Screening pregnant women to prevent neonatal group B streptococcal infection
Group B streptococci (GBS) are a leading cause of neonatal sepsis, and are acquired before birth from bacteria colonizing the maternal vagina. Studies have shown that active screening for colonization, together with intrapartum antibiotics given to carriers and at-risk groups, has reduced the incidence of early-onset GBS infection and is the recommended means of prevention in the US.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[55]Royal College of Obstetricians and Gynaecologists. The prevention of early onset neonatal group B streptococcal disease. Green-top guideline no. 36. Sep 2017 [internet publication].
http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14821/full
http://www.ncbi.nlm.nih.gov/pubmed/28901693?tool=bestpractice.com
[56]Powers RJ, Wirtschafter D; Perinatal Quality Improvement Panel of the California Perinatal Quality Care Collaborative. Prevention of group B streptococcus early-onset disease: a toolkit by the California Perinatal Quality Care Collaborative. J Perinatol. 2010 Feb;30(2):77-87.
http://www.ncbi.nlm.nih.gov/pubmed/19657350?tool=bestpractice.com
[72]Taminato M, Fram D, Torloni MR, et al. Screening for group B streptococcus in pregnant women: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2011;19(6):1470-8.
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-11692011000600026&lng=en&nrm=iso&tlng=en
http://www.ncbi.nlm.nih.gov/pubmed/22249684?tool=bestpractice.com
However, this has been disputed in a systematic review that concluded that, although intrapartum antibiotics in GBS-colonized mothers appear to reduce early-onset GBS disease, this may be the result of bias in study design and execution.[57]Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev. 2014 Jun 10;(6):CD007467.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007467.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/24915629?tool=bestpractice.com
The American College of Obstetricians and Gynecologists recommends a screening strategy for prevention of early-onset GBS infection.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
Since GBS screening and intrapartum antibiotics were introduced, the incidence of early-onset GBS infection has decreased by 80%.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[23]Chen KT, Ringer S, Cohen AP, et al. The role of intrapartum fever in identifying asymptomatic term neonates with early-onset neonatal sepsis, J Perinatol. 2002 Dec;22(8):653-7.
http://www.ncbi.nlm.nih.gov/pubmed/12478449?tool=bestpractice.com
Resistance to macrolides in GBS isolates has increased over this time.[73]Larsen JW, Serve JL. Group B streptococcus and pregnancy: a review. Am J Obstet Gynecol. 2008 Apr;198(4):440-8.
http://www.ncbi.nlm.nih.gov/pubmed/18201679?tool=bestpractice.com
Intrapartum antibiotic treatment has had no effect on the incidence of late-onset disease.
Cases of GBS infection continue to occur despite the introduction of screening, although universal screening results in a greater reduction in early-onset GBS disease than the risk-based approach as the latter misses opportunities for intrapartum antibiotic administration.[11]Schrag SJ, Zell ER, Lynfield R, et al. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med. 2002 Jul 25;347(4):233-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa020205#t=article
http://www.ncbi.nlm.nih.gov/pubmed/12140298?tool=bestpractice.com
[56]Powers RJ, Wirtschafter D; Perinatal Quality Improvement Panel of the California Perinatal Quality Care Collaborative. Prevention of group B streptococcus early-onset disease: a toolkit by the California Perinatal Quality Care Collaborative. J Perinatol. 2010 Feb;30(2):77-87.
http://www.ncbi.nlm.nih.gov/pubmed/19657350?tool=bestpractice.com
Most cases (if screening strategy is followed) occur in infants born to mothers who had negative GBS cultures on screening (64%), most of whom had an intrapartum risk factor for disease.[74]Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005 May;115(5):1240-6.
http://www.ncbi.nlm.nih.gov/pubmed/15867030?tool=bestpractice.com
About 4% to 6% of mothers who test negative at 35 to 37 weeks' gestation will be culture positive at term.[75]Yancey MK, Schuchat A, Brown LK, et al. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol. 1996 Nov;88(5):811-5.
http://www.ncbi.nlm.nih.gov/pubmed/8885919?tool=bestpractice.com
[76]Valkenburg-van den Berg AW, Houtman-Roelofsen RL, Oostvogel PM, et al. Timing of group B streptococcus screening in pregnancy: a systematic review. Gynecol Obstet Invest. 2010;69(3):174-83.
