Treatments for Secondary Postpartum Haemorrhage (Review)

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Treatments for secondary postpartum haemorrhage (Review)

Alexander J, Thomas PW, Sanghera J

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published inThe Cochrane Library

2009, Issue 3http://www.thecochranelibrary.com

Treatments for secondary postpartum haemorrhage (Review)

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
http://www.thecochranelibrary.com/http://www.thecochranelibrary.com/


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T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .

14INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iTreatments for secondary postpartum haemorrhage (Review)



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[Intervention Review]

Treatments for secondary postpartum haemorrhage

Jo Alexander1, Peter W Thomas2 , Jill Sanghera3

1School of Health and Social Care, Bournemouth University, Bournemouth, UK. 2 Dorset Research and Development Support Unit,

Poole Hospital NHS Trust, Poole, UK. 3 Institute of Health and Community Studies, Bournemouth University, Bournemouth, UK

Contact address: Jo Alexander, School of Health and Social Care, Bournemouth University, Christchurch Road, Bournemouth, Dorset,

BH1 3LG, [email protected]. (Editorial group: Cochrane Pregnancy and Childbirth Group.)

Cochrane Database of Systematic Reviews, Issue 3, 2009 (Status in this issue:Unchanged)Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

DOI: 10.1002/14651858.CD002867This version first published online:21 January 2002 in Issue 1, 2002.

Last assessed as up-to-date: 30 January 2008. (Help document - Dates and Statusesexplained)

This record should be cited as: Alexander J, Thomas PW, Sanghera J. Treatments for secondary postpartum haemorrhage.CochraneDatabase of Systematic Reviews2002, Issue 1. Art. No.: CD002867. DOI: 10.1002/14651858.CD002867.

A B S T R A C T

Background

Secondary postpartum haemorrhage is any abnormal or excessive bleeding from the birth canal occurring between 24 hours and 12

weeks postnatally. In developed countries, 2% of postnatal women are admitted to hospital with this condition, half of them undergoing

uterine surgical evacuation. Data are not available from developing countries.

Objectives

To evaluate the relative effectiveness and safety of the treatments used for secondary postpartum haemorrhage.

Search strategy

We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (31 January 2008), the reference lists of trial reports and

reviews and sought further sources from the first named authors of the papers identified.

Selection criteria

All randomised or quasi-randomised comparisons between drug therapies, surgical therapies and placebo or no treatment for the

management of secondary postpartum haemorrhage occurring between 24 hours and three months following a pregnancy of at least

24 weeks gestation.

Data collection and analysis

Two authors scrutinised reports of possibly eligible studies. The third author acted as an advisor or arbitrator.

Main results

Of the 47 papers (36 studies) identified, none met the inclusion criteria.

Authors conclusions

No information is available from randomised controlled trials to inform the management of women with secondary postpartum

haemorrhage.This topic mayhave received littleattention because it is perceivedas being associated with maternal morbidity rather than

mortality in developed countries; it is only recently that the extent and importance of postnatal maternal morbidity has been recognised.

A well-designed randomised controlled trial comparing the various therapies for women with secondary postpartum haemorrhage

against each other and against placebo or no treatment groups is needed.

1Treatments for secondary postpartum haemorrhage (Review)

mailto:[email protected]://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/DatesStatuses.pdfhttp://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/DatesStatuses.pdfmailto:[email protected]


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P L A I N L A N G U A G E S U M M A R Y

Treatments for secondary postpartum haemorrhage

No randomised controlled trials to inform the management of women with secondary postpartum haemorrhage

Sometimes women experience abnormal or excessive bleeding from the birth canal between 24 hours and 12 weeks after giving birth,

and this is called secondary postpartum haemorrhage. It is usually caused by a tear, an infection, or by fragments of the placenta

or membranes, or both, remaining in the uterus and causing infection or preventing the uterus from contracting. It can be painful,

disruptive to daily life with a new baby and can exacerbate extreme tiredness. Although the specific incidence is not known, in low-

income countries it is probably a serious cause of maternal mortality. In high-income countries, about 2% of women are admitted to

hospital with this condition. Treatments may include giving drugs to treat infection and/or control bleeding and/or a variety of surgical

procedures. Studies could have compared an individual treatment to another, combinations of treatments to others, and any individual

or combination of treatments to either a placebo or no treatment group. However, no trials were identified and so there is no good

evidence on which to base guidance. A well-designed trial is needed.

B A C K G R O U N D

Secondary postpartum haemorrhage is defined as any abnormal

or excessive bleeding from the birth canal occurring between 24

hours (Dewhurst 1966) and 12 weeks (Rome 1975) postnatally

and, as this definition includes no reference to the volume of blood

loss or the condition of the woman, the spectrum of the condi-

tion can vary from inconvenient to fatal. However, in developed

countries around 1% of postnatal women undergo surgical uter-

ine evacuation (evacuation of retained products of conception)for secondary postpartum haemorrhage (ACOG 1990;Dewhurst

1966;Glazener 1999) and a further 1% are admitted to hospi-

tal but managed conservatively (Alexander 1997;Glazener 1999).

Leaving aside any physical morbidity, it is generally acknowledged

that the postnatal period is a time of significant psychological up-

heaval for women and their families even without the added dis-

ruption of needing medical treatment and possibly admission to,

or extra time in, hospital (Raphael-Leff 1991). Secondary post-

partum haemorrhage is, however, a topic that has received little

attention because it is perceived as being associated with mater-

nal morbidity rather than mortality in developed countries (King

1989); it is only relatively recently that the importance of post-

natal maternal morbidity has been recognised (MacArthur 1991).It seems likely that this morbidity may include anaemia, which

would be worsened by secondary postpartum haemorrhage, and

serve to add to the extreme tiredness that many postnatal women

experience (Bick 1995).

