MSc Project Report 2014-2015library.lshtm.ac.uk/MSc_RSHR/2014-15/108664.pdf · 2016. 5. 19. · MSc...

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Candidate no: 108664 The prevalence and risk factors of puerperal sepsis in South Asia: a systematic review Supervisor: Laura Oakley Candidate number: 108664 Word count: 9592 Project length: Standard Submitted in part fulfilment of the requirements for the degree of MSc in Reproductive and Sexual Health Research September 2015 MSc Project Report 2014-2015

Transcript of MSc Project Report 2014-2015library.lshtm.ac.uk/MSc_RSHR/2014-15/108664.pdf · 2016. 5. 19. · MSc...

  • Candidate no: 108664

    The prevalence and risk factors of

    puerperal sepsis in South Asia: a

    systematic review

    Supervisor: Laura Oakley

    Candidate number: 108664

    Word count: 9592

    Project length: Standard

    Submitted in part fulfilment of the requirements for the degree of MSc in

    Reproductive and Sexual Health Research

    September 2015

    MSc Project Report

    2014-2015

  • Candidate no: 108664

  • Candidate no: 108664

    1

    CONTENTS

    ABSTRACT

    ACKNOWLEDGEMENTS

    1. INTRODUCTION

    2. AIMS & OBJECTIVES

    3. METHODS

    3.1 Criteria for selecting studies

    3.2 Search strategy

    3.3 Data collection

    3.4 Quality assessment

    3.4.1 Quality of case diagnosis

    3.4.2 Methodological quality

    3.5 Data synthesis and analysis

    4. RESULTS

    4.1 Search results

    4.2 Characteristics of included studies

    4.3 Quality of case diagnosis of puerperal sepsis

    4.4 Methodological quality of included studies

    4.5 The prevalence of puerperal sepsis

    4.5.1 Overall prevalence of puerperal sepsis

    4.5.2 Prevalence of puerperal sepsis by country

    4.5.3 Prevalence of puerperal sepsis by setting

    4.5.4 Prevalence of puerperal sepsis by quality of case diagnosis

    4.6 Meta-analysis of the prevalence of puerperal sepsis reported by high-quality

    studies.

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    4.7 Risk factors for puerperal sepsis

    5. DISCUSSION

    5.1 The overall prevalence of puerperal sepsis in South Asia

    5.2 The prevalence of puerperal sepsis by country

    5.3 The prevalence of puerperal sepsis by setting

    5.4 The prevalence of puerperal sepsis by the quality of case diagnosis

    5.5 Risk factors for puerperal sepsis

    5.6 Puerperal sepsis-related mortality

    5.7 Strengths of systematic review

    5.8 Limitations of systematic review

    5.9 Implications & recommendations for future research

    6. CONCLUSION

    REFERENCES

    APPENDIX 1. Search strategies

    APPENDIX 2: Joanna Briggs Institute critical appraisal checklist used for assessing

    methodological quality of included studies

    APPENDIX 3. Data extraction form

    APPENDIX 4: Included studies reporting additional types of puerperal infections that were

    not used in analysis

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    LIST OF FIGURES

    Figure 1. Identification and selection process of articles for inclusion in systematic review.

    Figure 2. Prevalence of puerperal sepsis reported by all included studies.

    Figure 3. Prevalence of puerperal sepsis by country.

    Figure 4. Prevalence of puerperal sepsis by setting.

    Figure 5. Prevalence of puerperal sepsis by quality of case diagnosis.

    Figure 6. Meta-analysis of the prevalence of puerperal sepsis reported by high-quality

    studies.

    LIST OF TABLES

    Table 1. International definitions of puerperal sepsis.

    Table 2. Characteristics of included studies reporting puerperal sepsis prevalence.

    Table 3. Critical appraisal results for included studies using the JBI Prevalence Critical

    Appraisal Checklist.

    Table 4. An overview of the characteristics of included studies. Table 5. Median prevalence and range of all included studies, overall and by strata.

    Table 6. Identified risk factors for puerperal sepsis.

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    ABSTRACT

    Background: Puerperal sepsis is a serious, yet highly preventable, cause of maternal

    mortality and morbidity in South Asia. No estimates for the prevalence of this condition exist

    for this region. The primary objective of this systematic review was to determine the

    prevalence of puerperal sepsis in South Asia. A secondary objective was to review risk

    factors leading to puerperal sepsis in this region.

    Methods: Comprehensive electronic searches of five databases were conducted. Studies

    reporting prevalence data for puerperal sepsis in South Asian countries were eligible for

    inclusion. Prevalence data was stratified by country, by setting (facility-based or population-

    based) and by quality of case diagnosis of puerperal sepsis. The methodological quality of

    included studies was assessed and meta-analysis was performed on a sub-set of high

    quality studies.

    Results: 23 studies were included in this review. The median prevalence of puerperal sepsis

    of all included studies was 3.84% of total deliveries (range 0% to 34.25%). The pooled

    prevalence of a sub-set of seven studies of high methodological quality was 3.20% of total

    deliveries (95% CI 2.03%, 5.02%). Clear trends in prevalence by country, setting and quality

    of diagnosis were difficult to discern. Identified risk factors for puerperal sepsis maternal

    factors such as pre-existing conditions, labour factors including peripartum bleeding,

    stillbirth, perineal tears, prolonged delivery and unhygienic practices, health service factors

    such as access to antenatal and obstetric care, and community factors such as lower

    socioeconomic status and unhygienic postpartum traditions.

    Conclusion: This systematic review is the first to attempt to estimate the prevalence of

    puerperal sepsis in South Asia. The findings from this review indicate a prevalence between

    3-4% of total deliveries. Although this estimate is relatively low, puerperal sepsis remains of

    public health importance as it is a significant cause of obstetric morbidity and mortality in

    South Asia, despite its highly preventable nature. Risk factors for puerperal sepsis are varied

    and include maternal, labour, health service and community factors, which should be the

    focus for prevention efforts.

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    ACKNOWLEDGEMENTS

    I would like to thank my personal tutor and project supervisor, Laura Oakley, for her

    invaluable guidance and feedback throughout every stage of completing this dissertation.

    Many thanks to Veronique Filippi who helped me to form the focus of my dissertation in the

    earlier stages, and to Clara Clavert for her advice on data analysis. I would like to also thank

    the MARCH Centre staff for giving me the opportunity to present my dissertation and for their

    useful feedback and suggestions.

    As a personal acknowledgement, I would like to thank my parents for their continued support

    and encouragement in pursuing my medical career and Masters. I would also like to express

    my appreciation to my friends for their endless moral support and for always listening.

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    1. INTRODUCTION

    Puerperal sepsis is a preventable postpartum complication that occurs when a recently

    delivered mother contracts an infection related to giving birth. It can rapidly progress along a

    spectrum of severity if untreated, leading to septicaemic shock and eventually death. In non-

    fatal cases, it can cause significant long-term morbidity such as chronic pelvic inflammatory

    disease and secondary infertility from tubal occlusion [1]. These serious consequences can

    be easily avoided with better infection control, prompt diagnosis and appropriate treatment

    [1]. Despite global progress in reducing maternal mortality, puerperal sepsis is a leading

    cause of preventable maternal deaths, accounting for up to 11% of maternal deaths

    worldwide [2]. The burden of maternal mortality is highest in the developing world, with

    southern Asia and sub-Saharan Africa together accounting for 83.8% of all maternal deaths

    [2]. South Asia has the highest proportion of maternal sepsis deaths globally (13.7%) [2], yet

    little current information exists regarding the epidemiology of puerperal sepsis in this region.

    Few reviews have attempted to produce estimates of the prevalence or incidence of

    puerperal sepsis. AbouZahr (2003) estimated the global incidence of puerperal sepsis to be

    4.4% of live births [3]. Dolea and Stein (2003) provide an incidence range of 0.07 to 9.3% of

    live births from data collected in developing countries between 1986 and 1998, although no

    studies from South Asian countries were identified or used in the review [4]. Seale et al.

    (2009) investigate the burden of puerperal sepsis in sub-Saharan Africa, with prevalence

    estimates reported by studies ranging from 0.1% to 17.9% [5]. Van Dillen et al. (2010)

    discuss the global epidemiology of puerperal sepsis, although specific regional figures of

    incidence were limited to high-income countries only [6]. Hussein and Walker (2010) suggest

    that the global incidence of puerperal sepsis in developing countries ranges from 0.1 to 10%

    of deliveries [7]. All of these reviews highlighted the difficulties in obtaining incidence

    estimates for puerperal sepsis, attributed to marked differences in study design, the

    diagnostic criteria used, and the setting, such as local conditions and whether the study is

    population-based or facility-based.

    Risk factors leading to puerperal sepsis are varied, including anaemia and other pre-existing

    maternal conditions, obstetric issues such as obstructed labour, health service factors such

    as poor hygiene and aseptic technique, and community factors such as socioeconomic

    status [1]. A better understanding of the determinants of puerperal sepsis is crucial in

    identifying factors that facilitate infection and in forming strategies for prevention.

