1. Timing of administration of prophylactic antibiotics for caesarean section: a systematic review and meta-analysis. Baaqeel H, Baaqeel R.

2. Scenario You are charged with formulating a local clinical policy in your hospital about antibiotics prophylaxis at caesarean sections

3. Aims and Objectives Background: What do current guidelines say about the above scenario? What would be the best primary study design to study the above question and why? Sources of bias (what is the likelihood that the reported results are true?): Critically appraise, do not simply accept on face value, the methods of this systematic review and those of its constituent studies.

4. Aims and Objectives (2) What is sensitivity analysis? Is the use of sensitivity analysis in this study appropriate? Findings: Derive the relatively risk reduction (RRR), absolute risk reduction (ARR) and number needed to treat (NNT) of using pre-operative prophylactic antibiotics on the overall maternal infectious morbidity.

5. Background Prophylactic antibiotics reduce infectious morbidity after elective and emergency caesarean sections. In some countries, routine practice is to administer prophylactic antibiotics after cord-clamping to reduce fetal exposure to antibiotics. Conflicting reports about the neonatal impact of in-utero fetal exposure prompted this systematic review.

6. Other existing guidelines National Institute for Health and Clinical Excellence. CG132: Caesarean section Section 7.6. Available from: http://guidance.nice.org.uk/CG132/http://guidance.nice.org.uk/CG132/ The Society of Obstetricians and Gynaecologists of Canada (SOGC). Antibiotic Prophylaxis in Obstetric Procedures. (SOGC clinical practical guideline no. 247). The Society of Obstetricians and Gynaecologists of Canada (SOGC); September 2010. Available from: http://www.sogc.org/guidelines/documents/gui247CPG1009E_000.pdf http://www.sogc.org/guidelines/documents/gui247CPG1009E_000.pdf American College of Obstetricians and Gynecologists (ACOG). Use of prophylactic antibiotics in labor and delivery. (ACOG practice bulletin; no. 120). Washington (DC): American College of Obstetricians and Gynecologists (ACOG). June 2011. Available from: http://www.guidelines.gov/content.aspx?id=34024 http://www.guidelines.gov/content.aspx?id=34024

7. The Review Question In women undergoing caesarean sections, are there differences in the rates of maternal and neonatal infectious morbidity in those receiving preoperative antibiotic prophylaxis compared with intraoperative administration?

8. Structured Question ParticipantsWomen undergoing any type of caesarean sections InterventionA single dose of prophylactic antibiotic given pre- operatively ComparisonA single dose of prophylactic antibiotic given intra-operatively OutcomesMaternal: febrile morbidity, endometritis, wound infection and pyelonephritis. Neonatal: neonatal sepsis, neonatal septic work- up and neonatal intensive-care unit (NICU) admission.

9. Methods Medline, Embase, Current Controlled Trials and Cochrane Central were searched. Only RCTs of x1 dose of antibiotic comparing preoperative with intraoperative administration were selected. Independently extracted data  A random effect model to estimate RRs and their 95 % CI  Conventional testing for heterogeneity was performed.  Sensitivity analysis was done if likelihood of bias is suspected.  GRADEPRO was used to grade quality of evidence.

11. Events / TotalRisk ratio and 95% CI (Random) After cordRiskLowerUpper Preopclampingratiolimit Endometritis27 / 115847 / 11550.5890.3690.942 Pyelonephritis 13 / 95612 / 9651.0900.4902.425 Total infectious morbidity 74 / 1158104 / 11550.7110.5170.977 Wound infection 28 / 115840 / 11550.7050.4361.140 0.010.1110100 PreoperativeAfter cord clamping Total Outcome Heterogeneity: Endometritis Tau² = 0.00; Chi² = 3.14, df = 5 (P = 0.68); I² = 0% Pyelonephritis Tau² = 0.00; Chi² = 2.18, df = 3 (P = 0.54); I² = 0% Total infectious morbidity Tau² = 0.02; Chi² = 5.83, df = 5 (P = 0.32); I² = 14% Wound infection Tau² = 0.00; Chi² = 1.53, df = 5 (P = 0.91); I² = 0% Neonatal pneumonia 4 / 5720 / 5613.3610.55220.470 Total Neonatal sepsis22 / 53927 / 5410.8140.4691.412 Total Neonatal septic workup 94 / 805101 / 7990.9290.7141.208 Total NICU admissions 60 / 112666 / 11290.9170.6541.284 Total Neonatal pneumonia Tau² = 0.00; Chi² = 0.03, df = 2 (P = 0.98); I² = 0% Neonatal sepsis Tau² = 0.00; Chi² = 0.33, df = 2 (P = 0.85); I² = 0% Neonatal septic workup Tau² = 0.00; Chi² = 2.73, df = 4 (P = 0.60); I² = 0% NICU admission Tau² = 0.00; Chi² = 3.12, df = 4 (P = 0.54); I² = 0%

12. Authors’ conclusions Implication for research: The review revealed no significant neonatal adverse effects with pre-operative administration. These results need to be confirmed by sufficiently powered multi-center trial. Implication for practice: Any consideration of a change in practice based on the evidence presented in this review should take into account the fact that the quality of the evidence for all reported outcomes is moderate.

13. Applicability of findings Do these results overturn the existing recommendations? Would you advocate the use of a) pre-operative antibiotics and b) this particular antimicrobial (a cephalosporin) based on the results this study?

14. Formula Relative risk reduction (RRR) (CER - EER)/CER Absolute risk reduction (ARR) (CER - EER) Number needed to treat (NNT) 1/ARR or 1/(CER - EER) CER= control group event rate; EER= experimental group event rate