optimal timing of prophylactic antibiotic for cesarean delivery: a randomized comparative study

Optimal timing of prophylactic antibiotic for cesareandelivery: A randomized comparative study

Nabendu Bhattacharjee1, Shyama Prasad Saha2, Kajal Kumar Patra1, Udayan Mitra1 andSamir Chandra Ghoshroy2

1Department of Obstetrics and Gynaecology, R.G. Kar Medical College, Kolkata, and 2Department of Obstetrics andGynaecology, North Bengal Medical College, Darjeeling, West Bengal, India

Abstract

Aim: Cesarean delivery is associated with a significantly higher postoperative infection rate than that follow-ing vaginal birth and other surgical procedures. This study compared whether antibiotic prophylaxis admin-istered preoperatively was more effective in preventing infectious morbidity following cesarean delivery thanadministration at cord clamping.Material and Methods: In a randomized comparative trial, 953 women with a period of gestation of more than34 weeks, scheduled to have cesarean section, were randomly assigned to the prophylactic single-dose anti-biotic administration either preoperatively (study group) or at cord clamping (control group). Primaryoutcome measure was postoperative maternal infectious morbidity and secondary outcome measures wereneonatal complications, and postoperative maternal hospital stay and stay of neonates in the neonatal intensivecare unit.Results: Wound complications in the form of indurations, erythema and discharge, were significantly fewer inthe study group as compared to the control group (10/476 vs 25/477, P = 0.010, conditional maximumlikelihood estimate of odds ratio = 0.388 and 95% confidence interval = 0.175–0.805). Women in the study groupalso had fewer incidents of endomyometritis when compared to the control group (1.47% vs 3.56%; P = 0.041;conditional maximum likelihood estimate of odds ratio = 0.404). There was no significant difference in neonataloutcomes between the two groups. Mean postoperative stay of mothers in hospital was significantly shorter inthe study group (P = 0.009, 95% confidence interval = -0.368 to -0.052) but neonatal intensive care unit stay ofneonates was similar in both groups.Conclusion: Administration of prophylactic antibiotic at 30–60 min before skin incision resulted in bettermaternal outcome when infectious morbidity and postoperative hospital stay were concerned, without influ-encing the neonatal outcome.Key words: antibiotic prophylaxis, cesarean delivery, cord clamping, preoperative.

Introduction

Infectious complications following obstetric surgicalprocedures are a significant source of maternal morbid-ity and potential mortality. The single most importantrisk factor for postpartum maternal infection is cesar-

ean delivery (CD).1,2 Compared with a vaginal birth,women undergoing cesarean delivery have a five- totwentyfold greater risk for infection and infectiousmorbidity.

Rising cesarean delivery rates are a global concern.Rates of cesarean section in many countries have

Received: July 29 2012.Accepted: February 12 2013.Reprint request to: Dr Nabendu Bhattacharjee, AD-289, Rabindrapally Krishnapur, PO – Profullakanan, Kolkata-700101, West Bengal,India. Email: [email protected]; [email protected]; [email protected]

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doi:10.1111/jog.12102 J. Obstet. Gynaecol. Res. Vol. 39, No. 12: 1560–1568, December 2013

1560 © 2013 The AuthorsJournal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology

mailto:[email protected]



increased beyond the World Health Organization(WHO) recommended level of 15%.3 A WHO survey of122 facilities in nine Asian countries found that theoverall rate of cesarean delivery was 27.3%.4 The WHOofficially withdrew its previous recommendation of a15% cesarean section rate in June 2010. Their officialstatement read ‘There is no empirical evidence for anoptimum percentage. What matters most is that allwomen who need cesarean sections receive them.’5 TheUS National Institutes of Health says that rises in ratesof cesarean sections are not, in isolation, a causefor concern, but may reflect changing reproductivepatterns.6