    Various definitions for puerperal sepsis exist, although none are used universally, which has

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    contributed to the difficulty in estimating its prevalence [7]. In addition, many articles refer to

    the terms ‘puerperal sepsis’, ‘maternal sepsis’, ‘puerperal infection’, ‘puerperal pyrexia’ and

    ‘puerperal fever’ synonymously or without clarification of their definition [7]. Table 1 lists the

    major international definitions of puerperal sepsis outlined in key documents by the World

    Health Organization and the ICD-10 classification system. These definitions describe

    puerperal sepsis as a clinical syndrome (a group of signs and symptoms) that may have

    various primary aetiologies ranging from genito-urinary tract infections to obstetric wound

    sepsis. The ICD-10 definition further incorporates extra-genitourinary complications

    occurring in the puerperium under codes 087 – 092 [9], as does the WHO (1995) document

    under the more general term ‘puerperal infection’ [8]. However, this review only addresses

    puerperal sepsis associated with genito-urinary tract infections and obstetric wound

    infections due to their direct association with the process of childbirth. The length of the

    puerperium (postpartum period) is often cited as 42 days after delivery [8], although this may

    vary between studies. The start of the puerperium is also disputed; the WHO (1995)

    document [8] states that puerperal sepsis can occur from the onset of rupture of membranes

    or labour, whereas the ICD-10 definition excludes sepsis during labour [9].

    Identifying the prevalence of puerperal sepsis in South Asia is important in order to assess

    the magnitude of this potentially life-threatening, yet preventable, condition in a region where

    the burden of maternal mortality is already high. The aim of this systematic review is to

    estimate the prevalence and review risk factors for puerperal sepsis in South Asia, using the

    UN Millennium Development Goals region country groupings [10], taking into account the

    study location, setting and the quality of case diagnosis of puerperal sepsis.

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    Table 1. International definitions of puerperal sepsis.

    Document Definition of puerperal sepsis

    The Prevention and Management of Puerperal Infections: Report of a Technical Working Group, Geneva, 20-22 May 1992 – World Health Organization (1995) [8]

    Puerperal sepsis is defined as infection of the genital tract occurring at any time between the onset of the rupture of the membranes or labour and the 42nd day postpartum in which fever and one or more of the following are present: ▪ Pelvic pain ▪ Abnormal vaginal discharge e.g. presence of pus ▪ Abnormal smell/ foul odour of discharge ▪ Delay in the rate of reduction of size of uterus (

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    2. AIMS & OBJECTIVES

    Overall aim

    To perform a systematic review of the relevant literature, published from 2000

    onwards, to estimate the prevalence of puerperal sepsis in South Asia, as well as

    review risk factors leading to puerperal sepsis in this region.

    Objectives

    ▪ Primary objective: to estimate the prevalence of puerperal sepsis in South Asia:

    - by country;

    - by setting (population-based vs. facility-based);

    - by quality of case diagnosis of puerperal sepsis.

    ▪ Secondary objective: to review risk factors associated with puerperal sepsis in

    South Asia.

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    3. METHODS

    3.1 Criteria for selecting studies

    Inclusion criteria

    ▪ Articles published from 2000 onwards were included.

    ▪ Grey literature or studies of any design reporting data on the prevalence of puerperal

    sepsis or associated puerperal infections in South Asian countries were included. For the

    purpose of this review, the country grouping of the Southern Asian region used by the UN

    MDG initiative was used, comprising the following countries: Afghanistan, Bangladesh,

    Bhutan, India, Iran, Maldives, Nepal, Pakistan and Sri Lanka [10].

    ▪ Only articles published in English were eligible for inclusion.

    Exclusion criteria

    ▪ Articles reporting data on sepsis or fever within the puerperium associated with extra-

    urogenital infections and incidental causes unrelated to childbirth were not included.

    ▪ As puerperal sepsis is a clinical syndrome, prevalence data of singular non-specific

    symptoms such as ‘discharge’ or ‘pain’ were not included. However, an exception to this

    criterion were reports of puerperal ‘fever’, which is identified by ICD-10 as a defining term of

    puerperal sepsis under code 085 [9], and is acknowledged as the key defining symptom of

    puerperal sepsis in the WHO (2008) definition [1] (see Table 1).

    ▪ Studies that identified cases of puerperal sepsis from study samples unrepresentative of all

    deliveries within the study’s reported setting (facility or population-based) were excluded.

    This included deliveries exclusive to women undergoing caesarean section, post-abortion

    cases, grand multiparous women, women with obstetric-related acute renal failure, women

    requiring emergency peripartum hysterectomy, and women with pre-term premature rupture

    of membranes. Furthermore, deliveries to women admitted to intensive care units and ‘near

    miss’ sepsis cases were excluded, as they would not include cases of less severe puerperal

    infection.

    ▪ Studies reporting data of mortality from puerperal sepsis without prevalence data were

    excluded.

    3.2 Search strategy

    Comprehensive electronic searches of the following databases were conducted: MEDLINE,

    Embase, Global Health, Popline and WHO Reproductive Health Library. The main concepts

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    of ‘puerperal sepsis’ and ‘epidemiology’ were searched in MEDLINE, Embase and Global

    Health databases using free text and MeSH headings. Region and country filters for South

    Asia were applied in order to focus search results. For Popline and WHO Reproductive

    Health Library databases, only the main concept of ‘puerperal sepsis’ was searched, with

    manual review of study location and relevant epidemiological data. All searches were

    conducted on 7th and 8th July 2015, with search results restricted to articles published from

    2000 onwards. No language restrictions were applied, but only papers available in English

    were included. Detailed search strategies for each database are provided in Appendix 1.

    Manual review of reference lists and citation tracking of salient articles were also conducted.

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    Figure 1. Identification and selection process of articles for inclusion in systematic review.

    3.3 Data collection

    Data was extracted from included articles using a standardised data extraction form

    comprising: the full title of study, author(s), year of publication, journal of publication, location

    of study, study design, study dates (follow-up period or study duration), study setting, study

    population, the case definition of puerperal sepsis/associated puerperal infections, the

    number of puerperal sepsis cases, the sample size (denominator), prevalence data, data on

    risk factors, and the method of case ascertainment. A template data extraction form can be

    found in Appendix 3.

    Databases searched: ▪ MEDLINE n =1,482 ▪ Embase n = 3,402 ▪ Global Health n = 1,831 ▪ WHO Reproductive Health Library n = 123 ▪ Popline n = 94 Total n = 6,932

    Duplicates removed: n = 1,526

    n = 5,406

    Excluded at title & abstract screen:

    n = 4,911

    n = 495 Articles excluded at full text review: ▪ No relevant data n = 196 ▪ General: Full text unobtainable n = 74 Not written in English n = 2 Studies published before 2000 n = 3 ▪ Population: Data not from S. Asia/not possible to extract S. Asia-specific data n = 18 Inappropriate denominator n = 87 ▪ Outcome: Puerperal sepsis mortality data only n = 59 Sepsis not childbirth-related n = 25 Non-specific symptoms n = 10 ▪ Other: Secondary publication n = 1

    n = 20

    Manual citation tracking:

    n = 3

    Included articles: n = 23

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    Due to the nature of delivery outcomes, the terms ‘prevalence’ and ‘incidence’ have been

    used with interchangeable definitions in studies reporting data on puerperal sepsis, with both

    terms referring to the number of puerperal sepsis cases (n) in a specified population (N) over

    a specified time period. Throughout this review, the term ‘prevalence’ has been used. ‘N’ is

    represented by the total number of deliveries from which ‘n’ puerperal sepsis cases have

    arisen, where one delivery may consist of one or more live-born or stillborn births [12]. In

    addition, this review uses the term ‘delivery’ to also represent any termination of pregnancy,

    including spontaneous or induced abortions.

    If a study did not readily provide prevalence data, it was calculated by dividing the total

    number of puerperal sepsis cases (n) by a suitable figure for the total number of deliveries

    (N). Where studies reported stratified prevalence data (for example, cases of puerperal

    sepsis by facility or by maternal body mass index), the total number of puerperal cases and

    the total number of deliveries in each stratum were totalled and an overall prevalence

    measure was calculated. Several studies reported prevalence data for more than one type of

    puerperal infection. It there was no overlap between the different types, an overall

    prevalence measure was calculated. If overlap existed between the prevalences of different

    types of puerperal infection, the most generic type, such as ‘puerperal fever’ or ‘puerperal

    sepsis’, was selected for analysis over more specific conditions such as ‘urinary tract

    infection’ or ‘wound infection’. Details of other types of puerperal infection reported by

    included studies that were not used in analysis can be found in Appendix 4.

    If supplied, data on risk factors for puerperal sepsis demonstrating statistical significance

    were also extracted from included studies.

    3.4 Quality assessment

    3.4.1 Quality of diagnosis

    The quality of each study’s diagnosis of puerperal sepsis cases was assessed in order to

    compare the prevalence of puerperal sepsis by high-, medium- and low-quality sub-groups.

