Bonet2017 PDF

Cochrane Database of Systematic Reviews
Routine antibiotic prophylaxis after normal vaginal birth for

reducing maternal infectious morbidity (Review)
Bonet M, Ota E, Chibueze CE, Oladapo OT
Bonet M, Ota E, Chibueze CE, Oladapo OT.

Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity.
Cochrane Database of Systematic Reviews 2017, Issue 11. Art. No.: CD012137.
DOI: 10.1002/14651858.CD012137.pub2.
www.cochranelibrary.com
Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity (Review)
Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . 4
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Analysis 1.1. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 1 Endometritis. . . . 27
Analysis 1.2. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 2 Urinary tract infection. 28
Analysis 1.3. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 3 Wound infection
(episiotomy dehiscence). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Analysis 1.4. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 4 Adverse effects of antibiotics
(skin rash). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Analysis 1.5. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 5 Length of maternal hospital
stay - days. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 32
Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity (Review) i
[Intervention Review]
Routine antibiotic prophylaxis after normal vaginal birth for

reducing maternal infectious morbidity
Mercedes Bonet1 , Erika Ota2 , Chioma E Chibueze3 , Olufemi T Oladapo1
1 UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human
Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland. 2 Global
Health Nursing, St. Luke’s International University, Graduate School of Nursing Sciences, Tokyo, Japan. 3 Department of Health Policy,
National Center for Child Health and Development, Tokyo, Japan
Contact address: Mercedes Bonet, UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and
Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization,
Avenue Appia 20, Geneva, CH-1211, Switzerland. bonetm@who.int.
Editorial group: Cochrane Pregnancy and Childbirth Group.

Publication status and date: New, published in Issue 11, 2017.
Citation: Bonet M, Ota E, Chibueze CE, Oladapo OT. Routine antibiotic prophylaxis after normal vaginal birth for re-
ducing maternal infectious morbidity. Cochrane Database of Systematic Reviews 2017, Issue 11. Art. No.: CD012137. DOI:
10.1002/14651858.CD012137.pub2.
ABSTRACT
Background
Infectious morbidities contribute to considerable maternal and perinatal morbidity and mortality, including women at no apparent
increased risk of infection. To reduce the incidence of infections, antibiotics are often administered to women after uncomplicated
childbirth, particularly in settings where women are at higher risk of puerperal infectious morbidities.
Objectives
To assess whether routine administration of prophylactic antibiotics to women after normal (uncomplicated) vaginal birth, compared
with placebo or no antibiotic prophylaxis, reduces postpartum maternal infectious morbidities and improves outcomes.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 August 2017), LILACS, ClinicalTrials.gov, the WHO
International Clinical Trials Registry Platform (ICTRP) (22 August 2017) and reference lists of retrieved studies.
Selection criteria
We planned to include randomised or quasi-randomised trials evaluating the use of prophylactic antibiotics versus placebo or no
antibiotic prophylaxis. Trials using a cluster-randomised design would have been eligible for inclusion, but we found none.
In future updates of this review, we will include studies published in abstract form only, provided sufficient information is available to
assess risks of bias. We will consider excluded abstracts for inclusion once the full publication is available, or the authors provide more
information.
Trials using a cross-over design are not eligible for inclusion in this review.
Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity (Review) 1
Data collection and analysis
Two review authors conducted independent assessment of trials for inclusion and risks of bias. They independently extracted data and
checked them for accuracy, resolving differences in assessments by discussion. They evaluated methodological quality using standard
Cochrane criteria and the GRADE approach.
We present the summaries as risk ratios (RRs) and mean difference (MDs) using fixed- or random-effect models. For one primary
outcome we found considerable heterogeneity and interaction. We explored further using subgroup analysis to investigate the effects
of the randomisation unit. All review authors discussed and interpreted the results.
Main results
One randomised controlled trial (RCT) and two quasi-RCTs contributed data on 1779 women who had uncomplicated vaginal births,
comparing different antibiotic regimens with placebo or no treatment. The included trials took place in the 1960s (one trial) and 1990s
(two trials). The trials were conducted in France, the USA and Brazil. Antibiotics administered included: oral sulphamethoxypyridazine
or chloramphenicol for three to five days, and intravenous amoxicillin and clavulanic acid in a single dose one hour after birth. We
rated most of the domains for risk of bias as high risk, with the exception of reporting bias and other potential bias.
The quality of evidence ranged from low to very low, based on the GRADE quality assessment, given very serious design limitations
of the included studies, few events and wide confidence intervals (CIs) of effect estimates.
We found a decrease in the risk of endometritis (RR 0.28, 95% CI 0.09 to 0.83, two trials, 1364 women,very low quality). However,
one trial reported zero events for this outcome and we rate the evidence as very low quality. There was little or no difference between
groups for the risk of urinary tract infection (RR 0.25, 95% CI 0.05 to 1.19, two trials, 1706 women,low quality), wound infection
after episiotomy (reported as wound dehiscence in the included trials) (RR 0.78, 95% CI 0.31 to 1.96, two trials, 1364 women, very
low quality) and length of maternal hospital stay in days (MD -0.15, 95% CI -0.31 to 0.01, one trial, 1291 women, very low quality).
Cost of care in US dollar equivalent was 2½ times higher in the control group compared to the group receiving antibiotics prophylaxis
(USD 3600: USD 9000, one trial, 1291 women). There were few or no differences between treated and control groups for adverse
effects of antibiotics (skin rash) reported in one woman in each of the two trials (RR 3.03, 95% CI 0.32 to 28.95, two trials, 1706
women, very low quality). The incidence of severe maternal infectious morbidity, antimicrobial resistance or women’s satisfaction
with care were not addressed by any of the included studies.
Authors’ conclusions
Routine administration of antibiotics may reduce the risk of endometritis after uncomplicated vaginal birth. The small number and
nature of the trials limit the interpretation of the evidence for application in practice, particularly in settings where women may be at
higher risk of developing endometritis. The use of antibiotics did not reduce the incidence of urinary tract infections, wound infection
or the length of maternal hospital stay. Antibiotics are not a substitute for infection prevention and control measures around the time
of childbirth and the postpartum period. The decision to routinely administer prophylactic antibiotics after normal vaginal births
needs to be balanced by patient features, childbirth setting and provider experience, including considerations of the contribution of
indiscriminate use of antibiotics to raising antimicrobial resistance. Well-designed and high-powered randomised controlled trials would
help to evaluate the added value of routine antibiotic administration as a measure to prevent maternal infections after normal vaginal
delivery.
PLAIN LANGUAGE SUMMARY

Routine antibiotic preventive treatment after normal vaginal birth for reducing maternal infections
What is the issue?
Infections that occur during childbirth can result in considerable ill health and even death for the mother or her infant. The risk of
infection is believed to be higher for births in healthcare facilities in low-resource settings than in well-resourced settings, as a result
of poor hygienic conditions, inadequate water and sanitation systems, overcrowding and low health professional-to-patient ratios. The
prescription of antibiotics after an uncomplicated vaginal birth has become routine practice to overcome this situation in some low-
resource settings.
Why is this important?
Faced with increasing antimicrobial resistance because of misuse and over-prescription of antibiotics, we need evidence about the effect
of routine intake of antibiotics for preventing infections after a normal vaginal pregnancy without complications.
What evidence did we find?
The review assessed whether routine antibiotic treatment after uncomplicated vaginal birth, compared with either placebo or no
antibiotics, prevents maternal infection. We searched for evidence in August 2017 in three databases. We identified three trials involving
1779 women. The quality of the evidence ranged from low to very low. Different antibiotics were administered in the three trials and
for different lengths of time. The trials took place in the 1960s (one trial) and 1990s (two trials), and were carried out in France, the
USA and Brazil.
Routine antibiotic administration reduced the number of women with infection of the lining of the uterus (endometritis) (2 trials,
1364 women) by 70%. The use of antibiotics did not reduce the incidence of urinary tract infections (2 trials, 1706 women), wound
infections after episiotomy (2 trials, 1364 women) or length of maternal hospital stay (1 trial, 1291 women).
There were no differences between the groups for skin rash due to antibiotics, reported in one woman in each of the two trials (1706
women). The cost of care was higher in the group that did not receive antibiotic prophylaxis. The incidence of severe maternal infections
and illness, antimicrobial resistance or women’s satisfaction with care were not addressed.
What does this mean?
The small number of trials limits the interpretation of the evidence for routine use of antibiotics after normal vaginal births. The low
incidence of endometritis in the studies suggests that a relatively large number of women may have to be treated to avoid a few case of
infection.
There needs to be a balance between women’s needs, childbirth setting and provider experience (for example, with frequent vaginal
examinations or interventions) and the public health threat of antibiotics resistance.
Further research from well-designed randomised controlled trials would help to evaluate the added value of routinely giving women
antibiotics after normal vaginal birth to prevent maternal infections.
Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity (Review) S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]
Routine antibiotic prophylaxis compared to no treatment/ placebo for preventing infections in women who had normal vaginal births
Patient or population: Wom en who had norm al vaginal births

Setting: Healthcare f acilities in Brazil, France and the USA.
Intervention: Routine antibiotic prophylaxis (am oxicillin/ clavulanic, chloram phenicol, sulpham ethoxypyridazine)
Comparison: Placebo or no treatm ent
Outcomes Anticipated absolute effects∗ (95% CI) Relative effect of participants Quality of the evidence Comments
(95% CI) (studies) (GRADE)
Risk with no treatment/ Risk with routine an-

placebo tibiotic prophylaxis
Incidence of not estim able not estim able not estim able 0 - No trial reported this
severe m aternal inf ec- (0 RCT) outcom e
tious m orbidity (includ-
ing septicaem ia, septic
shock, laparotom y/ hys-
terectom y f or inf ection,
m aternal intensive care
unit adm ission, or or-
gan f ailure)
Endom etritis Study population RR 0.28 1364 ⊕ -

(0.09 to 0.83) (2 RCTs) VERY LOW 1,2
23 per 1000 7 per 1000
(2 to 20)
Urinary tract inf ection Study population RR 0.25 1706 ⊕⊕ -

(0.05 to 1.19) (2 RCTs) LOW 1
32 per 1000 8 per 1000
(4 to 18)
Wound inf ection (epi- Study population RR 0.78 1364 ⊕ -

siotom y dehiscence) (0.31 to 1.96) (2 RCTs) VERY LOW 1,5
4
Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity (Review)
7 per 1000 10 per 1000