The most important source of microorganismsresponsible for post-cesarean section infection is thegenital tract, particularly if the membranes are rup-tured. Even in the presence of intact membranes,microbial invasion of the intrauterine cavity iscommon, especially with preterm labor.7 Infections arecommonly polymicrobial (caused by many organisms).Wound infections caused by Staphylococcus aureus andcoagulase negative staphylococci arise from contami-nation of the wound with the endogenous flora of theskin at the time of surgery.8

Much works have been done to study the effect ofprophylactic antibiotics in reducing infectious morbid-ity. The purpose of antibiotic prophylaxis in surgicalprocedures is not to sterilize tissues but to reduce thecolonization pressure of microorganisms introducedat the time of operation to a level that the patient’simmune system is able to overcome.9 Prophylaxis doesnot prevent infection caused by postoperative contami-nation. The agent must be administered in a way thatensures that serum and tissue levels are adequatebefore an incision is made and that therapeutic levelsof the agent can be maintained in serum and tissuesduring surgery and for a few hours (at most) after theincision is closed.10 The majority of studies suggest thata single dose is effective, but for lengthy procedures(>3 h) the dose should be repeated at intervals 1 or 2times of the half-life of the drug. It has also been sug-gested that with blood loss (>1500 mL), a second doseshould be given.11

There has been debate about the benefit of prophy-lactic antibiotics for a woman who has an electivecesarean section with intact membranes and withoutlabor. A meta-analysis of four studies found that anti-biotic prophylaxis resulted in a decrease in postopera-tive fever (relative risk [RR] 0.25; 95% confidenceinterval [CI] 0.14–0.44) and endometritis (RR 0.05;95%CI 0.01–0.38).12 Taken together, these data support

the recommendation to use prophylactic antibiotics forall women undergoing cesarean section. Cephalospor-ins are the most commonly used drugs for prophylaxisfor their broad antibacterial spectrum.13

Antibiotic prophylaxis for cesarean delivery hastraditionally been administered after clamping theumbilical cord due to apprehension of exposureof fetuses through placenta when given earlier.14,15

However, research in non-pregnant populationsundergoing surgery and recent studies involving preg-nant women have suggested that administration ofantibiotics prior to incision (ideally 30–60 min before,to allow for optimal concentration at the surgical site)may further reduce infection by about 50% comparedto administration during surgery or after umbilicalcord clamping.14,16–19 Moreover, these studies havefound no increase in adverse neonatal outcomes,including the need for sepsis workups and neonatalintensive care unit (NICU) admission.13,16,19 A review bythe Cochrane Database found that there is an inconsis-tent and variable application of current recommenda-tions in regard to appropriate timing, administrationand choice of drug used for antibiotic prophylaxis atthe time of cesarean delivery. From this perspective, aprospective, double-blinded, placebo-controlled, ran-domized clinical trial was performed to determinewhether antibiotic prophylaxis administered preop-eratively was more effective in preventing infectiousmorbidity following cesarean delivery than adminis-tration at cord clamping.

The aim of the study was directed to: (i) assess therates of maternal infectious morbidity following preop-erative administration of antibiotics compared to anti-biotic prophylaxis given at umbilical cord clamping;and (ii) weigh up the incidence of neonatal infectiousmorbidity (i.e. rates of sepsis workup, confirmedsepsis, and length of hospital stay) between the twoprocedures.

Methods

This was a prospective, double-blinded, placebo-controlled, randomized clinical trial. We conducted thestudy over a period of one and half years, from July2010 to December 2011 simultaneously in two teachinginstitutions of West Bengal, India (R.G. Kar MedicalCollege and Hospital, Kolkata and North BengalMedical College and Hospital, Darjeeling).

In total, 1060 pregnant women, who had more than34 weeks of gestation, requiring cesarean sections fordifferent indications were assessed for enrolment in

Antibiotic prophylaxis in cesarean

© 2013 The Authors 1561Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology

the study. As premature delivery at or below 34 weeksis an independent risk factor for adverse perinataloutcome, women who underwent cesarean delivery atthis stage were not considered for inclusion in thestudy.