    The following classification was used:

    ▪ Low quality diagnosis:

    - The study does not provide a case definition of puerperal sepsis and uses self-

    reported symptoms to identify cases.

    ▪ Medium quality diagnosis:

    - The study provides an acceptable case definition of puerperal sepsis, but uses self-

    reported symptoms to identify cases;

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    - or the study does not provide a case definition of puerperal sepsis, but uses a

    clinical source (including corroboration of self-reported symptoms by a physician/

    trained staff/ medical records) to identify cases.

    ▪ High quality diagnosis:

    - The study provides an acceptable case definition of puerperal sepsis, and uses a

    clinical source (including corroboration of self-reported symptoms by a physician/

    trained staff/ medical records) to identify cases.

    3.4.2 Methodological quality

    The methodological quality of each of the included studies was assessed using the Joanna

    Briggs Institution (JBI) critical appraisal checklist for studies reporting prevalence data [11]

    (see Appendix 2). A sub-set of high-quality studies could then be identified for meta-analysis.

    For the purpose of this review, the JBI criteria deemed to be the most indicative of a high-

    quality study were Question 1 (representative sample of the target population), Question 2

    (appropriate recruitment of study participants), Question 6 (the use of objective, standard

    criteria for measurement of the condition), and Question 7 (reliable measurement of the

    condition). However, Question 1 was difficult to assess in included studies due to a lack of

    reporting of whether or not abortions and stillbirths were included in the sample as a delivery

    outcome, so was not used in this selection process. Studies were therefore classified as

    high-quality if they demonstrated good overall quality by scoring a ‘yes’ across a minimum of

    6 out of 10 questions, of which a ‘yes’ was specifically scored in Question 2, Question 6 and

    Question 7 (see Table 3).

    3.5 Data synthesis and analysis

    Forest plots were used to present the prevalence of puerperal sepsis, expressed as a

    percentage, with 95% confidence intervals calculated using the binomial exact method.

    Prevalence data was stratified by country, by setting (facility-based or population-based) and

    by quality of case diagnosis of puerperal sepsis (low, medium or high). Meta-analysis was

    conducted on a sub-set of studies deemed to be of high methodological quality (see

    methods section 3.4.2), in order to provide a pooled estimate of the prevalence of puerperal

    sepsis in South Asia. The meta-analysis was conducted using the ‘metaprop’ command from

    RStudio 3.2.0 with the package ‘meta’ using a random-effects model. Risk factors identified

    as being statistically significant were extracted from included studies and tabulated.

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    4. RESULTS

    4.1 Search results

    Initial searches of the five databases produced a total of 6,932 results. After removing 1,526

    duplicates, the remaining 5,406 articles underwent title and abstract screening. A further

    4,911 articles were excluded and the full texts of the remaining 495 articles were assessed

    for eligibility. 20 suitable articles were identified for inclusion, with a further three articles

    identified by manual citation tracking. This produced a total of 23 studies included in this

    systematic review. See Figure 1 for a flow diagram detailing the identification and selection

    process of articles for inclusion in this review.

    4.2 Characteristics of included studies

    Geographical location

    Of the 23 included studies, 11 studies were conducted in India [14, 19, 21, 23, 24, 26, 27,

    29, 30, 32, 33], five in Bangladesh [13, 16, 25, 28, 35], five in Pakistan [15, 17, 18, 22, 31]

    and two in Nepal [20, 34]. No studies from other South Asian countries met the inclusion

    criteria for this review.

    Year of publication & period of data collection

    The included studies were published between 2000 and 2014, with data collection taking

    place between 1992 and 2012. Study periods ranged from one month to 8 years, with a

    median study period of 18 months.

    Study design

    Nine of the studies were cross-sectional in design, of which seven were prospective [13, 15,

    17, 22, 25, 26, 29] and two were retrospective [21, 24]. 10 were prospective cohort studies

    [14, 16, 19, 23, 27, 31-35], two were nested case-control studies within prospective cohorts

    [18, 28], and two were randomised controlled trials [20, 30].

    Study setting & participants

    11 studies were facility-based, of which one study used data from primary health centres

    [21], eight from tertiary facilities [18, 22-24, 28, 30-32], and two from a mix of secondary and

    tertiary facilities [25, 33]. The remaining 12 studies were population-based [13-17, 19, 20,

    26, 27, 29, 34, 35]. All of the studies used participants consisting of recently delivered

    women or pregnant women recruited for follow-up after delivery (see Table 2 for further

    details).

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    Case definition of puerperal sepsis & method of ascertainment

    12 studies provided a case definition of puerperal sepsis or an associated puerperal infection

    [13, 14, 16, 17, 20, 25, 26, 30-33, 35], whilst the remaining 11 of studies did not [15, 18, 19,

    21-24, 27-29, 34]. Eight of the studies identified puerperal sepsis cases using self-reported

    symptoms only [13, 15, 17, 19, 29, 30, 34, 35], 12 studies used a clinical diagnosis (i.e. by a

    physician/trained healthcare worker or from medical records) [14, 18, 21-26, 28, 31-33] and

    three studies used a combination of self-reported symptoms and/or clinical diagnosis [16, 20,

    27]. In facility-based studies that did not explicitly specify the method of ascertainment of

    sepsis cases, it was assumed that cases were identified by clinical diagnosis from a

    physician or trained healthcare worker.

    Risk factors for puerperal sepsis

    Seven of the 23 included studies also identified statistically significant risk factors for

    puerperal sepsis [13, 16, 17, 23, 28, 31, 35].

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    Table 2. Characteristics of included studies reporting puerperal sepsis prevalence.

    No. Author(s), year

    Region, Country

    Study design & period of data collection

    Setting Study Participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no. of deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    1 Goodburn et al., 2000 [13]

    Bangladesh Prospective cross-sectional study, 1992-1993 (18 months)

    Population-based, rural

    Mothers delivered at home with a non-formal birth attendant

    ▪ ‘Postpartum maternal infection’ –Deemed to be present if 2 or more of the following symptoms were reported: lower abdominal pain; fever; foul smelling discharge - (reported at 2 and 6 weeks postpartum).

    274 800 34.25 Self-reported symptoms

    2 Bang et al.,

    2004 [14]

    Gadchiroli

    district,

    Maharashtra

    – India

    Prospective

    cohort study,

    1995-1998

    (3 years)

    Population-

    based, rural

    (39 villages)

    All pregnant women

    in selected study

    villages

    ▪ ‘Puerperal fever’ – Temperature

    >37.8oC on any day during 2–28 days

    after delivery.

    93

    772

    12.04

    Clinical

    observations by

    trained health

    workers and

    physician

    3

    Fikree et

    al.,

    2004 [15]

    Karachi

    – Pakistan

    Prospective

    cross-

    sectional

    study,

    Aug-Nov 2000

    (3 months)

    Population-

    based

    (5 low socio-

    economic

    settlements)

    Muslim women

    interviewed between

    42 and 56 days

    postpartum following

    a live birth

    ▪ ‘High fever’

    – No case definition given.

    59

    525

    11.24

    Self-reported

    symptoms

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    Table 2. (continued)

    No. Author(s), Year

    Region, Country

    Study design & period of data collection

    Setting Study Participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no. of

    deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    4 Fronczak et al., 2005 [16]

    Dhaka – Bangladesh

    Prospective cohort study, Nov 1993-May 1995 (19 months)

    Population-based, (slum areas of 5 selected districts)

    Pregnant women living in selected slum areas

    ▪ ‘Pelvic infection’ – Two of the symptoms: abdominal tenderness, fever, or foul vaginal discharge occurring 3 or more days postpartum (reported at 72 hours, 7 days & examined between 14-22 days postpartum).

    14 1,506 0.93 Self-reported symptoms + corroboration by medical records for facility-based deliveries + physician examination 14 to 22 days postpartum

    5 Ghani et

    al.,

    2007 [17]

    Khyber

    Agency

    – Pakistan

    Prospective

    cross-

    sectional

    study,

    July 2005

    (1 month)

    Population-

    based

    Pregnant or

    postpartum married

    women between 15

    to 49 years

    ▪ ‘Vaginal infection’ – Perceived foul

    smelling discharge, fever, lower

    abdominal pain during postpartum

    period (40 days).

    162

    1,000

    16.20

    Self-reported

    symptoms

    6 Jaleel &

    Khan,

    2008 [18]

    Karachi

    – Pakistan

    Nested case

    control study,

    Jan-Dec 2007

    (1 year)

    Facility-

    based,

    urban

    (tertiary

    hospital)

    All women admitted

    for delivery and

    during puerperium

    ▪ ‘Pelvis sepsis’ & ‘puerperal sepsis’ used

    interchangeably (no postpartum period

    specified)

    – No case definition given.

