September 2007 Charity No Company Reg No Preventing early-onset group B Streptococcal infection in newborn babies

September 2007 Charity No Company Reg No Group B Streptococcus  Streptococcus agalactiae  Gram positive coccus  Normal body commensal of intestines and vagina  First recognised as a major perinatal pathogen in the 1970s  Commonest cause of bacterial infection in newborn babies  Underlying rate estimated as one per 1,000 newborn babies in the UK –UK research suggests the true incidence may be as high as 3.5 per 1000 (Luck et al, 2003)  Mortality rate approximately 10%  30% of survivors of GBS meningitis will have neurological sequelae  Early and late onset presentations  Up to 90% GBS infection apparent within 48 hours of birth  Remains uniformly sensitive to penicillin (some tolerance to clindamycin)

September 2007 Charity No Company Reg No Reported cases of GBS infection in England & Wales

September 2007 Charity No Company Reg No GBS – Colonisation  Normal flora in intestinal tract and vagina  Carriage is asymptomatic  Up to 30% adults carry GBS in intestines  Up to 25% of women carry GBS in the vagina  Occasionally in the throat (around 5%)  Colonisation can be intermittent  90% of adults do not have protective antibodies to GBS  GBS can traverse macroscopically intact amniotic membranes  GBS grows well in amniotic fluid  GBS survives well on skin of newborn infant

September 2007 Charity No Company Reg No Screening Antenatally for GBS carriage  Between 35 and 37 weeks  GBS carriage can be intermittent so best to swab close to delivery. –Research shows reliable tests done within 5 weeks of delivery are highly predictive of carriage at delivery (Yancey et al 1996)  Must take vaginal and rectal swabs  Low vaginal plus anorectal swabs are much more effective than HVS  Must use selective method with enrichment medium  Recognised as optimal for detecting GBS carriage by the Royal College of Obstetricians and The Health Protection Agency (BSOP 58)  Available privately (contact GBSS for availability) and from a handful of NHS hospitals  STANDARD CULTURE METHOD TOO INSENSITIVE FOR SCREENING  Standard culture method (direct plating) instead of using enriched culture medium reduces detection by 50%

September 2007 Charity No Company Reg No Options to reduce GBS infection in newborn babies  Waiting & treating babies after delivery  Too late for some & won’t prevent most GBS infection  Difficult to justify  Intrapartum antimicrobial prophylaxis (IAP)  Only method of prevention available at present  Largest study performed in Chicago –Boyer et al. N Eng J Med 1986;314:1665  Penicillin G recommended –Clindamycin recommended for penicillin-allergic women

September 2007 Charity No Company Reg No Options for selecting which women receive IAP  IAP to all women who have one or more risk factors (including incidental finding of GBS carriage/UTI)  IAP to all women identified as GBS carriers through screening (using enriched culture media) at weeks  IAP only to women where a rapid test is positive  IAP to all women identified as GBS carriers through screening (using enriched culture media) who also have one or more risk factors  IAP to all women found to carry GBS through screening AND ALSO to women with one or more risk factors

September 2007 Charity No Company Reg No Option 1: Risk Factor Approach IAP to all women with one or more risk factors IAP to all women with one or more of the following recognised risk factors:  pregnant woman has had a baby who developed a GBS infection  pregnant woman has GBS bacteria in her urine during the current pregnancy (which should be treated at the time of diagnosis)  pregnant woman has been found to carry GBS during the current pregnancy  pregnant woman has a raised temperature (≥37.8°C) during labour  labour or membrane rupture is preterm (<37 completed weeks of pregnancy)  prolonged rupture of membranes (≥18 hours before delivery) Advantages/disadvantages  Cheap (no bacteriological screening costs involved)  Relatively large amounts of antibiotics prescribed (about 30% of all women)  A significant number of cases will still occur (estimated 40%+)  Not tested in a trial