(3 to 32)
Adverse ef f ects of an- Study population RR 3.03 1706 ⊕ -

tibiotics (skin rash) (0.32 to 28.95) (2 RCTs) VERY LOW 1,3
0 per 1000 0 per 1000
(0 to 0)
Length of m aternal hos- The m ean length of M D 0.15 lower not estim able 1291 ⊕ -
pital stay m aternal hospital stay (0.31 lower to 0.01 (1 RCT) VERY LOW 4,5
(including m aternal re- higher)
adm ission to hospital)
was 5.12 days
Individual antim icrobial not estim able not estim able not estim able 0 - No trial reported this
resistance (0 RCT) outcom e
* The risk in the intervention group (and its 95% conf idence interval) is based on the assum ed risk in the com parison group and the relative effect of the intervention (and its
95% CI).
CI: Conf idence interval; RR: Risk ratio;
GRADE Working Group grades of evidence

High quality: We are very conf ident that the true ef f ect lies close to that of the estim ate of the ef f ect
M oderate quality: We are m oderately conf ident in the ef f ect estim ate: The true ef f ect is likely to be close to the estim ate of the ef f ect, but there is a possibility that it is
substantially dif f erent
Low quality: Our conf idence in the ef f ect estim ate is lim ited: The true ef f ect m ay be substantially dif f erent f rom the estim ate of the ef f ect
Very low quality: We have very little conf idence in the ef f ect estim ate: The true ef f ect is likely to be substantially dif f erent f rom the estim ate of ef f ect
1 Two studies with very serious design lim itations (-2).
2 Few events (-1).
3 Few events, wide conf idence interval crossing the line of no ef f ect (-1).
4
One study with very serious design lim itations (-2).
5
Wide conf idence interval crossing the line of no ef f ect (-1).
5
BACKGROUND There is a general belief that the risk of infection is higher for births
attended at a healthcare facility (facility-based births) in low-re-
Infections occurring during pregnancy, childbirth and the puer-
source settings as a result of poor hygienic conditions, poor water
perium are associated with considerable maternal and perinatal
and sanitation systems, overcrowding and low health professional-
morbidity and mortality. However, global data on the incidence
to-patient ratio (Hussein 2010). In addition, the prompt identifi-
of maternal infection morbidity are scarce. The World Health Or-
cation of micro-organisms and selective antibiotic prescription is
ganization (WHO) estimates the global incidence of puerperal in-
often limited in these settings.
fections at 4.4% among live births, representing over 5.7 million
cases a year (WHO 2005). Important variations exist between re-
gions, with higher incidence in low- and middle-income countries
(up to 7%) compared to high-income countries where the esti- Description of the intervention
mated incidence is lower (1% to 2%) (Dolea 2003). Hygiene and infection-control measures (hand-washing and dis-
Despite a relatively low incidence overall and the availability of infection, single use of gloves, and cleaning and sterilisation of
interventions for prevention and treatment, maternal sepsis is one equipment) are the basis for prevention of infection around the
of the leading causes of maternal mortality, accounting for about time of childbirth for women with uncomplicated vaginal births
one-tenth of global maternal deaths (Say 2014). Most of the deaths (Hussein 2010).
are recorded in Asia (12%) and Africa (10%), compared to only Antibiotic prophylaxis is characterised by the use of broad-spec-
2% in developed countries (Khan 2006). In addition to death and trum antibiotics (e.g. ampicillin, cephalosporin, a combination
acute morbidities, infections are associated with maternal long- of antibiotics) effective against the micro-organism most likely to
term disabilities and may also have considerable impact on new- cause infections, to be given before, during or immediately after
born morbidity and mortality. the procedure and for a short period of time (single dose or for less
than 24 hours), and in the absence of any sign of infection (ACOG
2011). Antibiotic prophylaxis given after normal birth has the po-
Description of the condition tential to further decrease infection risk, particularly in settings
where appropriate hygiene, infection-control measures and san-
In general, normal (uncomplicated) birth is considered as spon- itation during labour, childbirth and the postpartum period are
taneous in onset, low-risk at the start of labour and remaining not ensured, or where early detection of puerperal infections and
so throughout labour and childbirth. The infant is born sponta- laboratory investigations is limited. The goal of antibiotic prophy-
neously in the vertex position between 37 and 42 completed weeks laxis is to prevent infection by reaching therapeutic tissue levels at
of pregnancy. After birth, mother and infant are in good condition the time microbial contamination is most likely to occur (ACOG
(NICE 2014; WHO 1996). 2011).
Several pre-existing maternal conditions may increase the risk of There is growing evidence that different antibiotic regimens are
developing bacterial infections among women expected to have routinely prescribed following uncomplicated vaginal birth in low-
uncomplicated vaginal births. These include conditions such as resource settings to overcome failures of the health system and
malnutrition, anaemia, bacterial vaginosis and group B strepto- the high risk of infections in the postpartum period. Studies from
coccus infections (Hussein 2010; Tharpe 2008). In addition, com- India (Sharma 2013) and Vietnam (Ngoc 2005) show that over
plications during labour and childbirth (e.g. prolonged rupture of 90% of women giving birth vaginally receive antibiotics before
membranes, prolonged labour, lacerations of the genital tract and hospital discharge. This includes the use of a wide range of antibi-
retained products of conception) or provider interventions (e.g. otics (amoxicillin, ampicillin, cephalosporins, fluoroquinolones or
frequent vaginal examinations, operative vaginal birth (forceps, combinations of antibiotics), different routes (oral, intramuscular,
vacuum), and episiotomy) might increase the risk of infection in intravenous), and duration of administration (average of three to
the puerperium (Hussein 2010; Tharpe 2008). It is therefore not four days).
easy to identify women who might be at higher risk of developing
infection after normal birth, and for whom prophylactic antibi-
otics might be useful for preventing infections in the puerperium.
Moreover, diagnosis of maternal infection is based mainly on non-
How the intervention might work
specific clinical signs and symptoms (pelvic pain, fever, abnormal Bacterial infections around the time of childbirth are generally
smell/foul-odour vaginal discharge or delay in uterine involution) polymicrobial, including aerobic and anaerobic bacteria, and re-
that can manifest several days after childbirth, resulting in difficul- flect vaginal colonisation (Van Dillen 2010). Antibiotic prophy-
ties in prompt identification of cases, particularly after discharge laxis after normal vaginal birth could help to prevent maternal in-
from the hospital (Hussein 2010). Failure to recognise the onset fections by ensuring adequate antimicrobial serum and tissue con-
of infection contributes to delays in treatment and increased risk centrations during the postpartum period. To be effective, such
of morbidity and mortality (Acosta 2014). antibiotics have to be active against the predominant organisms
that cause postpartum infections and administered for the shortest All randomised controlled trials (RCTs), including quasi-ran-
period to minimise side effects and the impact of its routine use on domised trials and cluster-randomised trials, that compared the
emerging antimicrobial resistance. Indeed, exposure to antibiotics use of routine antibiotic prophylaxis after normal (uncomplicated)
in the postpartum might cause adverse effects to the mother or vaginal birth at the facility level, with either a placebo or no antibi-
the breast-fed neonate, including disruption of the normal flora, otic prophylaxis. In future updates of this review, we will include
increased risk of resistant bacterial infections, allergic reactions as studies published in abstract form only, provided sufficient infor-
well as increased healthcare costs (ACOG 2011). There are also mation is available to asses risks of bias. We will consider excluded
concerns about rising resistance to antibiotics at the facility and abstracts for inclusion once the full publication is available, or the
community level (WHO 2014). This might further complicate authors provide more information.
the choice of suitable prophylactic antibiotics, as generally broad- We exclude trials with a cross-over design.
spectrum antibiotics are required to cover common pathogens
(Newton 2008).
Types of participants
Women who had an uncomplicated vaginal birth at term. This
excludes women who presented with any complication during
Why it is important to do this review labour, as reported by trial authors (e.g. chorioamnionitis, pro-
The increasing trend observed in facility-based births may increase longed prelabour rupture of membranes (PRM), prolonged sec-
the risk of hospital-acquired infections after normal vaginal birth ond stage of labour, third- or fourth-degree vaginal tears, post-
if not accompanied by improvements in the quality of hygiene partum haemorrhage), or those who have had intrapartum pro-
and infection-control measures (Hussein 2011). However, the ev- cedures (operative vaginal birth or manual removal of placenta).
idence is unclear about the added effect of antibiotic prophylaxis Episiotomy was not considered a complication of labour.
on the prevention of postpartum infections after an uncompli-
cated vaginal birth.
Types of interventions
There are increasing public health concerns about emerging antibi-
otic resistance following misuse or overuse of antibiotics (WHO The main comparison of the review is the use of any routine antibi-
2014). This is also applicable to the obstetric populations and the otic prophylaxis after uncomplicated vaginal birth compared with
possibility of inadequate response to treatment of puerperal infec- either placebo or no routine antibiotic prophylaxis. We will not
tions due to early exposure to undereffective antibiotic prophylac- consider trials administering antibiotic prophylaxis during labour
tic regimens. Given the large proportion of women experiencing for inclusion.
uncomplicated vaginal birth, a universal application of antibiotics
to such women has the potential to lead to substantial clinical Types of outcome measures
benefits in terms of reducing infection risk, but could also lead to
direct harm for the woman and indirect harm to the general public
with increasing resistance to antibiotics, as described above. Primary outcomes
1. Incidence of severe maternal infectious morbidity
(including septicaemia, septic shock, laparotomy/hysterectomy
for infection, maternal intensive care unit (ICU) admission, or
OBJECTIVES organ failure) as reported by trial authors.
2. Endometritis (with or without myometritis and with or
To assess whether the routine administration of prophylactic an- without salpingitis causing maternal febrile morbidity), as
tibiotics to women after normal (uncomplicated) vaginal birth, reported by the trial authors.
compared with placebo or no antibiotic prophylaxis, reduces post- 3. Urinary tract infection (fever or dysuria and positive urine
partum maternal infectious morbidities and improves outcomes. culture).
Secondary outcomes
METHODS
1. Wound infection (perineal first- or second-degree tear,
vaginal tear or episiotomy), as reported by trial authors.
2. Adverse effects of antibiotics (Maternal: allergic reaction,
Criteria for considering studies for this review nausea, vomiting, diarrhoea, skin rashes, anaphylaxis. Neonatal:
allergic reaction, diarrhoea, skin rashes, anaphylaxis).
3. Length of maternal hospital stay (including maternal re-
Types of studies
admission to hospital).
4. Cost of care (including maternal re-admission to hospital, planned and ongoing trial reports, using the search terms given in
cost of antibiotic treatment). Appendix 2 (22 August 2017).
5. Individual antimicrobial resistance (e.g. no response to first-
line antibiotic treatment, culture of antibiotic-resistant bacterial Searching other resources
strains), as reported by trial authors.
We searched the reference lists of retrieved studies.
6. Women’s satisfaction with care, as reported by trial authors.
We did not apply any language or date restrictions to our search.
Search methods for identification of studies Data collection and analysis

