ARTICLE
Rapid Tests for Group B
Streptococcus
Colonization in
Laboring Women: A Systematic Review
Honest Honest, MBChB, Sushma Sharma, MRCOG, Khalid S. Khan, MRCOG
Department of Obstetrics and Gynecology, University of Birmingham, Birmingham Women’s Hospital, Birmingham, United Kingdom
The authors have indicated they have no financial relationships relevant to this article to disclose.
ABSTRACT
OBJECTIVES.We set out to determine the accuracy and rapidity of various intrapartum
group BStreptococcus(GBS) colonization tests.
STUDY DESIGN.We performed a systematic review of test-accuracy studies, which were identified without language restriction from Medline and Cochrane databases; bibliographies of known primary and review articles; and contact with authors, experts, and manufacturers. Studies were selected if they tested pregnant women intrapartum for GBS colonization and confirmed by “gold-standard” laboratory cultures. Two reviewers independently selected studies and extracted data on their
characteristics, quality, and results. Accuracy data were used to form 2 ⫻ 2
contingency tables. Heterogeneity was assessed, and LRs for positive and negative test results were pooled in subgroups of studies of various tests.
RESULTS.There were 29 test-accuracy studies in 15 691 women, evaluating 6 differ-ent tests: polymerase chain reaction (PCR), optical immunoassay (OIA), DNA hybridization, enzyme immunoassay, latex agglutination, and Islam starch me-dium tests. The methodologic quality of the studies was generally poor. The most accurate was the real-time PCR test, but it was less rapid than OIA test. Real-time PCR took 40 minutes to complete, whereas the OIA took 30 minutes.
CONCLUSIONS.Real-time PCR and OIA are candidates for rapid near patient intrapar-tum GBS testing to determine the need for antibiotic prophylaxis to prevent neonatal GBS disease. Before implementation in practice, a robust technology assessment of their accuracy, acceptability, and cost-effectiveness is required.
www.pediatrics.org/cgi/doi/10.1542/ peds.2005-1114
doi:10.1542/peds.2005-1114
Key Words
group B Streptococcus, rapid intrapartum test, systematic review
Abbreviations
GBS— group BStreptococcus
LR—likelihood ratio CI— confidence interval PCR—polymerase chain reaction OIA— optical immunoassay Accepted for publication Sep 20, 2005 Address correspondence to Honest Honest, MBChB, Department of Obstetrics and Gynecology, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TG, United Kingdom. E-mail: [email protected]. uk
G
ROUP B Streptococcus (GBS) is a frequent cause of severe early-onset infection in newborn infants, afflicting 1 to 2 per 2000 births.1–4It is associated with upto 50% neonatal mortality4 and significant long-term
morbidity, including impaired psychomotor
develop-ment, in up to 30% of survivors of early GBS infection.5
Administration of intrapartum antibiotic prophylaxis to mothers who are colonized with GBS (asymptomatic
carriage of GBS in the rectum or vagina)6may prevent
early-onset neonatal GBS disease.7,8 However, there is
worldwide variation in practice concerning strategies to identify women for targeted intrapartum antibiotic pro-phylaxis.
There are 2 main approaches to the screening strate-gies. One approach is based on universal maternal test-ing at weeks 35 to 37 of gestation with culture of a high
vaginal swab,1,4,7,9which has been the standard of care in
the United States. Another approach uses assessment
based on clinical risk factors,10–12which has been
recom-mended in the United Kingdom recently and has been added to the culture-based screening in the revised US guidelines of 2002. Currently, most cases of early-onset neonatal GBS disease occur in newborns of mothers negative for antenatal GBS cultures and risk factors. Cultures at weeks 35 to 37 of gestation miss the preterm
pregnancies that, though only 7% to 11% of births,13are
at the highest risk of serious neonatal GBS infection and
account for 32% to 38% of early-onset GBS disease.14,15
Furthermore, there is a poor correlation between ante-natal test results and intrapartum maternal GBS
coloni-zation after 1 to 2 weeks of test.16 The risk-based
ap-proach is inherently crude, with 1 recent study reporting that up to 65% of early-onset neonatal GBS cases did not
have any risk factors.17 Thus, in the United States,
de-spite combining the 2 screening strategies as advocated
by the revised guidelines,4invasive early-onset disease
incidence has declined only by 34%.18There is a need for
new screening strategies to prevent cases of early-onset GBS disease over and above the disease reduction al-ready achieved by antenatal culture, risk-based screen-ing, and selective chemoprophylaxis. Could a rapid in-trapartum test replace existing screening strategies or could it be used in conjunction with them? A key ele-ment in addressing these questions relates to the accu-racy with which the rapid test identifies mothers with GBS colonization.
Antibiotic prophylaxis carries disadvantages for the mother and infant, for example, potentially fatal
ana-phylaxis,19 medicalization of labor and neonatal
pe-riod, and infection with resistant organisms.9,20–23
Thus, because of poor accuracy, there is controversy concerning these screening strategies in the United
Kingdom.1,24
There are a number of considerations in developing rapid intrapartum tests for maternal colonization. The intermittent nature of maternal GBS colonization
prac-tically means that mothers should be tested for carriage at the onset of labor. However, standard microbiologic
cultures take ⬎24 hours for their results to become
available, a time scale too long to inform the decision concerning intrapartum antibiotic prophylaxis. For a rapid test to be useful in practice, it would have to be accurate compared with the standard culture. Should a rapid and accurate test exist, timely and targeted antibiotic prophylaxis could then be implemented. Thus far, the lack of a GBS test, accurate and rapid enough in early labor, has been considered an
im-pediment.4 However, there has not been a systematic
review to assess intrapartum feasibility and the
perfor-mance of purportedly rapid commercially available25–29
GBS tests. This background prompted us to undertake such a review using appropriate quality assessments and meta-analysis to obtain valid and reliable estimates of the accuracy of various intrapartum tests for maternal GBS colonization.