September 2007 Charity No Company Reg No Option 2: Screening Approach IAP to all women identified as GBS carriers IAP to all women identified as GBS carriers through screening (using enriched broth media) at 35+ weeks’ gestation Advantages/disadvantages  Selective enriched culture media is not routinely or widely available in the NHS when testing for GBS carriage, though recognised as optimal by RCOG & HPA  Relatively large amounts of antibiotics prescribed  Not tested in a trial  Most potential cases would be covered, but not all  A few women will be –ve when tested but +ve at delivery –Yancey research found 4% of women with negative results would become positive and 13% of women with positive results would become negative  Some carriers will miss or refuse screening  Some carriers will deliver before test conducted/test results available

September 2007 Charity No Company Reg No Option 3: Intrapartum Screening Approach Screen all women for GBS at onset of labour IAP only to women where a rapid test for GBS taken at the onset of labour is positive Advantages/disadvantages  Less antibiotic use, targetting only women carrying GBS at delivery  Relatively expensive  Will miss a significant number of cases  EXISTING RELIABLE TESTS ARE NOT FAST ENOUGH (taking 48 hours or more for the results to be available) –Most women would deliver before the results are available  EXISTING FAST TESTS ARE NOT RELIABLE ENOUGH –Too many women would be incorrectly told they don’t carry GBS  Not tested in a trial

September 2007 Charity No Company Reg No Option 4: Combined Approach 1 IAP to all GBS carriers with a risk factor IAP to all women identified as GBS carriers through screening (using enriched culture media) who also have one or more of the following risk factors: –Preterm labour or membrane rupture (<37 completed weeks of pregnancy) –Prolonged rupture of membranes (≥18 hours before delivery) –Maternal pyrexia (≥ 37.8 o C) –Previous baby with GBS infection Advantages/disadvantages  Expensive  Well researched  Smaller proportion of women receiving IAP  Mass screening using enriched culture method culture is more expensive  Many cases will still occur (estimated 40%+)

September 2007 Charity No Company Reg No Option 5: Combined Approach 2 IAP to GBS carriers & to women with 1+ risk factors IAP to all women found to carry GBS through sensitive screening in the current pregnancy AND to women with one or more risk factor, regardless of screening test result –Preterm labour or membrane rupture (<37 completed weeks of pregnancy) –Prolonged rupture of membranes (≥18 hours before delivery) –Maternal pyrexia (≥ 37.8 o C) –Previous GBS baby  More expensive  Relatively large amounts of antibiotics prescribed (around 30% of pregnant women)  More potential cases of GBS infection covered than restricting IAP to women with risk factors or carriage alone – estimated 80-90% prevention  Not tested in a trial

September 2007 Charity No Company Reg No UK Guidelines for Prevention: 1 - HPA HPA GBS Working Group  In 1998, the then Public Health Laboratory Service (PHLS) (subsequently incorporated into the Health Protection Agency (HPA)) established a multi-disciplinary GBS Working Group, whose remit was to produce evidence-based national guidelines for the control and prevention of invasive neonatal GBS disease  In June 2001, they issued their interim “good practice’ recommendations, advocating a risk based approach

September 2007 Charity No Company Reg No UK Guidelines for Prevention: 2 – NICE Antenatal Care NICE’S Antenatal Care Guidelines CG6, Oct 03  Don’t recommend screening as “evidence of its clinical effectiveness and cost effectiveness remains uncertain.”  Yet all the evidence shows screening and offering IV antibiotics in labour to higher-risk women is clinically effective. –Where such programmes have been introduced, there have been dramatic reductions in incidence, including the US, Australia, New Zealand, Belgium, France, Spain & Italy.  The cost effectiveness issue is less clear –a cost/benefit analysis of sponsored by the HTA, published September 2007 shows current practice is not cost effective – testing low-risk women and offering IAP to high risk women was shown to be most cost effective while limiting antibiotic use (Colbourne paper)  “pregnant women should be offered evidence based information and support to enable them to make informed decisions regarding their care … addressing women’s choices should be recognised as being integral to the decision making process.”  Yet information on GBS is not widely nor routinely available. And reliable tests are only available privately.

