Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality

Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P

Date of most recent substantive amendment: 21 August 2002

This review should be cited as: Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P. Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality (Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK: John Wiley & Sons, Ltd.

ABSTRACT

Background

Some previous studies suggested that prophylactic antibiotics given during pregnancy improved maternal and perinatal outcomes, some did not show any benefit and some even reported adverse effects.

Objectives

To determine the effect of prophylactic antibiotics during second and third trimester of pregnancy on maternal and perinatal outcomes.

Search Strategy

The Cochrane Pregnancy and Childbirth Group trials register (April 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002) and reference lists of articles were searched.

Selection Criteria

Randomized controlled trials comparing prophylactic antibiotic treatment with placebo or no treatment for women in the second or third trimester of pregnancy before labour.

Data collection and analysis

Trial quality assessment and data extraction were done by the reviewers.

Main Results

There were six randomized controlled trials which recruited 2184 women to detect the effect of prophylactic antibiotic administration in the second or third trimester on pregnancy outcomes. Antibiotic prophylaxis in unselected pregnant women reduced the risk of prelabour rupture of membranes (Peto odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.73). In women with a previous preterm birth there was a risk reduction in low birth weight (OR 0.48, 95% CI 0.27 to 0.84) and postpartum endometritis (OR 0.46, 95% CI 0.24 to 0.89). There was a risk reduction in preterm delivery (OR 0.48, 95% CI 0.28 to 0.81) in pregnant women with a previous preterm birth associated with bacterial vaginosis (BV) during the current pregnancy but there was no risk reduction in pregnant women with previous preterm birth without BV during pregnancy (OR 1.06, 95% CI 0.68 to 1.64). However, vaginal antibiotic prophylaxis during pregnancy did not prevent infectious pregnancy outcomes and there is a possibility of adverse effects such as neonatal sepsis (OR 8.07, 95% CI 1.36 to 47.77).

Reviewers' conclusions

Antibiotic prophylaxis given during the second or third trimester of pregnancy reduces the risk of prelabour rupture of the membranes when given routinely to pregnant women. Beneficial effects on birth weight and the risk of postpartum endometritis were seen for high risk women.

This review should be cited as:

Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality (Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK: John Wiley & Sons, Ltd.

BACKGROUND

Maternal genital tract infection or colonization by some infectious organisms can cause maternal and perinatal mortality and morbidity.

Preterm delivery is the most common cause of perinatal morbidity and mortality in the world. Moreover, prematurity is implicated in at least two thirds of early infant deaths (Cunningham 1997).

A wide spectrum of medical and demographic factors have been implicated in the etiology of preterm birth. These can be categorized into three groups: 1. medical and obstetric complications (eg hypertensive disorders, placental hemorrhage); 2. lifestyle factors (eg cigarette smoking, poor nutrition); 3. amniotic fluid infection caused by a variety of microorganisms located in the genital tract; 4. cervical incompetence. Approximately one third of preterm births were associated with chorioamniotic infection (Lettieri 1993).There are many microorganisms that have been proposed to be the cause of preterm prelabour rupture of membranes, preterm labour, or both, eg bacterial vaginosis, Trichomonas vaginalis, Neisseria gonorrhoeae, Ureaplasma urealyticum, Chlamydia trachomatis, Group B streptococci (Hillier 1995; Hardy 1984; Braun 1971; Gravett 1986; Regan 1981). Case detection and treatment in pregnant women are problematic and expensive, underscoring the need for other strategies.

Infections and related complications in pregnancy and childbirth are potentially preventable. However, the appropriate intervention is yet to be identified. Routine antenatal detection and treatment of infections, especially in countries with high prevalence, would be the most reasonable approach. Limited laboratory facilities make this strategy unrealistic in low resource settings. Diagnosis algorithms including clinical signs and symptoms and behavioral pattern are at times used for quick identification of infections for prompt care. Unfortunately, despite the fact that this approach may be useful in countries with limited resources, diagnostic algorithms have low sensitivity, predictive values and validity. In a situation where there is a scarcity of realistic options, a strategy of routine antibiotic prophylaxis might be a worthwhile alternative.