Secondary postpartum haemorrhage, which appears frequently to

be linkedwith genital tract infection, still results in maternal death

in developedcountries albeitvery occasionally. Inthe UK,one ma-

ternal death occurred due to secondary postpartum haemorrhage

between 1994 and 1996 (DoH 1999), but none between 2000

and 2002 (CEMACH 2004). It seems likely that related maternal

deaths are more common in developing countries, but data do not

appear to be available.

If secondary postpartum haemorrhage is sufficiently severe to re-

sult in admission to hospital, treatment usually falls into twobroad

categories: drug treatment or surgery, or both (Alexander 1997;

Weisenberg-Smith1993). The rationale for these treatments ap-

pears to be that the uterus has failed to contract adequately to

prevent bleeding from the placental site, the underlying cause of

this being retained products or intrauterine infection, or both (

Crowley 1984; King 1989; Rome 1975). However, the underlying

cause of the condition is often not established. Drug therapy con-

sists of oxytocics or antibiotics, or both; hormonal preparations

may also be given to regulate bleeding (RCOG 1994). Antibi-

otic regimens used for endometritis (inflammation of the lining

of the womb causing pain) after delivery are the subject of a sepa-

rate review (French 2004) but clearly endometritis and secondary

postpartum haemorrhage are not mutually exclusive conditions.

Surgery might involve evacuation of retained products (seeabove),cervical dilatation, repair of cervical tear or uterine rupture, molar

pregnancy treatment and, rarely, hysterectomy.

There is evidence to suggest that endometritis is increased among

women who have prelabour rupture of membranes at term (

Novak-Antolic 1997) or who are delivered by caesarean section (Calhoun 1995;Milligan 1992;Stovall 1998). Events in the im-

mediately preceding pregnancy, which have been suggested as pre-

disposing a woman to secondary postpartum haemorrhage, are

the mother smoking at the time the antenatal history was taken (

Marchant 2006); multiple pregnancy (King 1989;Thorsteinsson

1970); threatened miscarriage (Marchant 2006;Thorsteinsson

1970); antepartum haemorrhage (Thorsteinsson 1970); hospital

admission during the third trimester (Marchant 2006); precipi-

tate labour of less than two hours (Thorsteinsson 1970); the ad-

ministration of intravenous ergometrine (0.5 mg) as preventative

management for the third stage of labour (Begley 1990); pro-

longed third stage (Lester 1956;Marchant 2006;Thorsteinsson




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1970); incomplete placenta or membranes passed at birth, or

both (Dewhurst 1966;Lester 1956;Marchant 2006;Rome 1975;Thorsteinsson 1970); primary postpartum haemorrhage (Rome

1975); and not breastfeeding (Marchant 2006). A previous his-

tory of secondary postpartum haemorrhage predisposes to a re-

currence (Dewhurst 1966;Marchant 2006;Thorsteinsson 1970)

and it has been suggested that it is more common amongst mul-

tiparous women (seeGlazener 1995;King 1989).

There has been no systematic review to assess the relative effec-

tiveness of treatments for secondary postpartum haemorrhage.

O B J E C T I V E S

To evaluate the relative effectiveness and safety of the treatments

used for secondary postpartum haemorrhage.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All randomised comparisons between drug therapies, surgical

therapies and placebo or no treatment for the management of

secondary postpartum haemorrhage were eligible for inclusion.

Quasi-randomised studies (for example, alternate allocation, allo-

cation by hospital number, etc) were also eligible for inclusion.

Types of participants

Women from 24 hours to three months following a pregnancy of

at least 24 weeks gestation with a diagnosis of secondary postpar-

tum haemorrhage. Any definition of secondary postpartum haem-

orrhage would have beenaccepted providing the criteria used were

made clear within the paper concerned. Studies were eligible what-ever the location in which treatment was received and whatever

the length of the follow up.

Types of interventions

There are three types of drug treatment (antibiotics, oxytocics and

hormone therapy) and a variety of surgical treatments. We would

have assumed that variations in the effectiveness of drug treat-

ments within these broad bands were not important (for example,

different types of hormone therapy). Control groups could have

been given placebo or no treatment. Potentially studies could have

compared an individual treatment to another, combinations of

treatments to others, and any individual or combination of treat-

ments to either type of control group. All were of interest butspecifically:

antibiotics versus oxytocics;

antibiotics versus hormone therapy;

antibiotics versus placebo;

antibiotics versus no treatment;

antibiotics and oxytocics versus hormone therapy;

antibiotics and hormone therapy versus oxytocics;

antibiotics and oxytocics versus placebo;

antibiotics and oxytocics versus no treatment;

antibiotics and hormone therapy versus placebo;

antibiotics and hormone therapy versus no treatment;

oxytocics versus hormone therapy; oxytocics versus placebo;

oxytocics versus no treatment;

oxytocics and hormone therapy versus antibiotics;

oxytocics and hormone therapy versus placebo;

oxytocics and hormone therapy versus no treatment;

oxytocics, hormone therapy and antibiotics versus

placebo;

oxytocics, hormone therapy and antibiotics versus no

treatment;

hormone therapy versus placebo;

hormone therapy versus no treatment;

evacuation of retained products of conception versus

each type of drug treatment; evacuation of retained products of conception versus no

treatment or placebo separately;

other surgical interventions separately versus each type

of drug treatment;

other surgical interventions separately versus no treat-

ment or placebo separately.

Types of outcome measures

Primary outcomes

(Subgroup analyses - seebelow - would have been limited to these.)

