1. Preventing early-onset group B Streptococcal infection in newborn babies July 2009 Charity No. 1112065 Company Reg No 5587535

2. 2 Talk outline  Background  How can we reduce risk of GBS infection  Different tests available  International practice  UK practice  Research

3. Charity No. 1112065 Company Reg No 5587535 3 Group B Strep Support – when & why Registered charity set up in 1996 Funded by donations Objectives:  To inform health professionals & individuals how to prevent most EOGBS infection;  To offer information and support to families affected by GBS; and  To general continued support for research into preventing GBS infection Theo Plumb, 19-20 March 1996

4. Charity No. 1112065 Company Reg No 5587535 4 Group B Strep Support: what we do www.gbss.org.uk 01444 416176  Information materials  6 Leaflets  4 Posters  2 Stickers  Powerpoint

5. Charity No. 1112065 Company Reg No 5587535 5 Key References www.gbss.org.uk => Links => Research Papers www.gbss.org.uk

6. Charity No. 1112065 Company Reg No 5587535 6 GBSS Medical Advisory Panel  Professor Philip Steer, BSc, MD, FRCOG (Chair) Emeritus professor at Imperial College and consultant obstetrician at the Chelsea & Westminster Hospital in London  Dr Alison Bedford-Russell MRCP Consultant Neonatologist, Birmingham Heartlands Hospital  Dr A Christine McCartney OBE FRCPath Director, Regional Microbiology Network, Health Protection Agency Central Office

7. Charity No. 1112065 Company Reg No 5587535 7 Group B Streptococcus – background  Streptococcus agalactiae Group B Strep, Strep B, beta haemolytic Strep, GBS  Colonisation Intestinal (up to 30% of adults) & vaginal (up to 25% of women) Asymptomatic May be intermittent 90% of adults possess no protective antibodies to GBS  Infection Infections in adults: the elderly, pregnant women, others with other disease Most common cause of life-threatening infection in newborn babies  Underlying rate ~ 1/1000 live births overall  (Luck et al early-onset incl probable 3.6/1000, Lancet 2003)  60 babies a month develop GBS infection – 7 die & 3 suffer long term problems  More common than Sickle Cell & Thalassaemia, Hepatitis B, Syphilis, Spina bifida, Downs syndrome, HIV … all of which we screen for

8. Charity No. 1112065 Company Reg No 5587535 8 GBS infection in babies Early Onset  Up to 80% of GBS infection in babies  0-6 days (usually <24 hours)  Usually septicaemia, also meningitis & pneumonia 11% die Relatively high (1-3%) recurrence Late Onset  Up to 20% of GBS infection in babies  7+ days (rare after 3 months)  Usually meningitis with septicaemia 5% die 50% of GBS meningitis survivors have neurological sequelae

9. Charity No. 1112065 Company Reg No 5587535 9 Reducing risk of GBS infection in babies 1  Late onset GBS infection No medical intervention proven to prevent Good hygiene Education / alert In future – vaccination of women before/during pregnancy  At least a decade away due to medico-legal issues  Will prevent EO/LO and adult GBS infection

10. Charity No. 1112065 Company Reg No 5587535 10 Reducing risk of GBS infection in babies 2  Early onset GBS infection Intrapartum antibiotic prophylaxis (IAP)  Only proven effective method of prevention available  Largest study Chicago (Boyer et al. N Eng J Med 1986;314:1665) Oral antibiotics  No evidence it reduces EOGBS infection  Used to treat GBS in urine Intramuscular antibiotics before labour  May eradicate GBS colonisation for up to 6 weeks  Small studies – reduction of colonisation to 52% & 25% in treated group (87% and 82% in controls - Pinette et al 2005, Bland et al 2000)  no GBS infection in control or treated group Vaginal flushing with chlorhexidine  No evidence it reduces EOGBS infection

11. Charity No. 1112065 Company Reg No 5587535 11 Recognised risk factors for EOGBS infection  Previous baby with GBS infection x 10  GBS bacteriuria during pregnancy x 4  Intrapartum fever x 3  Preterm labour x 3  Prolonged rupture of membranes x 3  Maternal GBS colonisation during pregnancy x 4 But … there’s no way to know a woman is carrying GBS unless we look for it

12. Charity No. 1112065 Company Reg No 5587535 12 Testing for GBS carriage 1  When to swab? Before 35 weeks of pregnancy 35-37 weeks of pregnancy Intrapartum  Where to swab? (not speculum) High vaginal swab Low vaginal swab Low vagina & anorectal swab/s (>30% more effective than vaginal or cervical alone)  Who to swab? Health care professional Pregnant woman  What culture method to use? Direct agar plate - 24-48 hours to grow culture in lab Selective Enriched Culture Medium (ECM) - 24-48 hours to grow culture in lab Polymerase Chain Reaction (PCR) – minutes to hours to grow culture  PCR requires special equipment and special training

