Timing of administration of prophylactic
antibiotics for caesarean section: a systematic
review and meta-analysis.
Baaqeel H, Baaqeel R.
Scenario
You are charged with formulating a local clinical
policy in your hospital about antibiotics prophylaxis
at caesarean sections
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.
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.
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.
Other existing guidelines
• National Institute for Health and Clinical Excellence. CG132: Caesarean
section Section 7.6. Available from: 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
• 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
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?
Structured Question
Participants
Intervention
Comparison
Outcomes
Women undergoing any type of caesarean
sections
A single dose of prophylactic antibiotic given preoperatively
A single dose of prophylactic antibiotic given
intra-operatively
Maternal: febrile morbidity, endometritis, wound
infection and pyelonephritis.
Neonatal: neonatal sepsis, neonatal septic workup and neonatal intensive-care unit (NICU)
admission.
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.
•
Outcome
Events / Total
Risk ratio and 95% CI (Random)
After cord
clamping
47 / 1155
Risk Lower Upper
ratio limit limit
0.589 0.369 0.942
12 / 965
1.090
0.490 2.425
0.711
0.517 0.977
40 / 1155
0.705
0.436 1.140
4 / 572
0 / 561
3.361
0.552 20.470
Neonatal sepsis Total 22 / 539
27 / 541
0.814
0.469
Neonatal septic workup Total 94 / 805
101 / 799
0.929
0.714 1.208
0.917
0.654 1.284
Preop
Endometritis Total 27 / 1158
Pyelonephritis Total 13 / 956
Total infectious morbidity Total 74 / 1158 104 / 1155
Wound infection Total 28 / 1158
Neonatal pneumonia Total
NICU admissions Total 60 / 1126
66 / 1129
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 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%
1.412
0.01
0.1
Preoperative
1
10
100
After cord clamping
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.
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?
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