The following Methods section of this review is based on a standard
The following Methods section of this review is based on a standard
template used by Cochrane Pregnancy and Childbirth.
template used by Cochrane Pregnancy and Childbirth.
Electronic searches Selection of studies

We searched Cochrane Pregnancy and Childbirth’s Trials Register Two review authors (MB and CEC) independently assessed for
by contacting their Information Specialist (31 August 2017). inclusion all the studies we identified as a result of the search
The Register is a database containing over 23,000 reports of con- strategy, resolving any disagreement through discussion.
trolled trials in the field of pregnancy and childbirth. For full search We created a study flow diagram (Figure 1) to map out the number
methods used to populate Pregnancy and Childbirth’s Trials Regis- of records identified, included and excluded.
ter including the detailed search strategies for CENTRAL, MED-
LINE, Embase and CINAHL; the list of handsearched journals
Data extraction and management
and conference proceedings, and the list of journals reviewed via
the current awareness service, please follow this link to the edi- We designed a form to extract data, which two review authors
torial information about the Cochrane Pregnancy and Childbirth (MB and CEC) used for eligible studies, resolving discrepancies
in the Cochrane Library and select the ‘Specialized Register ’ sec- through discussion. We entered data into Review Manager 5 soft-
tion from the options on the left side of the screen. ware (RevMan 2014) and checked them for accuracy. Information
Briefly, Cochrane Pregnancy and Childbirth’s Trials Register is regarding one of the excluded papers was unclear and grouped
maintained by their Information Specialist and contains trials with a population excluded from our review objective. Efforts to
identified from: contact the author to retrieve segregated data and further details
1. monthly searches of the Cochrane Central Register of proved unsuccessful. In future updates, where information is un-
Controlled Trials (CENTRAL); clear we will try to contact authors of the original reports to pro-
2. weekly searches of MEDLINE (Ovid); vide further details.
3. weekly searches of Embase (Ovid);
4. monthly searches of CINAHL (EBSCO); Assessment of risk of bias in included studies
5. handsearches of 30 journals and the proceedings of major Two review authors (MB and CEC) independently assessed risks
conferences; of bias for each study, using the criteria outlined in the Cochrane
6. weekly current awareness alerts for a further 44 journals Handbook for Systematic Reviews of Interventions (Higgins 2011).
plus monthly BioMed Central email alerts. We resolved any disagreement by discussion or by involving a third
Two people screen the search results and review the full text of assessor (EO or OTO).
all relevant trial reports identified through the searching activities
described above. Based on the intervention described, each trial re-
port is assigned a number that corresponds to a specific Pregnancy (1) Random sequence generation (checking for possible
and Childbirth review topic (or topics), and is then added to the selection bias)
Register. The Information Specialist searches the Register for each We described for each included study the method used to generate
review using this topic number rather than keywords. This results the allocation sequence in sufficient detail to allow an assessment
in a more specific search set which has been fully accounted for in of whether it should produce comparable groups.
the relevant review sections (Included studies; Excluded studies). We assessed the method as:
In addition to the search carried out by the Information Specialist, • low risk of bias (any truly random process, e.g. random-
we searched LILACS using the search strategy given in Appendix number table; computer random-number generator);
1 (22 August 2017). • high risk of bias (any non-random process, e.g. odd or even
We also searched ClinicalTrials.gov and the WHO Interna- date of birth; hospital or clinic record number);
tional Clinical Trials Registry Platform (ICTRP) for unpublished, • unclear risk of bias.
(2) Allocation concealment (checking for possible selection • high risk of bias (e.g. numbers or reasons for missing data
bias) imbalanced across groups; ‘as treated’ analysis done with
We described for each included study the method used to con- substantial departure of intervention received from that assigned
ceal allocation to interventions prior to assignment and assessed at randomisation);
whether intervention allocation could have been foreseen in ad- • unclear risk of bias.
vance of or during recruitment, or changed after assignment.
We assessed the methods as: (5) Selective reporting (checking for reporting bias)
• low risk of bias (e.g. telephone or central randomisation;
We described for each included study how we investigated the
consecutively-numbered sealed opaque envelopes);
possibility of selective outcome reporting bias and what we found.
• high risk of bias (open random allocation; unsealed or non- We assessed the methods as:
opaque envelopes, alternation; date of birth); • low risk of bias (where it is clear that all of the study’s
• unclear risk of bias. prespecified outcomes and all expected outcomes of interest to
the review have been reported);
(3.1) Blinding of participants and personnel (checking for • high risk of bias (where not all the study’s prespecified
possible performance bias) outcomes have been reported; one or more reported primary
We described for each included study the methods used, if any, to outcomes were not prespecified; outcomes of interest are
blind study participants and personnel from knowledge of which reported incompletely and so cannot be used; study fails to
intervention a participant received. We considered that studies are include results of a key outcome that would have been expected
at low risk of bias if they were blinded, or if we judge that the to have been reported);
lack of blinding would be unlikely to affect results. We assessed • unclear risk of bias.
blinding separately for different outcomes or classes of outcomes.
We assessed the methods as: (6) Other bias (checking for bias due to problems not
• low, high or unclear risk of bias for participants; covered by (1) to (5) above)
• low, high or unclear risk of bias for personnel. We described for each included study any important concerns we
have about other possible sources of bias.
(3.2) Blinding of outcome assessment (checking for possible We assessed whether each study was free of other problems that
detection bias) could put it at risk of bias:
• low risk of other bias;
We described for each included study the methods used, if any, to
• high risk of other bias;
blind outcome assessors from knowledge of which intervention a
• unclear whether there is risk of other bias.
participant received. We assessed blinding separately for different
outcomes or classes of outcomes.
We assessed methods used to blind outcome assessment as: (7) Overall risk of bias
• low, high or unclear risk of bias. We made explicit judgements about whether studies are at high risk
of bias, according to the criteria given in the Handbook (Higgins
2011). With reference to (1) to (6) above, we assessed the likely
(4) Incomplete outcome data (checking for possible attrition
bias due to the amount, nature and handling of incomplete
magnitude and direction of the bias and whether we consider it
outcome data)
is likely to impact on the findings. We explored the impact of the
level of bias through undertaking sensitivity analyses.
We described for each included study, and for each outcome or
class of outcomes, the completeness of data including attrition and
exclusions from the analysis. We stated whether attrition and ex- Assessing the quality of the evidence using GRADE
clusions were reported and the numbers included in the analysis at We assessed the quality of the evidence using the GRADE ap-
each stage (compared with the total randomised participants), rea- proach, as outlined in the GRADE handbook related to the fol-
sons for attrition or exclusion where reported, and whether miss- lowing outcome for the main comparison.
ing data were balanced across groups or were related to outcomes. 1. Incidence of severe maternal infectious morbidity
In future updates, where sufficient information is reported or can (including septicaemia, septic shock, laparotomy/hysterectomy
be supplied by the trial authors, we will re-include missing data in for infection, maternal ICU admission, or organ failure) as
the analyses which we undertake. reported by the trial authors.
We assessed methods as: 2. Endometritis (with or without myometritis and with or
• low risk of bias (e.g. no missing outcome data or less than without salpingitis causing maternal febrile morbidity), as
20%; missing outcome data balanced across groups); reported by the trial authors.
3. Urinary tract infection (fever or dysuria and positive urine the effect of variation in the ICC. If we identify both cluster-
culture). randomised trials and individually-randomised trials, we plan to
4. Wound infection (perineal first- or second-degree tear, synthesise the relevant information. We will consider it reasonable
vaginal tear, episiotomy), as reported by trial authors. to combine the results from both if there is little heterogeneity
5. Adverse effects of antibiotics (Maternal: allergic reaction, between the study designs, and the interaction between the effect
nausea, vomiting, diarrhoea, skin rashes, anaphylaxis. Neonatal: of intervention and the choice of randomisation unit is considered
allergic reaction, diarrhoea, skin rashes, anaphylaxis). to be unlikely.
6. Length of maternal hospital stay (including maternal re- We will also acknowledge heterogeneity in the randomisation unit
admission to hospital). and perform a sensitivity analysis to investigate the effects of the
7. Individual antimicrobial resistance (e.g. no response to first- randomisation unit.
line antibiotic treatment, culture of antibiotic-resistant bacterial
strains), as reported by trial authors.
Cross-over trials
We used the GRADEpro Guideline Development Tool to import
data from Review Manager 5 (RevMan 2014) in order to create Cross-over trials are not eligible for inclusion in this review.
a ’Summary of findings’ table. We produced a summary of the
intervention effect and a measure of quality for each of the above Other unit of analysis issues
outcomes using the GRADE approach. The GRADE approach
Included studies had only two treatment groups. For future up-
uses five considerations (study limitations, consistency of effect,
dates, we will consider trials with more than two treatment groups
imprecision, indirectness and publication bias) to assess the quality
for inclusion if at least one intervention group is relevant to the
of the body of evidence for each outcome. The evidence can be
review. If multiple groups from one study are relevant for inclu-
downgraded from ’high quality’ by one level for serious (or by
sion, we plan to combine all relevant experimental intervention
two levels for very serious) limitations, depending on assessments
groups of the study into a single group, and to combine all relevant
for risk of bias, indirectness of evidence, serious inconsistency,
control intervention groups into a single control group.
imprecision of effect estimates or potential publication bias.
Dealing with missing data

