Maternal Infection Synthesis

Research gaps from Cochrane Reviews

(Cochrane Library Issue 3, 2006)

The faces indicate the direction of findings in each review:

JLikely to be effective
KBenefits and risks balanced
? Uncertain or limited effect
L Likely to be ineffective or potentially harmful

? Thus, important research implications are more likely to arise from reviews with uncertain findings.

J If a review shows an intervention to be beneficial,

K or that the risks and benefits are reasonably balanced, there may be less need for further research (at least for the major review question).

L If a review indicates that the intervention is likely to be ineffective or potentially harmful, or has been superseded, then this will often indicate that these research questions are of lower importance.

During pregnancy

INFECTION GENERALLY

?Prophylactic antibiotics for women with unspecified risk for maternal infection (Thinkhamrop 2002)

Need a trial of sufficient size to evaluate effects on reducing prelabour rupture of membranes

JProphylactic antibiotics reduce the risk of postpartum endometritis in high-risk pregnant women (Thinkhamrop 2002)

Need to identify the most appropriate type and dosage of antibiotics in high-risk pregnant women

KProphylactic antibiotics for women in preterm labour with intact membranes (maternal infection reduced but reduction not shown for neonatal infection and some suggestion of neonatal harm with antibiotics) (King 2002)

Need to research the type of antibiotic/s, especially addressing the possibility of improved outcomes with antibiotics active against anaerobes
Need to develop sensitive serological and/or bacteriological markers of subclinical infection for women in preterm labour with intact membranes

JAntibiotic treatment of asymptomatic bacteriuria (Smaill 2001)

Since antibiotics help prevent pyelonephritis and pre-term births, additional randomized trials of asymptomatic bacteriuria with a 'no treatment' arm are not advised
Sulphonamide, penicillin or nitrofurantoin are appropriate regimens for the management of asymptomatic bacteriuria, but the optimal time during pregnancy to perform the urine culture is unknown

?Dose of antibiotics for asymptomatic bacteriuria (Villar 2000)

Need to test whether single-dose drug is as effective as longer treatment regimens in prevention of preterm birth, pyelonephritis and recurrent infection (a WHO study of this is underway)

JAntibiotics for symptomatic urinary tract infections during pregnancy(Vazquez 2003)

Need to evaluate antibiotics such as nitrofurantoin, trimethoprim-sulfamethoxazole, cephalosporins and penicillins, in terms of duration (in single-dose or 3, 7, 10 or 15-day doses, or for the remainder of the pregnancy), acceptability (route and side effects), maternal outcomes, preterm birth and costs

?Antibiotics for treating bacterial vaginosis (McDonald 2005)

Future studies need to focus on earlier detection and treatment of bacterial vaginosis in the first trimester of pregnancy, or better still, pre-conception
Large trials are needed which can determine the effect of a screening programme for asymptomatic bacterial vaginosis on neonatal mortality and major measures of morbidity
Need to identify those subgroups of pregnant women who are at highest risk for adverse sequelae of bacterial vaginosis (including women with recurrent or persistent bacterial vaginosis)

SPECIFIC INFECTIONS

J Topical treatments for vaginal candidiasis (thrush) in pregnancy in pregnancy (Young 2001)

Longer acting formulations could be tried to improve compliance
Research into the relative safety of any systemic treatment may be of limited value since topical treatment usually works

J Antibiotics for treating chlamydia (Brocklehurst 1998)

Further trials of clindamycin and azithromycin with amoxycillin as control are needed

? Third trimester antiviral therapy for preventing recurrent genital herpes (Hollier 2004)

Cochrane protocol, Cochrane review in progress

JAntibiotics for treating gonorrhea (Brocklehurst 2002)

Any further trials of antibiotic treatment for gonorrhoea in pregnancy should include more substantive outcome measures (than microbiological cure) as well as adverse effects

? Prophylactic drugs for helminthic infections(Haider 2005)

Cochrane protocol, not yet covered in a Cochrane review

JAntiretrovirals for reducing the risk of mother-to-child transmission of HIV infection (Brocklehurst 2002)

Need to see if ongoing randomised trials of vaginal cleansing, vitamin and nutritional supplementation and breast versus artificial feeding show similar effectiveness to zidovudine or nevirapine

JAntibiotics for treating syphilis (Walker 2001)

No RCTs were located � while it is clear that penicillin is effective, the optimum regimens are uncertain

