Timing of antibiotic prophylaxis for caesarean section Sir, The well-conducted systematic review of Baaqeel and Baaqeel 1 highlights the important debate on the use of prophy- lactic antibiotics for caesarean section. 2 However, by their own admission, this is an update of a previous systematic review 3 which confirms that pre-inci- sional rather than post-cord-clamping administration of antibiotics in women undergoing caesarean section signifi- cantly reduces the rate of postoperative maternal infectious morbidity. How- ever, meta-analyses are only as good as the quality of studies included and such repetition may perpetuate earlier errors. Also by their own admission, 1 the studies included were heterogeneous with respect to sample size (range 90– 741) and downgraded to only moderate quality. In their Introduction, the authors state that it was the neonatal impact that prompted them to undertake the review, yet they record that the long- term effects on the offspring ‘are beyond the scope of this review’. This contra- diction may have been made in retro- spect because none of the studies had long-term follow-up data. As the initial composition of the infant gut microbiota is a key determi- nant in the development of childhood asthma and atopic disease, long-term follow up is essential if we are to examine the correlation between pre- incisional administration of antibiotics and administration after cord-clamping with respect to adverse infant outcome. 4 To overcome this problem of pooling small to medium-sized randomised controlled trials of only moderate qual- ity, and trying to make judgements on short-term and long-term outcome of the offspring, we have initiated a large, tricentre randomised controlled trial. Our sample size calculation of 2844 exceeds the total number of the six studies quoted in Baaqeel and Baaqeel’s review. 1 This study, in a homogeneous Scandinavian population, will be pow- ered to show an expected reduction (>25%) of the median baseline risk of poor outcome (optimal information) with robust follow up of the children for 5 years. We are using second-generation cephalosporins (drug of choice for this indication in Scandinavia) which have a broader spectrum than the narrow range first-generation cephalosporin used in the studies within the systematic review, 1 another aspect of the current debate on the use of prophylactic anti- biotics for caesarean section. 2 Though it is difficult to calculate a sample size sufficient to demonstrate significant changes in childhood immu- nity after exposure to antibiotics imme- diately before delivery, in our randomised controlled trial, using cul- ture-independent molecularly based techniques, we plan to measure changes in the infant gut microbiome from birth to 6 months of age. This will be linked to the development of asthma and allergic diseases in any of the partici- pating children at the age of 5 years through both interviews with the par- ents and using the Danish National Birth and Patient Registries. We hope that our study will remove the need for such meta-analyses 1,3 in the future. & References 1 Baaqeel H, Baaqeel R. Timing of administration of prophylactic antibiotics for caesarean section: a systematic review and meta-analysis. BJOG 2013;120:661–9. 2 Lamont RF, Sobel JD, Kusanovic JP, Vaisbuch E, Mazaki-Tovi S, Kim SK, et al. Current debate on the use of antibiotic prophylaxis for caesarean section. BJOG 2011;118:193– 201. 3 Costantine MM, Rahman M, Ghulmiyah L, Byers BD, Longo M, Wen T, et al. Timing of perioperative antibiotics for cesarean delivery: a metaanalysis. Am J Obstet Gynecol 2008;199:301–6. 4 Vael C, Vanheirstraeten L, Desager KN, Goossens H. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma. BMC Microbiol 2011;11:68. JS Jørgensen, a N Hyldig, b T Weber c & RF Lamont a,d a Department of Obstetrics and Gynaecology, University of Southern Denmark, Odense University Hospital, Odense, Denmark b Department of Plastic Surgery, University of Southern Denmark, Odense University Hospital, Odense, Denmark c Department of Obstetrics and Gynaecology, University of Copenhagen, Hvidovre Hospital, Copenhagen, Denmark d Division of Surgery, University College London, Northwick Park Institute of Medical Research Campus, London, UK Accepted 12 December 2012. DOI: 10.1111/1471-0528.12159 Timing of antibiotic prophylaxis for caesarean section Authors’ Reply Sir, We thank Jørgensen et al. 1 for their interest in our paper. 2 We appreciate the points raised; however, we take issue with some of them. First, the dismissive view on repeating meta- analyses and hence perpetuating earlier errors. Evidence-based practice is not about creating evidence, rather it is about synthesising the best available evidence, which needs to be periodically updated. A case in point is the pub- lished meta-analyses by the groups of Jørgensen and Lamont, 3,4 addressing questions reported in earlier multiple meta-analyses by others. Second, we re- read our paper to verify our alleged own admission of stating that the included studies were heterogeneous with respect to sample size and found no such statement. Variation in sample sizes of the included studies is not a recognised measure in assessing heter- ogeneity of studies included in a sys- tematic review. Our colleagues seem to confuse grading the quality of the body of evidence for each outcome with the quality of included studies. Rating the quality of evidence refers not to indi- vidual studies but to the pooled body of evidence. 5 778 ª 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2013 RCOG BJOG Exchange