The available body of literature on prophylactic antibiotics in pregnancy has yielded conflicting results. While some studies demonstrated that prophylactic antibiotic administration in pregnancy improved maternal and perinatal morbidity and mortality, other studies could not confirm this finding (Eschenbach 1991; McCormack 1987; Morales 1994; Newton 1989; Romero 1993; Oleszczuk 2000; Romero 1988). It is in view of this uncertainty that there is a need for a systematic review of the results of randomized controlled trials of antibiotic prophylaxis in pregnancy.

OBJECTIVES

To determine whether the routine administration of prophylactic antibiotics in the second or third trimester of pregnancy reduces adverse pregnancy outcomes.

CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW

Types of studies

Randomized controlled trials. Non-randomized (quasi-randomized) trials were excluded.

Types of participants

Women in the second or third trimester of pregnancy before labour and delivery.

Types of intervention

Prophylactic antibiotics versus placebo or no treatment.

Types of outcome measures

Maternal outcomes:
1) primary outcomes (directly related to infectious morbidity/mortality):
a. preterm labor;
b. preterm prelabour rupture of membranes (membrane rupture before gestational age of 37 weeks and before labor);
c. prelabour rupture of membranes (membrane rupture after gestational age of 37 weeks but before labor);
d. preterm delivery;
e. chorioamnionitis;
f. intrapartum fever needing treatment with antibiotics;
g. puerperal sepsis/postpartum endometritis, wound infection, urinary tract infection;
h. serious maternal complications of puerperal infection requiring laparotomy for infection, hysterectomy, death;
i. gonococcal cervicitis (postpartum detected).

2) Secondary outcomes:
a. maternal side effects of antibiotic prophylaxis;
b. duration of hospitalization;
c. satisfaction with care;
d. compliance.

Neonatal outcomes:
1) Primary outcomes (directly related to infectious morbidity/mortality):
a. mean gestational age;
b. low birth weight;
c. mean birth weight;
d. clinical neonatal sepsis;
e. blood culture confirming sepsis.

2) Secondary outcomes:
a. admission to neonatal intensive care unit;
b. ophthalmia neonatorum;
c. congenital abnormality;
d. small for gestational age;
e. abnormal neurological development;
f. perinatal mortality.

SEARCH STRATEGY FOR IDENTIFICATION OF STUDIES

See: Cochrane Pregnancy and Childbirth Group search strategy

This review has drawn on the search strategy developed for the Pregnancy and Childbirth Group as a whole. The full list of journals and conference proceedings as well as the search strategies for the electronic databases, which are searched by the Group on behalf of its reviewers, are described in detail in the 'Search strategies for the identification of studies section' within the editorial information about the Cochrane Pregnancy and Childbirth Group. Briefly, the Group searches on a regular basis MEDLINE, the Cochrane Controlled Trials Register and reviews the Contents tables of a further 38 relevant journals received via ZETOC, an electronic current awareness service.

Relevant trials, which are identified through the Group's search strategy, are entered into the Group's specialised register of controlled trials. Please see Review Group's details for more detailed information. Date of last search: April 2002.

In addition, The Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002) was searched using the terms "(antibio* or antimicrob*) and pregnan*". We selected trials in which the administration of antibiotics was done before documentation of any infections or complications of pregnancy which is the principle of antibiotic prophylaxis. Reference lists of identified studies were examined for additional trials.

METHODS OF THE REVIEW

All trials were assessed for eligibility in accordance with the specified criteria. Trials were assessed for methodological quality using the standard Cochrane criteria of allocation concealment (A = adequate; B = unclear; C = inadequate; D = allocation concealment was not used). Note was made of whether the trials were placebo controlled, and information on the blinding of outcome assessment and loss to follow up was collected. The effect of trial quality will be assessed in sensitivity analyses. Categorical data will be compared using Peto odds ratio and 95% confidence intervals. The following data were extracted from each publication:

1) information on the study setting (eg country, type of population, and socio-economic status);
2) detailed description of the antibiotic regimen used (including type of drug, dose, frequency, and timing);
3) definition of the outcomes. An 'intention to treat' analysis was performed. A summary of the odds ratio was calculated using a fixed effects model (as long as there is no significant heterogeneity among the trials);
4) effects of routine use of antibiotics during pregnancy in their allocated groups (unselected or unspecified risk; high risk or specified risks).