?Antibiotics for treating symptomatic trichomoniasis (G�lmezoglu 2002)

No maternal research implications were listed

LAntibiotics for treating asymptomatic trichomoniasis (G�lmezoglu 2002)

No maternal research implications were listed

? Treating toxoplasmosis in pregnancy (Peyron 1999)

A large study could randomise health care clinics to no screening (existing practice in some countries) or screening, with follow up of seronegative women and treatment if they seroconvert
In countries where screening is already routine, all women would be offered routine screening, but treatment after seroconversion would be randomised e.g. to the following groups: spiramycin, with sulphonamides and pyrimethamine if fetal infection was identified at amniocentesis; spiramycin alone; sulfadoxine-pyrimethamine alone; and sulfadiazine with pyrimethamine

? Timing and type of prenatal treatment for congenital toxoplasmosis (Thi�baut 2003)

Cochrane protocol, Cochrane review in progress

?Antibiotics for treating ureaplasma (Raynes-Greenow 2004)

No maternal research implications were listed

MISCARRIAGE (see Miscarriage umbrella for full list of research gaps)

J Significantly less infection seen for expectant compared with surgical management (Nanda 2006)

Expectant management needs to be compared with medical management of miscarriage � see below

J Vaginal misoprostol for the treatment of non-viable pregnancies before 24 weeks (Neilson 2006)

No research implications related to infection were given

Peri-Partum

ADMISSION PROCEDURES

?Routine perineal shaving on admission in labour (Basevi 2000)

Midwives and doctors who continue to perform routine perineal shaving on admission in labour may consider entering women into methodologically sound randomised controlled trials to evaluate the effectiveness and safety of their practice

CAESAREAN SECTION

JProphylactic antibiotics for women undergoing elective or non-elective cesarean section (Smaill 2002)

Further placebo controlled trials of the effectiveness of antibiotics with caesarean section are not ethically justified
Need to research methods to implement effective policies of routine prophylaxis for women undergoing caesarean section
Need to evaluate interventions to reduce further the incidence of infection e.g. topical antibiotics, and determine the role of surgical technique, pre- and intra-operative preparation and infection control policies on infection rates
Need to determine what role antimicrobial prophylactic regimens have in the development of antimicrobial resistance
Need to know more about the role of bacterial vaginosis and infectious complications following caesarean section and whether this has implications for current prophylactic recommendations

?Few differences seen betweenampicillin and first generation cephalosporins, broader spectrum agents or single versus multiple dose regimens (Hopkins 1999)

Need a RCT comparing pre-operative administration versus administration immediately after the cord is clamped

?Elective caesarean delivery versus vaginal delivery to reduce the incidence of perinatal transmission of the hepatitis C virus (McIntyre 2005)

Cochrane protocol, Cochrane review in progress

?Maternal infection after closure or non-closure of the peritoneum (Bamigboye 2003)

Need to research long-term benefits and possible complications of non-closure of the peritoneum at caesarean section (a multicentre trial of techniques of caesarean section is in progress)

?Effect of different techniques and materials for closure of the abdominal wall in caesarean section (Anderson 2004)

Need to research blunt needles which may protect operators and patients from blood-borne infections
There are currently no published trials looking at different suture techniques or materials for closure of the rectus sheath or subcutaneous fat at caesarean section

?Wound drainage after caesarean section (Gates 2005)

Further large trials are justified using blinded outcome assessment to examine the role of different types and sites of wound drain at caesarean section.
Comparing the use of drains in women with different degrees of obesity and in women having first or repeat caesareans and intrapartum or prelabour caesarean sections would be of interest.
Women's views and experience of drains have not been studied and could be included in future trials.

ENEMAS

?Two trials of enemas versus no enemas showed no differences for any maternal infections, but women not having enemas needed significantly more antibiotics (Cuervo 1999)

Blinded trials are needed

GROUP B STREPTOCOCCUS

J Intrapartum antibiotics for Group B streptococcal colonisation (Smaill 1996)

Need a sensitive rapid screening test to detect accurately women in labour who are colonized with GBS to make prevention strategies more efficient
Uncertain whether prophylaxis should only be given to women with identified risk factors or to all women colonized with GBS. Need better data on maternal risk factors for neonatal GBS in different populations if the impact of different prevention strategies is to be more accurately evaluated

? Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection (Stade 2004)