Measures of treatment effect
For included studies, we have noted levels of attrition. We explored
the impact of including studies with high levels of missing data
Dichotomous data in the overall assessment of treatment effect by using sensitivity
For dichotomous data, we present results as a summary risk ratio analysis.
(RR) with a 95% confidence interval (CI). For all outcomes, we carried out analyses, as far as possible, on an
intention-to-treat basis, i.e. we attempted to include all partici-
pants randomised to each group in the analyses, and analysed all
Continuous data participants in the group to which they were allocated, regardless
For continuous data, we calculated the mean difference (MD) of whether or not they received the allocated intervention. The
for outcomes measured in a similar way between trials. In future denominator for each outcome in each trial was the number ran-
updates we will use the standardised mean difference (SMD) where domised minus any participants whose outcomes are known to be
necessary to combine trials that measured the same outcome, but missing.
with different methods.
Assessment of heterogeneity
Unit of analysis issues We assessed statistical heterogeneity in each meta-analysis using
the Tau2 , I2 and Chi2 statistics. We regarded heterogeneity as
substantial if I2 is greater than 30% and either the Tau2 is greater
Cluster-randomised trials
than zero, or there is a low P value (less than 0.10) in the Chi2 test
We found no cluster-randomised trials. In future updates, we will for heterogeneity.
include cluster-randomised trials in the analyses along with indi-
vidually-randomised trials. We will adjust their sample sizes using
the methods described in the Handbook (Section 16.3.4 or 16.3.6), Assessment of reporting biases
using an estimate of the intracluster correlation co-efficient (ICC) We included three studies in the meta-analysis. For subsequent
derived from the trial (if possible), from a similar trial or from a updates, if there are 10 or more studies in the meta-analysis, we will
study of a similar population. If we use ICCs from other sources, investigate reporting biases (such as publication bias) using funnel
we will report this and conduct sensitivity analyses to investigate plots. We will assess funnel plot asymmetry visually. If asymmetry
is suggested by a visual assessment, we will perform exploratory 1. Incidence of severe maternal infectious morbidity
analyses to investigate it. (including septicaemia, septic shock, laparotomy/hysterectomy
for infection, maternal ICU admission, or organ failure) as
reported by trial authors.
Data synthesis 2. Endometritis (with or without myometritis and with or
We carried out statistical analysis using the Review Manager 5 without salpingitis causing maternal febrile morbidity), as
software (RevMan 2014). We used a fixed-effect meta-analysis for reported by the trial authors.
combining data where it was reasonable to assume that studies were 3. Urinary tract infection (fever or dysuria and positive urine
estimating the same underlying treatment effect, i.e. where trials culture).
are examining the same intervention, and the trials’ populations We assessed subgroup differences by interaction tests available
and methods are judged sufficiently similar. We observed clinical within RevMan (RevMan 2014). We reported the results of sub-
heterogeneity for one primary outcome (urinary tract infection) group analyses quoting the Chi2 statistic, P value, and the inter-
and one secondary outcome (wound infection (episiotomy dehis- action test I2 value.
cence)). It was sufficient to suspect that the underlying treatment
effects differed between trials, as evidenced by the substantial sta- Sensitivity analysis
tistical heterogeneity detected.
We undertook sensitivity analysis for one primary outcome based
We used a random-effects meta-analysis to produce an overall sum-
on the ’Risk of bias’ assessment for allocation concealment and at-
mary, as we considered the average treatment effect across trials to
trition rates. We conducted sensitivity analyses by removing stud-
be clinically meaningful. We treat the random-effects summary as
ies that were at high risk of bias (such as quasi-randomised studies)
the average of the range of possible treatment effects and we dis-
for these domains to assess whether this made any difference to
cuss the clinical implications of treatment effects differing between
the overall result, and by trial quality. There were no cluster-ran-
trials. If the average treatment effect is not clinically meaningful,
domised trials. If this is the case in future updates of this review,
we will not combine trials.
we will investigate the effect of different values of the ICC.
For this outcome, we used random-effects analyses, presenting
the results as the average treatment effect with a 95% confidence
interval, and the estimates of Tau2 and I2 .
RESULTS
Subgroup analysis and investigation of heterogeneity
We identified substantial heterogeneity, which we investigated
using subgroup analyses and sensitivity analyses. We considered Description of studies
whether an overall summary was meaningful, and used random-
effects analysis to produce it.
We planned to carry out the following subgroup analyses. Results of the search
1. High-income countries versus low- and middle-income The search of the Cochrane Pregnancy and Childbirth Group’s
countries. Trials Register retrieved 10 trial reports. We retrieved 259 records
2. Short-duration antibiotic prophylaxis regimens versus long- from LILACS, 54 from ClinicalTrials.gov and 10 from ICTRP.
duration regimens. Among these, we identified five duplicates from the same source.
We were able to introduce subgroups based on duration, short- We excluded reports due to lack of comparisons, randomisation
(single dose) versus long-term (several days with multiple doses). and irrelevance to review objective. We retrieved 13 full texts after
The low number of eligible studies limited further assessments. independent title and abstract screening by two review authors.
Subgroup analysis was to be restricted to this review’s primary These studies provided data on women who received antibiotics
outcomes. after normal vaginal births (see Figure 1).
Figure 1. Study flow diagram.
Further full-text evaluation identified three eligible trials which
contribute data to this review. We included one randomised con- excluded prior to assigning the 415 participants to treated (217)
trolled trial (RCT) and two quasi-RCTs. Studies provided indi- and placebo (198) groups. Exclusions were based on allergies to
vidual data on a different class of drugs, so we could not compare sulphonamides, intake of other antibiotics and the presence of
differences between different drug classes. indwelling catheters (Turck 1962) prior to randomisation.
One thousand two hundred and ninety-one women meeting the
Included studies following inclusion criteria were eventually analysed in Fernandez
1993: vaginal birth, absence of pyrexia (> 38° C) during labour
or the hour following delivery, an interval of less than 24 hours
Design between rupture of membranes and the onset of labour, absence
of any evidence of extragenital infection (e.g. urinary tract with
One RCT (Fernandez 1993) and two quasi-RCTs (Neto 1990;
absence of urination burning) and absence of known allergies to
Turck 1962) contributed data on 1779 women who had uncom-
the drug of choice (Amox-CA) or to β-lactams. Women with ev-
plicated vaginal births, comparing different antibiotic regimens
idence of amniotic fluid infection at the time of admission were
with placebo or no treatment. Two trials specifically assessed the
included (Fernandez 1993). In addition, 82 women were excluded
use of prophylactic antibiotics after in-out catheterisation of the
after randomisation. These included five in whom the antibiotic
urethra (Turck 1962) or episiotomy (Neto 1990). In the other
given was unknown, 71 women excluded due to antibiotic in-
study women were recruited in the labour ward as soon as they
jections after uterine exploration, and six other women who had
delivered (Fernandez 1993). Women were followed up at 10 days
more than a 24-hour interval between rupture of membranes and
(Neto 1990), two weeks (Fernandez 1993) and six weeks (Turck
labour onset. This left 1291 women for analysis. No differences
1962) after birth. We provide a detailed description of studies in
were reported between groups for maternal age, parity, body mass
the table Characteristics of included studies.
index, history of infection during pregnancy, other maternal mor-
In the studies, pregnant women were randomised into two groups,
bidity (diabetes, hypertension), gestational age, type of pregnancy
according to hospital registration number (Turck 1962), protocol
(singleton versus twins), time in labour ward, number of vaginal
number (odd/even number) (Neto 1990) or a random-number
examinations, number of urethral catheterisations, temperature
table in the labour ward (Fernandez 1993).
on admission to the labour ward or epidural anaesthesia.
The studies took place between 1961 and 1962 (Turck 1962),
Neto 1990 included data for 34 women in the intervention arm
1988 and 1989 (Neto 1990), and during 1989 (Fernandez 1993).
and 39 in the control no-treatment arm. No difference was re-
ported between groups for race, maternal age, parity, gestational
Sample sizes age, length of labour, length of rupture of membranes, and num-
ber of vaginal examinations.
Turck 1962 included 431 women, later excluding 16 participants.
The remaining 415 women were assigned to the treated (217)
or placebo groups (198). Neto 1990 included 80 women with
Interventions and comparisons
normal birth and episiotomy, of which 73 were followed-up and
included in the analysis, 34 in the intervention arm and 39 in the Treatment with antibiotic prophylaxis was compared to placebo
control non-treated arm. Fernandez 1993 included 1373 women, (Turck 1962) or no treatment (Fernandez 1993; Neto 1990).
of which 82 were excluded after randomisation and 1291 analysed. Antibiotics administered included: sulphamethoxypyridazine one
tablet a day from three to five days after in-out urethral catheterisa-
tion (Turck 1962), oral chloramphenicol 500 mg four times daily
Setting for 72 hours after episiotomy repair (Neto 1990), and intravenous
Two studies were conducted in high-income countries, in a public amoxicillin and clavulanic acid (®Augmentin, Beecham labora-
hospital in France (Fernandez 1993) and a private clinic in the USA tory) at 1.2 g at one hour after birth (Fernandez 1993). When
(Turck 1962). The remaining study was conducted in a public reported, the choice of the antibiotics by the authors was guided
hospital in Brazil (Neto 1990). by their broad spectrum (Fernandez 1993), ease of administration
and relatively low allergenicity (Turck 1962).
Participants
In Turck 1962, all the women had catheters inserted just prior Outcomes
to childbirth, from which urine analysis was done. In the second Outcomes addressed by the three eligible studies included two of
study of 431 pregnant women (Turck 1962), 16 women were our primary outcomes (incidence of endometritis, urinary tract in-
fection) and four of our secondary outcomes (wound infection, ad- the US Public Health Service, with the antibiotics and placebo
verse effects of antibiotics, length of maternal hospital stay and cost provided through Lederle laboratories.
of care). The studies did not report on other important outcomes
of this review (incidence of severe maternal infectious morbidity,
antimicrobial resistance and women’s satisfaction with care). Trialist declarations of interest
In one study (Fernandez 1993), endometritis was defined as Declarations of interest were not reported in any of the included
pyrexia of ≥ 38° C confirmed on two separate occasions and ac- studies (Fernandez 1993; Neto 1990; Turck 1962)
companied by pain on mobilisation of the uterus or fetid lochia or
both, and/or a leukocytosis of more than 10,000/mm3 ) that oc-
curred within two weeks following childbirth. A slightly different Excluded studies
definition was used by Neto 1990, as two of the following; fever, We excluded eight studies. Studies were excluded due to lack of
hypogastric pain, uterine involution, abnormal lochia, assessed at randomisation (Charles 1986), inclusion of women with assisted
10 days postpartum. In Turck 1962, urinary tract infection was vaginal births, or third-degree tears (Costa 1998; Yamagishi 2009),
diagnosed as the presence in urine of gram-negative bacteriuria prophylactic antibiotic administration during labour (Kampikaho
(more than 105 organisms per millilitre of urine), in addition to 1993; Oluwalana 2017) or just prior to birth (Cormier 1988;
symptoms or signs such as fever, dysuria, frequency, or flank pain Sharma 2014) and vaginal cleansing with antibiotics (Matthias
diagnosed by attending physicians. Neto 1990 defined episiotomy 1986). One study (Yamagishi 2009) provided non-segregated data;
dehiscence as wound rupture without signs of infection, and epi- our efforts to contact the author were unsuccessful, and we even-
siotomy infection as pain, heat, redness or purulent discharge and tually excluded the study. See Characteristics of excluded studies .
wound rupture. No definition was provided in Fernandez 1993.
Risk of bias in included studies
The risks of bias across studies and for the three included studies
Sources of funding
(which also contributed to the meta-analysis) are presented in a
Sources of trial funding were not mentioned in Fernandez 1993 ’Risk of bias’ table in Figure 2. We rated the risk of bias as high
or Neto 1990. Turck 1962 was supported by a training grant from for all three included studies.
Figure 2. Risk of bias summary: review authors’ judgements about each risk of bias item for each included
study.
Allocation
of attrition bias to be high risk for the other two studies (Fernandez
The choice of intervention for the control group had elements 1993; Neto 1990). In Neto 1990 information was not available
of randomisation in the three trials. However, two trials used a for all 80 women randomised. Six women in the intervention
non-random sequence generation (Neto 1990; Turck 1962) and group and one in the control group were missing from follow-
were considered at high risk of bias. In the Fernandez 1993 study, up at 10 days postpartum when outcomes were assessed. How-
random sequence generation was achieved through using a ran- ever, there were no differences reported in baseline characteris-
dom-number table (low risk of bias) - however, the sequence could tics among those followed up. In Fernandez 1993, 1373 women
easily have been broken by the head midwife who conducted the were conscripted with an intention to treat. Eighty-two of these
randomisation, and the random-number table was located in the women were excluded after randomisation from the treated group.
labour ward (Fernandez 1993). Among the 1291 eventually analysed, 91 unknowns (it was un-
The risk of selection bias due to poor allocation concealment was known whether they had infection or not) were reported.
high for all three included trials. Preservation of allocation conceal-
ment could have been broken due to an inadequate sequence of
randomisation in the two trials using non-random sequence gen- Selective reporting
eration (participant’s hospital registration number (Turck 1962), Two studies (Fernandez 1993; Neto 1990) reported on all pre-
and even/odd protocol number (Neto 1990)). Selection bias may specified outcomes and we therefore considered them to be at a
have been introduced by participants or investigators who may low risk of reporting bias. We assessed the Turck 1962 study as
have foreseen assignments. In the Fernandez 1993 study, the choice being at a high risk of reporting bias because the trial report did
of treatment was known before inclusion. not provide details on the frequency of some outcomes including
adverse effects and hospital stay.
Blinding
Other potential sources of bias
Performance bias We found no other important risks of bias for the three included
We rated blinding in terms of performance bias as low risk for one trials (Fernandez 1993; Neto 1990; Turck 1962).
study (Turck 1962), where the control group received an identical-
appearing placebo in prepackaged pill boxes, and distributed in Effects of interventions
double-blind fashion. We judged the risk of performance bias to
See: Summary of findings for the main comparison Routine
be high for the other two studies (Fernandez 1993; Neto 1990),
antibiotic prophylaxis compared to no treatment or placebo for
with no treatment in the control groups. preventing infections in women who had normal vaginal births
See Summary of findings for the main comparison table for results
Detection bias of the main comparison: use of prophylactic antibiotics, compared
to placebo or no treatment, after normal vaginal birth.
In terms of detection bias, the risk was high for two studies
(Fernandez 1993; Turck 1962). In the Fernandez 1993 study there
was was no blinding of the women nor the investigators. In the Routine antibiotic prophylaxis versus no
Turck 1962 study the clinical diagnosis of puerperal urinary tract treatment/placebo
infection was made by the attending physicians, who were unaware
whether the woman was receiving a drug or the placebo. However,
blinding could have been broken if the hospital registration num-
Primary outcomes
ber and sequence generation were known by the attending physi-
cian. We rated the third study (Neto 1990) as having an unclear
risk of bias for this domain as there was insufficient information
provided in the trial report. Incidence of severe maternal infectious morbidity (including
septicaemia, septic shock, laparotomy/hysterectomy for
infection, maternal intensive care unit (ICU) admission, or
Incomplete outcome data organ failure) as reported by trial authors
The risk of attrition bias was low in one study (Turck 1962), as The incidence of severe maternal infectious morbidity was not
data were provided for all participants included. We assessed risk addressed by any of the included studies.
Endometritis (with or without myometritis and with or in risk could explain the greater effect of antibiotics use to prevent
without salpingitis causing maternal febrile morbidity), as infection after episiotomy in Neto 1990. A random-effects model
reported by the trial authors. also equalised the weighting of the contributing studies. A fixed-
Prophylactic antibiotics after uncomplicated vaginal birth may effect model showed a very similar estimate (RR 0.78, 95% CI
reduce the risk of endometritis by 72% (risk ratio (RR) 0.28, 95% 0.38 to 1.61) without changes in the overall effect.
confidence interval (CI) 0.09 to 0.83, two trials, 1364 women, There were few or no differences between treated and control
very low-quality evidence, see Analysis 1.1). However, one trial was groups for reported adverse effects (RR 3.03, 95% CI 0.32 to
of very small size (73 women) and reported zero events for this 28.95, two trials, 1706 women, very low-quality evidence, see
outcome (Neto 1990). Analysis 1.4). One woman in each study recorded skin rash re-
lated to antibiotic intake, which resolved with cessation of the
drug (Turck 1962) and within a few hours in the other study
Urinary tract infection (fever or dysuria and positive urine (Fernandez 1993). In the former, one of the 217 women treated
culture) with sulphamethoxypyridazine developed a maculopapular rash
and had an untoward reaction of sufficient severity to warrant dis-
There was substantial heterogeneity (I2 = 67%, P = 0.08) for the
continuation of the drug. Turck 1962 also reported that “the inci-
risk of urinary tract infection between the two trials contribut-
dence of unexplained pyrexia, headache or dizziness” was similar
ing data. Pooled estimates from a random-effects model showed
in both groups. No other maternal or neonatal adverse effects were
that there was little or no difference in the risk of urinary tract
reported.
infection (RR 0.25, 95% CI 0.05 to 1.19, T2 = 0.84 , two trials,
There were few or no differences between treated and control
1706 women, low-quality evidence, see Analysis 1.2). We deemed
groups in the length of maternal hospital stay in days (mean dif-
a pooled estimate to be appropriate, as the effect sizes of both trials
ference -0.15, 95% CI -0.31 to 0.01, one trial (Fernandez 1993),
were in the same direction and the characteristics of the women
1291 women, very low-quality evidence, see Analysis 1.5). No data
were considered similar; both studies were conducted in high-in-
were provided for comparisons between groups in the other in-
come countries and most of the women had in-out catheterisation.
cluded studies. However, Turck 1962 reported that the length of
It is noteworthy that the 16 women who were excluded from Turck
hospital stay was slightly prolonged in women with symptomatic
1962 had the highest incidence of urinary tract infection. Four
illness, but that in general the length of hospital stay was similar
of 16 women not given either antibiotics or placebo had symp-
between the two groups.
toms of urinary infection early in the puerperium. This analysis
A 2½-fold increase in costs of care in the control group was re-
also presents our subgroup analysis according to the duration of
ported in Fernandez 1993, compared to antibiotic prophylaxis
prophylactic antibiotics and the risk of urinary tract infections, as
(USD 3600: USD 9000, one trial, 1291 women, see Analysis 1.6).
the two trials used short-duration (single dose) (Fernandez 1993)
These costs included prophylactic antibiotics, treatment of en-
or long-duration (3 to 5 days) (Turck 1962) regimens. Applying a
dometritis and hospitalisations. These estimates did not include
fixed-effect model produced, as expected, a narrower CI and sug-
expenditures related to prolonged hospitalisation of the newborn
gests a reduction in the risk of urinary tract infection (RR 0.25,
or subsequent management of possible secondary sterility.
95% CI 0.11 to 0.57). However, this analysis should be inter-
The incidence of antimicrobial resistance and women’s satisfaction
preted with caution, as the two included trials tested different an-
with care were not addressed by any of the included studies.
tibiotic regimens, used different comparison groups (placebo or
no treatment) and Turck 1962 had a quasi-randomised design.
Secondary outcomes DISCUSSION