After going through exclusion criteria, a total of953 women were ultimately included in the study.Exclusion criteria were: (i) patients with obstetric com-plications (such as pre-eclampsia and antepartumhemorrhage); (ii) patients with renal disease, heartdisease, diabetes mellitus etc.; (iii) patients who arefebrile during or prior to screening; (iv) patients whopresented with ruptured membranes with or withoutantibiotic prophylaxis; (v) any exposure to antibioticduring past 1 week; (vi) obstetrical indication for emer-gency cesarean delivery during labor (e.g. obstructedlabor, deep transverse arrest and severe fetal distress);and (vii) penicillin or cephalosporin allergy (allassessed women who did not give any history of peni-cillin allergy received a test dose of ceftriaxone beforefinal enrolment).

There is no skin test that can reliably predict whethera patient will manifest an allergic reaction to cepha-losporins.20 The correlation between the skin prick testresponses and radioallergosorbent test (RAST) forallergen-specific serum IgE is fairly good21 but not100%. RAST detects the serum level of IgE specific fora given antigen. The advantage of skin test is that it isrelatively inexpensive and allows screening of a largenumber of allergens at one time. The disadvantage isthat it sometimes sensitizes the allergic individuals tonew allergens and in some rare cases may induce sys-temic anaphylactic shock. Sometime hypersensitivitymay not be demonstrated by skin testing andceftriaxone-specific IgE. Consequently life-threateninganaphylaxis may develop within minutes of the firstdose of intravenous injection of ceftriaxone. Failure ofskin test to detect ceftriaxone-specific IgE and conse-quent untoward reaction has been observed.22 It isimpractical to subject every individual to RAST beforeadministration of a drug. Our institutional standardpractice is to inject 100 mg ceftriaxone intravenouslyslowly over 10 min and wait for a further 30 min torecognize any immediate allergic reaction beforegiving the full dose of the drug, although the dose–response correlation is usually not apparent for theprovocation of allergic reactions. Such an intravenoustest dose has become a standard practice in obstetricsin our state. In this study, all women who agreed toparticipate in the study and fulfilled the inclusion cri-teria but did not give any history of penicillin/

cephalosporin allergy received the test dose ofceftriaxone (100 mg) intravenously slowly over 10 minto recognize any immediate allergic reaction. This100-mg test dose was in addition to the full prophylac-tic dose given later at the time of cesarean section.Those women who did not show any sign of hypersen-sitivity to the drug were subjected to randomization(n = 953). No further test dose was used before givingprophylactic antibiotic or placebo injection as perprotocol.

Decisions for emergency cesarean delivery weretaken in some women after they went into labor butwhere maternal and fetal conditions were stableenough to delay the procedure for about 90–120 min(e.g. cephalopelvic disproportion, malpresentation,intrauterine growth restriction with oligohydramnios,detected in early labor) and those women wereincluded in the study.

A total of 953 women with a gestation period of morethan 34 weeks, scheduled to have cesarean sectionwere included in the study. Patients were divided intotwo groups (A and B) using a computer-generated ran-domization protocol resulting in 476 women in groupA (study group) and 477 women in group B (controlgroup).

After allocation, relevant history and patient particu-lars were recorded for each patient. In group A (studygroup) preoperative antibiotic (ceftriaxone 2 g intrave-nously) was administered to the mother 30–60 minprior to skin incision and in group B (control group)the same antibiotic was administered at umbilical cordclamping. We used a computer-generated randomiza-tion sequence to assign participants into two treatmentgroups and the allocation was concealed in sealed,sequentially numbered, brown envelopes (opaque),which had been prepared by the statistician of eachcentre and handed over to the sister-in-charge of theoperation theatre, Department of Obstetrics and Gyne-cology of the respective institutions. The researchersresponsible for treating the pregnant women allocatedthe next available number on entry into the trial in theDepartment of Obstetrics and Gynecology and theoperating surgeons collected the corresponding sealedenvelope directly from the operation theatre sister-in-charge. The envelope was opened just before perform-ing caesarean section and the drug therapy wasselected as per code. To make the study double-blindedthe drugs were supplied in small sealed bags contain-ing vial A (2 g ceftriaxone mixed with 10 mL water forinjection, antibiotic was dissolved just before adminis-tration by an independent third person who ultimately