METHODS
Our review was based on a prospective protocol
devel-oped using widely recommended methodology.30–33
Data Sources and Study Selection
Our search strategy included searches of Medline (1966 to August 2005) and the Cochrane Central Register of Controlled Trials, Cochrane Library (Issue 1, 2005). The databases were searched using relevant text words, Medical Subject Headings including all subheadings and their word variants. A total of 44 terms representing the concept (pregnancy OR labor) AND (GBS) AND (tests OR investigations OR diagnosis OR accuracy) were used. The terms for diagnosis and accuracy were adapted from
existing search filters.34–36 In addition, we checked the
reference lists of known reviews and primary articles to identify cited articles not captured by electronic searches and made contact with authors, experts, and manufac-turers.
(K.S.K.). A full list of excluded articles is available from the authors.
Data Extraction and Its Rationale
Information was extracted from each selected study on population and test characteristics including the time taken to perform the tests, methodologic quality, and accuracy results. Information on time gave us an in-dication of the feasibility of a test in the intrapartum setting for guiding decisions concerning antibiotic pro-phylaxis. It is reported that antibiotic should be used
for 2 hours before birth.6 We were interested in
intra-partum setting, because the fetus acquires GBS
infec-tion from colonized birth canal at this time.16,37 We
sought information on anorectal specimen in addition to vaginal specimen, because intestinal tract is a
com-mon reservoir and a source of spread to the vagina.16,37
Anorectal carriage of GBS is also an independent
pre-dictor of neonatal GBS.16,37,38We defined the gold
stan-dard for verification of rapid tests as appropriate mi-crobiologic culture of GBS (see below). Where accuracy data were not extractable, we contacted the corre-sponding author, by letter or email, to seek his or her assistance in data extraction. In cases of multiple publi-cations, complete information on characteristics and quality was extracted using all sources, but only the most recent and complete results were included in meta-analysis.
Methodologic Quality Assessment
We defined quality as the confidence that the study design, conduct, and analysis minimized bias in the
es-timation of test accuracy. Existing checklists39,40 and
empirical evidence41 relate bias to a number of items:
case-control design, nonprospective data collection, non-consecutive patient enrollment, inadequate description of participants and/or index tests, lack of blinding, partial or differential verification of index tests, and use of
different gold standards.39,41Items related to gold
stan-dards were critical to our review, as use of nonselective
medium during incubation decreases its validity.42,43
Therefore, we considered a study to be of high quality if it reported a prospective design, consecutive patient enrollment, an adequate test description, blinding of the test results, and use of selective medium for incuba-tion of specimen for gold-standard culture. In addiincuba-tion, we sought information on a priori estimation of sample size and its rationale. We also sought information on
whether a study explored for spectrum variation44
con-sidering predisposing factors, because test accuracy var-ies in relation to these. For GBS colonization, risk factors include prematurity, prelabor rupture of membranes,
and intrapartum fever.1
Data Synthesis
Data from individual studies were synthesized sepa-rately for the various tests. For each test, sensitivity,
specificity and likelihood ratios for positive (LR⫹) and
negative (LR⫺) results with confidence intervals (CI)
were calculated as measures of accuracy of individual studies. Heterogeneity was assessed graphically and statistically45,46within subgroups of studies stratified by test type. For graphical exploration, we used plots of
sensitivities versus 1⫺ specificity in the receiver
oper-ating characteristic space and forest plots of LRs of the
various rapid tests. Statistically, we used the 2 test for
heterogeneity to assess whether the differences be-tween studies could be explained by chance alone. We also checked for correlation between sensitivity and
specificity using Spearman’s rank correlation test.32
These evaluations helped assess the feasibility of pooling individual results in a meta-analysis, where correlation indicates dependency of sensitivity and specificity to variation in cutoff point and would make pooling of these measures independently inadvisable. As in our
previous publications,47,48summary LRs were generated
if pooling (using a random-effects model) was consid-ered appropriate. LRs are useful in indicating by how much a given test result will raise (when positive,
indi-cated by the value of LR⫹) or lower (ie, LR⫺) the
prob-ability of having GBS and would allow the determina-tion of posttest probabilities (ie, posttest probability⫽LR
⫻ pretest probability/{1 ⫹ [pretest probability⫻ (1 ⫺
LR)]}).47 We did not consider pooling sensitivities and
specificities separately, because they are not
indepen-dent values.49 For many tests, pooling could only be
undertaken in subgroups according to the subtype of test and site of swabs. Furthermore, pooling was strati-fied according to type of gold-standard culture used. We took extreme care to avoid multiple counting of the same patients in the meta-analysis.
Where a sufficient number of studies with contrasting features (study quality items and site of swabs) was available within subgroups of tests, we planned to use
metaregression analysis50,51to examine the relation
be-tween these features and accuracy. Our metaregression models assessed the effect of study quality (high or low) and site of swabs (vaginal or anorectal) on diagnostic
odds ratio (ratio of LR⫹/LR⫺), adjusting for test type.