http://www.ncbi.nlm.nih.gov/pubmed/20016190?tool=bestpractice.com
Differences in incidence of disease and in interpretation of the same literature has led different countries to adopt different prevention protocols.[2]Phares CR, Lynfield R, Farley M, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. 2008 May 7;299(17):2056-65.
https://jamanetwork.com/journals/jama/fullarticle/181853
http://www.ncbi.nlm.nih.gov/pubmed/18460666?tool=bestpractice.com
[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[21]Schuchat A. Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clin Microbiol Rev. 1998 Jul;11(3):497-513.
http://cmr.asm.org/cgi/content/full/11/3/497
http://www.ncbi.nlm.nih.gov/pubmed/9665980?tool=bestpractice.com
[62]Colbourn TE, Asseburg C, Bojke L, et al. Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. BMJ. 2007 Sep 29;335(7621):655.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995477
http://www.ncbi.nlm.nih.gov/pubmed/17848402?tool=bestpractice.com
[72]Taminato M, Fram D, Torloni MR, et al. Screening for group B streptococcus in pregnant women: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2011;19(6):1470-8.
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-11692011000600026&lng=en&nrm=iso&tlng=en
http://www.ncbi.nlm.nih.gov/pubmed/22249684?tool=bestpractice.com
[77]Shah V, Ohlsson A; Canadian Task Force on Preventive Health Care. Prevention of early-onset group B streptococcal (GBS) infection in the newborn: systematic review and recommendations CTFPHC technical report 01-6. May 2001 [interent publication].
https://canadiantaskforce.ca/wp-content/uploads/2016/09/2002-streptococcal-systematic-review-and-recommendations-en.pdf
[78]Colbourn T, Asseburg C, Bojke L, et al. Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses. Health Technol Assess. 2007 Aug;11(29):1-226.
http://www.ncbi.nlm.nih.gov/pubmed/17651659?tool=bestpractice.com
[79]Daniels J, Gray J, Pattison H, et al. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess. 2007 Aug;11(29):1-226.
http://www.ncbi.nlm.nih.gov/pubmed/19778493?tool=bestpractice.com
[80]Kotarski J, Heczko PB, Lauterbach R, et al. Polish Gynecological Society's recommendations regarding diagnosis and prevention of Streptococcus agalactiae infection in pregnant women and newborns [in Polish]. Ginekol Pol. 2008 Mar;79(3):221-3.
http://www.ncbi.nlm.nih.gov/pubmed/18592860?tool=bestpractice.com
[81]Yudin MH, van Schalkwyk J, Van Eyk N, et al. Antibiotic therapy in preterm premature rupture of the membranes. J Obstet Gynaecol Can. 2009 Sep;13(42):1-154.
http://www.ncbi.nlm.nih.gov/pubmed/19941711?tool=bestpractice.com
[82]Queensland Health Statewide Maternity and Neonatal Clinical Guidelines Program. Early onset group B streptococcal disease. April 2020 [internet publication].
https://www.health.qld.gov.au/__data/assets/pdf_file/0026/626732/g-gbs.pdf
[83]Money D, Allen VM. No. 298 - The prevention of early-onset neonatal group B streptococcal disease. J Obstet Gynaecol Can. 2018 Aug;40(8):e665-74.
http://www.ncbi.nlm.nih.gov/pubmed/30103891?tool=bestpractice.com
Evaluation of a screening program identified the following areas for improvement to reduce the number of missed opportunities for prevention:[84]Van Dyke MK, Phares CR, Lynfield R, et al. Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med. 2009 Jun 18;360(25):2626-36.
http://www.nejm.org/doi/full/10.1056/NEJMoa0806820#t=article
http://www.ncbi.nlm.nih.gov/pubmed/19535801?tool=bestpractice.com
Women who deliver preterm with unknown colonization status
For women who are allergic to penicillin, cefazolin is the preferred agent for those at low risk for anaphylaxis. Those at high risk from penicillin allergy receive either clindamycin (if isolate is sensitive and has no inducible resistance on laboratory testing) or a glycopeptide (e.g., vancomycin) (if resistance or inducible resistance is present, or sensitivities are unknown)
Women with false-negative screening results (by improved management processes for screening).
