women and appropriate neonatal sepsis evaluations. Ultimately, a more accurate screening test may further decrease the incidence of GBS disease.
The purpose of our study was to evaluate the test characteristics of a rapid, real-time intrapartum GBS NAAT by evaluating it against an intrapartum culture and comparing it with the antepartum screening culture in a busy delivery unit. Unlike previous studies, we collected data on maternal race and ethnicity and assessed the incidence of neonatal sepsis evaluations and neonatal intensive care unit admissions.
Materials and Methods
This was a prospective cohort study of pregnant women presenting to the labor and delivery unit at Beth Israel Deaconess Medical Center (Boston, MA) from January through June 2010. Institutional review board approval was obtained, and all women provided informed consent. Women aged ≥18 years with documented antepartum GBS culture results were eligible if they had not yet received intrapartum intravenous antibiotics. Eligible women were approached for participation 7 days of the week, during day and night shifts, depending on the availability of the physicians obtaining consent and collecting samples. Maternal race/ethnicity was self-reported.
Sample collection
Two intrapartum rectovaginal samples were collected simultaneously per CDC guidelines by 1 of 3 obstetrician-gynecologists. Following collection, the samples were brushed together to ensure uniform specimen on each swab. A charcoal swab was used for the intrapartum culture, and the swab used for the intrapartum NAAT (Xpert GBS Assay; Cepheid, Sunnyvale, CA) was included in the kit.
GBS culture
Results of the antepartum screening culture were obtained from each participant’s medical record. Antepartum cultures were performed according to CDC guidelines at either our institution’s Clinical Laboratory Improvement Amendments (CLIA)-certified clinical laboratory or 1 of 2 outside CLIA-certified laboratories. Study personnel were blinded to which laboratory conducted the antepartum culture.
The intrapartum GBS culture was performed by our institution’s laboratory, which was blinded to antepartum culture and intrapartum NAAT results. All cultures were performed at 35°C in 5% carbon dioxide. Charcoal swabs were inoculated into Todd-Hewitt broth (Remel, Lenexa, KS) containing gentamicin (8 μg/mL) and nalidixic acid (15 μg/mL) supplemented with 5% defibrinated sheep blood (Remel), and incubated for 18-24 hours. Broths were subcultured to tryptic soy agar plates (Remel) containing 5% defibrinated sheep blood, incubated for 18-24 hours, and examined for beta-hemolytic streptococci or possible nonhemolytic GBS. The presence of GBS was identified by latex agglutination with GBS-specific antiserum (PathoDx, Los Angeles, CA). If no GBS were present after 24 hours of incubation, the subculture was reincubated for 18-24 hours and reexamined for confirmation.
Intrapartum NAAT
The intrapartum NAAT were purchased from Cepheid and conducted according to the instructions. All tests were run by 1 investigator who was trained by an industry representative and blinded to antepartum and intrapartum culture results. The same investigator ran 1 positive and 1 negative control for each lot within each shipment of assay kits. A pure culture of GBS in a suspension at a density equivalent to 0.5 McFarland units diluted 1:100 was used for the positive control and the same density equivalent of enterococcus or alpha-hemolytic streptococcus was used for the negative control. Controls were provided by our institution’s laboratory.
Each single-use kit includes reagents to detect GBS, a sample-processing control, and an internal control. The GBS primers and probe target a 3′ DNA region adjacent to the cfb gene. If the intrapartum NAAT did not yield a positive or negative result secondary to a technical issue, the test was repeated with a new cartridge as per the package insert whenever an additional sample was available.
The intrapartum NAAT results were not used for clinical care; participants were treated based on the antepartum culture results per CDC guidelines. Results of the antepartum culture, the intrapartum culture, and the intrapartum NAAT were read independently of each other and recorded in separate locations.
Neonatal data
We extracted neonatal data from the medical records and assessed whether any of the following CDC-defined risk factors for neonatal GBS disease were present: intrapartum fever, chorioamnionitis, rupture of membranes for >18 hours, and positive maternal GBS antepartum culture. Adequate intrapartum antibiotic prophylaxis was defined as initiated at least 4 hours before delivery.
Statistical analysis
Based on previous studies and data from the manufacturer, we conservatively hypothesized a sensitivity of 85% for the antepartum culture and 91% for the NAAT. A sample size of 490 women was needed to yield 80% power to detect that difference for a 2-sided test with α = 0.05.
All analyses were performed using SAS 9.2 (SAS Institute Inc, Cary, NC). All tests were 2-sided, and P values < .05 were considered statistically significant. Data are presented as mean and SD, median and interquartile range, or proportion and 95% confidence interval. Comparisons were made using a χ 2 or Fisher’s exact test for categorical variables and parametric or nonparametric tests for continuous variables, as appropriate. The intrapartum GBS culture was considered the gold standard. Sensitivity, specificity, predictive values, and 95% confidence intervals were calculated. Samples with an indeterminate NAAT result were excluded from the denominator in calculations of sensitivity, specificity, and prevalence for the primary analysis. We also calculated the test characteristics assuming that the indeterminate NAAT results were discordant with the intrapartum culture.
CDC guidelines specify that a negative antepartum GBS culture is valid for 5 weeks. Thus, we performed a sensitivity analysis excluding women for whom >5 weeks elapsed between the antepartum and intrapartum cultures to recalculate test characteristics of the antepartum culture. We compared the incidence of discordant culture results among women with ≤5 weeks between the antepartum and intrapartum cultures to women with >5 weeks between cultures.
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