A large multi-centred double-blinded randomized trial measuring relevant outcomes including colonization of infants with GBS, early-onset GBS infection, early-onset GBS pneumonia and meningitis, and mortality rates is needed. The trial must overcome the methodological limitations of past trials

iMMERSION IN WATER

? Effect of immersion during pregnancy, labour and birth (Cluett 2002)

Maternal infection during pregnancy, labour or birth has not been reported in any of the studies included in this Cochrane review

INDUCTION OF LABOUR

?Not clear if amniotomy increases maternal infection (Bricker 2000)

Need to research different time intervals between the primary (amniotomy alone) and secondary intervention (addition of a pharmacological agent)

?Intravenous oxytocin and amniotomy versus amniotomy for maternal infection (Howarth 2001)

Need to research different time intervals between the primary (amniotomy alone) and secondary intervention (addition of a pharmacological agent)

?Mechanical methods for induction of labour for maternal infection (Boulvain 2001)

Future studies on mechanical methods for induction of labour should be of large sample size and report on substantive outcomes
Hyperstimulation, including the effect on fetal well-being, and maternal discomfort should be carefully assessed
An economic analysis comparing mechanical methods with prostaglandins for cervical ripening would be useful

?Membrane sweeping for induction of labour for maternal infection (Boulvain 2005)

Is sweeping of the membranes is more effective in specific subgroups (parity, state of cervix)?

?Intravenous oxytocin alone versus other methods of induction for maternal infection (Kelly 2001)

Need to look at different intervals of commencing oxytocin or different doses of oxytocin

L Prostaglandins versus oxytocin for induction of labour for maternal infection (Luckas 2000)

The large trials necessary to address this question are not justified

?Oral prostaglandin E2 for induction of labour for maternal infection (French 2001)

Oral misoprostol (synthetic prostaglandin) is likely to supersede the oral preparations of PGE2 that are in current use

OPERATIVE VAGINAL BIRTH

?Prophylactic antibiotics for operative vaginal birth (Liabsuetrakul 2004)

Only one trial which stopped early was located - future trials should be based on the principle of antibiotic prophylaxis for caesarean section with a single dose of intravenous ampicillin or first-generation cephalosporins after cord clamping

PRETERM PROM

JRoutine use of antibiotics (erythromycin) for preterm prelabour PROM (Kenyon 2003)

Future trials of antibiotic prophylaxis for preterm prelabour rupture of membranes need to measure long term outcomes (Kenyon 2003)

?Planned management for prelabour rupture of membranes at 34 to 37 weeks' gestation (Buchanan 2004)

Cochrane protocol, Cochrane review in progress

PREVENTING INFECTIONS

?Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV) (Lumbiganon 2004)

Since chlorhexidine solution is quite safe, not expensive and vaginal irrigation is not difficult to perform, there is a need for a well-designed randomized controlled trial with adequate sample size to evaluate this simple intervention, as well as determining the optimal volume of the solution used for irrigation

- TERM PROM

? Prelabour prophylactic antibiotics for term PROM (Flenady 2002)

Future trials of prelabour prophylactic antibiotics for term PROM should be blinded, adequately sized to address clinically important maternal and neonatal outcomes and include a cost analysis

JPlanned managementfor prelabour rupture of membranes at term (37 weeks or more) (Dare 2006)

Future trial design should attempt to blind outcomes such as maternal and neonatal infection and to report these outcomes in a standardised way.
Outcomes such as maternal satisfaction, maternal and neonatal infectious morbidity, other neonatal morbidities, and longer term child development/disability need to be included in future trials.

Intrapartum

?Antibiotics for treating intraamniotic infections (Hopkins 2002)

Need to look at comparisons of different regimens and to measure long term outcomes such as consequences of neonatal cerebral damage

Third stage of labour

?Prophylactic antibiotics for manual removal of retained placenta in vaginal birth (Chongsomchai 2006)

Multicentre randomised controlled trials comparing antibiotic prophylaxis and placebo or no antibiotic use to prevent endometritis after manual removal of placenta in vaginal birth are urgently needed
The sample size for detecting the decreased incidence of endometritis from 6% to 3% with 80% power and two tailed significant level of 0.05 is approximately 780 for a two group comparison

Postpartum

BREAST INFECTIONS

?Use of creams, friction, massage and the expression of colostrum for breast infections (Blyth 2004)

Cochrane protocol, Cochrane review in progress

?Antibiotics for mastitis (Ng 2005)

