Streptococcus B in pregnancy: to screen or not to screen?
BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e2803 (Published 18 April 2012) Cite this as: BMJ 2012;344:e2803All rapid responses
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Thank you for the responses. My primary interest in writing this piece was to examine several press stories covering Strep B screening. The problem is that many of the features in the lay press outlined the benefits but did not look at limitations and potential harms: this was and is remains important if we are to have a debate about screening for it. The one sided argument has regrettably taken place in the lay press; this article sought to address that.
Competing interests: I wrote the article
We were disappointed that a number of myths about Group B Strep screening were reiterated in the article “Streptococcus B in pregnancy: to screen or not to screen?”1
Dr McCartney is concerned that alongside the very apparent potential benefits of screening, the potential limitations and harms are also raised. Clearly any decision about screening should consider both. However, there are some statements in the article with which we take issue:
1. Risk of fatal anaphylaxis “The risks of antibiotic use include anaphylaxis, which is thought to be fatal in one in 10,000 women treated” is an unreferenced statement taken from the UK National Screening Committee’s 2008 review of antenatal screening for group B Streptococcus2. Potentially fatal anaphylaxis is clearly a risk but extremely rare. Law et al3 reported that 1.8 million women in the US will have been given benzylpenicillin (or ampicillin) between 1997 and 2001 and no deaths from anaphylaxis were reported. Furthermore, a review of UK data by the same authors showed no adverse drug reactions in a population of 630,000 over 6 months that were attributable to benzylpenicillin and they stated that "It can be concluded that the risk of death is negligible." Fatal anaphylaxis, although of concern, is a tiny risk.
2. Concerns about the use of broad spectrum antibiotics “Broad spectrum antibiotics lead to resistant organisms” and “The potential for long-term persistence of early-colonising bacteria suggests that much more thought should be given to the late consequences of perinatal broad-spectrum antibiotics.” This issue is of huge concern to many, including the charity’s medical advisory panel, one of whom co-authored one of the articles you quote4. The authors have written to the BMJ separately to provide the appropriate context for that statement.
3. Antibiotic resistance Studies in the USA5;6 have not shown an increase in antibiotic resistance in response to using antibiotics for early onset GBS prophylaxis except in very low birth weight babies7;8. In the latter, increased incidence of resistant E.coli infection was identified in babies whose mothers were given amoxicillin as intrapartum antibiotic prophylaxis. Anxieties raised by the ORACLE II study follow-up findings of an impaired outcome at the age of seven9 (an increase in cerebral palsy) applied only to the babies of women in threatened preterm labour given broad spectrum antibiotics (erythromycin 250mg qds orally) for up to 10 days, not high dose intravenous benzylpenicillin for 4-12 hours to women in established labour (The ORACLE I study of antibiotics given to women with ruptured membranes did not demonstrate any functional impairment at the age of 710).
4. Preterm labour Although it is true that “in several of the case studies in the media stories, the screening test for streptococcus B would not have helped,” the policy recommended by cost benefit analyses is not just to screen at 35-37 weeks, but to give benzylpenicillin to all women in preterm labour as well11-13. This is also the policy in countries which do screen, including the US14, Australia15, France16 and Spain17 which on average have seen a reduction in their incidence of early onset GBS infection of over 80%18.
5. Universal screening vs risk management “it may be that risk management rather than universal screening is more beneficial but will require nuanced discussion.” Perhaps, although research looking at just this issue repeatedly finds universal screening would be more cost effective and more clinically effective in the UK than the risk based strategy11-13;19 and these papers do not include in their analysis the fact that the Royal College of Obstetricians & Gynaecologists’s 2003 guideline20 is inconsistently applied21. A recently published UK study has shown that 81% of mothers who should have been offered intrapartum antibiotic prophylaxis because of risk factors did not receive it, and the authors estimated that 48% of babies who suffered EOGBS infection could have had their disease prevented22. Perhaps part of the problem with the risk-based strategy is that it is too complex – to be effective any strategy needs to be both easy to understand and easy to implement.