Cessation of abnormal vaginal bleeding (however deter-

mined by trialist) without need for further treatment;

serious maternal morbidity (as defined by trialist) or

death;

blood transfusion(s);

hysterectomy;

evacuation of retainedproducts(whenthis hadnot been

the intervention);

additional treatments;

cessation of signs of infection (however determined by

trialist).




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Secondary outcomes

Post-treatment ultrasound findings;

days in hospital as a result of secondary postpartum

haemorrhage;

interval from randomisation to cessation of abnormal

bleeding;

side-effectsof treatment(for example, nausea, vomiting,

hypertension, allergic reactions, uterine perforation);

economic outcomes;

womens level of satisfaction;

breast milk pharmacokinetics.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Groups Tri-

als Register by contacting the Trials Search Co-ordinator (31 Jan-

uary 2008).

The Cochrane Pregnancy and Childbirth Groups Trials Register

is maintained by the Trials Search Co-ordinator and contains trials

identified from:

1. quarterly searches of the Cochrane Central Register of

Controlled Trials (CENTRAL);

2. weekly searches of MEDLINE;

3. handsearches of 30 journals and the proceedings of ma-jor conferences;

4. weekly current awareness alerts for a further44 journals

plus monthly BioMed Central email alerts.

Details of the search strategies for CENTRAL and MEDLINE,

the list of handsearched journals and conference proceedings, and

the list of journals reviewed via the current awareness service can

be found in the Specialized Register section within the edito-

rial information about the Cochrane Pregnancy and Childbirth

Group.

Trials identified through the searching activities described above

are given a code (or codes) depending on the topic. The codes are

linked to review topics. The Trials Search Co-ordinator searches

the register foreach review using these codes rather than keywords.We did not apply any language restrictions.

Data collection and analysis

The full papers of the 36 studies identified by the search strategy

were considered against the selection criteria independently by

two of theauthors blind to their authorship, journal of publication

and results. We used a data extraction sheet. The third investigator

acted as an advisor or arbitrator, or both. Where contact addresses

were available, we wrote to the first named authors of the studies,

requesting details of any further work that they knew of.

If any of the studies had met our inclusion criteria, we would

have used the Review Manager software (RevMan 2000) to enterthe data and to check the accuracy of data entry. We would have

also used the methods outlined in the Cochrane Handbook for

Systematic Reviews of Interventions (Clarke 2000). For full details

of planned methods,seeAppendix 1.

R E S U L T S

Description of studies

See:Characteristics of excluded studies.Of the 36 studies (47 papers) identified by the literature search,

the seven papers identified from their reference lists and five iden-

tified following responses from first named authors, none were

considered suitable for inclusion in the review. Details of the latter

twelve papers are given in the Discussion section below. None

of the studies focused on the management of secondary postpar-

tum haemorrhage and none mentioned excessive bleeding in the

diagnostic criteria or definition of the condition being studied. It

had been intended to include only studies of women between 24

hours and three months postdelivery;in the event,very few studies

identified how long it was since the women had delivered.

Of the 36 studies identifiedby the literature review, nineconcernedthe management of endometritis following caesarean section, 15

themanagement of endometritis in general and11 the prophylaxis

of primary or secondary postpartum haemorrhage, endometritis,

endocervicitis, and perineal infection. Of the 24 studies concern-

ing the management of endometritis, 21 studied the use of antibi-

otics alone, one the use of cervical dilatation alone, one the use

of antibiotics alone but with both groups also undergoing cervical

dilatation and one the continued versus the non-continued use

of antibiotics. One study was a comparison of uterotonic drugs

for women of about three to five days postnatally, but solely to

compare breast milk pharmacokinetics.

Of the 36 studies identified, 32 stated that allocation had beenrandomised, but for only 12 were some details of the randomisa-

tion process described. In the remaining four studies the alloca-

tion was quasi-random. For details of the excluded studies,seetheCharacteristics of excluded studies table.

Risk of bias in included studies

No randomised trials were included.

Effects of interventions




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No randomised trials were included.

D I S C U S S I O N

A letter was sent to the first named author of 33 of the 36 studies.

A usable contact address was not available for the remaining three

papers. A second letter/e-mail and letter were sent to the non-

responders; eight replies were received.

Of the seven papers identified from the reference lists of the

36 studies, and the five identified following responses from first

named authors, two were non-randomised trials of different oxy-

tocic drugs for the management of the third stage of labour, fivewere case-study reports (three concerning secondary postpartum

haemorrhage (PPH), one primary and secondary PPH and one

primary PPH) and threewerecaseseries (oneexamining organisms

causing endometritis; one its presenting symptoms and timing;

andone themanagement of intractable primary PPH).One, trans-

lated, paper was a randomised comparison of uterotonic drugs for

women at one to five days postpartum who had not needed oxy-

tocic drugs.

A U T H O R S C O N C L U S I O N S

Implications for practice

No information is available from randomised controlled trials to

inform the management of women with secondary postpartum

haemorrhage.

Implications for research

A well-designed randomised controlled trial comparing the vari-

ous drug and surgical therapies for women with secondary post-

partum haemorrhage against each other and against placebo or no

treatment groups is needed. When devising exclusion criteria the

severity of blood loss will need careful consideration.

A C K N O W L E D G E M E N T S

We are grateful for the comments and encouragement that we

received from Sally Marchant, Jo Garcia, Cathryn Glazener and

Tim Hillard in relation to the original review. We would also like

to thank the Consumer Panel for their valuable input.

R E F E R E N C E S

References to studies excluded from this review

Andersen 1998 {published data only}

Andersen B, Andersen L, Sorensen T. Methylergometrine during the

early puerperium; a prospective randomizeddouble blindstudy.ActaObstetricia et Gynecologica Scandinavica1998;77:547.