How screening is performed
In the US, vaginal and rectal cultures are obtained at 36 to 37 weeks' gestation for all pregnant women except those with GBS bacteriuria during the current pregnancy, or those who have had a baby with GBS disease previously.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[85]Society for Maternal-Fetal Medicine. Eighteen things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2022 [internet publication].
https://web.archive.org/web/20230209025206/https://www.choosingwisely.org/societies/society-for-maternal-fetal-medicine
A single swab is taken from the lower vagina and rectum and cultured in enrichment broth and plated on selective media.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[86]American Society for Microbiology. Guidelines for the detection and identification of group B streptococcus. 29 July 2021 [internet publication].
https://asm.org/Guideline/Guidelines-for-the-Detection-and-Identification-of
The sensitivity of cultures is greatest when samples are kept at 39.2°F (4°C) prior to culture and processed within 24 hours of collection.[86]American Society for Microbiology. Guidelines for the detection and identification of group B streptococcus. 29 July 2021 [internet publication].
https://asm.org/Guideline/Guidelines-for-the-Detection-and-Identification-of
Laboratories should process samples by incubating first in an appropriate enrichment broth medium to optimize sensitivity of subsequent culture results.[86]American Society for Microbiology. Guidelines for the detection and identification of group B streptococcus. 29 July 2021 [internet publication].
https://asm.org/Guideline/Guidelines-for-the-Detection-and-Identification-of
Self-sampling has been found to be an accurate and acceptable alternative to clinician sampling.[87]Price D, Shaw E, Howard M, et al. Self-sampling for group B streptococcus in women 35 to 37 weeks pregnant is accurate and acceptable: a randomized cross-over trial. J Obstet Gynaecol Can. 2006 Dec;28(12):1083-8.
http://www.ncbi.nlm.nih.gov/pubmed/17169231?tool=bestpractice.com
Sensitivity testing should be performed on prenatal GBS isolates from penicillin-allergic women at high risk of anaphylaxis to penicillin or cephalosporins. Testing for inducible clindamycin resistance should be performed on isolates from penicillin-allergic women at high risk of anaphylaxis that are sensitive to clindamycin or resistant to erythromycin.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[86]American Society for Microbiology. Guidelines for the detection and identification of group B streptococcus. 29 July 2021 [internet publication].
https://asm.org/Guideline/Guidelines-for-the-Detection-and-Identification-of
Clinicians should inform the laboratory when sending urine samples from pregnant women. Urine results positive for GBS at ≥10⁴ colony forming units in either pure or mixed cultures should be reported.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
Response to a positive result
Intrapartum antibiotics are given to all women colonized with GBS. In addition, antibiotics are indicated for women with:[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[55]Royal College of Obstetricians and Gynaecologists. The prevention of early onset neonatal group B streptococcal disease. Green-top guideline no. 36. Sep 2017 [internet publication].
http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14821/full
http://www.ncbi.nlm.nih.gov/pubmed/28901693?tool=bestpractice.com
[63]National Institute for Health and Care Excellence (UK). Neonatal infection: antibiotics for prevention and treatment. April 2021 [internet publication].
https://www.nice.org.uk/guidance/ng195
Previous infant with invasive GBS infection
GBS bacteriuria or infection during current pregnancy
Unknown GBS status (culture not done, incomplete, or results unknown) and any of the following: intrapartum temperature ≥100.4°F (≥38°C); amniotic membrane rupture >18 hours; or delivery at <37 weeks' gestation.
Response to a negative result
Antibiotics are only indicated for women with:[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[55]Royal College of Obstetricians and Gynaecologists. The prevention of early onset neonatal group B streptococcal disease. Green-top guideline no. 36. Sep 2017 [internet publication].
http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14821/full
http://www.ncbi.nlm.nih.gov/pubmed/28901693?tool=bestpractice.com
[63]National Institute for Health and Care Excellence (UK). Neonatal infection: antibiotics for prevention and treatment. April 2021 [internet publication].
https://www.nice.org.uk/guidance/ng195
Previous infant with invasive GBS infection
GBS colonization, bacteriuria, or infection during current pregnancy
Unknown GBS status (culture not done, incomplete, or results unknown) and any of the following: intrapartum temperature ≥100.4°F (≥38°C); amniotic membrane rupture >18 hours; or delivery at <37 weeks' gestation.