N. Bhattacharjee et al.


did not participate in final outcome) and Vial B (10 mLwater for injection as placebo). Both vials were identi-cal. Registration numbers of the patients were men-tioned on the bag. While preparing the women forcesarean section, the on-duty resident doctor openedthe supplied sealed bag and either vial A or vial Bmedicine was administered intravenously and slowlyaccording to randomization. The exact time wasrecorded and the skin incision was made at least30 min after the injection (not later than 60 min). Simi-larly vial B or vial A was administered at the time ofcord clamping by the anesthetic staff in the samemanner. Providers and patients were blinded to thecontents of the bags. Cesarean sections were per-formed by resident medical officers and generallyspinal anesthesia was given. The standard technique ofcesarean section was modified by the Joel Cohenmethod for skin incision, two-layer closure of uterinelower segment and non-stitching of peritoneum.

Postoperative follow-up was done by residentdoctors who were blinded to the patients’ and babies’identity. Infection morbidity, such as endometritis, wasdiagnosed if there was maternal fever greater than 38°Con two separate occasions along with uterine fun-dal tenderness, tachycardia, or leukocytosis. Woundinfection was diagnosed if there was purulent dis-charge, erythema, and indurations of the incision site.Hematoma, seromas, or wound breakdowns in theabsence of previously discussed signs were not consid-ered wound infections. Neonatal sepsis was diagnosedby clinical examination, blood picture, C-reactiveprotein estimation and positive blood culture as appro-priate. Length of NICU stay, admission status and deci-sion to undertake a sepsis workup were determined bythe staff neonatologist who was blinded to groupassignment.

Primary outcome measure was postoperative mater-nal infectious morbidity and secondary outcome mea-sures were neonatal complications, and postoperativehospital stay of mother and stay of neonates at NICU.

From the hospital records of our institutions, weobserved that the average incidence of post-cesareaninfectious morbidity in mothers was 5.8% during thelast 5 years when antibiotics were used only afterclamping of umbilical cord. An incidence of 2% inmothers receiving pre-incision antibiotics was used tocalculate the sample size having a power of 80 settingalpha error at 0.05. The minimum sample size thuscalculated was 404 in each arm for power based onnormal approximation and 455 in each arm for powerbased on normal approximation with continuity cor-

rection (Fleiss, Statistical Methods for Rates and Pro-portions, formulas 3.18 and 3.19).

All data entries were visually double-checked by anindependent second investigator. The data were ana-lyzed using Open Source Epidemiologic Statistics forPublic Health (Open Epi, version 2.3.1; updated on2011/23/06) to compare the outcomes between thestudy group and the control group. A P-value less than0.05 was considered statistically significant. Statisticalmethods included the two samples independentt-tests, mid-p exact tests, maximum likelihood oddsratio estimate with confidence limits produced byseveral methods.

The study was approved by the Committee forEthical Consideration and Approval for HumanResearch, R. G. Kar Medical College and Hospital, andthe Medical Ethical Committee for Human Research,North Bengal Medical College and Hospital asrequired by Indian law. Before enrolments for thestudy entry, all women provided a written informedconsent meeting all local institutional requirements.

Results

Initially 1060 women were assessed for eligibility cri-teria to include in this study; however, 107 womenwere excluded from the study due to either notmeeting the inclusion criteria (n = 76) or refusal to par-ticipate (n = 31). In total, 953 women were thus ran-domized into two groups (A and B) resulting in 476patients in the study group (group A) and 477 mothersin control group (group B). Prophylactic antibiotic wasinjected 30–60 min before skin incision in group A andat cord clamping in group B. Subsequently, 18 womenfrom group A and 21 from group B were lost to follow-up. Hence, 458 women in group A and 456 in group Bcompleted the study. But all women in both groupswho received allocation intervention were analyzed aswe adopted the intention-to-treat protocol (Fig. 1).