Despite pointing out that the media often don’t mention the potential harms of screening, Dr McCartney omitted to mention one of its key benefits - the major falls seen in the incidence of early onset GBS disease in all western countries which have introduced screening14-17. We know of no country presenting before and after data that has not shown a substantial reduction in the incidence after screening was introduced. In contrast, in the UK the incidence of EOGBS infection has risen since the risk-based prevention guidelines were introduced by the Royal College of Obstetricians & Gynaecologists in 200320 and is continuing to do so. The Health Protection Agency has found that voluntarily reported cases in England, Wales and Northern Ireland have risen from 229 in 200323 to 302 in 201024. The incidence of EOGBS disease in England, Wales & Northern Ireland is now 0.41 per 1,000 live births, which is higher than the USA post-universal screening (0.34 per 1,000 live births in 200814).
It is in no-one’s interest to present a one-sided argument. It is vital that the issues surrounding screening are fully explored, although perhaps we can’t expect newspapers to cover all the arguments in detail. However, when the pros and cons are explored, it is imperative that the information about potential harms and potential benefits is equally accurate. The UK National Screening Committee will be issuing their review of GBS screening for public consultation in June 2012. All of us should ensure that the relevant issues – for and against – are considered appropriately, backed up by research. The UK National Screening Committee has recently deemed it appropriate to pilot screening for Maple Syrup urine disease which may save 7 lives a year (http://www.bbc.co.uk/news/health-17628169), which makes it even more illogical not to screen for GBS which has a higher incidence and mortality.
At GBSS, we want women to be given accurate and timely information about group B Strep and offered the opportunity to have a sensitive test for GBS carriage late in pregnancy. Women should not be forced to have GBS screening, but all should be entitled to accurate and balanced information, the offer of a sensitive test, and the option to say yes or no. Wouldn't it be great if we could agree evidence-based information and then give women a proper choice? Revolutionary, even.
Reference List
(1) McCartney M. Streptococcus B in pregnancy: to screen or not to screen? BMJ 2012; 344:e2803.
(2) Brocklehurst P, Kenyon SL, for UK National Screening Committee. Evaluation of antenatal screening for Group B Streptococcal (GBS) carriage against NSC Handbook Criteria . 8-10-2008.
(3) Law MR, Palomaki G, Alfirevic Z, Gilbert R, Heath P, McCartney C et al. The prevention of neonatal group B streptococcal disease: a report by a working group of the Medical Screening Society. J Med Screen 2005; 12(2):60-68.
(4) Bedford Russell AR, Murch SH. Could peripartum antibiotics have delayed health consequences for the infant? BJOG 2006; 113(7):758-765.
(5) Prevention of Perinatal Group B Streptococcal Disease, Revised Guidelines from CDC, 2010. Recommendations and Reports. November 19, 2010 / 59(RR10);1-32. 30-12-2010.
(6) Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Ped 2011; 127(5):817-826.
(7) Stoll BJ, Hansen NI, Higgins RD, Fanaroff AA, Duara S, Goldberg R et al. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J 2005; 24(7):635-639.
(8) Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med 2002; 347(4):240-247.
(9) Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt A et al. Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet 2008; 372(9646):1319-1327.
(10) Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N, Salt A et al. Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial. Lancet 2008; 372(9646):1310-1318.
(11) Colbourn TE, Asseburg C, Bojke L, Philips Z, Welton NJ, Claxton K et al. Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. BMJ 2007; 335(7621):655.
(12) Colbourn T, Asseburg C, Bojke L, Philips Z, Claxton K, Ades AE 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; 11(29):1-226, iii.
(13) Kaambwa B, Bryan S, Gray J, Milner P, Daniels J, Khan KS et al. Cost-effectiveness of rapid tests and other existing strategies for screening and management of early-onset group B streptococcus during labour. BJOG 2010; 117(13):1616-1627.
(14) Jordan HT, Farley MM, Craig A, Mohle-Boetani J, Harrison LH, Petit S et al. 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(12):1057-1064.