High risk pregnant women were defined as previous spontaneous preterm delivery, history of low birth weight (< 2,500 gm) or pre pregnancy weight less than 50 kg; or associate with bacterial vaginosis (BV) in that current pregnancy.

DESCRIPTION OF STUDIES

There were eight randomized controlled trials to assess the effect of antibiotics administration during pregnancy. We excluded two trials because of the timing of antibiotic administration during the current pregnancy in the first and second half of pregnancy in one trial (Gray 2001). Another trial was studied in twin gestation which has a higher risk of adverse pregnancy outcome with some different mechanisms from single pregnancy (Peters 1995). Six trials met the inclusion criteria for this review.

For a detailed description of studies see the table of 'Characteristics of included studies'. Three of the studies (Hauth 1995; McGregor 1990; Vermeulen 1999) were conducted in high income countries (USA, Netherlands) while the remaining three (Temmerman 1995; Gichangi 1997; Paul 1997) were reports from low and middle income countries (Kenya, India). Three trials (Hauth 1995; Gichangi 1997; Vermeulen 1999) enrolled only high risk pregnant women. All studies described adequately the characteristics of the women admitted into the study.

The antibiotics used in these studies were oral erythromycin, metronidazole, cefetamet-pivoxil, and parenteral ceftriaxone, and clindamycin vaginal cream.

The earliest of the six studies reviewed was published in 1990, four others were published in 1995 to 1997 and the latest one was published in 1999.

METHODOLOGICAL QUALITY

For the detailed information on methods see the table of 'Characteristics of included studies'.

The methodological quality of the trials was satisfactory. In all, the methods of randomisation were adequate. They were all placebo controlled double blind randomized trials. A large drop out was noted in one study (Temmerman 1995: 166 (41.5%) out of 400 women enrolled). The losses for some outcomes were higher than the figures given in the characteristics of studies tables (Temmerman 1995; Gichangi 1997). This might have influenced the results. However, there was no evidence that these drop outs occurred preferentially in one or the other arm of the trial. There were high drop out rates in the other studies too (Gichangi 1997 21%; Paul 1997 22%; Vermeulen 1999 15.5%). These high loss rates have the potential to introduce bias.

RESULTS

Six randomized controlled trials with a total of 2184 women were included to detect the effect of prophylactic antibiotic administration in the second or third trimester on pregnancy outcomes. There were many studies of antibiotic use to prevent preterm delivery, but other than the included studies, they were studies of antibiotic treatment after there was evidence of infection or complications of pregnancy eg, detected bacterial vaginosis (BV) or premature rupture of membranes before administration of antibiotics. They were thus trials of treatment, not prophylaxis. The time of included studies' publication occupied a range of almost ten years (1990 to 1999). Three trials with 1112 women (Hauth 1995; Gichangi 1997; Vermeulen 1999) enrolled only high risk pregnant women which was defined as previous spontaneous preterm delivery, history of low birth weight, association with BV in the current pregnancy or pre pregnancy weight less than 50 kg. Four studies used oral antibiotics: erythromycin alone (McGregor 1990; Paul 1997), erythromycin plus metronidazole (Hauth 1995), cefetamet-pivoxil (Gichangi 1997). One study used ceftriaxone intramuscular injection (Temmerman 1995) and one used clindamycin vaginal cream application (Vermeulen 1999).