There were few or no differences between the treated and control
groups for the risk of episiotomy wound infection, reported as
wound dehiscence, in the included trials (RR 0.78, 95% CI 0.31
Summary of main results
to 1.96, T2 = 0.15, I2 = 33%, P = 0.22, two trials, 1364 women, We found a marked reduction in the risk of puerperal endometritis
very low-quality evidence, see Analysis 1.3). There is substantial in women who received routine prophylactic antibiotics compared
heterogeneity in the analysis of risk of episiotomy infection. Al- to those who received either placebo or no treatment. There was
though the P value is not significant and the CI of the only two little or no difference between the groups for the risk of urinary
studies included in this analysis overlap greatly, we considered the tract infection, wound infection and length of hospital stay. Ad-
characteristics of women in both trials to be different. Indeed, one verse effects due to antibiotic intake were reported in one woman
trial included only low socioeconomic-class women from one pub- each in two studies. No data were provided on the incidence of
lic hospital in one middle-income country, while the other trial severe maternal infectious morbidity, antimicrobial resistance and
was conducted in a high-income country. This baseline difference women’s satisfaction with care.
The antibiotic prophylaxis regimens used in the included studies The frequency of routine antibiotic prophylaxis is high in low-
vary widely in terms of the class of antibiotic used and duration of and middle-income countries. Eligible studies provided data from
the course. Only one trial used a regimen in line with the current two high-income countries (France and the USA) and one low-
understanding of antibiotic prophylaxis as a short-term course of income country (Brazil) in the 1960s and 1990s. The risks of bias
less than 24 hours. However, our subgroup analysis according to ranged from high to low across several domains.
the duration of prophylaxis was limited to the urinary infections We found substantial heterogeneity in the incidence of urinary
outcome only, as not enough data were available for the other two tract infection between the two studies reporting this outcome.
primary outcomes in this review. It is also notable that women en- This analysis also allowed for exploration of the planned subgroup
rolled in all three trials underwent some type of intervention dur- analysis for difference in duration of treatment, suggesting differ-
ing normal vaginal birth, including episiotomy and in-out bladder ences between groups. This observation could also be interpreted
catheterisation, which may have increased their baseline risk of in terms of differences in the method of comparison or drug class
infection. between studies. However, the effect was similar and in the same
Administration of prophylactic antibiotics after normal vaginal direction for both subgroups, as evidenced by the overlap of con-
births may be successful in preventing puerperal endometritis. fidence intervals. However, the paucity of studies and frequencies
However, the nature of the studies and the low numbers of par- of participants limited further interpretation.
ticipants and low frequency of events (with one trial reporting no Finally, the two quasi-RCTs included in this review used antibiotics
events) limit firm conclusions on the benefits of systematic an- (chloramphenicol, sulphamethoxypyridazine) with limited use in
tibiotic prescriptions, more so in women who gave birth without current clinical practice, raising questions about any applicability
complications. of the results of these trials to current obstetric practice.
The cost of treatment and potential for prevention of endometri-
tis propose a possible benefit for routine antibiotic prophylaxis.
However, the low incidence of endometritis in the included stud- Quality of the evidence
ies suggests that many women may have to be treated to avoid few
We adjusted the outcome ’wound infection’ to include episiotomy
case of endometritis. The treatment of a large number of women
dehiscence as reported by authors as a sign of episiotomy infection.
who are not at risk of developing endometritis poses the problem
The assessments of risk of bias ranged from low to high, although
of exposing mothers and their babies to unnecessary treatments
most domains were at high risk of bias for the included studies,
and threats to increasing antimicrobial resistance patterns. A sep-
given inadequate concealment of allocations and blinding.
arate Cochrane Review looks at different antibiotic regimens for
The quality of evidence based on GRADE assessment ranged from
treatment of postpartum endometritis (Mackeen 2015).
low to very low across all reported outcomes (Summary of findings
The incidence of urinary tract infections was also relatively low.
for the main comparison), because of very serious design limita-
We found significant heterogeneity between studies for the inci-
tions, small sample sizes, few events and wide confidence intervals.
dence of urinary tract infection, but a pooled estimate was deemed
appropriate as the effect sizes in both trials were in the same di-
rection and showed some clinical overlap. However, this analysis
should be interpreted with caution, as it only included two trials
Potential biases in the review process
which tested different antibiotic regimens (drug class and dura- We adhered to the recommendations provided in the Cochrane
tion of treatment), used different comparison groups (placebo or Handbook for Systematic Reviews of Interventions (Higgins 2011).
no treatment) and follow-up periods, and one trial had a quasi- We also conducted an exhaustive search of several trial registries
randomised design. The differences between studies may have also (both English and non-English) and evaluated results for eligibility,
been influenced by catheterisation (although single), which may thus minimising potential biases.
have affected the relatively high incidence of infection, as seen in
both the control group and excluded women in one study.
The incidence of wound infection and length of stay were similar Agreements and disagreements with other
in both treated and untreated women, but the low number of studies or reviews
participants in the studies limits conclusions on the benefits of
To our knowledge, there are no other systematic reviews or studies
antibiotic intake. The reporting of adverse effects from antibiotics
related to the use of routine antibiotic prophylaxis for the pre-
in two studies is of concern, although as expected they were very
vention of maternal morbidity or mortality in women who had
low.
normal vaginal births.
Overall completeness and applicability of

