At least one implementation error (Table 1) was noted among 179 (57.9%) cases, including 126 (40.8%) with one error, 43 (13.9%) with two, and 10 (3.2%) with three errors (Table 2). The frequency of any implementation error among term patients was 57.2% (127 of 222) and 61.2% (52 of 85) among preterm patients (P=.53).
Errors in prenatal screening were observed in 80 (36.0%) term and seven (8.2%) preterm patients. The most frequent error was incorrect specimen collection; among 165 cases with available data on the anatomical site the health care provider most commonly swabbed, 55 (33.3%) were sites other than vaginal–rectal (33=vaginal–perianal, eight=vaginal–perineal, eight=vaginal only, three=cervical–vaginal, two=perianal only, one=perineal only). Of 209 mothers who delivered at term and underwent prenatal screening, 201 (96.2%) had data available on the gestational age at screening; 23 (11.4%) of those were screened before 35 weeks of gestation. Prenatal screens were unnecessarily performed on 23 (63.9% of 36) women with either GBS bacteriuria (n=22) or a previous neonate with GBS disease (n=1).
Errors in laboratory methods were documented in 38 cases (12.3% of all cases and 30.8% of cases with available laboratory data, n=121). Key information was frequently unavailable from worksheets and standard operating procedures. Data on prenatal specimen enrichment were available for 55 (45.4%) of those cases with laboratory records; 15 (27.3%) had specimens that did not undergo any enrichment. The actual incubation time for the enrichment broth, or the duration specified in the standard operating procedure, was available for 66 (54.5%) cases with laboratory records; 20 (30.3%) had a duration less than the recommended 18 hours. Among 170 cases with a negative prenatal screening result, laboratory records were obtained for 98 (57.6%); 70 of 98 (71.4%) had sufficient information to assess at least one laboratory practice, and 32 of 70 (45.7%) had evidence of errors.
Communication errors regarding GBS status affected 19 (6.2%) case-patients, including eight in whom GBS bacteriuria was noted during prenatal care but not in the labor and delivery record and 11 in whom a positive prenatal screening result was not conveyed to the labor and delivery record.
Intrapartum prophylaxis was indicated for 136 (44.0%) mothers of case-patients; 52 (38.2%) received no prophylaxis despite being in the hospital for 1 hour or longer before delivery (range 1.2 hours to 48 days), and eight (5.9%) received prophylaxis for less than 4 hours despite being in the hospital for 5 hours or more before delivery (range 8.5 hours to 11 days). Among 51 women with an indication for prophylaxis who received it, 19 (37.2%) received an incorrect antibiotic, including nine who received clindamycin (with no severe penicillin allergy or without antimicrobial susceptibility testing), nine who received cefazolin (with no penicillin allergy), and one who received vancomycin (with no severe penicillin allergy). Intrapartum prophylaxis errors were more commonly observed among preterm patients than among term (54.1% compared with 13.5%, P<.001).
For 15 cases in which optimal intrapartum prophylaxis was administered, we assumed no reduction in the number of observed cases. Among 122 patients in which prophylaxis was indicated but not received or was suboptimal, we estimated a potential decline to 71 to 72 cases (41–42% reduction) (Table 3). Among 167 women for whom indications for prophylaxis were not identified, 155 (92.8%) were screened prenatally and had a negative result; only five (3.2%) had correct prenatal screen timing, specimen collection, and laboratory methods. No potential reduction was assumed for those five cases and for two cases in which the mother received no prenatal care. For the remaining 160 cases in which no indication for prophylaxis was identified, we estimated a potential reduction to 34–130 cases (19–79% decline). Among all 309 cases, 50–51 cases (16%) might have been averted through improved use of intrapartum prophylaxis, and 22–118 (7–38%) might have been averted through improved prenatal screening (including specimen collection and laboratory methods). Overall, with optimal implementation the observed cases might have been reduced by 26–59%. The national early-onset GBS incidence rate of 0.3 cases per 1,000 live births in recent years2,3 might therefore be reduced to 0.12–0.22 cases per 1,000 live births.
Early-onset GBS disease incidence fell dramatically during the 1990s as a result of widespread use of intrapartum antibiotic prophylaxis and declined further following the 2002 recommendation for screening all pregnant women for GBS colonization.14 In recent years, the incidence plateaued, suggesting the limits of current prevention strategies might have been reached. However, this study demonstrates the potential for meaningful further disease reductions.
Improved intrapartum prophylaxis implementation, particularly among preterm deliveries, offers the most direct route to accomplish further reductions in early-onset GBS disease. Although some cases with suboptimal or no intrapartum prophylaxis were not preventable, most mothers of case-patients for whom prophylaxis was indicated were hospitalized long enough before delivery to receive adequate antibiotics. Incorrect choice of antibiotic was common for women with a penicillin allergy, a finding consistent with other studies of adherence to GBS prevention recommendations.9,14–16 Intrapartum prophylaxis errors were most common among preterm patients, a group at particularly high risk for illness and death resulting from GBS14 and where poor adherence to prophylaxis recommendations has been noted.9 Importantly, intrapartum prophylaxis is highly effective at preventing early-onset disease among preterm neonates.12
Frequent errors occurred in the collection of specimens and in the laboratory methods used to process them. However, the link between those errors and the persistent burden of early-onset GBS disease is not as clear. Prenatal screening results may be positive despite suboptimal methods, and women with false-negative results may receive intrapartum antibiotics for other reasons (eg, chorioamnionitis). Furthermore, missing data, particularly for laboratory practices, greatly limited our ability to estimate the potential reduction in patients in whom prophylaxis was not indicated. Nonetheless, improved adherence to recommendations for prenatal screening specimen collection and laboratory testing would likely reduce the proportion of false-negative screens and lead to some decrease in early-onset disease burden.