Cochrane protocol, not yet covered in a Cochrane review

ENDOMETRITIS (POSTPARTUM TREATMENT)

JAntibiotics for endometritis after birth (French 2004)

Any further studies that compare clindamycin and an aminoglycoside with an alternative regimen, should consider alternatives suitable for use in low-income countries
Any new regimen compared with clindamycin and an aminoglycoside include ototoxicity and nephrotoxicity as outcomes
Need to evaluate early switching to the oral route, as newer antibiotics have improved oral bioavailability
Role of endometrial cultures, collected under conditions where contamination is avoided, for targeting antibiotic therapy more specifically to individual women
Poor activity against penicillin resistant anaerobes was associated with failure of the regimen
No RCT looked at the effect of treatment on the infant of a breastfeeding mother

PERINEAL TRAUMA

?Prophylactic antibiotics for severe perineal tears (Buppasiri 2005)

No trials of prophylactic antibiotics in fourth-degree perineal tear during vaginal birth located - well-designed, multicentre, randomised controlled trials are needed

References

Anderson ER, Gates S. Techniques and materials for closure of the abdominal wall in caesarean section. The Cochrane Database of Systematic Reviews 2004, Issue 4
Bamigboye AA, Hofmeyr GJ. Closure versus non-closure of the peritoneum at caesarean section. The Cochrane Database of Systematic Reviews 2003, Issue 4.
Basevi V, Lavender T. Routine perineal shaving on admission in labour. The Cochrane Database of Systematic Reviews 2000, Issue 4
Blyth R, Smyth W, Flenady V. Antenatal nipple care for increasing the duration of breastfeeding. (Protocol) The Cochrane Database of Systematic Reviews 2004, Issue 1
Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanical methods for induction of labour. The Cochrane Database of Systematic Reviews 2001, Issue 4.
Boulvain M, Stan C, Irion O. Membrane sweeping for induction of labour. The Cochrane Database of Systematic Reviews 2005, Issue 1.
Bricker L, Luckas M. Amniotomy alone for induction of labour. The Cochrane Database of Systematic Reviews 2000, Issue 4.
Brocklehurst P. Antibiotics for gonorrhoea in pregnancy. The Cochrane Database of Systematic Reviews 2002, Issue 2
Brocklehurst P, Volmink J. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database of Systematic Reviews 2002, Issue 2.
Brocklehurst P, Rooney G. Interventions for treating genital chlamydia trachomatis infection in pregnancy. The Cochrane Database of Systematic Reviews 1998, Issue 4
Buchanan SL, Crowther CA, Morris J. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes at 34 to 37 weeks' gestation for improving pregnancy outcome. (Protocol) The Cochrane Database of Systematic Reviews 2004, Issue 2
Buppasiri P, Lumbiganon P, Thinkhamrop J, Thinkhamrop B. Antibiotic prophylaxis for fourth-degree perineal tear during vaginal birth. The Cochrane Database of Systematic Reviews 2005, Issue 4.
Chongsomchai C, Lumbiganon P, Laopaiboon M. Prophylactic antibiotics for manual removal of retained placenta in vaginal birth. The Cochrane Database of Systematic Reviews 2006, Issue 2
Cluett E R, Nikodem VC, McCandlish RE, Burns EE. Immersion in water in pregnancy, labour and birth. The Cochrane Database of Systematic Reviews 2002, Issue 2
Cuervo LG, Rodr�guez MN, Delgado MB. Enemas during labour. The Cochrane Database of Systematic Reviews 1999, Issue 4
Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). The Cochrane Database of Systematic Reviews 2006, Issue 1.
Flenady V, King J. Antibiotics for prelabour rupture of membranes at or near term. The Cochrane Database of Systematic Reviews 2002, Issue 3
French L. Oral prostaglandin E2 for induction of labour. The Cochrane Database of Systematic Reviews 2001, Issue 2.
French LM, Smaill FM. Antibiotic regimens for endometritis after delivery. The Cochrane Database of Systematic Reviews 2004, Issue 4
Gates S, Anderson ER. Wound drainage for caesarean section. Cochrane Database of Systematic Reviews 2005, Issue 1
G�lmezoglu AM. Interventions for trichomoniasis in pregnancy. The Cochrane Database of Systematic Reviews 2002, Issue 3