Demographic profiles of the patients in both groupswere comparable in relation to age, parity, gestationalage and indication for cesarean sections (Table 1). FromTable 2 it is evident that wound complications in theform of indurations, erythema and discharge were sig-nificantly less in the study group as compared to thecontrol group (10/476 vs 25/477, P = 0.010, conditionalmaximum likelihood estimate of odds ratio (CMLEOR) = 0.388 and 95%CI = 0.175–0.805). Women in thestudy group also had fewer incidents of endomyo-metritis when compared to the control group (1.47% vs3.56%; P = 0.041; CMLE OR = 0.404). None of the cases



Randomized (n = 953)

Allocated to prophylactic antibiotic administration at cord-clamping group

(n = 477)Received allocated intervention

(n = 477)Did not receive allocated intervention

(n = 0)

Excluded (n = 107)

Not meeting inclusion criteria (n = 76)

Refused to participate (n = 31)

Assessed for eligibility (n = 1060)

Lost to follow-up (n = 21)

Mothers completed the study(n = 456)

Analyzed (n = 477)

Excluded from analysis(n = 0)

Enr

ollm

ent

Allo

catio

nF

ollo

w-u

pA

naly

sis

Allocated to prophylactic antibiotic administration before skin-incision group

(n = 476)Received allocated intervention

(n = 476)Did not receive allocated intervention

(n = 0)

Lost to follow-up (n = 18)

Mothers completed the study(n = 458)

Analyzed (n = 476)

Excluded from analysis(n = 0)

Figure 1 Patients’ flow through chart.



in both groups required lengthy procedures (>3 h).Mean operative times (�standard deviation) were39.64 (�4.09) min and 40.05 (�3.96) min in groups Aand B, respectively. There was no significant differ-ence in neonatal outcomes between the two groups(Table 3). Mean postoperative stay of mothers in hos-pital was significantly less in the study group(P = 0.009, 95%CI = -0.368 to -0.052) but NICU stay ofneonates were similar in both groups (Table 4).

Discussion

Cesarean delivery is associated with a significantlyhigher postoperative infection rate than that following

vaginal birth and other surgical procedures. With theincrease in CD rates worldwide, such post-CD infec-tions are likely to become a significant health and eco-nomic burden. There is overwhelming evidence thatantibiotic prophylaxis for CD is effective in preventingmaternal infectious morbidity. These benefits are truefor both elective (scheduled) and non-elective (emer-gency or laboring) CD.23 Antibiotic prophylaxis forelective CD is also cost-effective.24,25

A single dose of antibiotics is as effective as multiple-dose regimens.23

The agent of choice for surgical prophylaxis shouldbe long-acting, inexpensive and have a low incidenceof side-effects.26 Most obstetricians use a single agent,

Table 1 Demographic profile

Characteristics Study group(n = 476)

Control group(n = 477)

P-value (95%CI)

Age in years (mean � SD) 23.08 � 3.48 23.24 � 4.69 0.550* (-0.685 to 0.365)BMI 24.19 � 2.61 24.07 � 2.72 0.487* (-0.219 to 0.459)Gestational age in weeks (mean � SD) 38.60 � 1.55 38.44 � 1.61 0.118* (-0.041 to 0.361)Socioeconomic statusAPL 183 (38.44%) 196 (41.09%) 0.405** (-8.86% to 3.57%)BPL 293 (61.46%) 281 (58.91%)Indication for CSEmergency 107 (22.48%) 112 (23.48%) 0.357** (-6.342% to 4.34%)Elective 369 (77.52%) 365 (76.52%)

*P-value (two-tailed). **Mid-P exact. APL, above poverty line; BMI, body mass index; BPL, below poverty line (according to Indian standard);CI, confidence interval; CS, cesarean section; SD, standard deviation.