For quality evaluation, if 3 of the quality items outlined above were met, we arbitrarily classified the study as high quality. Where a quality item presence was not explicitly stated, it was treated as “no” in the metare-gression analysis. We also undertook funnel plot (diag-nostic odds ratio versus 1/SE) analysis to examine for
publication and related biases.52 All of the statistical
RESULTS
Literature Identification and Study Quality
On electronic literature search, 1296 citations were found, which were scrutinized as shown in Fig 1. Of these, 23 articles (29 studies) that met the predefined selection criteria were selected. Some articles
contrib-uted ⬎1 study in our review, because they evaluated
⬎1 test. There were 6 different types of tests for the
diagnosis of GBS colonization: polymerase chain
reac-tion (PCR) in 2 studies (914 women)25,53; optical
immu-noassay (OIA) in 5 studies (1970 women)27,54–57; DNA
hybridization in 2 studies (268 women)58,59; enzyme
im-munoassay in 9 studies (3569 women; 1 study54
evalu-ated 2 different enzyme immunoassay tests)28,54,57,60–64;
latex agglutination in 10 studies (8451 women)28,29,62–69;
and Islam starch medium tests in 2 studies (519
wom-en).26,70
As shown in Fig 2, the quality of the studies was poor in many respects: only 4 recruited mothers
consecutive-ly27–29,53; only 4 blinded the test from the gold
stan-dard27,53,59,61; and only 12 used an adequate gold standard
(selective enrichment culture).* None of the studies ex-plored for spectrum variation. Although only 1
com-puted sample size a priori,53 3 studies had a sample of
⬎1000 women.28,67,69
Most studies obtained vaginal swabs for tests and gold standards without speculum examination. The tech-nique for obtaining specimens with these swabs was poorly described, but in 12 it was clear that specimens were obtained from the lower third of the vagina.† Only 4 studies obtained high vaginal swabs using speculum
*Refs 8, 25, 26, 53, 54, 56 – 60, 62, and 69.
†Refs 25 26, 28, 53–56, 58, 59, 62, and 69.
FIGURE 1
Study selection process for systematic review of tests for detecting GBS intrapartum maternal colonization.aList is
available from the authors.bThe total number of studies
examination,29,63,65,68 and only 4 studies also examined
the accuracy of rectal swabs.25,27,62,70 The prevalence of
GBS colonization in these studies varied from 5% to
32%.27,65
Rapidity of Intrapartum Tests for GBS Colonization
The time taken to undertake the tests is detailed in Table 1. For PCR it was 40 to 100 minutes, for OIA it was 30 minutes, for DNA hybridization it was 60 to 1440 minutes, for enzyme immunoassay it was 5 to 10 min-utes, for latex agglutination it was 70 to 85 minmin-utes, and for Islam starch medium tests it was 120 to 1400 min-utes. The rapidity of PCR tests varied according to type, with real time taking 40 minutes and conventional tak-ing 100 minutes. For enzyme immunoassay and latex agglutination, the rapidity varied with the heaviness of colonization, and the more heavily colonized specimens tested more quickly. DNA hybridization, Islam starch medium, and latex agglutination tests took too long to be feasible as rapid intrapartum tests. Enzyme immuno-assay, although rapid, was less accurate than either PCR or OIA.
Accuracy of Various Intrapartum Tests for GBS Colonization
Because of multiplicity of test types, sites of swabs, and
gold standards, there were forty-two 2 ⫻ 2 tables to
compute test accuracy (Table 2). When examining studies with selective culture as the gold standard, the 2 most accurate tests were real-time PCR and OIA (Fig 3).
Real-time PCR had a LR⫹ of 38.80 (95% CI:
6.05–248.72) and LR⫺ of 0.06 (95% CI: 0.03– 0.11);
median sensitivity of 0.96 (95% CI: 0.88 – 0.99) and median specificity of 0.98 (95% CI: 0.96 – 0.99).
Sum-mary LR⫹for OIA was 14.7 (95% CI: 10.6 –20.3),
sum-mary LR⫺was 0.47 (95% CI: 0.31– 0.73), median
sen-sitivity was 0.48 (range: 0.37– 0.72) and median specificity was 0.97 (range: 0.96 – 0.99). Metaregression
analysis showed that test accuracy did not vary
accord-ing to overall quality (P⫽ .58) or the addition of
ano-rectal swab (P⫽.064). Funnel plot analysis did not show
any evidence of asymmetry to indicate the presence of publication or related bias for the largest subgroup of studies.
DISCUSSION
Our review shows that many of the GBS tests, with the exception of real-time PCR and OIA, took either too long or were not of sufficient accuracy to be feasible for maternal intrapartum testing to aid decision making concerning antibiotic prophylaxis to prevent neonatal GBS disease. Although OIA seemed less accurate than real-time PCR, the latter was only evaluated in 2 small studies, 1 of which was a relatively small study. In light of the poor methodologic quality of the existing studies and the imprecision of the evidence for PCR, a robust technology assessment comparing the most promising tests (PCR and OIA) is needed before reaching recom-mendations for practice.
The strength of our inferences depends on the rigor of our methodology. We complied with existing guidelines for reviews of test-accuracy studies.30–33We did limit our search to a couple of databases, but we did not apply language restrictions. In light of input from experts and manufacturers, we feel reasonably confident that
rele-vant studies have not been missed.71 Cognizant that
meta-analysis of test-accuracy studies are fraught with difficulty because of poor methodologic quality of the primary studies, we scrutinized the selected studies for their quality considering recent recommendations and
checklists.39,40Case-control design that may overestimate
accuracy was not found in the selected studies. However, other quality criteria concerning tests and gold standards were commonly poorly adhered to. Our quality assess-FIGURE 2
ments were also affected by lack of reporting in some instances. Although assessment of heterogeneity on the receiver operating characteristic space and exploration for reasons behind heterogeneity were planned a priori, they were hampered because of the small number of studies in the review. In the presence of unexplained heterogeneity, we proceeded with caution, pooling data for summary LRs with a random effects model in line with the current recommendation but not
sensitiv-ity or specificsensitiv-ity measures.46 Our inferences are
sup-ported by the most methodologically sound selected studies, particularly those with an appropriate gold standard.