(15) Daley AJ, Isaacs D. Ten-year study on the effect of intrapartum antibiotic prophylaxis on early onset group B streptococcal and Escherichia coli neonatal sepsis in Australasia. Pediatr Infect Dis J 2004; 23(7):630-634.
(16) Albouy-Llaty M, Nadeau C, Descombes E, Pierre F, Migeot V. Improving perinatal Group B streptococcus screening with process indicators. J Eval Clin Pract 2011.
(17) Andreu A, Sanfeliu I, Vinas L, Barranco M, Bosch J, Dopico E et al. [Decreasing incidence of perinatal group B streptococcal disease (Barcelona 1994-2002). Relation with hospital prevention policies]. Enferm Infecc Microbiol Clin 2003; 21(4):174-179.
(18) Rodriguez-Granger J, Alvargonzalez JC, Berardi A, Berner R, Kunze M, Hufnagel M et al. Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project. Eur J Clin Microbiol Infect Dis 2012.
(19) Daniels JP, Gray J, Pattison HM, Gray R, Hills RK, Khan KS. Intrapartum tests for group B streptococcus: accuracy and acceptability of screening. BJOG 2011; 118(2):257-265.
(20) RCOG. Royal College of Obstetricians and Gynaecologists (2003) RCOG Guideline No. 36. Prevention of early onset neonatal group B streptococcal disease. http://www rcog org uk/files/rcog-corp/uploaded-files/GT36GroupBStrep2003 pdf [ 2003 Available from: URL:http://www.rcog.org.uk/files/rcog-corp/uploaded-files/GT36GroupBStrep200...
(21) Royal College of Obstetricians and Gynaecologists andLondon School of Hygiene and Tropical Medicine. The prevention of early-onset neonatal group B streptococcus disease in UK obstetric units. www rcog org uk/files/rcog-corp/uploaded-files/neonatal_audit_full_250507 pdf [ 2007 Available from: URL:www.rcog.org.uk/files/rcog-corp/uploaded-files/neonatal_audit_full_25050...
(22) Vergnano S, Embleton N, Collinson A, Menson E, Russell AB, Heath P. Missed opportunities for preventing group B streptococcus infection. Arch Dis Child Fetal Neonatal Ed 2010; 95(1):F72-F73.
(23) CDR Weekly. Pyogenic and non-pyogenic streptococcal bacteraemia England Wales and Northern Ireland. 2003. CDR Weekly 14 No 16. 2004.
(24) Health Protection Agency. Pyogenic and non-pyogenic streptococcal bacteraemia, England, Wales and Northern Ireland: 2010. Health Protection Agency Report 2011; 5(46).
Competing interests: Professor Philip Steer, Dr Alison Bedford Russell, Dr A Christine McCartney OBE, and Ms Philippa Cox form the medical advisory panel of the charity Group B Strep Support
Margaret McCartney’s article on screening for group B streptococcus in pregnancy quotes from our 2006 review (originally instigated by a request from the National Screening Committee) concerning potential long term impacts of broad-spectrum antibiotics on immune and metabolic development of the infant (1). Indeed, since we performed this review, there has been substantial further evidence to show that specific gut bacteria (eg bacteroides, clostridia sp. in mice) are specifically required for development of regulatory T cells within the infant host (2), while other bacteria may promote excess weight gain (3,4). Therefore acquired perinatal dysbiosis may indeed have long term impacts.
While these studies, admittedly so far mostly from animal models, should provoke caution in the widespread perinatal use of broad-spectrum antibiotics, the situation is much simpler for group B streptococcal (GBS) disease. The balance of risks clearly favours administration of a narrow-spectrum antibiotic to which GBS is highly sensitive. Intrapartum antibiotic prophylaxis with benzyl penicillin allows effective eradication of this common and frequently lethal neonatal infection, with a much lesser likelihood of long term impact upon perinatal imprinting events mediated by the normal flora. This benefit-risk calculation is less favourable for other commonly used broad spectrum antibiotics, the chief offenders being erythromycin, amoxicillin and cefotaxime, either potentially less effective against GBS because of emerging resistance (5) or substantially more disruptive of intestinal ecology as well as promoting emergence of antibiotic resistant gram-negative pathogens within a neonatal unit (6-8).