Results from trials for women with unspecified risk or unselected women:

Studies of antibiotic prophylaxis during the second or third trimester (range 26 to 34 weeks of gestational age) in unselected pregnant women reported the following outcomes: preterm prelabour rupture of membranes, prelabour rupture of membranes, preterm delivery, chorioamnionitis, postpartum endometritis, low birth weight, mean birth weight, congenital abnormality, small for gestational age, perinatal mortality. There was only a significant risk reduction for prelabour rupture of membranes (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.73) in one trial (McGregor 1990). There was almost risk reduction on postpartum endometritis (OR 0.49, 95% CI 0.23 to 1.06) from the data of two trials (McGregor 1990; Temmerman 1995).

Results from trials for women specified as at high risk:

High risk group trials reported the following outcomes: preterm delivery, postpartum endometritis, gonococcal infection (postpartum detected), mean gestational age, low birth weight, mean birth weight, neonatal sepsis. Postpartum detected gonococcal infection is a non-prespecified outcome assessed. There was a significant risk reduction in preterm delivery (OR 0.48, 95% CI 0.28 to 0.81) in pregnant women with previous preterm delivery associated with BV during the current pregnancy but there was no risk reduction in pregnant women with previous preterm delivery without BV in that current pregnancy (OR 1.06, 95% CI 0.68 to 1.64). There was a risk reduction on postpartum endometritis (OR 0.46, 95% CI 0.24 to 0.89), gonococcal infection (detected postpartum) (OR 0.35, 95% CI 0.13 to 0.89) and low birth weight (OR 0.48, 95% CI 0.27 to 0.84) in pregnant women with a history of preterm delivery. There was also a significant increase in mean gestational age (weighted mean difference (WMD) 0.70, 95% CI 0.01 to 1.39) and higher mean birth weight (WMD 155.00 95% CI 6.22 to 303.78) on prophylactic antibiotic use in women with a previous low birth weight baby (< 2500 gm).

Vaginal antibiotic prophylaxis did not prevent adverse pregnancy outcomes but increased the risk of neonatal sepsis (OR 8.07, 95% CI 1.36 to 47.77).

Other results:

The included studies did not report any serious adverse effects of antibiotic prophylaxis. There were no data reported on some maternal outcomes that we planned to assess, including preterm labor, intrapartum fever needing treatment with antibiotics, puerperal sepsis, wound infection, urinary tract infection, serious maternal complications (puerperal infection requiring laparotomy for infection, hysterectomy, death), maternal side effects, duration of hospitalization and satisfaction with care. There were limited data to assess congenital abnormality and perinatal mortality. We also found limited data to evaluate the effect of antibiotics on low birth weight in unselected women. There were two trials in this analysis; one reported in unselected and another one reported in high risk group, which have effects in opposite directions. There were no data on the following neonatal outcomes: blood culture confirming sepsis, admission to neonatal intensive care unit, ophthalmia neonatorum and abnormal neurological development.

We found one study that reported compliances with medication which were different between the groups (73% in treatment group versus 84% in control group). In this trial, the treatment and control group received the identical-appearing treatment bottles and tablets that were either erythromycin base or placebo.

DISCUSSION

The methodological quality of the six included trials was satisfactory. They were all randomized double blind placebo controlled trials with satisfactory methods of randomisation. They were from both high income and low and middle income countries. The sample size for unselected pregnant women might not be enough to demonstrate differences for important uncommon outcomes.

The results of this study showed that antibiotic prophylaxis during the second or third trimester of pregnancy were effective in reducing risk of prelabour rupture of membranes in unselected pregnant women and low birth weight, postpartum endometritis and gonococcal infection (detected postpartum) in high risk pregnant women. We need more data to evaluate whether routine use antibiotics in pregnant women can prevent other substantive adverse pregnancy outcomes.

REVIEWER'S CONCLUSIONS

Implications for practice

High risk women should be considered for antibiotic prophylaxis during the second or third trimester of pregnancy. We do not have enough data to recommend routine use of antibiotics for pregnant women in general.

Implications for research

Further studies to identify the most appropriate type and dosage of antibiotics in high risk pregnant women should be conducted. Since this review also showed some suggestion about the effectiveness of antibiotic prophylaxis in reducing prelabour rupture of membranes, a trial of adequate sample size should be considered to assess this possibility.