Our systematic review informs the design of the technology assessment required to develop a strategy for administering antibiotic prophylaxis according to intrapartum maternal testing to prevent neonatal GBS. The assessment should be undertaken in a hierarch-ical fashion, based on methodologhierarch-ically robust
frame-works for evaluation of tests,72,73comparing tests based
on real-time PCR and OIA. Initially, their accuracy in detecting GBS colonization among women in labor should be established, taking specimens from the lower vagina without the need for speculum examina-tion. The role of rectal swabs, emphasized as an
inde-pendent predictor of neonatal GBS,16,37 needs to be
considered in this assessment, because it has been ne-glected by existing studies. The effect of prior risk
cate-gorization on test accuracy, that is, spectrum variation,44
should be examined using multivariable analysis.74,75
In addition, the acceptability of intrapartum testing for GBS colonization to different social and ethnic groups should be examined. Finally, cost-effectiveness of intra-partum testing and targeted prophylaxis for preventing neonatal GBS should be evaluated in light of the out-come of the accuracy comparison of real-time PCR
vis-a`-vis OIA, comparing it with others strategies,1,4 using
either decision analytic modeling or a direct randomized, controlled trial. In fact, this terminal analysis would yield highly pertinent, potentially practice changing re-sults for communities that had adopted a specific strat-egy (eg, the United States, Canada, or Australia). In light of the emerging evidence from our review, we believe that any screening recommendation for practice needs to be reevaluated.
ACKNOWLEDGMENTS
We thank the United Kingdom National Health Service Health Technology Assessment program for funding a primary study (grant 02/38/04) on GBS intrapartum screening.
We thank Dr Jim Gray, consultant microbiologist at Birmingham Women’s Hospital, for expert advice and contact with manufacturer. We also thank Mary Publi-cover, head librarian at Birmingham Women’s Hospital
TABLE 2 Results of Individual Studies on Various Rapid Maternal Intrapartum Tests for GBS Colonization
Test Types Authors Gold Standard Site TP FP FN TN Sens (95% CI) Spec (95% CI) LR⫹(95% CI) LR⫺(95% CI)
PCR
Real-time PCR (LightCycler)
Bergeron et al25 Selective culture Anus and
lower vaginaa
32 0 1 79 0.97 (0.84–1.00) 1.00 (0.95–1.00) 152.94 (9.64–2426.32) 0.03 (0.00–0.21)
Lower vagina 20 1 0 91 1.00 (0.83–1.00) 0.99 (0.94–1.00) 92.00 (13.10–646.18) 0.02 (0.00–0.37) Anus 30 1 0 81 1.00 (0.88–1.00) 0.9 (0.93–1.00) 82.00 (11.69–575.19) 0.02 (0.00–0.26) Conventional PCR Bergeron et al25 Selective culture Anus and
lower vagina
32 0 1 79 0.97 (0.84–1.00) 1.00 (0.95–1.00) 152.94 (9.64–2426.32) 0.03 (0.00–0.21)
Lower vagina 20 1 0 91 1.00 (0.83–1.00) 0.99 (0.94–1.00) 92.00 (13.10–646.18) 0.02 (0.00–0.37) Anus 30 2 0 80 1.00 (0.88–1.00) 0.98 (0.91–1.00) 41.00 (10.43–161.17) 0.02 (0.00–0.26) Real-time PCR
(SmartCycler)
Davies et al53 Selective culture Anus and
lower vagina
140 27 9 626 0.94 (0.89–0.97) 0.96 (0.94–0.97) 22.72 (15.67–32.96) 0.06 (0.03–0.12)
Pooled LRsa 38.80 (6.05–248.72) 0.06 (0.03–0.11)
OIA
Strep B OIA Baker54 Selective culture Lower vagina 25 4 43 235 0.37 (0.25–0.49) 0.98 (0.96–1.00) 21.97 (7.92–60.95) 0.64 (0.54–0.77)
Strep B OIA Nguyen et al56 Selective culture Lower vagina 42 18 45 416 0.48 (0.37–0.59) 0.96 (0.94–0.98) 11.64 (7.05–19.23) 0.54 (0.44–0.66)
Strep B OIA Park et al57 Selective culture Vagina 72 18 28 394 0.72 (0.62–0.81) 0.96 (0.93–0.97) 16.48 (10.32–26.32) 0.29 (0.21–0.40)
Pooled LRsa 14.67 (10.60–20.29) 0.47 (0.31–0.73)