September 2007 Charity No Company Reg No UK Guidelines for Prevention: 3 - RCOG Royal College of Obstetricians & Gynaecologists Green Top Guideline No 36 "Prevention of early onset neonatal Group B streptococcal disease" 2003 (due for review November 2006)  Risk factor approach  Gives estimates of relative risk for morbidity or mortality for recognised risk factors  Calculations significantly underestimate true incidence of GBS infection in the UK and so underestimate the relative risks while overestimating the numbers needed to treat for benefit  Authors of the source of incidence figures (Heath et all, 2004) estimates an under- reporting of 21-42%  Incidence figures take no account of probable cases of GBS infection (Luck et al 2002)  Will prevent most lethal cases of EOGBS infection when fully implemented (RCOG audit dated Jan 2007 shows few hospitals fully comply)  Until sensitive screening is routinely available for all pregnant women, GBSS endorses these guidelines  This is a key starting position to preventing early onset GBS infection, but even more cases could be prevented through offering sensitive screening to pregnant women

September 2007 Charity No Company Reg No GBSS Recommendation: 1 Sensitive tests for GBS carriage using rectal & vaginal swabs taken should be freely available to all women at weeks of pregnancy IAP should be offered to  all women identified as GBS carriers in the current pregnancy,  all women who have previously had a GBS baby, and  all women who deliver < 37 completed weeks of pregnancy where a sensitive test result for GBS carriage is either positive or unavailable

September 2007 Charity No Company Reg No GBSS Recommendation: 2 Until sensitive tests for GBS carriage is freely and routinely available to all women at weeks of pregnancy:  Pregnant women should be informed about GBS  Pregnant women should be informed that a sensitive test for GBS is available privately, and given information on how to obtain it  IAP should be offered to  All women who have previously had a GBS baby  All women found during the current pregnancy to have GBS in the urine (which should be treated at the time of diagnosis)  All women identified as carriers (using any screening method) during the current pregnancy  All women not screened using sensitive tests who have one or more of the following risk factors –Prolonged rupture of membranes (≥18 hours before delivery) –Preterm labour or membrane rupture (<37 completed weeks of pregnancy) –Maternal pyrexia (≥ 37.8 o C)

September 2007 Charity No Company Reg No Intrapartum Antimicrobial Prophylaxis Penicillin G  3 g (or 5 mU) IV initially and then 1.5 g (or 2.5 mU) at 4-hourly intervals until delivery. Clindamycin  For women who are allergic to penicillin, 900 mg IV every 8 hours until delivery. Intravenous antibiotics should be given for at least 4 hours before delivery, where possible  lesser times are better than nothing and 2+ hours should give considerable reassurance.

September 2007 Charity No Company Reg No Option 6: IAP Chart

September 2007 Charity No Company Reg No Paediatric prevention strategy for babies born at higher risk

September 2007 Charity No Company Reg No Babies Colonised with GBS  Culture results are ‘history’  Swabs from baby  Vaginal swab at time of delivery  Antibiotic treatment for a healthy colonised baby is not indicated  Can send baby home  ‘Educate’ parents  what symptoms to watch for  what to do if they develop

September 2007 Charity No Company Reg No Transmission of GBS to baby

September 2007 Charity No Company Reg No Types of GBS infection (1)  Early-onset GBS infection (EOGBS)  Apparent within first 6 days of life, and usually within hours of delivery  Usually septicaemia with pneumonia  Typical symptoms –Grunting –Poor feeding –Lethargy –Low blood pressure –Irritability –Low blood sugar –Abnormally high or low temperature –Abnormally high or low heart rates –Abnormally high or low breathing rates  Even with the best medical care, 10% of babies with EOGBS die