ACKNOWLEDGEMENTS

The authors thank Dr Metin Gulmezoglu for his suggestions and encouragement to complete this review.

POTENTIAL CONFLICT OF INTEREST

None known.

TABLES

Characteristics of included studies

Study	Gichangi 1997
Methods	Randomized double blind placebo controlled trial.
Participants	320 pregnant women during GA 28-32 wks. With a history of LBW (less than 2500 gm), stillbirth or early perinatal death. (High risk.)
Interventions	Treatment group received a single dose of 2 gm cefetamet-pivoxil and the control group received a placebo which was not mentioned about the appearance of the placebo tablet.
Outcomes	A total of 253 of 320 women delivered in the study center. Out of the 253, there are 134 in the treatment group and 119 in the placebo group. The mean birth weight in the treatment group was higher than in the placebo group.
Notes	Nairobi, Kenya and Ghent, Belgium. November 1995-February 1996. 83% of the treatment group and 74% of the placebo group delivered at the study center, the rest were delivered elsewhere and could not be traced for follow-up.
Allocation concealment	B
Study	Hauth 1995
Methods	A 2:1 double blind randomised placebo controlled trial.
Participants	624 pregnant women during GA 22-24 wks, at risk of preterm delivery because of previous preterm delivery or prepregnancy weight less than 50 kg, were randomised. 433 were in the treatment group and 191 were in the placebo group. (High risk.)
Interventions	Treatment group had 250 mg metronidazole three times a day for 7 days, and erythromycin 333 mg three times a day for 14 days, while an identical preparation containing lactose was given to the placebo group.
Outcomes	26% of trial group delivered preterm, as compared with 68% of the placebo group .
Notes	Alabama, Birmingham. May 1989-December 1993. Lost follow-up rate was 8 from 624.
Allocation concealment	A
Study	McGregor 1990
Methods	Randomized double blind placebo controlled trial.
Participants	235 pregnant women during GA 26-30 wks. (Unselected pregnant women.)
Interventions	They were given identical prepared bottles and tablets that were either erythromycin base 333 mg or placebo taking one tablet three times a day for one week.
Outcomes	Prelabour rupture of membranes occurred less frequently (p<0.01) among women who received erythromycin (6%) versus placebo (16%).
Notes	Denver Colorado and Seattle, Washington. October 1985-August 1988. Lost follow-up rate was 4 from 235.
Allocation concealment	A
Study	Paul 1997
Methods	Randomized double blind placebo controlled trial.
Participants	437 pregnant women during GA 26-34 wks. (Unselected pregnant women.)
Interventions	The treatment group received erythromycin sterate 500 mg and placebo (no description of placebo tablet) in the control group twice a day for 6 wks.
Outcomes	Of 437 women enrolled into the trial, there were 219 in the erythromycin group and 218 in the placebo group. There were no differences in their mean birth weight, incidence of LBW or incidence of preterm delivery in the treatment and the control groups.
Notes	Lost follow-up rate was 29 from 437 and drop-outs without specified reason in 66 from 437.
Allocation concealment	B
Study	Temmerman 1995
Methods	Randomized double blind placebo controlled trial.
Participants	400 pregnant women during GA 28-32 wks. (Unselected pregnant women.)
Interventions	Single dose of 250 mg ceftriaxone IM versus placebo 3.5 ml 0.9% NaCl IM.
Outcomes	Mean birth weight in the ceftriaxone group 153 gm higher than in the placebo group i.e. 3209 versus 3056; (p = 0.01).
Notes	Nairobi, Kenya. 60% of the treatment group and 57% of the placebo group were delivered at the study center; the rest were delivered elsewhere. Lost follow-up rate was 166 from 400.
Allocation concealment	A
Study	Vermeulen 1999
Methods	Randomized double blind placebo controlled trial.
Participants	168 pregnant women during GA 26-32 wks. With a history of preterm delivery in the preceeding pregnancy. (High risk.)
Interventions	Clindamycin 2% vaginal cream, or placebo (identical looking cream), applied daily for 7 days.
Outcomes	No difference was found in overall preterm birth between the treatment and the control groups.
Notes	12 hospitals in The Netherlands January 1, 1994-December 31, 1996. Lost follow-up rate or incomplete medication taken was 13 from 83 of treatment group and 13 from 85 in placebo group.
Allocation concealment	C