    5 735 0.68 Clinical

    diagnosis

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    Table 2. (continued)

    No. Author(s), Year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no. of

    deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    7 Patra et al., 2008 [19]

    Chhainsa village, Haryana – India

    Prospective cohort study, Aug 2002-July 2003 (1 year)

    Population-based, rural

    All women who experienced childbirth during the study period in Chhainsa village followed up to 6 weeks postpartum

    ▪ ‘High fever’ up to 42 days postpartum – No case definition given.

    44

    211

    20.85

    Self-reported symptoms

    8 Christian

    et al.,

    2009 [20]

    Sarlahi district

    – Nepal

    Cluster-

    randomised

    controlled

    trial,

    Jan 2000-Feb

    2001

    (1 year)

    Population-

    based,

    rural

    (30 villages)

    Pregnant married

    women living with

    their husbands,

    having at least 1 live

    birth (control arm:

    vitamin A

    supplements; trial

    arms: folic

    acid/zinc/iron

    supplement

    combinations)

    ▪ ‘Puerperal sepsis’ – Measured

    temperature ≥ 100.4 °F OR “hot to the

    touch” on 2 or more days of the first

    10 days postpartum exclusive of the first

    day, and foul smelling vaginal discharge

    on 2 or more days.

    242

    3,564

    6.79

    Self-reported

    symptoms +/-

    temperature

    measurement

    by trained

    interviewer in

    first 10 days

    postpartum

    9 Iyengar K.

    & Iyengar

    S.,

    2009 [21]

    Southern

    Rajasthan

    – India

    Retrospective

    cross-

    sectional

    study,

    Jan 2000-Dec

    2008

    (8 years)

    Facility-

    based,

    rural

    (2 primary

    health

    centres)

    Women in labour or

    presenting with

    antenatal, post-

    partum or post-

    abortion

    complications

    ▪ ‘Puerperal fever’ (no postpartum

    period specified)

    – No case definition given.

    6

    3,171

    0.19

    Medical records

  • Candidate no: 108664

    20

    Table 2. (continued)

    No. Author(s), Year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no. of

    deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    10 Shamshad et al., 2010 [22]

    Abbottabad – Pakistan

    Prospective cross-sectional study, Jan 2005-Dec 2007 (2 years)

    Facility-based (Ayub Teaching Hospital; tertiary)

    Obstetrical patients admitted over study period, including those presenting with post-abortion complications

    ▪ ‘Puerperal sepsis’ (within 42 days of termination of pregnancy) – No case definition given.

    92

    5,268

    1.75

    Medical records

    11 Joshi et al.,

    2011 [23]

    Pune

    – India

    Prospective

    cohort study,

    Aug 2005-Sept

    2007

    (2 years)

    Facility-

    based,

    urban

    (tertiary

    hospital)

    Women receiving

    prenatal care at the

    study hospital

    ▪ ‘Postpartum fever’ (no postpartum

    period specified)

    – No case definition given.

    38 1,200 3.17 Clinical

    diagnosis

    12 David et

    al.,

    2012 [24]

    Vellore, Tamil

    Nadu

    – India

    Retrospective

    cross-

    sectional

    study,

    2005-2010

    (5 years)

    Facility-

    based,

    (1 urban

    health

    centre, 1

    tertiary

    health

    centre, other

    government

    & private

    hospitals)

    All women admitted

    in labour to the study

    facilities, including

    patients transferred

    intrapartum or in the

    1st week postpartum

    ▪ ‘Puerperal sepsis’ (in the first week

    postpartum)

    – No case definition given.

    0

    1,873

    0

    Medical records

  • Candidate no: 108664

    21

    Table 2. (continued)

    No. Author(s), Year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no. of

    deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    13 Huda et al., 2012 [25]

    Matlab & Chandpur – Bangladesh

    Prospective cross-sectional study, 2007-2008 (1 year)

    Facility-based, rural (4 public hospitals & 26 private hospitals; mixed secondary & tertiary)

    Women who gave birth during 2007-2008, excluding spontaneous and induced abortion cases

    Puerperal infection up to 42 days postpartum, including: ▪ ‘Severe: septic shock or septicaemia’ – Genital source of infection and hyperthermia (fever 38.3°C and above for >48 hours) or hypothermia and low blood pressure (systolic

  • Candidate no: 108664

    22

    Table 2. (continued)

    No. Author(s), year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no. of

    deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    14

    Iyengar, 2012 [26]

    Rajasthan – India

    Prospective cross-sectional study, Jan 2007-Dec 2010 (3 years)

    Population-based, rural (49 villages)

    Recently delivered women

    Puerperal infection in the first week postpartum, including: ▪ ‘Uterine infection’ – Temperature above 38 °C and one of the following symptoms: pain in lower abdomen, abnormal vaginal discharge, uterus not contracted well, history of heavy vaginal bleeding. ▪ ‘Upper urinary tract infection’ – Temperature above 38oC and one of the following symptoms: burning in micturition, flank pain. ▪ ‘Only fever’ – Temperature above 38 °C TOTAL:

    64 28 73 165

    4,975 4,975 4,975

    4,975

    1.29 0.56 1.47 3.32

    Clinical examination by nurse-midwives

    15 Iyengar et

    al.,

    2012 [27]

    Rajasthan

    – India

    Prospective

    cohort study,

    June 2008-July

    2010

    (2 years)

    Population-

    based,

    rural

    Women who

    delivered during the

    study period and

    were contacted

    during the early

    postpartum period

    ▪ ‘Fever’ – Temperature >38 °C reported

    by nurse-midwife/doctor (in the first

    week postpartum);

    or ‘infected episiotomy/sepsis’ (in the

    first week postpartum) – No case

    definition given.

    9

    1,542

    0.58

    Home visit

    examinations by

    nurse-midwives

    + self-reported

    symptoms

  • Candidate no: 108664

    23

    Table 2. (continued)

    No. Author(s), year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/

    associated puerperal infections

    Cases (n)

    Total no. of

    deliveries (N)

    Prevalence n/N (%)

    Method of case

    ascertainment

    16 Mannan et al., 2012 [28]

    Dhaka – Bangladesh

    Nested case-control study, July 2006-June 2007 (1 year)

    Facility-based, urban (Sir Salimullah Medical College Hospital, Azimpur Maternity Center, some selected private hospitals; tertiary)

    Pregnant women screened for gestational diabetes mellitus (GDM)

    ▪ ‘Puerperal sepsis’ (up to 4 weeks postpartum) – No case definition given.

    17 144 11.81 Clinical diagnosis

    17 Shriraam

    et al.,

    2012 [29]

    Mugalivakkam,

    Kancheepuram

    district, Tamil

    Nadu

    – India

    Prospective

    cross-

    sectional

    study,

    Nov 2008-Feb

    2009

    (3 months)

    Population-

    based,

    rural

    All women who

    delivered in the last 6

    months and

    completed 42 days

    puerperium

    ▪ ‘Puerperal sepsis’ (within 42 days

    postpartum)

    – No case definition given.

    14

    365

    3.84

    Self-reported

    symptoms

    18 Gupta et

    al.,

    2013 [30]

    New Delhi

    – India

    Prospective

    randomised

    controlled

    trial,

    Oct 2005-

    March 2007

    (18 months)

    Facility-based,

    urban

    (Lok Nayak

    Hospital;

    tertiary)

    Asymptomatic

    women in antenatal

    clinic screened for

    abnormal vaginal

    flora (control arm: no

    treatment, trial arm:

    antibiotics)

    ▪ ‘Postpartum fever’ / ‘puerperal

    pyrexia’ (used interchangeably) –

    An oral temperature of ≥38.0°C on

    any 2 of the first 10 days after

    delivery, exclusive of the first 24

    hours.

    13

    743

    1.75

    Self-measured

    & self-reported

    symptoms

  • Candidate no: 108664

    24

    Table 2. (continued)

    No. Author(s), Year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no.of deliveries

    (N)

    Prevalence n/N (%)

    Method of

    case

    ascertainment

    19 Khaskheli et al., 2013 [31]

    Jamshoro, Hyderabad, Sindh - Pakistan

    Prospective cohort study, Jan-Dec 2011 (1 year)

    Facility-based (tertiary hospital)

    Women delivering in this hospital or referred within 42 days after delivery

    ▪ ‘Puerperal pyrexia/ sepsis’ – Elevated body temperatures, abdominal distention, dehydration, foul smelling lochia, rise in total leukocyte count, intra-peritoneal collection, uterine collection, retained products of conception (within 42 days postpartum).

    129 3,316 3.89 Clinical diagnosis (detailed history, examination & investigations)

    20

    Dasgupta

    et al.,

    2014 [32]

    Pondicherry

    – India

    Prospective cohort study, 2 year period beginning Oct 2010

    Facility-

    based

    (JIPMER;

    tertiary)

    Pregnant women up to 16 gestation wks on 1st antenatal visit, including abortion cases

    ▪ ‘Puerperal wound sepsis’ – Includes post- lower segment caesarean section wound discharge and episiotomy wound gape (postpartum period unspecified).