Yet even with optimal implementation of all GBS prevention activities, some burden of early-onset disease would persist. Therefore, additional approaches to GBS prevention are needed. Molecular assays for GBS have raised the possibility of rapid intrapartum testing as a potential improvement over prenatal screening.15–19 However, suboptimal sensitivity of available assays on nonenriched specimens, test complexity, turnaround time, and inability to detect resistance to clindamycin currently limit their use.1 Among the mothers of case-patients in this study, more than half had no indication for GBS prophylaxis because they either had no prenatal screen or the prenatal screen yielded false-negative results. Such mothers might be detected by a highly sensitive, low-complexity, point-of-care test.
Maternal GBS vaccines have been shown to be safe and immunogenic20 and phase II clinical trials are currently underway.21 An efficacious GBS vaccine could help prevent both those early-onset cases which are unavoidable under current prevention strategies, and those in which lapses in implementation of prenatal screening or use of intrapartum prophylaxis have occurred. An additional benefit of maternal GBS vaccines is the potential to reduce late-onset GBS disease, the incidence of which has been unchanged by intrapartum antibiotic prophylaxis and is now similar to that of early-onset GBS disease in the United States.5,22 Vaccines would also have certain limitations, including lack of protection against serotypes not included in the vaccine and likely reduced effectiveness in preterm neonates, yet these novel tools, in conjunction with current approaches, could potentially reduce invasive neonatal GBS disease even further.
The study is subject to several limitations. Because of incomplete data particularly from laboratory records, it is likely that some implementation errors went undetected. In addition, some of the data sources, including health care providers' self-reported specimen collection techniques and laboratory standard operating procedures, were not specific to the case and may not reflect what occurred with the specimen collected from the case-patient’s mother. Finally, case-only data do not reflect prevention practices at the population level.
Prenatal care providers, labor and delivery staff, and laboratory personnel all have a critical role to play in effective perinatal GBS disease prevention. Resources available to improve prevention include a mobile application to provide patient-specific guidance in accordance with the 2010 GBS prevention guidelines (www.cdc.gov/groupbstrep/resources/multimedia.html) and sample standard operating procedure documents for GBS detection (www.cdc.gov/groupbstrep/lab/sops.html). Other GBS prevention tools such as improved intrapartum tests and maternal vaccines may open pathways to new approaches in the future. In the meantime the results of this study show that the maximum benefit of current GBS prevention strategies has not yet been reached and that provision of intrapartum prophylaxis when indicated should be prioritized.
1. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep 2010;59:1–36.
6. Schuchat A. Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clin Microbiol Rev 1998;11:497–513.
7. Schrag SJ, Zywicki S, Farley MM, Reingold AL, Harrison LH, Lefkowitz LB, et al.. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000;342:15–20.
8. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep 2002;51:1–22.
9. Van Dyke MK, Phares CR, Lynfield R, Thomas AR, Arnold KE, Craig AS, et al.. Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med 2009;360:2626–36.
10. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al.; Active Bacterial Core Surveillance Team. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002;347:233–9.
11. Yancey MK, Schuchat A, Brown LK, Ventura VL, Markenson GR. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol 1996;88:811–5.
12. Fairlie T, Zell ER, Schrag S. Effectiveness of intrapartum antibiotic prophylaxis for prevention of early-onset group B streptococcal disease. Obstet Gynecol 2013;121:570–7.
13. Allegaert K, van Mieghem T, Verbesselt R, de Hoon J, Rayyan M, Devlieger R, et al.. Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. Am J Obstet Gynecol 2009;200:170.e1–7.
14. Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, et al.; Active Bacterial Core surveillance/Emerging Infections Program Network. Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005. JAMA 2008;299:2056–65.
15. Daniels JP, Gray J, Pattison HM, Gray R, Hills RK, Khan KS, et al.; GBS Collaborative Group. Intrapartum tests for group B streptococcus: accuracy and acceptability of screening. BJOG 2011;118:257–65.
16. de Tejada BM, Pfister RE, Renzi G, Francois P, Irion O, Boulvain M, et al.. Intrapartum Group B streptococcus detection by rapid polymerase chain reaction assay for the prevention of neonatal sepsis. Clin Microbiol Infect 2011;17:1786–91.
17. Alfa MJ, Sepehri S, De Gagne P, Helawa M, Sandhu G, Harding GK. Real-time PCR assay provides reliable assessment of intrapartum carriage of group B Streptococcus. J Clin Microbiol 2010;48:3095–9.
18. Edwards RK, Novak-Weekley SM, Koty PP, Davis T, Leeds LJ, Jordan JA. Rapid group B streptococci screening using a real-time polymerase chain reaction assay. Obstet Gynecol 2008;111:1335–41.
19. Honest H, Sharma S, Khan KS. Rapid tests for group B Streptococcus colonization in laboring women: a systematic review. Pediatrics 2006;117:1055–66.
20. Edwards MS. Group B streptococcal conjugate vaccine: a timely concept for which the time has come. Hum Vaccines 2008;4:444–8.
21. Madhi SA, Dangor Z, Heath PT, Schrag S, Izu A, Sobanjo-Ter Meulen A, et al.. Considerations for a phase-III trial to evaluate a group B Streptococcus polysaccharide-protein conjugate vaccine in pregnant women for the prevention of early- and late-onset invasive disease in young-infants. Vaccine 2013;31(suppl 4):D52–7.
© 2014 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
22. Jordan HT, Farley MM, Craig A, Mohle-Boetani J, Harrison LH, Petit S, et al.; Active Bacterial Core Surveillance (ABSs)/Emerging Infections Program Network, CDC. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, population-based analysis. Pediatr Infect Dis J 2008;27:1057–64.