Response if screening not done
Antibiotics are indicated for women with:[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[55]Royal College of Obstetricians and Gynaecologists. The prevention of early onset neonatal group B streptococcal disease. Green-top guideline no. 36. Sep 2017 [internet publication].
http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14821/full
http://www.ncbi.nlm.nih.gov/pubmed/28901693?tool=bestpractice.com
[63]National Institute for Health and Care Excellence (UK). Neonatal infection: antibiotics for prevention and treatment. April 2021 [internet publication].
https://www.nice.org.uk/guidance/ng195
Previous infant with invasive GBS infection
GBS colonization, bacteriuria, or infection during current pregnancy
Unknown GBS status (culture not done, incomplete, or results unknown) and any of the following: intrapartum temperature ≥100.4°F (≥38°C); amniotic membrane rupture >18 hours; or delivery at <37 weeks' gestation.
Screening for GBS carriage at onset of labor
The difficulties associated with culture-based screening, and the potential for women who screen negative at 36 to 37 weeks' gestation to be positive at delivery (approximately 4%) and for women who screen positive but are no longer carrying at delivery (approximately 13%), have led several investigators to look for more rapid diagnostic tests that can be carried out at the onset of labor.[75]Yancey MK, Schuchat A, Brown LK, et al. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol. 1996 Nov;88(5):811-5.
http://www.ncbi.nlm.nih.gov/pubmed/8885919?tool=bestpractice.com
Polymerase chain reaction (PCR) testing is one such possible method that has a high sensitivity and specificity and can be carried out in 30 to 45 minutes.[88]Bergeron MG, Danbing KE, Menard C, et al. Rapid detection of group B streptococci in pregnant women at delivery. N Engl J Med. 2000 Jul 20;343(3):175-9.
https://www.nejm.org/doi/full/10.1056/NEJM200007203430303#t=article
http://www.ncbi.nlm.nih.gov/pubmed/10900276?tool=bestpractice.com
However, none of the available tests are sufficiently accurate and none are cost effective.[86]American Society for Microbiology. Guidelines for the detection and identification of group B streptococcus. 29 July 2021 [internet publication].
https://asm.org/Guideline/Guidelines-for-the-Detection-and-Identification-of
In addition the logistics of running a PCR assay 24 hours a day, 7 days a week in real clinical practice prohibit its use in many settings.[79]Daniels J, Gray J, Pattison H, et al. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess. 2007 Aug;11(29):1-226.
http://www.ncbi.nlm.nih.gov/pubmed/19778493?tool=bestpractice.com
Point-of-care tests are also under development, but none are currently in routine use or endorsed by any of the national guidelines. The use of any such product would have to be evaluated and endorsed locally.
Screening for GBS at the onset of preterm labor or at the time of preterm premature rupture of membranes should be undertaken in cases where GBS status has not been assessed in the preceding 5 weeks. Antibiotic prophylaxis should be commenced and subsequently discontinued if negative screening results become available or if the mother does not enter true labor and the membranes remain intact. Screening should be repeated between 36 and 37 weeks' gestation if the mother has not yet delivered.[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
US guidelines endorse the use of nucleic acid amplification testing (NAAT) in this setting where it is available. NAAT can be used for intrapartum testing of vaginal-rectal samples from women with unknown GBS colonization status and no intrapartum risk factors (temperature >100.4°F [>38°C] or rupture of amniotic membranes >18 hours) at the time of testing and who are delivering at term. Antibiotic prophylaxis is recommended for women with positive intrapartum NAAT results or if an intrapartum risk factor subsequently develops (regardless of the NAAT result).[6]The American College of Obstetricians and Gynecologists. Prevention of group B streptococcal early-onset disease in newborns: ACOG Committee Opinion Summary, Number 797. Obstet Gynecol. 2020 Feb;135(2):489-92.
https://journals.lww.com/greenjournal/Fulltext/2020/02000/Prevention_of_Group_B_Streptococcal_Early_Onset.41.aspx
http://www.ncbi.nlm.nih.gov/pubmed/31977793?tool=bestpractice.com
[86]American Society for Microbiology. Guidelines for the detection and identification of group B streptococcus. 29 July 2021 [internet publication].
https://asm.org/Guideline/Guidelines-for-the-Detection-and-Identification-of