We stand by our conclusion from 2006 (1) that “The classic microbiological dictum, of never using a broad-spectrum antibiotic when a narrow-spectrum one will do, has probably a unique resonance for the perinatologist.” But that does not exclude supporting the use of an appropriate targeted narrow-spectrum antibiotic to prevent death or serious illness.
References
1. Bedford Russell AR, Murch SH. Could peripartum antibiotics have delayed health consequences for the infant? BJOG 2006;113:758-765.
2. Barnes MJ, Powrie F. Immunology. The gut's Clostridium cocktail. Science 2011; 331: 289-90.
3. Blaser M. Antibiotic overuse: Stop the killing of beneficial bacteria. Nature 2011; 476 :393-394.
4. Ajslev TA, Andersen CS, Gamborg M, Sørensen TI, Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes (Lond) 2011; 35: 522-529.
5. Garland SM, Cottrill E, Markowski L, et al. Antimicrobial resistance in group B streptococcus: the Australian experience. J Med Microbiol 2011; 60: 230-235.
6. de Man P, Verhoeven BA, Verbrugh HA, Vos MC, van den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet 2000; 355: 973-978.
7. Stoll BJ, Hansen N, Fanaroff AA, et al 2002. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med 2002; 347: 240-247.
8. Stoll BJ, Hansen NI, Higgins RD, et al. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J 2005; 24: 635-639.
Competing interests: ABR is Paediatric Adviser to Group B Strep Support and has been an adviser to the National Screening Commitee on Group B streptococcus.
As Margaret McCartney points out, screening for Group B streptococcus at 35-37 weeks omits the preterm babies most at risk of this infection. An additional problem is that carriage of the organism during pregnancy is intermittent, so women found to be colonised at 35-37 weeks can be negative at the time of labour, and vice versa.(1)
A solution is the use of rapid molecular testing for Group B streptococcus when women present in labour. PCR-based testing has shown 98.5% sensitivity and 99.6% specificity when compared with conventional culture, with results available within 75 minutes. (2) As point-of-care tests they could be performed by midwifes or healthcare assistants rather than needing laboratory staff and results would be available 24/7.
This approach, compared with the 35-37 week screening strategy, would better prevent neonatal Group B streptococcus infection from colonised women and avoid unnecessary antibiotic prophylaxis in non-colonised women.
1. Goodman JR, Berg RL, Gribble RK et al. Longitudinal study of group B streptococcus carriage in pregnancy. Infect Dis Obstet Gynecol. 1997;5:237-43
2. El Helali N, Nguyen J-C, Ly A, Giovangrandi Y, Trinquart L. Diagnostic accuracy of a rapid real-time polymerase chain reaction assay for universal intrapartum Group B streptococcus screening. Clin Infect Dis 2009;49:417-23
Competing interests: No competing interests
I read with interest the discussion of McCartney (1) on the screening of Streptococcus B in pregnancy. This discussion followed a death of a newborn infected by a Streptococcus B. Her mother did not benefit from antepartum screening of streptococcus B.
In France, the screening of Streptococcos B in the vagina is recommended at the end of the third trimester of pregnancy (34-37 weeks of gestation). The results of the test are obtained in 48 hours.
Implications of this screening are that women who have Streptococcus B in their vagina, will have an antibiogramme and will know the best antibiotic adapted to their situation. Usually there is no antepartum treatment as this treatment does not prevent recurrences. Until labour starts women with vaginal Streptococus B had antibiotics (usually Penicillin G or A in the absence of known allergy) to protect the foetus against genital ascendant infection when the amniotic membranes rupture. The antibiotics are stopped postnatally if there are no signs of infection in the newborn. The second advantage is that women with vaginal Streptococcus B will benefit from induced labour if the amniotic membranes are prematurely ruptured as the foetus is exposed to ascending genital infection.