Andrinopoulos 1983 {published data only}

Andrinopoulos GC, Mendenhall HW. Prostaglandin F2 in the man-

agement of delayed postpartum hemorrhage. American Journal of Obstetrics and Gynecology1983;15:2178.

Apuzzio 1985a{published data only}

Apuzzio JJ, Ganesh V, PelosiMA, Landau I, Kaminetzky HA, Kamin-

ski Z, et al.Comparative clinical evaluation of ceftizoxime with clin-

damycin and gentamicin and cefoxitin in the treatment of postce-

sarean endomyometritis. Surgery, Gynecology and Obstetrics1985;

161:51822.

Apuzzio 1985b {published data only}

Apuzzio J, Kaminski Z, Gamesh V, Louria D. Comparative clinical

evaluation of ticarcillin plus clavulanic acid versus clindamycin plus

gentamicin in treatment of post-cesarean endomyometritis. Ameri-

can Journal of Medicine1985;79:1647.

Arabin 1982 {published data only}

Arabin B, Ruttgers H, Kubli F. Influence of a routine use of

methergine on puerperal infection and breast feeding. Proceedings

of 8th European Congress of Perinatal Medicine; 1982 Sept 7-10;

Brussels, Belgium. 1982:81.

Arabin 1986 {published data only}Arabin B, Ruttgers H, Kubli F. Effects of routine administration of

methylergometrin during the puerperium on involution, maternal

morbidity, and lactation.Geburtshilfe und Frauenheilkunde1986;46:

21520.

Arredondo-Garcia{published data only}

Arrendondo-Garcia JL, Figueroa-Damian R, Ortiz-Ibarra FJ, Sosa-

Gonzalez IA. Endometritis etiology:diagnosis and treatment. Expe-

rience of the Instituto Nacional de Perinatologia.Current Therapeu-tic Research1993;54(5):52939.

Baumgarten 1983 {published data only}

Baumgarten K, Schmidt J, Horvat A, Neumann M, Cerwenka R,

Gruber W, et al.Uterine motility after post-partum application ofsulprostone and other oxytocics. European Journal of Obstetrics &Gynecology and Reproductive Biology1983;16:18192.

Bhattacharya 1988 {published data only}

Bhattacharya P, Devi PK, Jain S, Kanthamani CR, Raghavan KS.

Prophylactic use of 15(S)15 methyl PGF2alpha by intramuscular

route for control of postpartum bleeding - a comparative trial with

methylergometrine. Acta Obstetricia et Gynecologica Scandinavica

Supplement1988;145:135.

Bischoff 1956 {published data only}

BischoffP, UpchurchK, CarterJ. Theuse ofsulfisoxazole creamin the

postpartum patient. American Journal of Obstetrics and Gynecology

1956;71:1135.




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Briggs 1989 {published data only}

Briggs GG, Ambrose P, Nageotte MP. Gentamicin dosing in postpar-tum women with endometritis. American Journal of Obstetrics and

Gynecology1989;160:30913.

Cormier 1988 {published data only}

Cormier P, Leng JJ, Janky E, Brouste V, Duthil B. Antibiotic prophy-

laxis with cefotetan in the prevention of post-partum and post-abor-

tum infectious complications in endo-uterine investigations. Revue

Francaise de Gynecologie et d Obstetrique1988;83:82932.

Corson 1977 {published data only}

Corson SL, Bolognese RJ. Postpartum uterine atony treated with

prostaglandins.American Journal of Obstetrics and Gynecology1977;

129(8):9189.

Del Priore 1996 {published data only}

Del Priore G, Jackson-Stone M, Shim EK, Garfinkel J, EichmannMA, Frederiksen MC. A comparison of once-daily and 8-hour gen-

tamicin dosing in the treatment of postpartum endometritis.Obstet-

rics & Gynecology1996;87:9941000.

Dinsmoor 1991 {published data only}

Dinsmoor MJ, Newton ER, Gibbs RS. A randomized, double-blind,

placebo-controlled trial of oral antibiotic therapy following intra-

venous antibiotic therapy for postpartum endometritis.Obstetrics &Gynecology1991;77:602.

Faro 1987 {published data only}

Faro S, Phillips LE, Baker JL, Goodrich KH, Turner RM, Riddle

GD. Comparative efficacy and safety of mezlocillin, cefoxitin, and

clindamycin plus gentamicin in postpartum endometritis.Obstetrics

& Gynecology1987;69:7606.

Faro 1988 {published data only}

FaroS, Martens M, Phillips LE,HamillH, SmithD, RiddleG. Ticar-

cillin disodium/clavulanate potassium vs clindamycin/gentamicin in

the treatment of postpartum endometritis. Journal of ReproductiveMedicine1988;33:6036.

Fernandez 1990 {published data only}

Fernandez H, Claquin C, Guibert M, Papiernik E. Suspected post-

partum endometritis: a controlled clinical trial of single-agent an-

tibiotic therapy with amox-CA (augmentin R) vs ampicillin-metron-

idazole plus or minus aminoglycoside.European Journal of Obstetrics& Gynecology and Reproductive Biology1990;36:6974.

Fernandez 1993 {published data only}

Fernandez H, GagnepainA, Bourget P, Peray P, FrydmanR, Papiernik

E, et al.Antibiotic prophylaxis against postpartum endometritis af-ter vaginal delivery: a prospective randomized comparison between

Amox-CA (Augmentin) and abstention. European Journal of Obstet-

rics & Gynecology and Reproductive Biology1993;50:16975.

