GBS in Pregnancy To screen or not to screen?

1. Max Brinsmead PhD FRANZCOG July 2012 GBS in PregnancyTo screen or not to screen?

2. Preamble • Group B Streptococcus is the most frequent cause of severe neonatal infection within 7 days of birth • Incidence 0.5 – 1.5 per 1000 • Risk of death is 10 – 30% • And there is also morbidity in survivors • 15 – 30% of pregnant women are carriers of GBS (Varies with climate) • 50% of their infants will become colonised during birth and • 1 – 2 % will develop sepsis • Intrapartum antibiotics significantly reduces the rate of neonatal GBS sepsis

3. Possible strategies • Identify and treat high risk patients – no screening • UK (unchanged view in 2012) • Screen all and treat all GBS carriers • USA and many Australian hospitals • Screen all and treat only those with additional risk factors • Canada

4. Before embarking on a program of screening all pregnant women a number of questions need to be answered...

5. Questions to be answered: • Will screening identify all those who need treatment? • Is treatment effective? • Is treatment safe? • Would another strategy be just as effective?

6. Does screening identify all who need treatment? • Must use selective culture medium • Best to use vaginal AND rectal swab • Best done at 35 – 37 weeks • High but not 100% correlation with carriage at term • And this does not detect those who labour before the swab result is available • And not required for all other risk groups: • Previous GBS-affected baby • Febrile in labour • Incidentally-detected GBS

7. Does screening identify all who need treatment? • So the answer is basically NO

8. Does screening identify all at risk from GBS? But there’s more… • It is agreed that intrapartum antibiotics are effective only against early onset (EO) disease • Has no effect on the incidence of late onset GBS sepsis (>7 days of age) • The postpartum administration of antibiotics to the neonate is not an option • Rapid intrapartum testing or the antenatal detection of the high risk mother is the best option for the future • A role for immunisation?

9. Is treatment effective? • There are no RCTs • Observational studies show that intrapartum antibiotics reduce the risk of neonatal GBS sepsis by 50 – 95% • Meta analysis by RCOG says 86% • But this could be due to effects of antibiotics on the diagnosis • No study has shown that Rx reduces overall rate of neonatal sepsis or death • Rate of GBS sepsis fell by 33 – 70% in the US after introduction of universal screening • But rate of neonatal deaths from GBS is the same in the UK • And rate of GBS sepsis in black US babies rose 70%

10. Is treatment effective? • Strictly speaking the answer is “unproven”

11. Is the treatment safe? • There are no RCTs • Some 15 – 30% of all women require treatment • You have to treat 714 women to prevent one case of neonatal sepsis • And 7000 women to prevent one neonatal death • Risk of fatal maternal anaphylaxis 1:100,000 • This means one maternal death for every seven (7) babies saved • Unknown risks from non-fatal anaphylaxis • Unknown problems from antibiotic use

12. Is the treatment safe? • So the answer is “maybe NOT”

13. Disadvantages of universal screening • The medicalization of birth • Costs of screening and treatment • Potential effects of antibiotics on neonatal gut flora • Use penicillin not Ampicillin or Amoxil • Emergence of resistant organisms

14. Other strategies? • Intrapartum rapid screening using PCR or optical immunoassay (OIA) • Second to universal treatment with antibiotics this is the most cost effective • Immunization against GBS • Looks promising

15. So why do I practise universal screening for GBS? • A personal close call with GBS sepsis in 2003 • We call this a case series of one! • US experience of a universal screening policy • Has significantly reduced the incidence of early-onset GBS infection • Peer pressure • Most large units in Australia now screening • Any affected patient who is not screened is very unhappy • It’s easier to remember and… • It’s very acceptable to women

16. Case History Page 1 Olivia G Age 28 G4P0 • Black flashing eyes • Attending for 12m with recurrent miscarriage • Two in the first trimester • One in the second trimester • New partner • Spontaneous conception • Bleeding of unknown cause at 18 and 33w • Wedding at 36w • Admitted at 37w with “a few contractions”

17. Case History Page 2 • Awake all night with fever, backache and sweats • Membranes intact • Temp 37.3 No uterine tenderness • CTG – Baseline 170 bpm & reduced STV • “Probably viraemia” but for FBC, HVS & UMCS • At 1200 hrs CTG improved & Olivia now afebrile • BUT WCC >25,0000 and 96% neutrophils • “A few gram pos cocci in the HVS” • Rx IV Ampicillin 1G at 12 midday

18. Case History Page 3 • At 4 pm Olivia is in established labour • CTG – baseline 170 bpm and little STV • VE: 2 – 3 cm, effaced ARM Clear liqour • Rx IV Ampicillin 1G repeated • At 5 pm CTG and Cx unchanged • Making preparations for em CS but • theatre busy until 6 pm • anaesthetist meeting the mayor and • assistant on the beach with 30 teenagers • At 5:45 pm – Olivia wants to push!

19. Case History Page 4 • Delivery assisted by ventouse and forceps • Big episiotomy and lotsa stitches HB 63 two days later • Gram stain of gastric aspirate “teeming with gram positive cocci” • Neonatal FBC showing classic signs of bacterial sepsis • Maternal HVS, urine, fetal gastric aspirate, body swabs and blood all grew GBS • Baby treated with IV antibiotics and did well

20. New Engl J Med July 2002: • A multicentre retrospective cohort study of 629,912 livebirths 1998 - 99 • Selected 5144 births by random stratification • Risk of neonatal GBS sepsis was significantly lower in those hospitals where screening was practised compared to those where a risk-based approach was used (RR 0.46, 95% CI 0.36-0.60) • This difference could not be corrected by failure to treat for identified risk factors

22. 2012 Update 1 • Immunisation remains elusive because of the number of subtypes • Rapid testing with PCR proves disappointing but direct plating onto culture medium at the bedside can hasten the detection • Professional women in Hong Kong had a significantly higher rate of colonisation than “housewives” • Someone has shown that it is more cost effective to simply treat any woman who has previously been GBS colonised rather than re screen and treat • Self collection of swabs is as good as professional collection • The doses of Clindamycin previously recommended are not sufficient • In a retrospective cohort study of 254 early-onset GBS sepsis in neonates in the US 61% were born to women who were screen negative • The others occurred in patients who had not been screened

23. 2012 Update 2 The US CDC has reviewed its guidelines, endorsed universal screening and made some further modifications… • RCT’s of vaginal chlorhexidine disappointing • Only 4 cases of non fatal anaphylaxis reported in the US since universal screening and treatment recommended in 1996 • 1 – 4 % of patients will have maculopapular rash • Penicillin-resistant GBS seen in Japan and ↑MIC noted elsewhere • 32% GBS resistant to Erythromycin and • 20% resistant to Clindamycin (same group) • Use Cephalosporin and Vancomycin • Urine colony count >105 significant (screening not required) • Women scheduled for elective CS should be screened at 35 – 37 weeks in case they have PROM • Revised doses of Penicillin and Clindamycin • Revised alogorithm for observation of GBS-exposed and intrapartum-treated babies (secondary prevention)