Table 2 Post-cesarean infectious morbidity of mother

Outcome Study group(n = 476)


P-value (95%CI) CMLE OR (95%CI)

Operative time 39.64 � 4.09 40.05 � 3.96 0.116* (-0.922 to 0.102)Fever (2nd day onwards) 26 (5.46%) 33 (6.92%) 0.355** (-5.519% to -0.761%) 0.778 (0.453–1.323)Wound complications

(indurations, erythema,discharge)

10 (2.10%) 25 (5.24%) 0.010** (-1.711% to 0.455%) 0.388 (0.176–0.805)

Wound dehiscence 2 (0.42%) 5 (1.05%) 0.288** (-4.077% to -0.109%) 0.398 (0.053–2.032)Endomyometritis 7 (1.47%) 17 (3.56%) 0.041** (-4.077% to -0.109%) 0.404 (0.155–0.966)

*P-value (two-tailed). **Mid-P exact. CI, confidence interval; CMLE OR, conditional maximum likelihood estimate of odds ratio.

Table 3 Neonatal morbidity

Variable Study group(n = 476)


P-value* (95%CI) CMLE OR (95%CI)

Sepsis 15 (3.152%) 19 (3.98%) 0.495 (-3.186% to 1.522%) 0.784 (0.386 to 1.570)Fever 8 (1.68%) 12 (2.51%) 0.381 (-2.654% to 0.983%) 0.663 (0.256 to 1.645)Poor feeding 9 (1.89%) 12 (2.51%) 0.522 (-2.488% to 1.238%) 0.747 (0.30 to 1.807)Perinatal asphyxia 5 (1.05%) 6 (1.26%) 0.775 (-1.563% to 1.149%) 0.833 (0.233 to 2.877)NICU admission 39 (8.19%) 42 (8.59%) 0.737 (-4.152% to 2.929%) 0.924 (0.584 to 1.461)

*Mid-P exact. CI, confidence interval; CMLE OR, conditional maximum likelihood estimate of odds ratio; NICU, neonatal intensive care unit.



commonly a cephalosporin, as the antibiotic of choicefor prophylaxis. Various previous studies27–33 alreadyestablished ceftriaxone as an effective antibiotic forprophylaxis against postoperative infectious morbidi-ties following cesarean section. The ceftriaxone concen-trations in serum present at 24 h exceed the minimalbactericidal concentrations for common bacterialspecies.31

There is a lack of consensus regarding the timing ofsuch prophylaxis in cesarean deliveries. The usualobstetric practice so far has been to give prophylacticantibiotics at cord clamping to avoid the unnecessaryfetal exposure. Some have noticed a shift in early neo-natal sepsis from group B streptococci to Escherichiacoli and other Gram-negative organisms, with evenchange in the resistance patterns of these organ-isms.26,33,34 Moore et al.35 and Daley et al.36 exploredpotential associations between intra-partum antimi-crobial prophylaxis use and changes in the causes ofearly onset sepsis and concluded that antibiotic pro-phylaxis declined the incidence of early onset infec-tion due to group B streptococci. Daley et al. observedthat there was also a trend to decreasing early onsetE. Coli sepsis in all babies.

In this study we had evaluated the effectiveness ofprophylactic antibiotics when given preoperatively ascompared to intraoperative administration of the sameat cord clamping and whether the benefits if any wereat the cost of increasing neonatal morbidities. We hadused a single dose of 2-g intravenous ceftriaxone asprophylaxis in our study. Maximum plasma concentra-tion following intravenous infusion of ceftriaxone isachieved after 30 min of infusion. In a study by Patelet al.37 on ‘Pharmacokinetics of Ceftriaxone in Humans’using three different dose regimens, the authorsshowed that mean plasma concentrations observed atthe end of the 30-min infusion were 82, 151, and257 ug/mL after 0.5-, 1-, and 2-g doses, respectively.The plasma concentration-time curves of ceftriaxone inthe post-infusion phase were biphasic, with a relativelyshort distribution phase (overall mean distributionhalf-life, 0.17 h) followed by a slow elimination phase(overall mean elimination half-life, 6.1 h). They had

also shown that ceftriaxone exhibited a relatively longelimination half-life and a relatively small volumeof distribution (9.1 L) and plasma clearance(17.4 mL/min).