GA = gestational age
IM = intramuscular
LBW = low birth weight
wks = weeks

Characteristics of excluded studies

Study	Reason for exclusion
Gray 2001	Pregnant women were enrolled at varying gestations, and treatment could not be provided on a fixed schedule during pregnancy. In this trial, the intervention was given in the first half of gestation in 529 and second half in 851. This is unlikely to have biased the comparison between randomization arms because the trimester of enrollment was similar in the 2 arms. Nevertheless, the variable timing of treatment during pregnancy may have reduced the efficacy of antibiotic on adverse pregnancy outcomes.
Peters 1995	The objective of this study was to determine whether prophylactic treatment with oral broad-spectrum antimicrobial therapy improves pregnancy outcomes in twin gestations. Since in twin gestations, the perinatal morbidity and mortality is higher than singleton gestations because of an increased incidence of preterm labor which is mainly due to mechanical distention of the uterus or combined with other factors.

REFERENCES

References to studies included in this review

Gichangi 1997 {published data only}

Gichangi PB, Ndinya-Achola JO, Ombete J, Nagelkerke NJ, Temmerman M. Antimicrobial prophylaxis in pregnancy: a randomized placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history. American Journal of Obstetrics and Gynecology 1997;177:680-4.

Hauth 1995 {published data only}

Hauth JC, Goldenberg LR, Andrews WW, DuBard MB, Copper RL. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. New England Journal of Medicine 1995;333:1732-6.

McGregor 1990 {published data only}

McGregor JA, French JI, Richter R, Vuchetich M, Bachus V, Seo K et al. Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment. American Journal of Obstetrics and Gynecology 1990;163:1580-91.

Paul 1997 {published data only}

Paul VK, Singh M, Buckshee K. Erythromycin treatment of pregnant women to reduce the incidence of low birth weight and preterm deliveries. International Journal of Gynecology and Obstetrics 1998;62:87-8.

Temmerman 1995 {published data only}

Temmerman M, Njagi E, Nagelkerke N, Ndinya-Achola J, Plummer FA, Meheus A. Mass antimicrobial treatment in pregnancy, a randomized, placebo-controlled trial in a population with high rates of sexually transmitted diseases. Journal of Reproductive Medicine 1995;40:176-80.

Vermeulen 1999 {published data only}

Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. British Journal of Obstetrics and Gynaecology 1999;106:652-7.

References to studies excluded from this review

Gray 2001

Gray RH, Wabwire-Mangen F, Kigozi G, Sewankambo NK, Serwadda D, Moulton LH et al. Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda. American Journal of Obstetrics and Gynecology 2001;185:1209-17.

Peters 1995

Peter MT, Brown CEL, Buam A, Risser R. Randomized, double-blind, placebo-controlled trial of amoxycillin/clavulanic acid to prevent preterm delivery in twin gestation. Infectious Diseases in Obstetrics and Gynecology 1995;3:158-63.

Additional references

Braun 1971

Braun P, Lee Y, Klein JO, Marcy M, Klein TA, Charles D. Birth weight and genital mycoplasma in pregnancy. New England Journal of Medicine 1971;284:167-74.

Cunningham 1997

Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC, Hankins GDV et al. Williams Obstetrics. 20th Edition. Connecticus: Appleton & Lange, 1997.

Eschenbach 1991

Eschenbach DA, Nugent RP, Rao VA, Cotch MF, Gibbs RS, Lipscomb KA et al. A randomized placebo controlled trial of erythromycin for the treatment of ureaplasma urealyticum in preventing premature delivery. American Journal of Obstetrics and Gynecology 1991;164:734-42.