Figueroa-Damian 1992 {published data only}

Figueroa-Damian R, Angel-Muller E, Sosa-Gonzalez i, Arredondo-

Garcia JL. Gyneco-obstetrical infections by anaerobic bacteria [In-

fecciones ginecoobstetricas por bacterias anaerobias]. Ginecologia yObstetricia de Mexico1992;60:16270.

Figueroa-Damian 1996 {published data only}

Figueroa-Damian R, Villagrana-Zesati R, San Martin-Herrasti

J, Arredondo-Garcia J. Comparison of therapeutic efficacy of

piperacillin/tazobactam vs. ampicillin plus gentamicin in the treat-

ment of post-cesarean endometritis [Comparacion de la eficacia ter-

apeutica de piperacilina/tazobactam vs ampicilina mas gentamicina

en el tratamiento de endometritis poscesarea]. Ginecologia y Obste-tricia de Mexico1996;64:2148.

Friedman 1957 {published data only}

Friedman EA. Comparative clinical evaluation of postpartum oxyto-

cics. American Journal of Obstetrics and Gynecology1957;73:1306

13.

Gall 1996 {published data only}

Gall

S, Koukol DH. Ampicillin/sulbactam vs clindamycin/gentamicin in

the treatment of postpartum endometritis. Journal of Reproductive

Medicine1996;41:57580.

Gibbs 1988 {published data only}

Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A ran-

domized trial of intrapartum vs immediate postpartum treatment ofwomen with intra-amniotic infection.Obstetrics & Gynecology1988;

72:8238.

Goldstein 1986 {published data only}

Goldstein AI, Kent DR, David A. Prostaglandin E2 vaginal supposi-

tories in the treatment of intractable late-onset postpartum haemor-

rhage - a case report. Journal of Reproductive Medicine1983;28(6):

4256.

Greenberg 1987 {published data only}

Greenberg RN, Reilly PM, Weinandt WJ, Wilson KM, Bollinger

M, Ojile JM. Comparison trial of clindamycin with aztreonam or

gentamicin in the treatment of postpartum endometritis. Clinical

Therapeutics1987;10:369.

Groeber 1960 {published data only}

Groeber WR, Bishop EH. Methergine and ergonovine in the third

stage of labour. Obstetrics & Gynecology1960;15(1):858.

Grunberger 1983 {published data only}

Grunberger W. Postpartum uterus involution and lactation levels in

randomized comparison between Prostin E2 tablets and Methergin-

Dragees [Postpartale Uterusinvolution und Laktationsmengen im

randomisierten Vergleich von ProstinE2Tabletten mit Methergin

Dragees].Gynakologische Rundschau1983;23:1007.

Lancheros 1997 {published data only}

Lancheros S, Gaitan H. Comparison between two therapeutic sched-

ules: gentamicin plus gentamicyn and pefloxacin plus metronidazol

in post-cesarean endometritis treatment. A clinical trial. Acta Obste-

tricia et Gynecologica Scandinavica1997;76:28.

Ledee 2001 {published data only}

Ledee N, Ville Y, Musset D, Mercier F, Frydman R, Fernandez H.

Management in intractable obstetric haemorrhage: an audit on 61

cases. European Journal of Obstetrics & Gynecology and ReproductiveBiology2001;94(2):18996.

Maccato 1991 {published data only}

Maccato ML, Faro S, Martens MG, Hammill HA. Ciprofloxacin

vs gentamicin/clindamycin for postpartum endometritis. Journal ofReproductive Medicine1991;36:85761.

Martens 1989 {published data only}

Martens MG,FaroS, Hammill HA,Maccato M, RiddleG, Smith D.

Ampicillin/sulbactam vs clindamycin in the treatment of postpartum

endomyometritis.Southern Medical Journal1989;82:39.




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McGregor 1989 {published data only}

McGregor JA, Christensen FB. A comparison of ampicillin plus sul-bactam vs clindamycin and gentamicin for treatment of postpartum

infection.International Journal of Gynecology & Obstetrics1989;S2:359.

Mitra 1997 {published data only}

Mitra A, Whitten K, Laurent S, Anderson W. A randomized, prospec-

tive study comparing once-daily gentamicin versus thrice-daily gen-

tamicin in the treatment of puerperal infection. American Journal of

Obstetrics and Gynecology1997;177:78692.

Moodie 1976 {published data only}

Moodie JE, Moir DD. Ergometrine, oxytocin and extradural anal-

gesia.British Journal of Anaesthesia1976;48:571.

Morales 1989 {published data only}

Morales WJ, Collins EM,AngelJL, Knuppel RA.Shortcourse of an-tibiotic therapy in treatment of postpartum endomyometritis.Amer-

ican Journal of Obstetrics and Gynecology1989;161:56872.

Paraskevaides 1993 {published data only}

Paraskevaides E, Stuart B, Gardeil F. Secondary postpartum haem-

orrhage from nondehisced lower caesarean section scar: a case for

hysteroscopy. Australian and New Zealand Journal of Obstetrics and

Gynaecology1993;33(4):427.

Perry 1997 {published data only}

Perry K, Theilman G, Coker K, Martin J. A prospective random-

ized trial comparing Gentamicin administered every 8 hours versus

Gentamicin administered every 24 hours for the treatment of postce-

sarean section endometritis. American Journal of Obstetrics and Gy-

necology1997;176:S59.

Pond 1979 {published data only}

Pond DG, Bernstein EP, Love KR, Morgan JR, Velland H, Smith

JA. Comparison of ampicillin with clindamycin plus gentamicin in

the treatment of postpartum uterine infection. Canadian MedicalAssociation Journal1979;120:5337.