evidence AUTHORS’ CONCLUSIONS
Implications for practice satisfaction with care. Improved quantification of relative costs is
also encouraged. Measures to improve the quality of studies to
The scarcity of data and inherent limitations observed in the in-
ensure the exclusion of bias is encouraged. Consistency and better
cluded trials limit interpretation of the evidence for routine use of
reporting for methods of concealment, blinding, and other sources
antibiotics in cases of normal vaginal births. The available evidence
of potential bias will improve the quality of future evaluations for
is insufficient to support the use of routine antibiotic prophylaxis
the effectiveness of routine antibiotic prophylaxis in cases of nor-
in women who had normal vaginal births. The relatively low in-
mal vaginal births.
cidence of puerperal endometritis and urinary tract infections re-
ported in the included trials does not support the routine use of
prophylactic antibiotics for prevention of these conditions in the
postpartum. A very large number of women would be unneces-
sarily exposed to antibiotics to prevent few cases of endometritis, ACKNOWLEDGEMENTS
with the inherent risks of side effects of antibiotics and increasing As part of the prepublication editorial process, this review has been
antibiotic resistance. commented on by four peers (an editor and three referees who are
external to the editorial team) and the Group’s Statistical Adviser.
More evidence is needed to inform practice. In the interim, a bal-
ance among health provider experience, settings, participant char- This work was supported by the UNDP/UNFPA/UNICEF/
acteristics and eventual cost in cases of uncomplicated births, in- WHO/World Bank Special Programme of Research, Develop-
cluding considerations of the contribution of indiscriminate use of ment and Research Training in Human Reproduction (HRP), De-
antibiotics to raising antimicrobial resistance, needs to be consid- partment of Reproductive Health and Research (RHR), World
ered when making routine prescriptions of antibiotic prophylaxis. Health Organization.
Chioma E Chibueze’s work was financially supported by the The
Implications for research Grant of National Center for Child Health and Development,
Lack of evidence on the effect of routine antibiotic prescription for Japan 27B-10, 26A-5.
prevention of other infectious morbidities including septicaemia, The World Health Organization and Erika Ota and Chioma E
septic shock, antimicrobial resistance and maternal satisfaction Chibueze retain copyright and all other rights in their respective
with treatment calls for further research. Well-designed and high- contributions to the manuscript of this review as submitted for
powered randomised controlled trials are needed to evaluate the publication.
added value of routine antibiotic administration to prevent mater-
nal infections after normal vaginal birth using antibiotic regimens This project was supported by the National Institute for Health
that are widely available in different settings and considered safe Research, via Cochrane Infrastructure funding to Cochrane Preg-
for use in the obstetric population. nancy and Childbirth. The views and opinions expressed therein
are those of the authors and do not necessarily reflect those of the
Such trials could address the effect on the incidence of severe ma- Systematic Reviews Programme, NIHR, NHS or the Department
ternal infectious morbidity, antimicrobial resistance and maternal of Health.
REFERENCES
References to studies included in this review no parto normal com episiotomia]. ACM: Arquivos
Catarinenses de Medicina 1990;19(2):97–102.
Fernandez 1993 {published data only}
Turck 1962 {published data only}
Fernandez H, Gagnepain A, Bourget P, Peray P, Frydman
Turck M, Goffe BS, Petersdorf RG. Bacteriuria of
R, Papiernik E, et al. Antibiotic prophylaxis against
pregnancy: relation to socioeconomic factors. New England
postpartum endometritis after vaginal delivery: a prospective
Journal of Medicine 1962;266(17):857–60.
randomized comparison between Amox-CA (Augmentin®)
and abstention. European Journal of Obstetrics & Gynecology
and Reproductive Biology 1993;50(3):169–75. References to studies excluded from this review
Neto 1990 {published data only}