Strep B OIA Baker54 Direct culture Lower vagina 25 4 22 254 0.53 (0.38–0.68) 0.98 (0.96–1.00) 34.31 (12.51–94.07) 0.48 (0.35–0.65)
Strep B OIA Carroll et al55 Direct culture Lower vagina 26 29 7 282 0.79 (0.61–0.91) 0.91 (0.87–0.94) 8.45 (5.73–12.47) 0.23 (0.12–0.45)
Pooled LR 16.01 (3.35–76.39) 0.35 (0.17–0.74)
OIA Biostar Samadi et al27 Direct culture Rectum and
vagina
21 12 35 220 0.38 (0.25–0.51) 0.95 (0.91–0.97) 7.25 (3.80–13.84) 0.66 (0.54–0.81)
DNA hybridization MicroProbe
(1 h)
Rosa et al58 Selective culture Perianal and
lower vaginaa
3 0 33 157 0.08 (0.02–0.22) 1.00 (0.98–1.00) 29.89 (1.58–566.27) 0.92 (0.83–1.01)
GeneProbe (9 h)
Ryan et al59 Selective culture Perianal and
lower vagina
23 0 1 51 0.96 (0.79–1.00) 1.00 (0.93-)1.00 97.76 (6.19–1544.94) 0.04 (0.01–0.28)
MicroProbe (16 h)
Rosa et al58 Selective culture Perianal and
lower vagina
29 4 7 153 0.81 (0.64–0.92) 0.97 (0.94–0.99) 31.62 (11.86–84.30) 0.20 (0.10–0.39)
GeneProbe (25 h)
Ryan et al59 Selective culture Perianal and
lower vagina
19 0 5 51 0.79 (0.58–0.93) 1.00 (0.93–1.00) 81.12 (5.10–1289.78) 0.21 (0.10–0.45)
Enzyme Immunoassay
Icon Armer et al60 Selective culture Vagina 5 0 39 138 0.11 (0.04–0.25) 1.00 (0.97–1.00) 33.98 (1.92–602.56) 0.89 (0.80–0.99)
Quidel Baker54 Selective culture Lower vagina 15 4 111 372 0.12 (0.07–0.19) 0.99 (0.97–1.00) 11.19 (3.78–33.10) 0.89 (0.83–0.95)
Icon Baker54 Selective culture Lower vagina 19 0 107 376 0.15 (0.09–0.23) 1.00 (0.99–1.00) 115.77 (7.04–1903.65) 0.85 (0.79–0.91)
Equate Greenspoon et al62 Selective culture Lower vagina 2 3 4 241 0.33 (0.04–0.78) 0.99 (0.96–1.00) 27.11 (5.50–133.66) 0.67 (0.38–1.19)
Icon Park et al57 Selective culture Vagina 39 1 61 411 0.39 (0.29–0.49) 1.00 (0.99–1.00) 160.68 (22.34–1155.50) 0.61 (0.52–0.72)
Pooled LRsa 36.29 (10.79–121.97) 0.80 (0.70–0.92)
Icon Simpson et al64 Direct culture Lower vagina 11 0 5 101 0.69 (0.41–0.89) 1.00 (0.96–1.00) 138.00 (8.52–2234.41) 0.31 (0.15–0.65)
Equate Skoll et al28 Direct culture Lower vagina 20 12 73 947 0.22 (0.14–0.31) 0.99 (0.98–0.99) 17.19 (8.68–34.04) 0.79 (0.71–0.88)
Icon Gentry et al61 Direct culture Vagina 4 13 20 257 0.17 (0.05–0.37) 0.95 (0.92–0.97) 3.46 (1.22–9.79) 0.88 (0.73–1.05)
Equate Hagay et al63 Direct culture Ectocervix 12 29 38 581 0.24 (0.13–0.38) 0.95 (0.93–0.97) 5.05 (2.75–9.27) 0.80 (0.68–0.93)
Pooled LRs 9.37 (3.26–26.76) 0.78 (0.67–0.92)
Latex agglutination
Directgen Clark et al66 Selective culture Vagina 28 16 64 206 0.30 (0.21–0.41) 0.93 (0.89–0.96) 4.22 (2.40–7.42) 0.75 (0.65–0.86)
Bactigen Greenspoon et al62 Selective culture Lower vagina 2 11 4 233 0.33 (0.04–0.78) 0.95 (0.92–0.98) 7.39 (2.08–26.34) 0.70 (0.40–1.23)
Bactigen Isada and Grossman et al68
Selective culture Ectocervix 11 28 8 384 0.58 (0.33–0.80) 0.93 (0.90–0.95) 8.52 (5.04–14.39) 0.45 (0.27–0.77)
Not mentioned Stiller et al69 Selective culture Lower vagina 181 21 16 882 0.92 (0.87–0.95) 0.98 (0.96–0.99) 39.51 (25.84–60.41) 0.08 (0.05–0.13)
Pooled LRsa 10.37 (3.13–34.38) 0.38 (0.07–1.96)
Wellcogen (Heavy colonization)
Winn et al29 Direct culture Ectocervix and
vagina
7 0 36 236 0.16 (0.07–0.31) 1.00 (0.98–1.00) 80.80 (4.70–1389.22) 0.84 (0.73–0.96)
Wellcogen Brady et al65 Direct culture Ectocervix 22 2 3 473 0.88 (0.69–0.97) 1.00 (0.98–1.00) 209.00 (52.03–839.56) 0.12 (0.04–0.35)
Directgen Green et al67 Direct culture Midvagina 42 26 26 4157 0.62 (0.49–0.73) 0.99 (0.99–1.00) 99.37 (64.88–152.21) 0.38 (0.28–0.52)
Wellcogen Simpson et al64 Direct culture Lower vagina 30 0 8 228 0.79 (0.63–0.90) 1.00 (0.98–1.00) 358.18 (22.36–5737.43) 0.21 (0.11–0.39)
Streptex Skoll et al28 Direct culture Lower vagina 14 7 79 960 0.15 (0.08–0.24) 0.99 (0.99–1.00) 20.80 (8.61–50.24) 0.86 (0.79–0.93)
Education Resource Centre, for assistance in on-line search and retrieval of articles.