    10

    199

    5.03

    Clinical diagnosis

    21 Hussein et al., 2014 [33]

    Gujarat state – India

    Prospective

    cohort study,

    Nov 2010-Feb

    2012

    (15 months)

    Facility-

    based

    (6 hospitals;

    mixed

    secondary

    and tertiary)

    Women

    delivering in the

    study hospitals,

    excluding

    spontaneous and

    induced abortion

    cases

    ▪ ‘Puerperal sepsis and other puerperal

    infections’ – As specified in ICD-10 codes 085

    and 086, including infections of obstetric

    surgical wounds, genital tract and urinary tract

    infections following delivery (up to 42nd day

    postpartum).

    319

    8,124

    3.93

    Clinical

    diagnosis

    22 Karkee et

    al.,

    2014 [34]

    Kaski district

    – Nepal

    Prospective

    cohort study,

    Dec 2011-Oct

    2012

    (10 months)

    Population-

    based,

    mixed

    urban/rural

    Women at least 5

    months pregnant

    completing

    follow-up

    interview

    ▪ ‘Postpartum severe fever’ (within 45 days

    after delivery)

    – No case definition given.

    17

    639

    2.66

    Self-reported

    symptoms

  • Candidate no: 108664

    25

    Table 2. (continued)

    No. Author(s), year

    Region, Country

    Study design & period of data collection

    Setting Study participants

    Case definition of puerperal sepsis/ associated puerperal infections

    Cases (n)

    Total no.of deliveries

    (N)

    Prevalence n/N (%)

    Method of

    case

    ascertainment

    23 Sikder et

    al.,

    2014 [35]

    Bangladesh

    (northwest)

    Prospective

    cohort study,

    Dec 2007-June

    2011

    (4 months)

    Population-

    based,

    rural

    Pregnant women living with their husbands completing postpartum maternal morbidity interviews

    ▪ ‘Sepsis’ - High fever and foul-smelling vaginal discharge OR high fever and lower abdominal pain (30 days postpartum). If the woman had an induced abortion or miscarriage, these symptoms must have occurred within 7 days of the termination of pregnancy. ‘Near miss’ sepsis cases are defined as reports of nearly dying plus high fever.

    3,259

    42,124 7.74 Self-reported symptoms

  • Candidate no: 108664

    26

    4.3 Quality of case diagnosis of puerperal sepsis

    All 12 studies that provided a case definition of puerperal sepsis or associated puerperal

    infection used a diagnostic criteria acceptable under either the WHO or ICD-10 definitions

    (see Table 1). However, the quality of a study’s diagnosis of puerperal sepsis also depends

    on the method by which cases were ascertained. Clinical sources, including physicians,

    trained healthcare workers/interviewers and medical records, are likely to provide a more

    valid diagnosis of puerperal sepsis than self-reported symptoms [36].

    Using the classification described in the methods section 3.4.1, four studies provided a low

    quality diagnosis of puerperal sepsis cases [15, 19, 29, 34], 12 studies provided a medium

    quality diagnosis [13, 17, 18, 20-24, 27, 28, 30, 35], and seven studies provided a high

    quality diagnosis [14, 16, 25, 26, 31-33] (see Table 4).

  • Candidate no: 108664

    27

    4.4 Methodological quality of included studies

    Each of the included studies were critically appraised using the JBI Prevalence Critical

    Appraisal Checklist, consisting of ten questions addressing key methodological study

    elements (see Appendix 2) [11].

    Table 3. Critical appraisal results for included studies using the JBI Prevalence Critical Appraisal Checklist.

    Y = yes, N = no, U = unclear, N/A = not applicable

    Study author(s) & year

    Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Included in meta-analysis

    Goodburn et al., 2000 [13]

    U Y U Y N Y N Y Y N/A -

    Bang et al., 2004 [14] U Y U Y Y Y Y Y U N/A ✓

    Fikree et al., 2004 [15] N Y U Y N N N Y U N/A -

    Fronczak et al., 2005 [16] U Y U Y Y Y Y Y U N/A ✓

    Ghani et al., 2007 [17] U Y U Y Y Y N Y U N/A -

    Jaleel & Khan, 2008 [18] U Y Y Y N N Y Y N Y -

    Patra et al., 2008 [19] U Y Y Y N N N Y U N/A -

    Christian et al., 2009 [20] N Y U N Y Y N Y Y Y -

    Iyengar K. & Iyengar S.,

    2009 [21] U Y Y N N N Y U U Y -

    Shamshad et al., 2010 [22]

    U Y Y Y N N Y U N N/A -

    Joshi et al., 2011 [23] U Y U Y N N Y Y U Y -

    David et al., 2012 [24] U Y Y N N N Y U U N/A -

    Huda et al., 2012 [25] N Y Y Y Y Y Y Y Y N/A ✓

    Iyengar, 2012 [26] U Y Y Y Y Y Y Y Y N/A ✓

    Iyengar et al., 2012 [27] Y Y Y N N N Y Y Y Y -

    Mannan et al., 2012 [28] U Y U N N N Y Y U Y -

    Shriraam et al., 2012

    [29] U Y U Y N N N Y Y N/A -

    Gupta et al., 2013 [30] U Y Y Y Y Y N Y N Y -

    Khaskheli et al., 2013

    [31] U Y Y Y Y Y Y Y N N/A ✓

    Dasgupta et al., 2014 [32]

    U Y Y N Y Y Y Y Y Y ✓

    Hussein et al., 2014 [33] N Y Y Y Y Y Y Y Y Y ✓

    Karkee et al., 2014 [34] U Y U Y N N N Y Y N/A -

    Sikder et al., 2014 [35] Y Y Y Y Y Y N Y Y N/A -

  • Candidate no: 108664

    28

    All included studies used a sample consisting of recently delivered women or pregnant

    women recruited for postpartum follow-up, representing the total number of deliveries within

    that particular study setting. However, the studies varied as to whether they included

    stillbirths and/or abortions as a delivery outcome. Two studies limited delivery outcomes to

    live births only [15, 20] and two studies explicitly excluded abortions [25, 33], therefore

    potentially underestimating the total number of deliveries and the number of sepsis cases as

    a result of abortion or stillbirth events. Studies marked unclear under Q1 in Table 3 did not

    mention whether both stillbirths and abortions were included in the study [13, 14, 16-19, 21-

    24, 26-32, 34, 35].

    All studies reported an appropriate method of recruitment of study participants, with most

    providing sufficient detail regarding the characteristics of the setting and participants. 13

    studies reported conducting a calculation for an adequate sample size; those which did not

    were given an unclear status for Q3 (see Table 3). Most studies reported the reasons for

    non-response, although few studies additionally described how non-responders differed from

    responders with regards to their socio-demographic characteristics. All studies which

    identified subpopulations amongst participants used objective criteria to classify subgroups.

    12 studies provided an objective criterion for the diagnosis of puerperal sepsis cases [13, 14,

    16, 17, 20, 25, 26, 30-33, 35], all of which were valid under the WHO or ICD-10 definitions

    (see Table 1). However, the time period assigned to the puerperium in which sepsis cases

    were identified differed between studies, ranging from the first seven days to the first 56

    days postpartum, with a median of 40 days. Four studies did not specify a postpartum period

    [18, 21, 23, 32]. Studies with earlier postpartum cut-offs may have missed sepsis cases

    arising at later time periods, and those which did not provide any case definition may be

    subject to measurement or classification bias. Cases were ascertained by different methods

    across the studies, including self-reported symptoms and clinical sources (see Table 2).

    Those studies relying on self-reported symptoms [13, 15, 17, 19, 20, 29, 30, 34, 35] may be

    prone to information bias due to the subjectivity of self-perceived illness and the potential of

    recall bias in retrospective study designs.

  • Candidate no: 108664

    29

    Table 4. An overview of the characteristics of included studies.

    *BNG = Bangladesh, NPL = Nepal, IND = India, PAK = Pakistan

    No. Author(s), year Location* Setting Quality of diagnosis of puerperal sepsis

    BNG NPL IND PAK Facility- based

    Pop- based

    High Med Low

    1 Goodburn et al., 2000 [13] ✓ ✓ ✓

    2 Bang et al., 2004 [14] ✓ ✓ ✓

    3 Fikree et al., 2004 [15] ✓ ✓ ✓

    4 Fronczak et al., 2005 [16] ✓ ✓ ✓

    5 Ghani et al., 2007 [17] ✓ ✓ ✓

    6 Jaleel & Khan, 2008 [18] ✓ ✓ ✓

    7 Patra et al., 2008 [19] ✓ ✓ ✓

    8 Christian et al., 2009 [20] ✓ ✓ ✓

    9 Iyengar K. & Iyengar S., 2009 [21]

    ✓ ✓ ✓

    10 Shamshad et al., 2010 [22] ✓ ✓ ✓

    11 Joshi et al., 2011 [23] ✓ ✓ ✓

    12 David et al., 2012 [24] ✓ ✓ ✓

    13 Huda et al., 2012 [25] ✓ ✓ ✓

    14 Iyengar, 2012 [26] ✓ ✓ ✓

    15 Iyengar et al., 2012 [27] ✓ ✓ ✓

    16 Mannan et al., 2012 [28] ✓ ✓ ✓

    17 Shriraam et al., 2012 [29] ✓ ✓ ✓

    18 Gupta et al., 2013 [30] ✓ ✓ ✓

    19 Khaskheli et al., 2013 [31] ✓ ✓ ✓

    20 Dasgupta et al., 2014 [32] ✓ ✓ ✓

    21 Hussein et al., 2014 [33] ✓ ✓ ✓

    22 Karkee et al., 2014 [34] ✓ ✓ ✓

    23 Sikder et al., 2014 [35] ✓ ✓ ✓

  • Candidate no: 108664

    30

    4.4 Selection of studies for meta-analysis

    After visual inspection of data, performing a statistical meta-analysis for all included studies

    was deemed to be inappropriate due to considerable heterogeneity. Therefore, a sub-set of

    studies of high methodological quality was instead selected for meta-analysis using key

    criteria from the JBI Critical Appraisal Checklist (see Appendix 2), as described in the

    methods section 3.4.2. Using this criteria, seven studies were identified as high-quality [14,

    16, 25, 26, 31-33] and were included in formal meta-analysis.