September 2007 Charity No Company Reg No Types of GBS infection (2)  Late-onset GBS infection (LOGBS)  Develops 6 days-3 months  Usually meningitis with septicaemia  Typical symptoms of late-onset GBS infection –Fever –Poor feeding and/or vomiting –Impaired consciousness –Plus any symptoms of meningitis  Even with the best medical care –10% of babies sick with LOGBS die –up to 50% of survivors of GBS meningitis suffer long term handicaps

September 2007 Charity No Company Reg No Baby successfully treated for GBS infection  GBS infections have a relatively high incidence of recurrence (1-3%)  Consider low dose oral penicillin daily for 3 months

September 2007 Charity No Company Reg No The Future: Vaccination  Best approach for preventing both EOGBS and LOGBS infection, plus maternal GBS infection  Target would be pregnant women or women before they become pregnant  Vaccine needs to be multivalent  Medical research is urgently needed into developing a viable vaccine for group B Strep infection

September 2007 Charity No Company Reg No Key References  Centers for Disease Control & Prevention. Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines from CDC. MMWR Reports & Recommendations Vol. 51(No. RR 11) 16 August  Heath PT, Balfour G, Weisner AM, Efstratiou A, Lamagni TL, Tighe H, O'Connell LAF, Cafferkey M, Verlander NQ, Nicoll A & McCartney AC on behalf of the PHLS GBS Working Group. Group B streptococcal disease in UK and Irish Infants <90 days of age. Lancet 2004 Jan 24, Vol 363(9405):292.  Luck S, Torny M, d'Agapeyeff K, Pitt A, Heath P, Breathnach A & Bedford Russell A. Estimated early-onset group B streptococcal neonatal disease. Lancet, 2003 Jun 07; 361(9373):  PHLS Communicable Disease Surveillance Unit. Incidence of group B streptococcal disease in infants aged less than 90 days. CDR weekly Vol. 12(No 16):3. 18 April  Colbourn TE, Asseburg C, Bojke L, Philips Z, Welton NJ, Claxton K, Ades AE, and Gilbert RE. Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. BMJ : 655  Royal College of Obstetricians & Gynaecologists Clinical Green Top Guideline. Prevention of Early Onset Neonatal Group B Streptococcal Disease (36) – Nov 2003  Law MR, Palomaki G, Alfirevic Z, Gilbert G, Heath P, McCartney C, Reid T, Schrag S on behalf of the Medical Screening Society Working Group on GBS disease. The prevention of neonatal group B streptococcal disease. J Med Screen 2005;12:  Yancey MK, Schuchat A, Brown LK, Ventura VL, Markenson GR. The accuracy of late antenatal screening cultures in predicting genital GBS colonization at delivery. Obstet Gynecol Nov 1996; 88(5):811-5.

September 2007 Charity No Company Reg No Group B Strep Support  Registered charity set up in 1996  Aims:  To inform health professionals and individuals how most EOGBS infection can be prevented; and  To offer information and support to families affected by GBS;  To generate continued support for research into preventing GBS infections.  Funded by donations

September 2007 Charity No Company Reg No GBSS Materials Available LEAFLETS  GBS & pregnancy (introduction for pregnant women)  Congratulations on the safe arrival of your baby (introduction for parents of a health baby)  Understanding your baby’s GBS infection (introduction for parents of a GBS baby)  For women who carry GBS (detailed leaflet for women who know they carry GBS)  If your baby was infected by GBS (detailed leaflet for parents of babies affected by GBS)  GBS: The Facts (detailed leaflet, including medical reference list) POSTERS  Pregnant? (for pregnant women)  Labour & Delivery Prevention Guidelines  Understanding your baby’s GBS infection – for SCBUs  Saving Babies’ Lives – A2 STICKERS  GBS Alert - 35 per page for pregnant women’s notes  I am GBS Aware - 35 per page for pregnant women’s notes

September 2007 Charity No Company Reg No GBSS Medical Advisory Panel  Professor Philip Steer, BSc, MD, FRCOG (Chair)  Professor of Obstetrics, Academic Department of Obstetrics and Gynaecology, Imperial College Faculty of Medicine, Chelsea and Westminster Hospital  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