REFERENCES
1. Brocklehurst P. Green Top guideline: prevention of early on-set neonatal group B streptococcal disease. 2003. Available at: www.rcog.org.uk/resources/Public/pdf/GroupB㛭strep㛭no36.pdf. Accessed September 13, 2005
2. Luck S, Torny M, d’Agapeyeff K, et al. Estimated early-onset group B streptococcal neonatal disease. Lancet. 2003;361: 1953–1954
3. Regan JA, Klebanoff MA, Nugent RP, et al. Colonization with group B streptococci in pregnancy and adverse outcome. VIP Study Group.Am J Obstet Gynecol.1996;174:1354 –1360 4. 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(RR-11):1–22
5. Adriaanse AH, Lagendijk I, Muytjens HL, Nijhuis JG, Kollee LA. Neonatal early onset group B streptococcal infection: a nine-year retrospective study in a tertiary care hospital.J Peri-nat Med.1996;24:531–538
6. Boyer KM, Gadzala CA, Kelly PD, Gotoff SP. Selective intra-partum chemoprophylaxis of neonatal group B streptococcal early-onset disease. III. Interruption of mother-to-infant trans-mission.J Infect Dis.1983;148:810 – 816
7. Moore MR, Schrag SJ, Schuchat A. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-strepto-coccal disease on the incidence and ecology of early-onset neonatal sepsis.Lancet Infect Dis.2003;3:201–213
8. Smaill F. Intrapartum antibiotics for group B streptococcal colonisation [Cochrane review]. In: The Cochrane Library. Is-sue 4. Chichester, United Kingdom: Wiley; 2003
9. Prevention of group B streptococcal infection in newborns: recommendation statement from the Canadian Task Force on Preventive Health Care.CMAJ2002;166:928 –930
10. PHLS Group B Streptococcus Working Group.Commun Dis Rep CDR Wkly.1998;8:439, 442
11. Beardsall K. Guidelines for group BStreptococcus.Arch Dis Child Fetal Neonatal Ed.2001;84:F77–F78
12. Gilbert GL, Hewitt MC, Turner CM, Leeder SR. Epidemiology and predictive values of risk factors for neonatal group B streptococcal sepsis. Aust N Z J Obstet Gynaecol. 2002;42: 497–503
13. Aveyard P, Cheng KK, Manaseki S, Gardosi J. The risk of preterm delivery in women from different ethnic groups.
BJOG.2002;109:894 – 899
14. Beardsall K, Thompson MH, Mulla RJ. Neonatal group B strep-tococcal infection in South Bedfordshire, 1993–1998.Arch Dis Child Fetal Neonatal Ed.2000;82:F205–F207
15. Oddie S, Embleton ND. Risk factors for early onset neonatal group B streptococcal sepsis: case-control study. BMJ.2002; 325:308
16. Boyer KM, Gadzala CA, Kelly PD, Burd LI, Gotoff SP. Selective intrapartum chemoprophylaxis of neonatal group B strepto-coccal early-onset disease. II. Predictive value of prenatal cul-tures.J Infect Dis.1983;148:802– 809
17. Lyytikainen O, Nuorti JP, Halmesmaki E, et al. Invasive group FIGURE 3
Meta-analysis of subgroup studies using selective culture for gold standard showing summary LRs for intrapartum test of maternal GBS colonization.aAccuracy result was
derived from reporting at 1 hour; the rest of the results, from 8, 16, and 25 hours, which were too long to be of use for intrapartum testing, were excluded.bHeterogeneity
within meta-analysis. See Table 2 for details of individual results and their meta-analysis.
TABLE 2 Continued
Test Types Authors Gold Standard Site TP FP FN TN Sens (95% CI) Spec (95% CI) LR⫹(95% CI) LR⫺(95% CI)
Bactigen Greenspoon et al62 Selective culture Anus 5 30 11 204 0.31 (0.11–0.59) 0.87 (0.82–0.91) 2.44 (1.10–5.42) 0.79 (0.56–1.10)
Wellcogen (light colonization)
Winn et al29 Direct culture Ectocervix and
Vagina
0 16 0 88
Bactigenb Green et al67 Direct culture Midvagina 36 21 27 4167 0.57 (0.44–0.70) 0.99 (0.99–1.00) 113.96 (70.71–183.66) 0.43 (0.32–0.57)
Islam starch medium
Islam starch Reardon et al26 Selective culture Lower vaginaa 22 0 1 189 0.96 (0.78–1.00) 1.00 (0.98–1.00) 356.25 (22.32–5685.75) 0.04 (0.01–0.30)
Islam starch Wang and Richardson70
Direct culture Vagina 13 7 16 127 0.45 (0.26–0.64) 0.95 (0.90–0.98) 8.58 (3.75–19.61) 0.58 (0.42–0.81)
Islam starch Reardon et al26 Direct culture Lower vagina 11 0 14 177 0.44 (0.24–0.65) 1.00 (0.98–1.00) 157.46 (9.56–2592.93) 0.56 (0.40–0.79)
Pooled LRs 28.33 (1.26–636.46) 0.57 (0.45–0.72)
Islam starch Wang and Richardson70
Direct culture Rectum 8 6 10 120 0.44 (0.22–0.69) 0.95 (0.90–0.98) 9.33 (3.66–23.80) 0.58 (0.39–0.88)
Strep indicatesStreptococcus; TP, true-positive; FP, false-positive; FN, false-negative; TN, true-negative; Sens., sensitivity; Spec., specificity.
aValues used for Fig 3.
B streptococcal infections in Finland: a population-based study.