    4.5 The prevalence of puerperal sepsis

    4.5.1 Overall prevalence of puerperal sepsis

    The reported prevalence of puerperal sepsis varied across all included studies (see Figure

    2), with a median of 3.84% of total deliveries and a large range of 0% to 34.25%.

    4.5.2 Prevalence of puerperal sepsis by country

    Large variations in prevalence also existed within countries (see Figure 3). Nepal had the

    highest median prevalence of 11.76%; however this is calculated from two studies only with

    a wide range from 2.66% to 20.85%. The median prevalence in Bangladesh was 7.74%, with

    a range from 0.88% to 34.25%. The prevalence tended to be lower in Pakistan (median

    3.89%, range 0.19% to 16.20%) and India (median 3.32%, range 0% to 12.05%).

    4.5.2 Prevalence of puerperal sepsis by setting

    When stratified by setting (see Figure 4), the prevalence tended to be lower and less varied

    in facility-based studies (median 1.75%, range 0.19% to 11.81%) compared to population-

    based studies (median 7.26%, range 0.58% to 34.25%,).

    4.5.4 Prevalence of puerperal sepsis by quality of case diagnosis

    Figure 5 shows the prevalence of puerperal sepsis stratified by the quality of case diagnosis.

    In studies with a high quality case diagnosis, the prevalence ranged from 0.58% to 12.05%,

    with a median of 3.89%. Studies with a medium quality case diagnosis demonstrated a lower

    median prevalence of 2.46%, with a range from 0% to 34.25%. Prevalence data from studies

    with a low quality case diagnosis tended to be more varied, with a median of 7.54% and a

    range from 2.66% to 20.85%.

  • Candidate no: 108664

    31

    4.6 Meta-analysis of the prevalence of puerperal sepsis reported by high-quality

    studies

    Meta-analysis was performed on a subset of seven studies deemed to be of high

    methodological quality (see Figure 6). The pooled prevalence of puerperal sepsis was 3.20%

    of total deliveries (95% CI 2.03%, 5.02%). The I-squared and tau-squared test indicate

    substantial statistical heterogeneity among this sub-set of studies (p

  • Candidate no: 108664

    32

    Figure 2. Prevalence of puerperal sepsis reported by all included studies.

    1 David et al. identified 0 puerperal sepsis cases, which is unable to be displayed.

    Study identifier

    Goodburn et al., 2000

    Bang et al., 2004

    Fikree et al., 2004

    Fronczak et al., 2005

    Ghani et al., 2007

    Jaleel & Khan, 2008

    Patra et al., 2008

    Christian et al., 2009

    Iyengar K. & Iyengar S., 2009

    Shamshad et al., 2010

    Joshi et al., 2011

    David et al., 20121

    Huda et al., 2012

    Iyengar, 2012

    Iyengar et al., 2012

    Mannan et al., 2012

    Shriraam et al., 2012

    Gupta et al., 2013

    Hussein et al., 2014

    Dasgupta et al., 2014

    Karkee et al., 2014

    Sikder et al., 2014

    Khaskheli et al., 2013

    Prevalence % (95% CI)

    34.25 (30.96, 37.65)

    12.05 (9.83, 14.55)

    11.24 (8.67, 14.26)

    0.93 (0.51, 1.55)

    16.20 (13.97, 18.63)

    0.68 (0.22, 1.58)

    20.85 (15.58, 26.97)

    6.79 (5.98, 7.67)

    0.19 (0.07, 0.41)

    1.75 (1.41, 2.14)

    3.17 (2.25, 4.32)

    n/a

    0.88 (0.51, 1.41)

    3.32 (2.84, 3.85)

    0.58 (0.27, 1.10)

    11.81 (7.03, 18.2)

    3.84 (2.11, 6.35)

    1.75 (0.93, 2.97)

    3.93 (3.51, 4.37)

    5.03 (2.43,1, 9.05)

    2.66 (1.56, 4.22)

    7.74 (7.48, 8.00)

    3.89 (3.26, 4.60)

    0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40

    Prevalence of puerperal sepsis %

  • Candidate no: 108664

    33

    Figure 3. Prevalence of puerperal sepsis by country.

    1 David et al. identified 0 puerperal sepsis cases, which is unable to be displayed.

    Country

    Bangladesh

    India

    Pakistan

    Nepal

    Goodburn et al., 2000

    Bang et al., 2004

    Fikree et al., 2004

    Fronczak et al., 2005

    Ghani et al., 2007

    Jaleel & Khan, 2008

    Patra et al., 2008

    Christian et al., 2009

    Iyengar K. & Iyengar S., 2009

    Shamshad et al., 2010

    Joshi et al., 2011

    David et al., 20121

    Huda et al., 2012

    Iyengar, 2012Iyengar et al., 2012

    Mannan et al., 2012

    Shriraam et al., 2012

    Gupta et al., 2013Hussein et al., 2014

    Dasgupta et al., 2014

    Karkee et al., 2014

    Sikder et al., 2014

    Khaskheli et al., 2013

    Prevalence % (95% CI)

    34.25 (30.96, 37.65)

    12.05 (9.83, 14.55)

    11.24 (8.67, 14.26)

    0.93 (0.51, 1.55)

    16.20 (13.97, 18.63)

    0.68 (0.22, 1.58)

    20.85 (15.58, 26.97)

    6.79 (5.98, 7.67)

    0.19 (0.07, 0.41)

    1.75 (1.41, 2.14)

    3.17 (2.25, 4.32)

    n/a

    0.88 (0.51, 1.41)

    3.32 (2.84, 3.85)0.58 (0.27, 1.10)

    11.81 (7.03, 18.2)

    3.84 (2.11, 6.35)

    1.75 (0.93, 2.97)3.93 (3.51, 4.37)

    5.03 (2.43,1, 9.05)

    2.66 (1.56, 4.22)

    7.74 (7.48, 8.00)

    3.89 (3.26, 4.60)

    0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40

    Prevalence of puerperal sepsis %

  • Candidate no: 108664

    34

    Figure 4. Prevalence of puerperal sepsis by setting.

    1 David et al. identified 0 puerperal sepsis cases, which is unable to be displayed.

    Study setting

    Facility-based

    Population-based

    Goodburn et al., 2000

    Bang et al., 2004

    Fikree et al., 2004

    Fronczak et al., 2005

    Ghani et al., 2007

    Jaleel & Khan, 2008

    Patra et al., 2008

    Christian et al., 2009

    Iyengar K. & Iyengar S., 2009

    Shamshad et al., 2010

    Joshi et al., 2011

    David et al., 20121

    Huda et al., 2012

    Iyengar, 2012

    Iyengar et al., 2012

    Mannan et al., 2012

    Shriraam et al., 2012

    Gupta et al., 2013

    Hussein et al., 2014

    Dasgupta et al., 2014

    Karkee et al., 2014

    Sikder et al., 2014

    Khaskheli et al., 2013

    Prevalence % (95% CI)

    34.25 (30.96, 37.65)

    12.05 (9.83, 14.55)

    11.24 (8.67, 14.26)

    0.93 (0.51, 1.55)

    16.20 (13.97, 18.63)

    0.68 (0.22, 1.58)

    20.85 (15.58, 26.97)

    6.79 (5.98, 7.67)

    0.19 (0.07, 0.41)

    1.75 (1.41, 2.14)

    3.17 (2.25, 4.32)

    n/a

    0.88 (0.51, 1.41)

    3.32 (2.84, 3.85)

    0.58 (0.27, 1.10)

    11.81 (7.03, 18.2)

    3.84 (2.11, 6.35)

    1.75 (0.93, 2.97)

    3.93 (3.51, 4.37)

    5.03 (2.43,1, 9.05)

    2.66 (1.56, 4.22)

    7.74 (7.48, 8.00)

    3.89 (3.26, 4.60)

    0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40

    Prevalence of puerperal sepsis %

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    Figure 5. Prevalence of puerperal sepsis by quality of case diagnosis.