Gravett 1986

Gravett MG, Nelson HP, DeRouen T, Critchlow C, Eschenbach DA, Holmes KK. Independent associations of bacterial vaginosis and chlamydia trachomatis infection with adverse pregnancy outcome. JAMA 1986;256:1899-905.

Hardy 1984

Hardy PH, Nell EE, Spence MR, Hardy JB, Graham DA, Rosenbaum RC. Prevalence of six sexually transmitted disease agents among pregnant innercity adolescents and pregnancy outcome. Lancet 1984;8:333-7.

Hillier 1995

Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH et al. Association between bacterial vaginosis and preterm delivery of low-birth weight infant. New England Journal of Medicine 1995;333:1737-42.

Lettieri 1993

Lettieri L, Vintzileos AM, Rodis JF, Albini SM, Saladia CM. Does idiopathic preterm labor resulting in preterm birth exist?. American Journal of Obstetrics and Gynecology 1993;168:1480-5.

McCormack 1987

McCormack WM, Rosner B, Lee YH, Munoz A, Kass CD. Effect on birth weight of erythromycin in treatment of pregnant women. Obstetrics and Gynecology 1987;69:202-7.

Morales 1994

Morales JW, Schorr S, Albritton J. Effect of metronidazole in patients with preterm birth in preceeding pregnancy and bacterial vaginosis: A placebo controlled double blind study. Obstetrics and Gynecology 1994;171:345-9.

Newton 1989

Newton ER, Dinsmoor MJ, Gibbs RS. A randomised blinded placebo controlled trial of antibiotics in idiopathic preterm labour. Obstetrics and Gynecology 1989;74:562-6.

Oleszczuk 2000

Oleszczuk JJ, Keith LG. Vaginal infection: prophylaxis and perinatal outcome-a review of the literature. International Journal of Fertility 2000;45(6):358-67.

Regan 1981

Regan JA, Chao S, James SL. Premature rupture of membranes, preterm delivery, and group B streptococcal colonization of mothers. American Journal of Obstetrics and Gynecology 1981;141:184-6.

Romero 1988

Romero R, Mazor M. Infection and preterm labor. Clinical Obstetrics and Gynecology 1988;31:553-83.

Romero 1993

Romero R, Sibai B, Caritis S, Paul R, Depp R, Rosen M et al. Antibiotic treatment of preterm labour with intact membranes: a multicenter randomised double blinded controlled trial. American Journal of Obstetrics and Gynecology 1993;169:764-74.

GRAPHS

To view a graph or table, click on the outcome title of the summary table below.

To view graphs using MetaView, click on the "Show metaview" link at the top of the graph.

01 Prophylactic antibiotics versus placebo
Outcome title	No. of studies	No. of participants	Statistical method	Effect size
01 preterm labor	0	0	Peto Odds Ratio 95% CI	Not estimable
02 preterm prelabour rupture of membranes	1	229	Peto Odds Ratio 95% CI	0.33 [0.08, 1.34]
03 prelabour rupture of membranes	1	229	Peto Odds Ratio 95% CI	0.32 [0.14, 0.73]
04 preterm delivery	6	1310	Peto Odds Ratio 95% CI	0.83 [0.62, 1.12]
05 preterm delivery in all high risk pregnancy	3	758	Peto Odds Ratio 95% CI	0.76 [0.54, 1.07]
06 chorioamnionitis	1	229	Peto Odds Ratio 95% CI	0.61 [0.10, 3.60]
07 intrapartum fever needing antibiotic treatment	0	0	Peto Odds Ratio 95% CI	Not estimable
08 puerperal sepsis/postpartum endometritis	3	627	Peto Odds Ratio 95% CI	0.48 [0.29, 0.78]
09 serious maternal complications of puerperal infection requiring laparotomy for infection, hysterectomy, death	0	0	Peto Odds Ratio 95% CI	Not estimable
10 maternal side effects of antibiotic prophylaxis (severe side effects)	0	0	Peto Odds Ratio 95% CI	Not estimable
11 duration of hospitalization	0	0	Weighted Mean Difference (Fixed) 95% CI	Not estimable
12 gonococcal infection; postpartum detected	1	204	Peto Odds Ratio 95% CI	0.35 [0.13, 0.89]
13 satisfaction with care	0	0	Peto Odds Ratio 95% CI	Not estimable
14 compliance	1	229	Peto Odds Ratio 95% CI	0.54 [0.29, 1.01]
15 mean gestational age	1	253	Weighted Mean Difference (Fixed) 95% CI	0.70 [0.01, 1.39]
16 low birth weight	3	808	Peto Odds Ratio 95% CI	0.75 [0.51, 1.08]
17 mean birth weight	3	808	Weighted Mean Difference (Fixed) 95% CI	0.83 [-84.98, 86.63]
18 neonatal sepsis	1	142	Peto Odds Ratio 95% CI	8.07 [1.36, 47.77]
19 blood culture confirming sepsis	0	0	Peto Odds Ratio 95% CI	Not estimable
20 admission to neonatal intensive care unit	0	0	Peto Odds Ratio 95% CI	Not estimable
21 opthalmia neonatorum	0	0	Peto Odds Ratio 95% CI	Not estimable
22 congenital abnormality	2	463	Peto Odds Ratio 95% CI	1.74 [0.18, 16.84]
23 small for gestational age	1	229	Peto Odds Ratio 95% CI	1.31 [0.41, 4.17]
24 abnormal neurological development	0	0	Peto Odds Ratio 95% CI	Not estimable
25 perinatal mortality	3	624	Peto Odds Ratio 95% CI	0.52 [0.16, 1.71]