Neto S, Goncalves JA, De Andrade LF. Clinical evaluation Charles 1986 {published data only}
of the chloramphenicol use as a prophylactic antibiotic Charles DA, Larsen B. Pharmacokinetics of cefotaxime,
in the vaginal delivery with episiotomy [Avaliacao clinica moxalactam, and cefoperazone in the early puerperium.
do emprego do cloranfenicol como antibiotico profilatico Antimicrobial Agents and Chemotherapy 1986;29(5):873–6.
Cormier 1988 {published data only} Dolea 2003
Cormier P, Leng JJ, Janky E, Brouste V, Duthil B. Prevention Dolea C, Stein C. Global Burden of Disease 2000. Evidence
using cefotetan of post-partum and post-abortion infectious and Information for Policy (EIP). Geneva: World Health
complications in intra-uterine procedures. Revue Francaise Organization, 2003.
de Gynecologie et d’Obstetrique 1998;83(12):829–32. Higgins 2011
Costa 1998 {published data only} Higgins JPT, Green S, editor(s). Cochrane Handbook
Costa HF, Ávila ID, Gonçalves MM. Prophylactic antibiotic for Systematic Reviews of Interventions Version 5.1.0
treatment in obstetrics: comparison of regimens. Revista (updated March 2011). The Cochrane Collaboration,
Brasileira de Ginecologia e Obstetrícia 1998;20(9):509–15. 2011. Available from handbook.cochrane.org.
Kampikaho 1993 {published data only} Hussein 2010
Kampikaho A, Irwig LM. A randomized trial of penicillin Hussein J, Walker L. Chapter 8: Puerperal sepsis in low- and
and streptomycin in the prevention of post-partum infection middle-income settings: past, present and future. Maternal
in Uganda. International Journal of Gynecology & Obstetrics and Infant Deaths: Chasing Millennium Development Goals
1993;41(1):43–52. 4 & 5. London: RCOG Press, 2010:131–47.
Matthias 1986 {published data only} Hussein 2011
Mathias L, Kahhale S, Nestarez JE, Mathias AC, Cabaritti Hussein J, Mavalankar DV, Sharma S, D’Ambruoso L.
M. Prophylatic antibiotic in labor [Antibioticoterapia A review of health system infection control measures
profilática no parto]. Arquivos Brasileiros de Medicina 1986; in developing countries: what can be learned to reduce
60(4):321–4. maternal mortality. Globalization and Health 2011;7:14.
[PUBMED: 21595872]
Oluwalana 2017 {published data only}
Khan 2006
∗
Oluwalana C, Camara B, Bottomley C, Goodier S, Bojang
Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look
A, Kampmann B, et al. Azithromycin in labor lowers
PF. WHO analysis of causes of maternal death: a systematic
clinical infections in mothers and newborns: a double-blind
review. Lancet 2006;367(9516):1066–74. [PUBMED:
trial. Pediatrics 2017;139(2):e20162281.
16581405]
Roca A, Oluwalana C, Bojang A, Camara B, Kampmann
B, Bailey R, et al. Oral azithromycin given during labour Mackeen 2015
decreases bacterial carriage in the mothers and their Mackeen AD, Packard RE, Ota E, Speer L. Antibiotic
offspring: a double-blind randomized trial. Clinical regimens for postpartum endometritis. Cochrane Database
Microbiology & Infection 2016;22(6):565.e1–9. of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/
Roca A, Oluwalana C, Camara B, Bojang A, Burr S, Davis 14651858.CD001067.pub3
TM, et al. Prevention of bacterial infections in the newborn Newton 2008
by pre-delivery administration of azithromycin: study Newton ER. Antibiotics in maternal-fetal
protocol of a randomized efficacy trial. BMC Pregnancy and medicine. www.glowm.com/section˙view/
Childbirth 2015;15(1):302. heading/Antibiotics%2520in%2520Maternal-
Sharma 2014 {published data only} Fetal%2520Medicine/item/175. Available from,
2008 (accessed 31 October 2017). [DOI: 10.3843/
Sharma SK, Rogers BB, Alexander JM, McIntire DD,
Leveno KJ. A randomized trial of the effects of antibiotic GLOWM.10175
prophylaxis on epidural-related fever in labor. Anesthesia & Ngoc 2005
Analgesia 2014;118(3):604–10. Ngoc NT, Sloan NL, Thach TS, Liem le KB, Winikoff B.
Incidence of postpartum infection after vaginal delivery
Yamagishi 2009 {published data only} in Viet Nam. Journal of Health, Population, and Nutrition
Yamagishi Y, Izumi K, Tanaka K, Watanabe K, Mikamo 2005;23(2):121–30. [PUBMED: 16117363]
H. Evaluation of antimicrobial prophylaxis after normal
NICE 2014
delivery. Japanese Journal of Antibiotics 2009;62(2):103–15.
National Institute for Health and Care Excellence.
Additional references Intrapartum care: care of healthy women and their
babies during childbirth (Clinical Guideline 109).
ACOG 2011 www.nice.org.uk/guidance/cg190 2014 (accessed 31
American College of Obstetricians and Gynecologists. October 2017).
ACOG Practice Bulletin No. 120: Use of prophylactic RevMan 2014 [Computer program]
antibiotics in labor and delivery. Obstetrics and Gynecology The Nordic Cochrane Centre, The Cochrane Collaboration.
2011;117(6):1472–83. [PUBMED: 21606770] Review Manager (RevMan). Version 5.3. Copenhagen:
Acosta 2014 The Nordic Cochrane Centre, The Cochrane Collaboration,
Acosta CD, Kurinczuk JJ, Lucas DN, Tuffnell DJ, Sellers S, 2014.
Knight M. Severe maternal sepsis in the UK, 2011-2012: Say 2014
a national case-control study. PLoS Medicine 2014;11(7): Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB,
e1001672. [PUBMED: 25003759] Daniels J, et al. Global causes of maternal death: a WHO
systematic analysis. Lancet. Global Health 2014;2(6): WHO 1996
e323–33. [PUBMED: 25103301] World Health Organization. Care in normal birth:
a practical guide. Report. Geneva: World Health
Sharma 2013 Organization, 1996.
Sharma M, Sanneving L, Mahadik K, Santacatterina M, WHO 2005
Dhaneria S, Stålsby Lundborg C. Antibiotic prescribing in World Health Organization. The World Health Report
women during and after delivery in a non-teaching, tertiary 2005: Make every mother and child count. www.who.int/
care hospital in Ujjain, India: a prospective cross-sectional whr/2005/whr2005˙en.pdf 2005 (accessed October 2015).
study. Journal of Pharmaceutical Policy and Practice 2013;6:
WHO 2014
9. [PUBMED: 25848538]
World Health Organization. Antimicrobial Resistance Global
Report on Surveillance. Geneva: WHO, 2014.
Tharpe 2008
Tharpe N. Postpregnancy genital tract and wound References to other published versions of this review
infections. Journal of Midwifery & Women’s Health 2008;53
(3):236–46. [PUBMED: 18455098] Bonet 2016
Bonet M, Ota E, Chibueze CE, Oladapo OT. Routine
Van Dillen 2010 antibiotic prophylaxis after normal vaginal birth for
Van Dillen J, Zwart J, Schutte J, Van Roosmalen J. reducing maternal infectious morbidity. Cochrane Database
Maternal sepsis: epidemiology, etiology and outcome. of Systematic Reviews 2016, Issue 5. [DOI: 10.1002/
Current Opinion in Infectious Diseases 2010;23(3):249–54. 14651858.CD012137
[PUBMED: 20375891] ∗
Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Fernandez 1993
Methods Randomised controlled trial
Participants 1291 (610 treated and 681 control) pregnant women with uncomplicated vaginal births
in 1 public hospital recruited between January 1, 1989 and December 31, 1989.
Inclusion criteria were the following: vaginal delivery, absence of pyrexia (> 38° C) during
labour or the hour following delivery, an interval of < 24 hours between rupture of
membranes and the onset of labour, absence of any evidence of extragenital infection (e.
g. urinary tract with absence of urination burning) and absence of known allergies to
the drug of choice (Amox-CA) or to β-lactams
82 women were excluded after randomisation. These included 5 in whom the antibiotics
given was unknown (no endometritis), 71 women excluded due to antibiotic injections
after uterine exploration, and 6 other women who had more than a 24-hour interval
between membranes and labour onset
Interventions Intravenous amoxicillin/clavulanic antibiotic 1 hour after birth (Augmentin® (Beecham

laboratories)) versus no antibiotic prophylaxis.
Antibiotics were administered in a single dose and at 1.2 gr by intravenous injection, 1
hour after birth in the intervention group.
No injection was given to the control group.
Outcomes Endometritis, puerperal fever (temperature above 38° C during labour or the hour fol-
lowing delivery), urinary tract infection, lymphangitis, thromboembolic component,
hemorrhagic component, chlamydia serology positive (> 1/64), episiotomy dehiscence,
organism identified (from endometritis cases), specimens examined
In the absence of morbidities, women were discharged on the 5th day
Follow-up lasted for 2 weeks post-delivery
Notes France
Funding: not reported
Conflicts of interest: not reported
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection Low risk Random-numbers table, the head midwife randomised
bias) according to a random-number table in the labour ward
as soon as delivery had taken place
Allocation concealment (selection bias) High risk The choice of treatment was known before inclusion
Blinding of participants and personnel High risk Neither the women nor the medical team were blinded,
(performance bias) Outcomes were only from the experimental group who
All outcomes all received treatment, while the control group received
Fernandez 1993 (Continued)
no treatment
Blinding of outcome assessment (detection High risk No blinding of intervention group from which the out-
bias) comes were derived
All outcomes
Incomplete outcome data (attrition bias) High risk For prespecified outcomes, all 1291 women were ac-
All outcomes counted for. It is not possible to know the distribution of
the women excluded after randomisation in the 2 groups
Selective reporting (reporting bias) Low risk All outcomes were reported, regardless of low incidence;
some unknowns were also reported
Other bias Low risk No other sources of bias noted
Neto 1990
Methods Quasi-randomised controlled trial
Participants 80 women with normal labour and episiotomy in 1 public hospital recruited between
October 1988 and September 1989
73 women were included in analysis, 34 in intervention arm and 39 in control arm
Interventions Intervention arm received oral chloramphenicol 500 mg 4 times daily for 72 hours after
episiotomy repair
Control arm received no treatment
Outcomes Outcomes measured include episiotomy dehiscence (wound rupture without signs of
infection), episiotomy infection (pain, heat, redness or purulent discharge and wound
rupture), and puerperal endometritis assessed at 10 days postpartum (defined as 2 of the
following; fever, hypogastric pain, uterine involution, abnormal lochia)
Notes Florianopolis, Brazil. All women were from low social class and attended by a resident
doctor in Obstetrics and Gynaecology
Exclusion of 7 women lost to follow-up at 10 days postpartum
Funding: not reported
Risk of bias
Random sequence generation (selection High risk Randomised according to protocol number (even
bias) and odd numbers)
Allocation concealment (selection bias) High risk Allocation concealment based on protocol number
Neto 1990 (Continued)
Blinding of participants and personnel High risk Not double-blinded. Control arm received no
(performance bias) treatment or placebo
All outcomes
Blinding of outcome assessment (detection Unclear risk Unknown. No information on whether physicians
bias) who evaluated the women at 10 days postpartum
All outcomes were blinded to the treatment allocation
Incomplete outcome data (attrition bias) High risk 6 women in intervention group and 1 in control
All outcomes group were lost to follow-up but no differences re-
ported in baseline characteristics among those fol-
lowed-up
Selective reporting (reporting bias) Low risk All outcomes were reported
Turck 1962
Methods Quasi-randomised controlled trial
Participants 431 - 16 women excluded pre-randomised (217 treated, 198 control) pregnant women
who had normal spontaneous deliveries preceded by catheterisation of the urethra, in 1
private hospital recruited between 1 December 1961 and 1 May 1962
Interventions Antibiotics (given after birth) versus placebo

Experimental intervention: sulphamethoxypyridazine (2 tablets (1.0 gm) were given on
the first day and 1 tablet daily thereafter). Duration of therapy lasted on average for 5
days, with variations from 3 to 5 days dependent on the length of admission
Outcomes Postpartum urinary tract Infection (fever, dysuria, frequency, flank pain) and adverse
effects
Notes USA. Most women were white, from middle-income group and well-educated
Women with infections requiring antibiotic treatment at the time of admission and
those with known hypersensitivity to sulphonamides or requiring an indwelling urethral
catheter after delivery were excluded
Funding: Training grant of the US Public Health Service. The sulfamethoxypyridazine
(Kynex) and placebo were provided through Lederle laboratories
Risk of bias
Random sequence generation (selection High risk Participant’s hospital registration number (inade-
bias) quate sequence generation)
Turck 1962 (Continued)
Allocation concealment (selection bias) High risk Participant’s hospital registration number limited
protection of allocation concealment
Blinding of participants and personnel Low risk Outcome group: identical-appearing placebo in
(performance bias) prepackaged pill boxes, distributed in double-blind
All outcomes fashion
Blinding of outcome assessment (detection High risk Outcome group: the clinical diagnosis of puerperal
bias) urinary tract infection was made by the attending
All outcomes physicians, who were unaware whether the woman
was receiving a drug or the placebo
Note: but blinding could have been broken if the
hospital registration number and sequence gener-
ation were known by the attending physician
Incomplete outcome data (attrition bias) Low risk No missing outcome data
All outcomes
Selective reporting (reporting bias) High risk No details on the frequency of some outcomes (hos-
pital stay, adverse effects)
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Charles 1986 Non-randomised trial, focuses on drug pharmacokinetics
Cormier 1988 Antibiotics were administered immediately prior to a procedure (this included curettage, manual removal of the
placenta or manual examination of the uterus)
Costa 1998 The trial randomised a group of women with medium risk of infection; includes assisted vaginal delivery, vaginal,
cervical or rectal tears
Kampikaho 1993 Antibiotics were started during labour
Matthias 1986 A randomised control trial in which the comparison group received skin/vulval cleansing. All women in both
control and antibiotics groups had operative deliveries including episiotomies
Oluwalana 2017 Antibiotics administered during labour
Sharma 2014 Antibiotics were administered immediately prior to initiation of epidural labour analgesia
(Continued)
Yamagishi 2009 We could not extract separate data for those with uncomplicated vaginal births. Women who had third-degree
perineal lacerations were included among those who received prophylactic antibiotics
DATA AND ANALYSES
Comparison 1. 1. Antibiotic prophylaxis versus no treatment/placebo
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Endometritis 2 1364 Risk Ratio (M-H, Fixed, 95% CI) 0.28 [0.09, 0.83]
2 Urinary tract infection 2 1706 Risk Ratio (M-H, Random, 95% CI) 0.25 [0.05, 1.19]
2.1 Short-duration 1 1291 Risk Ratio (M-H, Random, 95% CI) 0.51 [0.18, 1.45]
prophylaxis
2.2 Long-duration prophylaxis 1 415 Risk Ratio (M-H, Random, 95% CI) 0.11 [0.03, 0.46]
3 Wound infection (episiotomy 2 1364 Risk Ratio (M-H, Random, 95% CI) 0.78 [0.31, 1.96]
dehiscence)
4 Adverse effects of antibiotics 2 1706 Risk Ratio (M-H, Fixed, 95% CI) 3.03 [0.32, 28.95]
(skin rash)
5 Length of maternal hospital stay 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected
- days
6 Cost of care (cost of antibiotic Other data No numeric data
prophylaxis, prolonged
hospitalisation and treatment
of endometritis)
Analysis 1.1. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 1