    1 David et al. identified 0 puerperal sepsis cases, which is unable to be displayed.

    Quality of diagnosis

    High

    Medium

    Low

    Goodburn et al., 2000

    Bang et al., 2004

    Fikree et al., 2004

    Fronczak et al., 2005

    Ghani et al., 2007

    Jaleel & Khan, 2008

    Patra et al., 2008

    Christian et al., 2009

    Iyengar K. & Iyengar S., 2009

    Shamshad et al., 2010

    Joshi et al., 2011

    David et al., 20121

    Huda et al., 2012

    Iyengar, 2012

    Iyengar et al., 2012

    Mannan et al., 2012

    Shriraam et al., 2012

    Gupta et al., 2013

    Hussein et al., 2014

    Dasgupta et al., 2014

    Karkee et al., 2014

    Sikder et al., 2014

    Khaskheli et al., 2013

    Prevalence % (95% CI)

    34.25 (30.96, 37.65)

    12.05 (9.83, 14.55)

    11.24 (8.67, 14.26)

    0.93 (0.51, 1.55)

    16.20 (13.97, 18.63)

    0.68 (0.22, 1.58)

    20.85 (15.58, 26.97)

    6.79 (5.98, 7.67)

    0.19 (0.07, 0.41)

    1.75 (1.41, 2.14)

    3.17 (2.25, 4.32)

    n/a

    0.88 (0.51, 1.41)

    3.32 (2.84, 3.85)

    0.58 (0.27, 1.10)

    11.81 (7.03, 18.2)

    3.84 (2.11, 6.35)

    1.75 (0.93, 2.97)

    3.93 (3.51, 4.37)

    5.03 (2.43,1, 9.05)

    2.66 (1.56, 4.22)

    7.74 (7.48, 8.00)

    3.89 (3.26, 4.60)

    0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40

    Prevalence of puerperal sepsis %

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    Table 5. Median prevalence and ranges of all included studies, overall and by strata.

    Figure 6. Meta-analysis of the prevalence of puerperal sepsis reported by high-quality studies.

    Strata Median prevalence (%) Range (%)

    All included studies

    3.84 0 – 34.25

    By country Bangladesh India Nepal Pakistan

    7.74 3.32 11.76 3.89

    0.88 – 34.25 0 – 12.05 2.66 – 20.85 0.19 – 16.20

    By setting Facility-based Population-based

    1.75 7.26

    0 – 11.81 0.58 – 34.25

    By quality of case diagnosis High quality Medium quality Low quality

    3.89 2.46 7.54

    0.58 – 12.05 0 – 34.25 3.54 – 13.64

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    37

    4.7 Risk factors for puerperal sepsis

    Of the 23 studies included in this review, eight studies identified a number of statistically

    significant risk factors for puerperal sepsis, which can be categorised as maternal factors,

    labour factors, health service factors and community factors (see Table 6.)

    Table 6. Identified risk factors for puerperal sepsis.

    Type of risk factor Risk factors for puerperal sepsis

    Maternal factors Age 35 yrs [35] Nulliparity [35] Higher parity [16] Mid upper arm circumference

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    5. DISCUSSION

    5.1 The overall prevalence of puerperal sepsis in South Asia

    Findings from this systematic review suggest that the prevalence of puerperal sepsis in

    South Asia falls between 3-4% of all deliveries, as identified from the median prevalence of

    23 included studies (3.84%) and the pooled prevalence of seven high-quality studies

    (3.20%). However, it is difficult to establish a single reliable estimate due wide variations in

    reported prevalence by individual studies (ranging from 0% to 34.25%), as well as significant

    statistical heterogeneity that is likely to be attributed to clinical and methodological variation

    between studies.

    No previous reviews have provided an estimate of the overall prevalence of puerperal sepsis

    in South Asia specifically. Nonetheless, the median and pooled prevalence estimates found

    by this review were comparable to the global estimate of 4.4% of live births produced by

    AbouZahr (2003) [3]. As was the case with this review, wide prevalence ranges were also

    identified for Sub-Saharan Africa by Seale et al. (2009) (range 0.1% to 17.9%) [5], and for

    developing countries by Dolea and Stein (2003) (range 0.07% to 9.3%) [4] and Hussein and

    Walker (2010) (range 0.1% to 10%) [7]. All of these reviews highlighted the difficulty in

    estimating prevalence due to marked differences in study characteristics. This systematic

    review therefore stratified prevalence data by the following key study features: country of

    study, setting (facility-based or population-based), and the quality of case diagnosis of

    puerperal sepsis.

    5.2 The prevalence of puerperal sepsis by country

    Despite stratification by country, wide variations in the prevalence of puerperal sepsis

    persisted, making it difficult to discern any country-level trends. It should be noted that only

    studies from India, Bangladesh, Pakistan and Nepal met the inclusion criteria for this

    systematic review, therefore generalisability of results to the remaining South Asian

    countries is limited.

    5.3 The prevalence of puerperal sepsis by setting

    The prevalence of puerperal sepsis tended to be lower and less varied in facility-based

    studies (median 1.75%) compared to population-based studies (median 7.26%). It is likely

    that facility-based studies identified fewer puerperal sepsis cases than population-based

    studies due to the admission of patients with more severe infection only [20], as well as

    missed sepsis cases among women with limited access to facilities due to factors such as

    distance, financial constraints and cultural beliefs [4]. Furthermore, postpartum infections

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    can manifest several days after delivery, therefore cases that occur after being discharged

    without re-admission often go undiagnosed and under-reported, particularly in settings with

    no postnatal follow-up [7] [37].

    Regardless of whether the recruitment of study participants was facility-based or population-

    based, the proportions of women giving birth in a facility or at home varied within studies,

    accounting for some of the variation in prevalence estimates. It is suggested that more

    puerperal sepsis cases arise from home births than facility births due to higher levels of

    unclean practices [25], such as traditions of inserting home-made substances into the vagina

    [4] and restricted bathing postpartum [17]. The lack of skilled birth attendance at home births

    is also associated with less hygienic delivery practices [13] [25]. On the other hand, facilities

    may face higher rates of nosocomial puerperal infection as a result of suboptimal hygiene

    standards and increased risk from multiple pelvic examinations, caesarean sections and

    other invasive procedures [6] [26] [39]. The need for prevention and control of infections in

    facilities is becoming a more pressing issue as the utilisation of already over-burdened

    health facilities increases [31]. Despite the significant role that the place of delivery plays in

    the contraction of puerperal infection, few studies specify the number of puerperal sepsis

    cases by facility births and home births. Future research should not only identify puerperal

    sepsis cases by study setting, but also consider the place of delivery and the presence of

    skilled birth attendants.

    5.4 The prevalence of puerperal sepsis by the quality of case diagnosis

    Studies with a high-quality case diagnosis of puerperal sepsis reported a median prevalence

    of 3.89%. This is likely to be a more reliable prevalence estimate than those ascertained

    from studies with a medium-or low- quality diagnosis because of the use of an appropriate

    definition and a clinical source of case ascertainment rather than self-report. However, the

    comparability of prevalence estimates remains limited due to variations in the definitions and

    types of puerperal infection included by individual studies. This may have led to an

    overestimation or underestimation of prevalence, as some cases identified by some studies

    will have been missed by others. For example, several studies include cases of puerperal

    fever alone, whereas other study definitions would consider this insufficient for a diagnosis of

    puerperal sepsis without other symptoms present. AbouZahr (2003) suggests that puerperal

    fever is a reliable index of puerperal sepsis, as most causes of temperature elevation in the

    puerperium are associated with pelvic infection [3]. However, it would also encompass cases

    of fever associated with non-genitourinary infection and other incidental causes [7],

    overestimating the prevalence of puerperal sepsis. The postpartum time period in which

    cases were identified also varied between studies, so studies with earlier cut-offs may have

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    missed infections that manifested in later days or weeks. Furthermore, several studies

    reported overlapping data for different types of puerperal infection, of which only the most

    generic type was selected for analysis, underestimating the total number of puerperal sepsis

    cases. It is therefore clear that reliable prevalence estimates of puerperal sepsis are difficult

    to obtain without a universal diagnostic criterion.

    The quality of a study’s case diagnosis is also dependent on the method of ascertainment of

    puerperal sepsis cases. Clinical diagnosis by trained healthcare workers are considered to

    be a more valid method of determining puerperal sepsis than self-reported symptoms [42]. It

    has been noted that self-reported symptoms tend to over-estimate the incidence of clinically

    present morbidities [4] [16], which may be due to self-perception of symptoms such as ‘fever’

    without accurate measurement, and over-reporting by participants who feel obliged to report

    something [19]. These may have been contributing factors to the anomalously high

    prevalence estimates of 34.25%, 16.20% and 20.85% reported by Goodburn et al. (2000)

    [13], Ghani et al. (2007) [17] and Patra et al. (2008) [19] respectively. Self-reported

    symptoms may also underestimate prevalence due to limitations in recall and the perception

    of postpartum morbidities as insignificant or normal [19]. Nonetheless, self-reported

    symptoms remain important in determining health behaviour patterns and the perceived

    discomfort and interference to women’s daily lives [15] [19]. It may also be the only feasible

    method to collect data on maternal morbidities in resource-poor settings [4].