13. Charity No. 1112065 Company Reg No 5587535 13 Testing for GBS carriage 2  NHS – not routine but if offered: 35+ weeks of pregnancy High vaginal swab, sometimes using speculum Direct agar plating to culture  Misses up to 50% of carriers (many false negatives)  Positive result highly reliable  Handful of NHS hospitals + privately (~£32) - ECM test: 35+ weeks of pregnancy Low vaginal and anorectal swab Enriched culture medium  1-5 weeks of delivery, 87% +ve, 96% -ve, Yancey et al  Private – PCR (not validated for use in UK) 35+ weeks of pregnancy, potentially intrapartum Low vaginal and rectal swab Approved by FDA & Health Canada & bears CE mark for Europe  Very close to 100% ECM test is optimal for detecting GBS carriage (RCOG Greentop 36 & HPA BSOP58)

14. Charity No. 1112065 Company Reg No 5587535 14 Who should be offered intrapartum antibiotic prophylaxis? Women with recognised risk factors: 50-60% cases prevented* GBS carriers this pregnancy: 80-90% cases prevented* GBS carriers this pregnancy who have risk factors: <50% cases prevented* GBS carriers this pregnancy AND also women who have risk factors: >80-90% cases prevented *Maternal screening to prevent neonatal Group B streptococcal disease. J Med Screen 2002;9:191

15. Charity No. 1112065 Company Reg No 5587535 15 UK – RCOG guideline summary 1 RCOG Green Top Guideline No 36 issued November 2003  Antenatal Routine screening for GBS not recommended Antenatal treatment with penicillin is not recommended  Intrapartum Clinicians should discuss the use of IAP in the presence of known risk factors including incidental carriage. Risk factors include  Prematurity < 37 weeks  prolonged rupture of membranes >18 hours  fever in labour > 38C The argument for prophylaxis becomes stronger for >= 2 risk factors. IAP should be considered if GBS is detected incidentally in the vagina or the urine in the current pregnancy IAP offered to women with a previous baby with neonatal GBS disease.

16. Charity No. 1112065 Company Reg No 5587535 16 UK – RCOG guideline summary 2 RCOG Green Top Guideline No 36 issued November 2003  Intrapartum (cont) No good evidence to support IAP to women in whom GBS carriage was detected in a previous pregnancy or undergoing planned C-section. IAP unnecessary for women with preterm rupture of membranes unless they are in established labour. IAP regime is Penicillin G as soon as possible after the onset of labour and at least 2 hours before delivery.  3g Penicillin G given intravenously, then 1.5g every 4 hours during labour.  Intravenous clindamycin 900mg 8–hourly for penicillin allergic women. If chorioamnionitis is suspected, broad-spectrum antibiotic therapy including an agent active against GBS should replace GBS-specific antibiotic prophylaxis

17. Charity No. 1112065 Company Reg No 5587535 17 Reported cases of GBS bacteraemia in infants*, England & Wales 2000-2007 Source: Health Protection Agency, 2008 *excludes a small number of infants with imprecise age data

18. Charity No. 1112065 Company Reg No 5587535 18 What happens in the UK – RCOG audit 1  89% of the 227 units responded  78% of protocols offered risk based IAP  22% recommended a risk-based bacteriological testing strategy Previous GBS baby (Offer) 159 93% Bacteriuria in current pregnancy (Offer) 146 85% Incidental GBS in current pregnancy (Offer) 144 84% Fever during labour > 38°C (Discuss) 104 61% Prolonged ROM 18 hours or over (Discuss) 89 52% Preterm labour less than 37 weeks (Discuss) 84 49% Suspected chorioamnionitis (Offer) 66 39% Maternal GBS carriage before pregnancy (No) 29 17% RCOG Audit of reported practice in England, Scotland, Wales and Northern Ireland – January 2007

19. Charity No. 1112065 Company Reg No 5587535 19 What happens in the UK – RCOG audit 2  34 united specified prolonged ROM as >24 hours (instead of 18 hours)  6/29 units giving guidance on the timing of testing used the recommended 35–37 week period.  4/31 units giving guidance on swab sites for testing recommended low vagina & anorectal  No protocol recommended the use of an enriched culture medium  26% gave variant antibiotic regimes for IAP RCOG Audit of reported practice in England, Scotland, Wales and Northern Ireland – January 2007 “The variation in the protocol recommendations would not be of concern if it had been clearly linked to local circumstances or published evidence. This did not appear to be the case.” RCOG Audit

20. Charity No. 1112065 Company Reg No 5587535 20 What happens in the UK – GBSS understanding 1  Most pregnant women know little about GBS Not part of routine antenatal care / limited info available from their health professionals ECM test not widely available, or even mentioned ….  Women want to be informed about GBS and be offered the option of a sensitive GBS test: (GBSS online survey, 693 participants so far) 97% - all pregnant women should be routinely informed about GBS by their doctor or midwife 96% - all women should be routinely offered a sensitive test for GBS late in pregnancy 96% would do a sensitive test if offered freely on the NHS 97% - pregnant women should be told about the private GBS test  15% would be happy to pay for it  74% would be willing to pay for it though believe it should be free on the NHS  11% would not be willing to pay for it  Most NHS hospitals don’t offer ECM testing Most health professionals don’t realise the NHS test is inferior to the ECM test ECM testing is pretty much only available privately … but you’ll only get it if you know about it Huge variability in knowledge about GBS