COVER SHEET

Title	Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality
Reviewer(s)	Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P
Contribution of reviewer(s)	GJ Hofmeyr and O Adetoro prepared the original protocol, commented on the draft of the review and approved the final version of the review. J Thinkhamrop revised the protocol, conducted the literature search, analysed and interpreted the data, drafted and approved the final version of the review. P Lumbiganon revised the protocol, interpreted the data, drafted and approved the final version of the review.
Issue protocol first published	2000/3
Issue review first published	2002/4
Date of most recent amendment	Information not available
Date of most recent SUBSTANTIVE amendment	21 August 2002
Most recent changes	Information not supplied by reviewer
Date new studies sought but none found	Information not supplied by reviewer
Date new studies found but not yet included/excluded	Information not supplied by reviewer
Date new studies found and included/excluded	Information not supplied by reviewer
Date reviewers' conclusions section amended	Information not supplied by reviewer
Contact address	Dr Jadsada Thinkhamrop Associate Professor Department of Obstetrics and Gynecology, Faculty of Medicine Khon Kaen University Khon Kaen 40002 THAILAND tel: +66 43 8728669 jadsada@kku.ac.th fax: +66 43 348395
Cochrane Library number	CD002250
Editorial group	Cochrane Pregnancy and Childbirth Group
Editorial group code	HM-PREG

SOURCES OF SUPPORT

External sources of support

HRP-UNDP/UNFPA/WHO/World Bank Special Programme in Human Reproduction, Geneva SWITZERLAND

Internal sources of support

Khon Kaen University THAILAND
University of the Witwatersrand SOUTH AFRICA
Ogun State University NIGERIA

SYNOPSIS

Routine antibiotic treatment in second and third trimester of pregnancy can reduce some infectious morbidity on pregnancy outcomes

Maternal genital tract infection or colonization by some infectious organisms can cause maternal and perinatal mortality and morbidity. Antibiotics have been used during the second and third trimester to try to prevent these infections. The review of trials found that antibiotics reduce the risk of prelabour rupture of membranes in unselected pregnant women and low birth weight and postpartum endometritis in high risk pregnant women. Further study to identify the most appropriate type and dosage of routine use antibiotics in pregnant women should be conducted.

Index Terms

Medical Subject Headings (MeSH)

Antibiotic Prophylaxis ; Endometritis [prevention & control]; Fetal Membranes, Premature Rupture [prevention & control]; Fetal Weight [drug effects]; Pregnancy Outcome ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Pregnancy, High-Risk

Mesh check words: Female Human Pregnancy

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