Rodriguez-Ballestero {published data only}

Rodriguez-Ballesteros R, Alarcon-Aburto V, De Los Angeles Madri-

gal-De La Campa M, Valerio-Castro E. Antibiotics short course in

post-cesarean endometritis treatment [Esquema corto de antibioticos

en el tratamiento de endometritis posterior a cesarea]. Ginecologia y

Obstetricia de Mexico1996;64:35962.

Rubin 1961 {published data only}

Rubin A. Use of a sulfonamide vaginal cream post partum. A con-trolled blind study of 700 patients. American Journal of Obstetricsand Gynecology1961;82:8602.

Sen 1980 {published data only}

Sen P, Apuzzio J, Reyelt C, Kaminski T, Levy F, Kapila R, et

al.Prospective evaluation of combinations of antimicrobial agents for

endometritis after cesarean section. Surgery, Gynecology and Obstet-rics1980;151:8992.

Sorrell 1981 {published data only}

Sorrell TC, Marshall JR, Yoshimori R, Chow AW. Antimicrobial

therapy of postpartumendomyometritis. II. Prospective randomized

trial of mezlocillin vs ampicillin. American Journal of Obstetrics andGynecology1981;141:24651.

Takagi 1976 {published data only}

Takagi S, Yoshida T, Togo Y, Tochigi H, Abe M, Sakata H, et al.Theeffects of intramyometrial injection of prostaglandin F2 on severe

postpartum haemorrhage. Prostaglandins1976;12(4):56579.

Vogel 2004 {published data only}

VogelD, BurkhardtT, Rentsch K, Schweer H, WatzerB, Zimmerman

R, et al.Misoprostol versus methylergometrine: pharmacokinetics in

human milk. American Journal of Obstetrics and Gynecology 2004;191:216873.

Walss-Rodriguez 1990 {published data only}

Walss-Rodriguez RJ, Rocha-Avila LC. Puerperal deciduometritis.

Importance of mechanical cervical dilatation.Ginecologia y Obstetri-

cia de Mexico1990;58:2703.

Whitten 1997 {published data only}

Whitten K, Mitra A, Laurent S, Anderson B. A randomized, prospec-tive study comparing once daily Gentamicin with thrice daily Gen-

tamicin in the treatment of puerperal endometritis.American Journal

of Obstetrics and Gynecology1997;176:S32.

Additional references

ACOG 1990

American College of Obstetrics and Gynecology. Diagnosis and

management of postpartum haemorrhage. International Journal of

Gynecology & Obstetrics1990;36:15963.

Alexander 1997

Alexander J, Garcia J, Marchant S. The BLiPP Study - a sur-

vey and case control study. Final report to the South and WestNHS Executive Research and Development Committee (Response

mode). Bournemouth: Institute of Health and Community Studies.Bournemouth University, 1997. [: ISBN 1858990947]

Begley 1990

Begley CM. A comparison of active and physiological management

of the third stage of labour. Midwifery1990;6:317.

Bick 1995

Bick DE, MacArthur C. The extent, severity and effect of health

problems after childbirth. British Journal of Midwifery1995;3(1):2731.

Calhoun 1995

Calhoun BC, Brost B. Emergency management of sudden puerperal

fever. Obstetrics and Gynecology Clinics of North America1995;22(2):

35767.

CEMACH 2004

Confidential Enquiry into Maternal and Child Health. Whymothers

die 2000-2002. The sixth report of the Confidential Enquiries into

Maternal Deaths in the United Kingdom. London: RCOG Press,

2004.

Clarke 2000

Clarke M, Oxman AD, editors. Cochrane Reviewers Handbook

4.1.1 [updated December 2000]. In: The Cochrane Library

[database on CDROM]. The Cochrane Collaboration. Oxford: Up-

date Software 2001, Issue 2.

Crowley 1984

Crowley J. Post-delivery bleeding due to group B beta-haemolytic

streptococcal infection. New Zealand Medical Journal1984;97:377.




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Dewhurst 1966

Dewhurst CJ. Secondary postpartum haemorrhage. Journal of Ob-stetrics & Gynaecology of the British Commonwealth 1966;73:538.

DoH 1999

Department of Health. Why mothers die - report on confidential en-

quiries into maternal deaths in the United Kingdom 1994-1996. Lon-don: Department of Health, 1999.

French 2004

French LM, Smaill FM. Antibiotic regimens for endometritis af-

ter delivery. Cochrane Database of Systematic Reviews2004, Issue 4.

[DOI: 10.1002/14651858.CD001067.pub2]

Glazener 1995

Glazener CMA, Abdalla M, Stroud P, Naji S, Templeton A, Russel

IT. Postnatal maternal morbidity: extent, causes, prevention and

treatment. British Journal of Obstetrics and Gynaecology1995;102:2827.

Glazener 1999

Glazener CMA. Investigation of postnatal experience and care in

Grampian [Unpublished PhD thesis]. Aberdeen: University of Ab-erdeen, 1999.

King 1989

King PA, Duthie SJ, Dong ZG, Ma HK. Secondary postpartum

haemorrhage. Australian and New Zealand Journal of Obstetrics and

Gynaecology1989;29(4):3948.

Lester 1956

Lester WM, Bartholomew RA, Colvin ED, Grimes WH, Fish JS,

GallowayWH. The roleof retainedplacentalfragments in immediate

and delayed postpartum hemorrhage. American Journal of Obstetrics

and Gynecology1956;72(6):121426.

MacArthur 1991

MacArthur C, Lewis M, Knox EG.Health after childbirth. London:HMSO, 1991.

Marchant 2006

Marchant S, Alexander J, Thomas P, Garcia J, Brocklehurst P, Keene

J. Risk factors for hospital admission related to excessive and/or pro-

longed postpartum vaginal blood loss after the first 24 h following

childbirth.Paediatric and Perinatal Epidemiology2006;20:392402.Milligan 1992

Milligan DA, Brady K, Duff P. Short-term parenteral antibiotic ther-

apy for puerperal endometritis. Journal of Maternal-Fetal Medicine

1992;1:603.