Emerg Infect Dis.2003;9:469 – 473
18. Diminishing racial disparities in early-onset neonatal group B streptococcal disease United States: 2000 –2003. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5323a2. htm. Accessed September 13, 2005
19. Weiss ME, Adkinson NF. Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy. 1988;18: 515–540
20. Berkowitz K, Regan JA, Greenberg E. Antibiotic resistance patterns of group B streptococci in pregnant women.J Clin Microbiol.1990;28:5–7
21. Fernandez M, Hickman ME, Baker CJ. Antimicrobial suscepti-bilities of group B streptococci isolated between 1992 and 1996 from patients with bacteremia or meningitis.Antimicrob Agents Chemother.1998;42:1517–1519
22. Pearlman MD, Pierson CL, Faix RG. Frequent resistance of clinical group B streptococci isolates to clindamycin and eryth-romycin.Obstet Gynecol.1998;92:258 –261
23. Stoll BJ, Hansen N, Fanaroff AA, et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants.
N Engl J Med.2002;347:240 –247
24. National Collaborating Centre for Women’s and Children’s Health. NICE clinical guidelines: antenatal care—routine care for the healthy pregnant woman. 2003. Available at: www. rcog.org.uk/resources/Public/pdf/Antenatal㛭Care.pdf. Accessed September 13, 2005
25. Bergeron MG, Ke D, Menard C, et al. Rapid detection of group B streptococci in pregnant women at delivery.N Engl J Med.
2000;343:175–179
26. Reardon EP, Noble MA, Luther ER, Wort AJ, Bent J, Swift M. Evaluation of a rapid method for the detection of vaginal group B streptococci in women in labor.Am J Obstet Gynecol.1984; 148:575–578
27. Samadi R, Stek A, Greenspoon JS. Evaluation of a rapid optical immunoassay-based test for group BStreptococcuscolonization in intrapartum patients.J Matern Fetal Med.2001;10:203–208 28. Skoll MA, Mercer BM, Baselski V, Gray JP, Ryan G, Sibai BM.
Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients.Obstet Gynecol.1991;77:322–326 29. Winn HN, McLennan M, Amon E. Clinical assessment of the
rapid latex agglutination screening test for group B Strepto-coccus.Int J Gynaecol Obstet.1994;47:289 –290
30. Deville WL, Buntinx F, Bouter LM, et al. Conducting system-atic reviews of diagnostic studies: didactic guidelines.BMC Med Res Methodol.2002;2:9
31. Honest H, Khan KS.Systematic Reviews of Test Accuracy Studies in Reproductive Child Health. Oxford, United Kingdom: Update Software; 2002. WHO Reproductive Health Library No. 5 32. Irwig L, Tosteson AN, Gatsonis C, et al. Guidelines for
meta-analyses evaluating diagnostic tests.Ann Intern Med.1994;120: 667– 676
33. Khan KS, Ter Riet G, Popay J, Nixon J, Kleijnen J. Conducting the Review: CRD Report No. 4 —Undertaking Systematic Re-views of Research on Effectiveness. 2001. Available at: www. york.ac.uk/inst/crd/report4.htm. Accessed September 13, 2005 34. Bachmann LM, Coray R, Estermann P, Ter Riet G. Identifying diagnostic studies in Medline: reducing the number needed to read.J Am Med Inform Assoc.2002;9:653– 658
35. Deville WL, Bezemer PD, Bouter LM. Publications on diagnos-tic test evaluation in family medicine journals: an optimal search strategy.J Clin Epidemiol.2000;53:65– 69
36. Wilczynski NL, Walker CJ, McKibbon KA, Haynes RB. Assess-ment of methodologic search filters in Medline.Proc Annu Symp Comput Appl Med Care.1993;601– 605
37. Dillon HC Jr, Gray E, Pass MA, Gray BM. Anorectal and vaginal
carriage of group B streptococci during pregnancy.J Infect Dis.
1982;145:794 –799
38. Hoogkamp-Korstanje JA, Gerards LJ, Cats BP. Maternal car-riage and neonatal acquisition of group B streptococci.J Infect Dis.1982;145:800 – 803
39. Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative.BMJ.2003;326:41– 44
40. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assess-ment of studies of diagnostic accuracy included in systematic reviews.BMC Med Res Methodol.2003;3:25
41. Lijmer JG, Mol BW, Heisterkamp S, et al. Empirical evidence of design-related bias in studies of diagnostic tests.JAMA.1999; 282:1061–1066
42. Baker CJ, Clark DJ, Barrett FF. Selective broth medium for isolation of group B streptococci. Appl Microbiol. 1973;26: 884 – 885
43. Fenton LJ, Harper MH. Evaluation of colistin and nalidixic acid in Todd-Hewitt broth for selective isolation of group B strep-tocci.J Clin Microbiol.1979;9:167–169
44. Lachs MS, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection.Ann Intern Med.1992;117:135–140
45. Song F, Sheldon TA, Sutton AJ, Abrams KR, Jones DR. Meth-ods for exploring heterogeneity in meta-analysis.Eval Health Prof.2001;24:126 –151
46. Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F. Sys-tematic reviews of trials and other studies.Health Technol Assess.
1998;2:1–276
47. Honest H, Bachmann LM, Gupta JK, Kleijnen J, Khan KS. Accuracy of cervicovaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systematic review. BMJ.