21. Charity No. 1112065 Company Reg No 5587535 21 What happens in the UK – GBSS understanding 2  Many health professionals aren’t fully informed about GBS You can’t have a water birth if you carry GBS It’s an STD … where did you get that from? Once a carrier, always a carrier - you’ll always need IAP in labour now It’s nothing to worry about – it’s topic of the month just now It comes and goes so often it’s not worth testing for The NHS test for GBS is just as good as the private test We’ll do several tests for you – it’ll pick up GBS on one of them if it’s there We’ll give the baby antibiotics after he’s born and he’ll be fine You’ll have to be attached to a drip and monitored throughout your labour You only need IAP for the last 4 hours before delivery, so don’t come to hospital till then Your baby will..... die / be brain damaged / stillborn Oral antibiotics will get rid of carriage … we’ll just keep treating it until it does We don’t treat GBS in the urine now … you just need antibiotics in labour Until we’ve got rid of it, you mustn’t … get pregnant / have sex / breastfeed your baby / give blood Well, they would recommend a private test – they’re on commission ….

22. Charity No. 1112065 Company Reg No 5587535 22 Petitions to Prime Minister Response: Current policy, based on advice from the UK National Screening Committee (UKNSC), the Royal College of Obstetricians and Gynaecologists (RCOG) and the National Institute for Health and Clinical Excellence (NICE), is not to offer routine screening for GBS to all pregnant women because there is insufficient evidence to demonstrate that the benefits of doing so would outweigh the harm. In line with the RCOG guideline on early onset (EO) GBS infection, healthcare professionals are encouraged to use clinical risk factors to identify women whose infants are at increased risk of developing EO GBS infection. Petitions to the Prime Minister asking for all women to have the chance to be tested for Group B Strep

23. Charity No. 1112065 Company Reg No 5587535 23 UK Bodies - Summary  RCOG Green Top Guideline No 36 November 2003 – being reviewed, hopefully due 2010/1  UK National Screening Committee – next review December 2009 Screening for this condition should not be offered.  National Institute for Clinical Excellence Antenatal Care: routine care for the healthy pregnant woman 2003 – next review March 2011. Reviewed March 2008 (no updates to the GBS sections despite requests from a number of stakeholders) Pregnant women should not be offered routine antenatal screening for group B streptococcus because evidence of its clinical and cost- effectiveness remains uncertain. Pregnant women should be offered information based on the current available evidence together with support to enable them to make informed decisions about their care. How can women make an informed decision if they’re not being informed?

24. Charity No. 1112065 Company Reg No 5587535 24 What do other countries do?  ECM testing: USA, Canada, France, Belgium, Germany, Slovenia, Spain, Czech Republic, Bulgaria, Italy, Australia  All research where screening introduced shows reduction >70% in EOGBS infection incidence since testing introduced  Risk factor strategy: New Zealand  BUT women can opt for ECM testing in pregnancy  Combined risk factors PLUS testing None All countries which have introduced testing for GBS and intrapartum antibiotic prophylaxis have seen significant falls in their incidence of neonatal GBS infection

25. Charity No. 1112065 Company Reg No 5587535 25 What do other countries do? Schrag, New Engl J Med 2000 342: 15-20 Incidence of EO and LO GBS in 3 active surveillance areas in USA

26. Charity No. 1112065 Company Reg No 5587535 26 Research – cost effectiveness 1 BMJ. 2007 Sep 29;335(7621):655

27. Charity No. 1112065 Company Reg No 5587535 27 Research – cost effectiveness 2 Colbourn et al BMJ. 2007 Sep 29;335(7621) Baby life years saved Costs compared with current practice

28. Charity No. 1112065 Company Reg No 5587535 28 Research – cost effectiveness 3  Current best practice in the UK is clearly not cost effective  Testing higher risk women would not be cost effective, as even those with negative results would be better off treated  Culture testing of low risk term women, combined with treatment without testing for the rest, would be the most cost effective strategy  Concerns Anaphylaxis - US experience 0/ 1,800,000 fatal anaphylaxis (Law et al), though 7 reports of maternal anaphylaxis, resulting in 5 babies not developing normally after birth Antibiotic resistance - GBS remains universally susceptible to penicillin

29. Charity No. 1112065 Company Reg No 5587535 29 What GBSS wants to see  identified as GBS carriers in the current pregnancy  with ≥ 1 other risk factors (no testing required) previous baby with GBS infection positive urine sample during this pregnancy preterm labour or rupture of membranes <37 completed weeks of pregnancy prolonged rupture of membranes ≥18 hours before delivery maternal pyrexia ≥ 37.8 o C Pregnant women should be informed about GBS, including offering the ECM testing, as a routine part of their antenatal care ECM tests for GBS carriage using rectal & vaginal swabs offered freely to all low-risk women at 35-37 weeks of pregnancy Intravenous antibiotics in labour should be offered to women: Knowledge of GBS status empowers choice

30. Charity No. 1112065 Company Reg No 5587535 30 What it’s all about …. ……. healthy babies