Novak-Antolic 1997

Novak-Antolic Z, Pajntar M, Verdenik I. Rupture of the membranes

and postpartum infection. European Journal of Obstetrics & Gynecol-

ogy and Reproductive Biology1997;71:1416.

Raphael-Leff 1991

Raphael-Leff J. Psychological processes of childbearing. London: Chap-

man and Hall, 1991.

RCOG 1994

Royal College of Obstetricians and Gynaecologists. Bleeding afterchildbirth. London: RCOG, 1994.

RevMan 2000

The Cochrane Collaboration. Review Manager (RevMan). 4.1 for

Windows. Oxford, England: The Cochrane Collaboration, 2000.

Rome 1975

Rome RM. Secondary postpartum haemorrhage. British Journal of Obstetrics and Gynaecology1975;82:28992.

Stovall 1998

Stovall TG, Ambrose SE, Ling FW, Anderson GD. Short-course an-

tibiotic therapy for the treatment of chorioamnionitis and postpar-

tum endomyometritis. AmericanJournal of Obstetrics and Gynecology

1998;159(2):4047.

Thorsteinsson 1970Thorsteinsson VT, Kempers RD. Delayed postpartum bleeding.

American Journal of Obstetrics and Gynecology1970;107(4):56571.

Weisenberg-Smith1993

Weisenberg-Smith S. Literature review of secondary postpartum

bleeding. National Perinatal Epidemiology Unit, Oxford, Unpub-

lished 1993. Indicates the major publication for the study




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C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of excluded studies [ordered by study ID]

Andersen 1998 Not concerning treatment of secondary postpartum haemorrhage.

Andrinopoulos 1983 Case study report, not a RCT.

Apuzzio 1985a Not concerning treatment of secondary postpartum haemorrhage.

Apuzzio 1985b Not concerning treatment of secondary postpartum haemorrhage.

Arabin 1982 Not concerning treatment of secondary postpartum haemorrhage.

Arabin 1986 Not concerning treatment of secondary postpartum haemorrhage.

Arredondo-Garcia Not concerning treatment of secondary postpartum haemorrhage.

Baumgarten 1983 Not concerning treatment of secondary postpartum haemorrhage.

Bhattacharya 1988 Not concerning treatment of secondary postpartum haemorrhage.

Bischoff 1956 Not concerning treatment of secondary postpartum haemorrhage.

Briggs 1989 Not concerning treatment of secondary postpartum haemorrhage.

Cormier 1988 Not concerning treatment of secondary postpartum haemorrhage.

Corson 1977 Not concerning treatment of secondary postpartum haemorrhage.

Del Priore 1996 Not concerning treatment of secondary postpartum haemorrhage.

Dinsmoor 1991 Not concerning treatment of secondary postpartum haemorrhage.

Faro 1987 Not concerning treatment of secondary postpartum haemorrhage.

Faro 1988 Not concerning treatment of secondary postpartum haemorrhage.

Fernandez 1990 Not concerning treatment of secondary postpartum haemorrhage.

Fernandez 1993 Not concerning treatment of secondary postpartum haemorrhage.

Figueroa-Damian 1992 Not concerning treatment of secondary postpartum haemorrhage.




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(Continued)

Figueroa-Damian 1996 Not concerning treatment of secondary postpartum haemorrhage.

Friedman 1957 Not concerning treatment of secondary postpartum haemorrhage.

Gall 1996 Not concerning treatment of secondary postpartum haemorrhage.

Gibbs 1988 Not concerning treatment of secondary postpartum haemorrhage.

Goldstein 1986 Case study report, not a RCT.

Greenberg 1987 Not concerning treatment of secondary postpartum haemorrhage.

Groeber 1960 Not concerning treatment of secondary postpartum haemorrhage.

Grunberger 1983 Not apparently concerning treatment of secondary postpartum haemorrhage.

Lancheros 1997 Not concerning treatment of secondary postpartum haemorrhage.

Ledee 2001 Concerning treatment of both primary and secondary postpartum haemorrhage. Audit of 61 case studies.

Maccato 1991 Not concerning treatment of secondary postpartum haemorrhage.

Martens 1989 Not concerning treatment of secondary postpartum haemorrhage.

McGregor 1989 Not concerning treatment of secondary postpartum haemorrhage.

Mitra 1997 Not concerning treatment of secondary postpartum haemorrhage.

Moodie 1976 Not concerning treatment of secondary postpartum haemorrhage.

Morales 1989 Not concerning treatment of secondary postpartum haemorrhage.

Paraskevaides 1993 Case study report, not a RCT.

Perry 1997 Not concerning treatment of secondary postpartum haemorrhage.

Pond 1979 Not concerning treatment of secondary postpartum haemorrhage.

Rodriguez-Ballestero Not concerning treatment of secondary postpartum haemorrhage.

Rubin 1961 Not concerning treatment of secondary postpartum haemorrhage.

Sen 1980 Not concerning treatment of secondary postpartum haemorrhage.




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(Continued)

Sorrell 1981 Not concerning treatment of secondary postpartum haemorrhage.

Takagi 1976 Concerning treatment of both primary and secondary postpartum haemorrhage. Case study report, not a

RCT.

Vogel 2004 Not apparently concerning treatment of secondary postpartum haemorrhage.

Walss-Rodriguez 1990 Not concerning treatment of secondary postpartum haemorrhage.

Whitten 1997 Not concerning treatment of secondary postpartum haemorrhage.