2002;325:301
48. Honest H, Bachmann LM, Coomarasamy A, Gupta JK, Kleijnen J, Khan KS. Accuracy of cervical transvaginal sonography in predicting preterm birth: a systematic review.Ultrasound Obstet Gynecol.2003;22:305–322
49. Rutter CM, Gatsonis CA. Regression methods for meta-analysis of diagnostic test data.Acad Radiol.1995;2(suppl 1):S48 –S56; discussion S65–S67, S70 –S71
50. Thompson SG, Higgins JP. How should meta-regression anal-yses be undertaken and interpreted? Stat Med. 2002;21: 1559 –1573
51. van Houwelingen HC, Arends LR, Stijnen T. Advanced meth-ods in analysis: multivariate approach and meta-regression.Stat Med.2002;21:589 – 624
52. Song F, Khan KS, Dinnes J, Sutton AJ. Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accu-racy.Int J Epidemiol.2002;31:88 –95
53. Davies HD, Miller MA, Faro S, Gregson D, Kehl SC, Jordan JA. Multicenter study of a rapid molecular-based assay for the diagnosis of group B Streptococcus colonization in pregnant women.Clin Infect Dis.2004;39:1129 –1135
54. Baker CJ. Inadequacy of rapid immunoassays for intrapartum detection of group B streptococcal carriers.Obstet Gynecol.1996; 88:51–55
55. Carroll KC, Ballou D, Varner M, Chun H, Traver R, Salyer J. Rapid detection of group B streptococcal colonization of the genital tract by a commercial optical immunoassay.Eur J Clin Microbiol Infect Dis.1996;15:206 –210
57. Park CH, Ruprai D, Vandel NM, Hixon DL, Mecklenburg FE. Rapid detection of group B streptococcal antigen from vaginal specimens using a new Optical ImmunoAssay technique.Diagn Microbiol Infect Dis.1996;24:125–128
58. Rosa C, Clark P, Duff P. Performance of a new DNA probe for the detection of group B streptococcal colonization of the genital tract.Obstet Gynecol.1995;86:509 –511
59. Ryan KM, Lencki SG, Elder BL, Northern WI, Khamis HJ, Bofill JA. DNA probe for beta-hemolytic group BStreptococcus. Diag-nostic accuracy in threatened preterm labor. J Reprod Med.
1999;44:587–591
60. Armer T, Clark P, Duff P, Saravanos K. Rapid intrapartum detection of group B streptococcal colonization with an en-zyme immunoassay.Am J Obstet Gynecol.1993;168:39 – 43 61. Gentry YM, Hillier SL, Eschenbach DA. Evaluation of a rapid
enzyme immunoassay test for detection of group B Strepto-coccus.Obstet Gynecol.1991;78:397– 401
62. Greenspoon JS, Fishman A, Wilcox JG, Greenspoon RL, Lewis W. Comparison of culture for group BStreptococcusversus en-zyme immunoassay and latex agglutination rapid tests: results in 250 patients during labor.Obstet Gynecol.1991;77:97–100 63. Hagay ZJ, Miskin A, Goldchmit R, Federman A, Matzkel A,
Mogilner BM. Evaluation of two rapid tests for detection of maternal endocervical group B Streptococcus: enzyme-linked immunosorbent assay and gram stain.Obstet Gynecol.1993;82: 84 – 87
64. Simpson AJ, Mawn JA, Heard SR. Assessment of two methods for rapid intrapartum detection of vaginal group B strepto-coccal colonisation.J Clin Pathol.1994;47:752–755
65. Brady K, Duff P, Schilhab JC, Herd M. Reliability of a rapid latex fixation test for detecting group B streptococci in the genital tract of parturients at term. Obstet Gynecol. 1989;73: 678 – 681
66. Clark P, Armer T, Duff P, Davidson K. Assessment of a rapid latex agglutination test for group B streptococcal colonization of the genital tract.Obstet Gynecol.1992;79:358 –363
67. Green M, Dashefsky B, Wald ER, Laifer S, Harger J, Guthrie R. Comparison of two antigen assays for rapid intrapartum detec-tion of vaginal group B streptococcal colonizadetec-tion.J Clin Micro-biol.1993;31:78 – 82
68. Isada NB, Grossman JH, III. A rapid screening test for the diagnosis of endocervical group B streptococci in pregnancy: microbiologic results and clinical outcome.Obstet Gynecol.1987; 70:139 –141
69. Stiller RJ, Blair E, Clark P, Tinghitella T. Rapid detection of vaginal colonization with group B streptococci by means of latex agglutination.Am J Obstet Gynecol.1989;160:566 –568 70. Wang E, Richardson H. A rapid method for detection of group
B streptococcal colonization: testing at the bedside. Obstet Gynecol.1990;76:882– 885
71. McManus RJ, Wilson S, Delaney BC, et al. Review of the usefulness of contacting other experts when conducting a lit-erature search for systematic reviews.BMJ. 1998;317:1562– 1523
72. Fryback DG, Thornbury JR. The efficacy of diagnostic imaging.
Med Decis Making.1991;11:88 –94
73. Guyatt GH, Tugwell PX, Feeny DH, Haynes RB, Drummond M. A framework for clinical evaluation of diagnostic technologies.
CMAJ.1986;134:587–594
74. Dawid AP. Properties of diagnostic data distributions. Biomet-rics.1976;32:647– 658
75. Miettinen OS, Henschke CI, Yankelevitz DF. Evaluation of diagnostic imaging tests: diagnostic probability estimation.
DOI: 10.1542/peds.2005-1114
2006;117;1055
Pediatrics
Honest Honest, Sushma Sharma and Khalid S. Khan
Systematic Review
Colonization in Laboring Women: A
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Rapid Tests for Group B
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