In our study, although additional 100-mg intrave-nous test dose had been used to detect a hypersensitivereaction (used in both groups) and timings of whichwere variable in respect to timing of caesarean section(minimum time interval was 90 min), the tissue concen-tration achieved due to such a small dose was of littleclinical significance and was unlikely to affect theoutcomes.

In two double-blind placebo-controlled trials by Waxet al.38 and Thigpen et al.,39 the authors had observedthat there was no difference in maternal infectiousmorbidity whether antibiotics were given before skinincision or at cord clamping.

But in our present study, postoperative maternalinfectious morbidities, such as incidence of woundinfections and endomyometritis, were more in thecontrol group (at cord clamping administration group)as compared to the study group (preoperative admin-istration group) and this was statistically significant.The studies done by Wax et al. and Thigpen et al. wereon laboring women only and sample sizes were alsosmall. But the majority of the women in our studyunderwent elective cesarean delivery before going intolabor and the study was conducted using a largersample size. These might be the probable reasons fordifference in outcomes in our study when compared tothose of the abovementioned studies. Our results weresimilar to the findings observed by Sulivan et al.16 intheir prospective, randomized, double-blind, placebo-controlled trial using prophylactic cefazolin prior toskin incision. They also observed that this dosing didnot result in increased neonatal septic workups or com-plications which were similar to our observations.

Bromberger et al.40 demonstrated that exposure toantibiotics during labor did not change the clinicalspectrum of disease or the onset of clinical signs ofinfection within 24 h of birth for term infants withgroup B Streptococcus (GBS) infection and concludedthat 48 h stay is not required to monitor asymptomatic

Table 4 Postoperative hospital stay of mother & NICU stay of baby

Study group(n = 476)


P-value(two-tailed)

95%CI of difference

Maternal stay in days (mean � SD) 4.36 � 1.15 4.57 � 1.33 0.009 -0.368 to -0.052NICU stay in days (mean � SD) 5.65 � 3.61 5.77 � 3.86 0.620 -0.595 to 0.355

CI, confidence interval; NICU, neonatal intensive care unit.



term infants exposed to intrapartum antibiotics foronset of GBS infection.

Smaill and Hofmeyr, in a Cochrane review in 2002,observed that hospital stay was reduced in patientswho received prophylactic antibiotics by 0.47 days(95%CI 0.88–0.19) compared to patients without suchprophylaxis.27 In our study, mean postoperative hospi-tal stay of women in the pre-incision antibiotic groupwas significantly less when compared to that of womenwho received antibiotic at cord clamping (P = 0.009,95%CI = -0.368 to -0.052). But NICU stay of neonatesdid not vary with the timing of maternal antibioticadministration.

In our study we could analyze a reasonably largesample size for assessment of fetomaternal outcomeaccording to timing of prophylactic antibiotic admin-istrations. In this study there was not a single caseof discontinued intervention after randomizationbecause of the nature of selection. Intention-to-treatprinciple was adopted for analyzing the results. Theweakness of this study was that we could notcompare the pharmacokinetics of antibiotics in indi-vidual patients. Non-estimation of blood loss duringsurgery (and in the immediate postoperative period)is another weakness of the study though significanthemorrhage requiring blood transfusion was nil inboth groups.

Administration of prophylactic antibiotic at30–60 min before skin incision resulted in better mater-nal outcome when infectious morbidity and postopera-tive hospital stay were concerned, without influencingthe neonatal outcome. This is likely to be cost-effectivealso, considering the fact that incidence of cesareansection has progressively increased over the last 2decades.

Acknowledgments

We would like to acknowledge the contribution of thestaff of the Pharmacy Departments of R. G. KarMedical College and North Bengal Medical College,West Bengal, India, who have been of immense help inconduction of the present study.

Disclosure

The authors have no commercial or other conflicts ofinterest, that is, financial or otherwise. The authors haveno commercial affiliations to disclose.

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optimal timing of prophylactic antibiotic for cesarean delivery: a randomized comparative study

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