RCT = randomised controlled trial




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D A T A A N D A N A L Y S E S

This review has no analyses.

A P P E N D I C E S

Appendix 1. Planned methods

Sifting studies

This will be carried out by the Contact person and a co-author independently and blind to authorship. The abstracts of all identifiedstudies will be assessed against the Selection criteria. Those that obviously do not satisfy them will be discarded. The remainder will be

retrieved in full and their eligibility assessed without consideration of their results. Disagreements will be resolved by discussion between

two authors and, if necessary, with the third author. If disagreement persists, we will seek a final decision from the Topic Editor.

Critical appraisal of studies

Both authors will assess all trials for methodological quality independently. Quality of allocation concealment will be assessed using

scores A (adequate concealment), B (uncertainty about adequacy of concealment) and C (not adequately concealed) as described in

the Cochrane Handbook for Systematic Reviews of Interventions (Clarke 2000). All trials will be included in the primary analyses

regardless of score. Quality will be taken into account in a sensitivity analysis where the robustness of the results will be tested by

removing the lower quality studies.

Since there is the potential for blinding of allocation in these trials, we will also score trials according to whether they were double-

blinded (0 = no, 1 = yes but only stated, 2 = yes described and appropriate), and we will identify those trials which did not provide

a description of withdrawals and dropouts. These quality assessments will be used for descriptive purposes, and to inform further

sensitivity analyses.

Data extraction

Two authors will independently extract data for each eligible trial. The data will be entered on printed data sheets with prespecified

outcomes. Completed data sheets will be compared and any discrepancies resolved before analysis. If agreement cannot be reached, we

will seek a final decision from the Topic Editor.

Any data that do not fit the outcomes prespecified by the authors will be collected, clearly labelled as not prespecified and reported.

In order to minimise the risk of bias, we plan to base our conclusions on the prespecified outcomes only. Data needed for subgroup

analysis will also be collected.

Analysis

All primary outcomes are dichotomous, and will be compared individually between the (potentially) 20 drug treatment and controlgroup combinations. The effectof each treatment on each outcome in each study will be summarised by odds ratios and95% confidence

intervals. Results will be displayed graphically. Heterogeneity between studies for eachparticular treatmentor control group combination

and particular outcome will be tested using a chi-squared test. If not significant, a fixed-effect model will be assumed, and the results

from the studies pooled using the Mantel-Haenszel method. If significant, we will assess whether variation between studies can be

explained by differences in methodological quality, or (cautiously, because of interpretational difficulties in comparing non-randomised

groups) differences in population or intervention. The use of a random-effects model will also be considered.

Of interest will be whether there is heterogeneity between studies investigating treatment and placebo compared with treatment and

no treatment, for each of the types of treatment. If there is no evidence of heterogeneity, we will also take a broader view and conduct

an additional meta-analysis combining the placebo controlled and no treatment controlled studies. A similar approach will be taken

for studies investigating the effect of hormone therapy; if there is evidence of heterogeneity between studies using oestrogen therapy

and those using progesterone therapy, then separate meta-analyses will be conducted.




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If there are sufficient studies, funnel plots will be used to assess the risk of publication bias.

A 5% level of statistical significance will be used throughout. It is recognised that there are potentially a large amount of significance

tests to be done, and accordingly an increased chance of type I errors. Interpretation of results will be done cautiously, particularly

where P values are greater than 0.01 or results are inconsistent, or both.

A number of formal subgroup analyses will be done. Greater interpretational weight will be given to subgroups identifiable within

studies rather than between studies (where interpretation is much less reliable). Parity (primiparae versus multiparae), whether rupture

of membranes had occurred prior to the onset of labour or not, the type of delivery (normal vaginal; vaginal operative including breech;

caesarean section) and whether the placenta or membranes, or both, were complete will be included in the subgroup analysis. Specific

tests of the treatment x subgroup interactions (using logistic regression) will be carried out to aid proper interpretation of the subgroup

analysis.

We will conduct sensitivity analyses to assess the robustness of the results. This may involve the removal of smaller studies (publicationbias), or studies of relatively poor methodological quality, or both. It may also include assessment of publication bias, or other types of

bias by looking at robustness of the results under various scenarios that assume certain levels of bias.

W H A T S N E W

Last assessed as up-to-date: 30 January 2008.

12 February 2008 Amended Converted to new review format.

31 January 2008 New search has been performed Search updated. One new trial identified and excluded (Grunberger 1983).

H I S T O R Y

Protocol first published: Issue 4, 2000

Review first published: Issue 1, 2002

C O N T R I B U T I O N S O F A U T H O R S

Jo Alexander and Peter Thomas developed and wrote the protocol. Jo Alexander and Jill Sanghera identified relevant papers and reviewed

them against the prespecified selection criteria. Peter Thomas arbitrated when consensus could not be reached. Jo Alexander, Peter

Thomas and Jill Sanghera wrote the final review. Jill Sanghera was not a contributor to this update.




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D E C L A R A T I O N S O F I N T E R E S T

None known.

S O U R C E S O F S U P P O R T

Internal sources

School of Health and Social Care, Bournemouth University, UK.

External sources

Dorset Research and Development Support Unit, Poole Hospital, UK.

D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W

The title of the protocol which preceded this review was Drug treatment for secondary postpartum haemorrhage. As the search terms

used would also have identified any papers concerning surgical treatment, when the first named authors were written to, they were

asked for details of any further work that they knew of concerning either drug or surgical treatments. This review therefore covers both.

I N D E X T E R M S

Medical Subject Headings (MeSH)

Postpartum Hemorrhage [therapy]

MeSH check words

Female; Humans; Pregnancy



Treatments for Secondary Postpartum Haemorrhage (Review)

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