Endometritis.
Review: Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity
Comparison: 1 1. Antibiotic prophylaxis versus no treatment/placebo
Outcome: 1 Endometritis
Study or subgroup Antibiotics No treatment Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Fernandez 1993 4/610 16/681 100.0 % 0.28 [ 0.09, 0.83 ]
Neto 1990 0/34 0/39 Not estimable
Total (95% CI) 644 720 100.0 % 0.28 [ 0.09, 0.83 ]

Total events: 4 (Antibiotics), 16 (No treatment)
Heterogeneity: not applicable
Test for overall effect: Z = 2.29 (P = 0.022)
Test for subgroup differences: Not applicable
0.01 0.1 1 10 100

Favours antibiotics Favours no treatment
Analysis 1.2. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 2 Urinary
tract infection.
Outcome: 2 Urinary tract infection

M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
1 Short-duration prophylaxis
Fernandez 1993 5/610 11/681 55.2 % 0.51 [ 0.18, 1.45 ]
Subtotal (95% CI) 610 681 55.2 % 0.51 [ 0.18, 1.45 ]

2 Long-duration prophylaxis
Turck 1962 2/217 17/198 44.8 % 0.11 [ 0.03, 0.46 ]
Subtotal (95% CI) 217 198 44.8 % 0.11 [ 0.03, 0.46 ]

Total (95% CI) 827 879 100.0 % 0.25 [ 0.05, 1.19 ]
Heterogeneity: Tau2 = 0.84; Chi2 = 3.01, df = 1 (P = 0.08); I2 =67%
Test for subgroup differences: Chi2 = 2.88, df = 1 (P = 0.09), I2 =65%
0.01 0.1 1 10 100

Analysis 1.3. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 3 Wound
infection (episiotomy dehiscence).
Outcome: 3 Wound infection (episiotomy dehiscence)
Favours no
Study or subgroup Favours antibiotics treatment Risk Ratio Weight Risk Ratio
M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
Fernandez 1993 6/610 5/681 42.9 % 1.34 [ 0.41, 4.37 ]
Neto 1990 5/34 11/39 57.1 % 0.52 [ 0.20, 1.35 ]
Total (95% CI) 644 720 100.0 % 0.78 [ 0.31, 1.96 ]

Total events: 11 (Favours antibiotics), 16 (Favours no treatment)
Heterogeneity: Tau2 = 0.15; Chi2 = 1.49, df = 1 (P = 0.22); I2 =33%
0.05 0.2 1 5 20
Analysis 1.4. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 4 Adverse
effects of antibiotics (skin rash).
Outcome: 4 Adverse effects of antibiotics (skin rash)

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Fernandez 1993 1/610 0/681 47.5 % 3.35 [ 0.14, 82.05 ]
Turck 1962 1/217 0/198 52.5 % 2.74 [ 0.11, 66.84 ]
Total (95% CI) 827 879 100.0 % 3.03 [ 0.32, 28.95 ]

Heterogeneity: Chi2 = 0.01, df = 1 (P = 0.93); I2 =0.0%
0.01 0.1 1 10 100

Analysis 1.5. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 5 Length of

maternal hospital stay - days.
Outcome: 5 Length of maternal hospital stay - days
Mean Mean
Study or subgroup Antibiotics No treatment Difference Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Fernandez 1993 610 4.97 (1.43) 681 5.12 (1.57) -0.15 [ -0.31, 0.01 ]
-2 -1 0 1 2
Analysis 1.6. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 6 Cost of care
(cost of antibiotic prophylaxis, prolonged hospitalisation and treatment of endometritis).
Cost of care (cost of antibiotic prophylaxis, prolonged hospitalisation and treatment of endometritis)
Study Experimental Control
Fernandez 1993 3600 USD 9000 USD
APPENDICES
Appendix 1. LILACS search strategy

Step 1: ((antibiotico) OR (antibiótico) OR (antibiotics))
Step 2: ((parto) AND (vaginal) OR (vaginal delivery) OR (vaginal birth))
Appendix 2. ICTRP and ClinicalTrials.gov search terms

vaginal AND delivery AND antibiotics
vaginal AND birth AND antibiotics
CONTRIBUTIONS OF AUTHORS
All review authors were involved in development of the protocol.
M Bonet and CE Chibueze assessed relevant trials, extracted, entered and checked data from trials into RevMan.
M Bonet and CE Chibueze interpreted the data and drafted the review.
All authors read and approved the final version of the review for publication.
DECLARATIONS OF INTEREST
Mercedes Bonet: none known.
Erika Ota: none known.
Chioma E Chibueze’s work was financially supported by the The Grant of National Center for Child Health and Development, Japan
27B-10, 26A-5.
Olufemi T Oladapo: none known.
SOURCES OF SUPPORT
Internal sources
• The Grant of National Center for Child Health and Development, 27B-10, 26A-5, Japan.
External sources
• UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human
Reproduction (HRP), the Department of Reproductive Health and Research (RHR), World Health Organization, Geneva,
Switzerland.
• Japan Agency for Medical Research and Development, Japan.
The National Research Center for Child Health and Development, Japan receives government funding (AMED No.27300101) from
the Clinical Research Program for Child Health and Development, AMED, Japan to support the Cochrane Pregnancy and
Childbirth Satellite in Japan.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

The name of the outcome ’puerperal infection’ was revised to endometritis.
There are no further differences between the published protocol (Bonet 2016) and this full review.

Bonet2017 PDF

Uploaded by

Document Informationclick to expand document information

Document Informationclick to expand document information

Copyright:

Available Formats

Bonet2017 PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Bonet2017 PDF

Uploaded by

Copyright:

Available Formats

Cochrane Database of Systematic Reviews

Routine antibiotic prophylaxis after normal vaginal birth for

Bonet M, Ota E, Chibueze CE, Oladapo OT

Bonet M, Ota E, Chibueze CE, Oladapo OT.

Routine antibiotic prophylaxis after normal vaginal birth for

Mercedes Bonet1 , Erika Ota2 , Chioma E Chibueze3 , Olufemi T Oladapo1

Editorial group: Cochrane Pregnancy and Childbirth Group.

PLAIN LANGUAGE SUMMARY

Patient or population: Wom en who had norm al vaginal births

Risk with no treatment/ Risk with routine an-

Endom etritis Study population RR 0.28 1364 ⊕ -

Urinary tract inf ection Study population RR 0.25 1706 ⊕⊕ -

Wound inf ection (epi- Study population RR 0.78 1364 ⊕ -

7 per 1000 10 per 1000

Adverse ef f ects of an- Study population RR 3.03 1706 ⊕ -

CI: Conf idence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

Search methods for identification of studies Data collection and analysis

Electronic searches Selection of studies

Dealing with missing data

Secondary outcomes DISCUSSION

Overall completeness and applicability of

Neto 1990 {published data only}

Characteristics of included studies [ordered by study ID]

Methods Randomised controlled trial

Interventions Intravenous amoxicillin/clavulanic antibiotic 1 hour after birth (Augmentin® (Beecham

Bias Authors’ judgement Support for judgement

Other bias Low risk No other sources of bias noted

Methods Quasi-randomised controlled trial

Bias Authors’ judgement Support for judgement

Other bias Low risk No other sources of bias noted

Methods Quasi-randomised controlled trial

Interventions Antibiotics (given after birth) versus placebo

Bias Authors’ judgement Support for judgement

Other bias Low risk No other sources of bias noted

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Charles 1986 Non-randomised trial, focuses on drug pharmacokinetics

Kampikaho 1993 Antibiotics were started during labour

Oluwalana 2017 Antibiotics administered during labour

Comparison 1. 1. Antibiotic prophylaxis versus no treatment/placebo

Analysis 1.1. Comparison 1 1. Antibiotic prophylaxis versus no treatment/placebo, Outcome 1

Comparison: 1 1. Antibiotic prophylaxis versus no treatment/placebo

Study or subgroup Antibiotics No treatment Risk Ratio Weight Risk Ratio

Neto 1990 0/34 0/39 Not estimable

Total (95% CI) 644 720 100.0 % 0.28 [ 0.09, 0.83 ]

0.01 0.1 1 10 100

Comparison: 1 1. Antibiotic prophylaxis versus no treatment/placebo

Outcome: 2 Urinary tract infection

Study or subgroup Antibiotics No treatment Risk Ratio Weight Risk Ratio

Subtotal (95% CI) 610 681 55.2 % 0.51 [ 0.18, 1.45 ]

Subtotal (95% CI) 217 198 44.8 % 0.11 [ 0.03, 0.46 ]

0.01 0.1 1 10 100

Comparison: 1 1. Antibiotic prophylaxis versus no treatment/placebo

Outcome: 3 Wound infection (episiotomy dehiscence)

Neto 1990 5/34 11/39 57.1 % 0.52 [ 0.20, 1.35 ]

Total (95% CI) 644 720 100.0 % 0.78 [ 0.31, 1.96 ]