    Clinical diagnoses ascertained by healthcare workers or from medical records are not

    without fault, as they may be subject to misclassification by facilities with with poor record-

    keeping [25] and limited awareness of the clinical presentation of puerperal sepsis. Signs

    and symptoms vary depending on the source of infection [37] as well as the degree of

    severity of sepsis [40] [41], which can make specific diagnosis ambiguous to healthcare

    workers. For greater accuracy in diagnosing sepsis, Seale et al. (2009) [5] recommend the

    use of adequate microbiological investigations. No included studies in this review used

    microbiological tests to confirm a diagnosis of puerperal sepsis, although one study

    (Khaskheli et al., 2013 [31]) performed blood tests as supplementary investigations. The lack

    of microbiological and blood testing in studies is likely to reflect the technical difficulties in

    obtaining uncontaminated samples [42], as well as the limited capacity of utilising such tests

    in resource-poor settings.

    5.5 Risk factors for puerperal sepsis

    Risk factors leading to the development of puerperal sepsis are varied. Maternal factors

    identified by studies include malnutrition in pregnant women, indicated by anaemia [16] and

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    a small mid-upper arm circumference [35], which increases the risk of infection due to a

    weakened immune system response [35]. The risk pertained by overweight and obese

    mothers [23] [30] is of increasing concern as the prevalence of obesity is rising in developing

    countries, particularly amongst women [43]. Pre-existing reproductive tract and urinary tract

    infections [13] [16] can develop into sepsis following delivery, therefore detection and

    treatment during pregnancy may reduce the prevalence of puerperal sepsis [13]. Poor

    glycaemic control in gestational diabetes is suggested to increase the risk of postpartum

    infection [28] [44], which would also require screening and effective management. Sikder et

    al. (2014) identify unwanted pregnancy as a risk factor for sepsis, which may be attributed to

    decreased pregnancy care and attention and reduced attendance to antenatal care [35].

    Other maternal risk factors identified include the extremes of ages (35 years)

    [35], parity (nulliparity [35] or high parity [16]) and adverse obstetric history [35].

    Risk factors that facilitate infection around the time of delivery include prolonged rupture of

    membranes [31] and a long duration of labour [13], as the cervix remains open for a

    lenghtened time and natural barriers to ascending infections from the vagina are impaired

    [22]. Infection control measures are needed to prevent unhygienic practices around the time

    of delivery, such as putting a hand into the vagina [13] or using unclean material to staunch

    the flow of lochia [17]. Other determinants during labour include intrapartum bleeding,

    perineal tears and stillbirth [16].

    Health service factors associated with puerperal sepsis and other postpartum morbidities

    include poor utilisation of antenatal care resulting in an unbooked status at delivery [31], and

    limited access to health facilities for delivery [17]. Antenatal care is beneficial in screening

    and treating complications such as anaemia, vaginal infections and urinary tract infections,

    as well as raising awareness of the need for care at delivery [17]. It is suggested that

    facilities are more attentive to aseptic measures that may not be performed in home births,

    such as handwashing, use of a clean delivery service, clean cord cutting, perineal hygiene

    and providing antibiotics after delivery [22]. This highlights the important role of

    comprehensive good-quality antenatal and delivery services in reducing the prevalence of

    puerperal sepsis.

    Community risk factors for puerperal sepsis include lower socioeconomic status of mothers

    [17], which may be associated with illiteracy, a lack of knowledge of signs and symptoms,

    limited availability of obstetric care, and poorer hygiene and general health [4] [22].

    Traditional practices resulting in poor hygiene, such as not taking a bath postpartum [17],

    highlight the need to develop an understanding of the socio-cultural aspects that may

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    facilitate puerperal infection.

    The risk factors discussed above are consistent with findings by the reviews undertaken for

    developing countries [4] [7], as well as those identified in sub-Saharan Africa [5].

    Nonetheless, risk factors are likely to differ in relative importance depending on the region

    and setting. A key determinant of puerperal infection that is additionally mentioned in several

    reviews is caesarean section [4] [5] [6] [7], which may increase rates of puerperal sepsis in

    facilities due to increasing trends in surgical delivery. It should be noted that in this

    systematic review, risk factors for puerperal sepsis were identified from included studies as a

    secondary objective, and therefore were not investigated comprehensively.

    5.6 Puerperal sepsis-related mortality

    Mortality from puerperal sepsis was not investigated as an outcome in this review, but is an

    important indicator of the magnitude of this condition. Without early diagnosis and

    management, puerperal sepsis can rapidly progress along a clinical spectrum of morbidity

    [31], leading to severe septicaemia and death. South Asia is identified to have the highest

    proportion of global maternal deaths from sepsis at 13.7%, with 107,000 maternal sepsis

    deaths occurring between 2003 and 2009 [2], and approximately 9,400 deaths occuring in

    2013 [45]. Therefore, despite a relatively low estimated prevalence, puerperal sepsis

    remains an important problem in South Asia due to potentially severe sequalae and its

    impact on maternal mortality.

    5.7 Strengths of systematic review

    This systematic review is the first to estimate the prevalence of puerperal sepsis in South

    Asia. It also provides a summary of risk factors for puerperal infection identified from

    included studies. A comprehensive search strategy of several databases was used (see

    Appendix 1), including a manual review of reference lists and forward citation tracking to

    identify any studies missed by formal database searching.

    5.8 Limitations of systematic review

    This systematic review is limited by the identification of a small number of studies

    reporting the prevalence of puerperal sepsis, of which only seven were deemed to be of

    high methodological quality. Furthermore, included studies were located in four countries

    only, so the generalisability of findings to the remaining South Asian countries is

    restricted. Risk factors for puerperal sepsis were only identified from included studies

    reporting prevalence data, therefore a comprehensive list was not provided.

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    The validity of the pooled prevalence estimate obtained by meta-analysis is limited due to

    the analysis of a very small number of studies and significant statistical heterogeneity in

    study outcomes. This is likely to be a result of differences in study location, setting, the

    definition of puerperal sepsis used and the method of case ascertainment, as discussed

    previously. Other differences in included studies that may have contributed to the large

    discrepancies in prevalence estimates include variations in study design, quality, sample

    size, participant characteristics (including socioeconomic status, living standards and

    access to healthcare), and whether abortions and stillbirths were included as delivery

    outcomes. Furthermore, most included studies investigated study participants from very

    select populations or facilities, limiting the generalisability of findings to the whole region

    or country.

    5.9 Implications & recommendations for future research

    In order to obtain more reliable prevalence estimates, it is important that studies use an

    established standard definition of puerperal sepsis, as well as objective clinical methods

    of ascertaining cases. Studies should also endeavour to collect population-representative

    data of good quality that is inclusive of all delivery outcomes. Key sub-groups, such as

    setting and place of delivery, should be identified between and within studies to account

    for differences in prevalence and improve the comparability of prevalence estimates.

    The risk factors for puerperal sepsis identified in this review have implications for

    improving infection control and other prevention efforts. These include the detection and

    management of antepartum maternal conditions such as anaemia, gestational diabetes

    and pre-existing infections, ensuring good hygienic practice during and after delivery, and

    improving access to good-quality obstetric care, including antenatal services and

    postnatal follow-up. A more comprehensive review of risk factors should be conducted to

    detect other determinants of puerperal sepsis that may have been missed.

    In order to truly assess the magnitude of puerperal sepsis in South Asia, more data is

    needed regarding sepsis-related mortality, as well as the burden of long-term morbidities

    such as chronic pelvic inflammatory disease and secondary infertility, which appear to be

    neglected in literature. Additionally, effective and feasible interventions for prevention and

    treatment need to be identified in order to address and reduce the prevalence of

    puerperal sepsis.

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    44

    6. CONCLUSION

    This systematic review is the first to attempt to estimate the prevalence of puerperal

    sepsis in South Asia. Although a single reliable estimate of puerperal sepsis in South

    Asia is difficult to establish, the findings from this systematic review indicate a relatively

    low prevalence between 3-4%. Nonetheless, this should not detract from the public health

    importance of this condition, as it remains a significant cause of obstetric morbidity and

    mortality in South Asia despite its highly preventable nature. Risk factors for puerperal

    sepsis are varied and include maternal, labour, health service and community factors,

    which should be the focus for prevention efforts.

    Producing better estimates for the prevalence of puerperal sepsis is important in

    accurately measuring the magnitude of this condition and assessing progress in

    improving maternal outcomes, particularly in South Asia where the global burden of

    maternal sepsis deaths is highest [2]. This can only be achieved when good-quality data

    is regularly collected using a standard definition of puerperal sepsis and a representative

    population inclusive of all delivery outcomes.

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    46

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