Preterm contractions are not an argument against screening for Streptococcus B. Indeed, cultures of vaginal swab samples are done at the same time as tocolysis and the delivery rarely occurs before the results of vaginal cultures. Moreover, the majority of deliveries do not occur before term.
Anaphylaxis with penicillin in the absence of previous allergy is exceptional. In the case of allergy to penicillin, we could prescribe macrolides.
The most used antibiotics is penicillin. Antibiotics are prescribed for a short period, therefore assumptions on asthma, gut flora and immune system are not founded. They are preferable to severe infection of the newborn and the threat to his or her life. Screening for Streptococcus B is also recommended in the United States where the streptococcus is screened in the vagina and also in the anus.
As foetal infections by streptococcus B are severe and threaten the baby’s life, antepartum screening of Streptococcus B is effective and recommended.
References
1. McCartney M. Streptococcus B in pregnancy: to screen or not to screen? BMJ. 2012 Apr 18;344:e2803. doi: 10.1136/bmj.e2803.
Competing interests: No competing interests
There is currently no universal screening tool offered in the UK in the NHS for the detection of Streptococcus B in pregnancy.
This is primarily because the available screening tools are not highly sensitive for detection and not highly specific for complete exclusion of the condition in pregnancy.
The other concern is the accurate timing to offer the screening tool, if we offer around 35-37 weeks gestation this only forms a subgroup of the pregnant women in the population and may not completely cover all the women with carrier status.
The current screening tool may take 16-72hours before a report is available to treat the patient, this may not be practical for a patient who is in labour.
The other concern is that when screened and treated with intrapartum antibiotics this will only reduce the risk of early onset neonatal Group B Streptococcal (GBS) infection. Early onset GBS (0-6days) tend to be associated with pneumonia and septicaemia and the mechanism maybe birth related like ascending infection from maternal genital tract. However the late onset GBS (7-90 days) is more likely associated with meningitis and the associated acquisition is through vertical or nosocomial transmission.
Therefore, if we had a perfect screening tool with a high sensitivity and specificity and a reliable beside test available, this could eradicate early onset GBS neonatal infection.
References.
1 Royal College of Obstetricians and Gynaecologists. Prevention of early onset neonatal Group B
Streptococcal disease.
2 http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317132860736
Competing interests: No competing interests
Re: Streptococcus B in pregnancy: to screen or not to screen?
Group B streptococci (GBS) are the leading cause of life-threatening neonatal bacterial infections in developed countries1. Taking a cue from a study wayback in 1989 by Kollee et al, we suggest that in order to avoid various problems of antibiotics (resistance, systemic side effects including diarrhea, anaphylaxis etc) we must give local antiseptics like chlorhexidine or say, Povidone Iodine.
10 ml of a chlorhexidine gel containing hydroxypropylmethylcellulose was introduced into the vagina during labor in 17 parturients, who were known to be carriers of groupBstreptococci from the first trimester of pregnancy2. In none of the newborns from these mothers colonization by groupBstreptococci did occur. Vaginal application of chlorhexidine may prevent transmission of groupBstreptococci, and serve as an alternative to intrapartum prophylaxis using antibiotics2. A large multicenter randomized controlled study should be performed to confirm this hypothesis2. It is also accepted that pregnant women should avoid douching. Intrapartum vaginal antiseptic lavage can be highly beneficial, but this is a completely different irrigation event than repetitive vaginal douching which can lead to ascending infection to birth canal3.
References:
1. [No authors listed] Preventing neonatal group B streptococcal infection. Intrapartum antibiotic prophylaxis in some high-risk situations.Prescrire Int. 2011 Mar;20(114):72-7.
2. Kollée LAA, I. Speyer van Kuijck M.A.P 1, R. Koopman1,European Journal of Obstetrics & Gynecology and ReproductiveBiology Volume 31, Issue 1, April 1989, Pages 47–51.
3. Martino JL and Vermund SH. Epidemiologic Reviews, Volume 24, Issue 2, Pp. 109-124.
Competing interests: No competing interests