Haider BA, Bhutta ZA. Effects of interventions for helminthic infections in pregnancy. (Protocol) The Cochrane Database of Systematic Reviews 2005, Issue 4.
Hollier L, Wendel GD. Third trimester antiviral therapy for preventing recurrent genital herpes at delivery. (Protocol) The Cochrane Database of Systematic Reviews 2004, Issue 4
Hopkins L, Smaill F. Antibiotic prophylaxis regimens and drugs for cesarean section. The Cochrane Database of Systematic Reviews 1999, Issue 2 � lasted searched October 1998
Hopkins L, Smaill F. Antibiotic regimens for management of intraamniotic infection. The Cochrane Database of Systematic Reviews 2002, Issue 3
Howarth GR, Botha DJ. Amniotomy plus intravenous oxytocin for induction of labour. The Cochrane Database of Systematic Reviews 2001, Issue 3
Kelly AJ, Tan B. Intravenous oxytocin alone for cervical ripening and induction of labour. The Cochrane Database of Systematic Reviews 2001, Issue 3
Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm rupture of membranes. The Cochrane Database of Systematic Reviews 2003, Issue 2 � last searched August 2004
King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. The Cochrane Database of Systematic Reviews 2002, Issue 4.
Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam M. Antibiotic prophylaxis for operative vaginal delivery. The Cochrane Database of Systematic Reviews 2004, Issue 3.
Lumbiganon P, Thinkhamrop J, Thinkhamrop B, Tolosa JE. Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV). The Cochrane Database of Systematic Reviews 2004, Issue 4
McDonald H, Brocklehurst P, Parsons J. Antibiotics for treating bacterial vaginosis in pregnancy. The Cochrane Database of Systematic Reviews 2005, Issue 1
McIntyre PG, Tosh K, McGuire W. Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission. (Protocol) The Cochrane Database of Systematic Reviews 2005, Issue 4.
Nanda K, Peloggia A, Grimes D, Lopez L, Nanda G. Expectant care versus surgical treatment for miscarriage. The Cochrane Database of Systematic Reviews 2006, Issue 2
Neilson JP, Hickey M, Vazquez J. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database of Systematic Reviews 2006, Issue 3
Ng C, Jahanfar S, Teng CL. Antibiotics for mastitis in breastfeeding women. (Protocol) The Cochrane Database of Systematic Reviews 2005, Issue 3
Peyron F, Wallon M, Liou C, Garner P. Treatments for toxoplasmosis in pregnancy. The Cochrane Database of Systematic Reviews 1999, Issue 3
Raynes-Greenow CH, Roberts CL, Bell JC, Peat B, Gilbert GL. Antibiotics for ureaplasma in the vagina in pregnancy. The Cochrane Database of Systematic Reviews 2004, Issue 1
Smaill F. Intrapartum antibiotics for Group B streptococcal colonisation. The Cochrane Database of Systematic Reviews 1996, Issue 1
Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy. The Cochrane Database of Systematic Reviews 2001, Issue 2
Smaill F, Hofmeyr GJ. Antibiotic prophylaxis for cesarean section. The Cochrane Database of Systematic Reviews 2002, Issue 3
Stade B, Shah V, Ohlsson A. Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection. The Cochrane Database of Systematic Reviews 2004, Issue 3
Thi�baut R, Gilbert RE, Gras L, Ch�ne G. Timing and type of prenatal treatment for congenital toxoplasmosis. (Protocol) The Cochrane Database of Systematic Reviews 2003, Issue 1
Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P. Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality. The Cochrane Database of Systematic Reviews 2002, Issue 4.
Vazquez JC, Villar J. Treatments for symptomatic urinary tract infections during pregnancy. The Cochrane Database of Systematic Reviews 2003, Issue 4
Villar J, Widmer M, Lydon-Rochelle MT, G�lmezoglu AM, Roganti A. Duration of treatment for asymptomatic bacteriuria during pregnancy. The Cochrane Database of Systematic Reviews 2000, Issue 2
Walker GJA. Antibiotics for syphilis diagnosed during pregnancy. The Cochrane Database of Systematic Reviews 2001, Issue 3
Young GL, Jewell D. Topical treatment for vaginal candidiasis (thrush) in pregnancy. The Cochrane Database of Systematic Reviews 2001, Issue 4
Zupan J, Garner P, Omari AAA. Topical umbilical cord care at birth. The Cochrane Database of Systematic Reviews 2004, Issue 3