Ishaque et al. BMC Public Health 2011, 11(Suppl 3):S3 http://www.biomedcentral.com/1471-2458/11/S3/S3 overall quality of evidence of an outcome was also assessed and graded according to the CHERG adaptation of the GRADE technique [20]. This assessment was based on three components: 1) the volume and consis- tency of the evidence; 2) the size of the effect, or risk ratio; and 3) the strength of the statistical evidence for an association between the intervention and outcome, as reflected by the p-value [20,21]. Quantitative data synthesis We performed meta-analyses where data were available from more than one study for an outcome. The primary outcomes of interest were stillbirths and perinatal mor- tality. The reason for including perinatal mortality as an outcome was based on the fact most of the studies do not report disaggregated data for stillbirths but do that by combining stillbirths with early neonatal deaths (i.e. perinatal mortality). This exercise is in accordance with the basics of CHERG rules which take into account the biological plausibility of the intervention and limitations of measured outcomes [20]. For example studies may not collect the outcome of interest (e.g., pneumonia mortality) but may collect data on severity of disease (e.g. hospital admission). CHERG rules will thus con- sider a range of outcomes (where necessary) and choose a point estimate which is the most conservative and represent the expected effect of the intervention based on biological plausibility [20]. We used dichotomous values for pooling the data, except for insecticide-treated mosquito nets (ITNs) where data were pooled by generic inverse variance method of meta-analysis. The summary estimates were described as relative risk (RR) or Odd ratios (OR) with 95 % confidence interval (CI). The assessment of statisti- cal heterogeneity among trials pooled data was done by visual inspection (i.e. the overlap of the confidence intervals among the studies), Chi square (P-value) and I2 values. An I2 value greater than 50% was taken to repre- sent substantial heterogeneity in the pooled data. In case of substantial heterogeneity, causes were explored by sensitivity analysis. A random effects model was used for the meta-analysis in case of substantial heterogene- ity. All the analyses were conducted using Review Man- ager 5 [22]. We applied the CHERG Rules for Evidence Review to recommend a final estimate for reduction in stillbirth from interventions for a specific maternal infection during pregnancy [20]. Results A total of 1155 hits were identified from our search strategies (Figure 1). After screening the titles and abstracts, 84 studies were initially considered eligible. We thoroughly reviewed the abstracts and full texts, where available and 25 studies were selected for Page 3 of 12 inclusion in the meta-analyses (Additional file 3). Addi- tional File 4 outlines the characteristics of included studies. Syphilis No randomized trials were found for treatment of syphilis and its effect on prevention on stillbirths. However, a random-effects meta-analysis of 8 observa- tion studies by Blencowe et al. in this supplement has shown an estimated reduction of 80 % (RR 0.20, 95% CI 0.12 - 0.34) in syphilis related stillbirths with use of penicillin [23]. It is however important to note that none of the included studies in this meta-analysis made any attempt to control for systematic differences between treated and untreated women (confounding). For example women not attending antenatal clinic and/ or not complying with complex penicillin treat- ment regimens may differ in their risk profiles for still- birth, preterm delivery and neonatal death from fully compliant infected women. Malaria There were 6 randomized controlled trials that addressed prevention of malaria during pregnancy by IPTp or ITN. As the effects of IPTp and ITNs used dur- ing pregnancy have similar causal pathways for prevent- ing stillbirth, and as there is no evidence of a synergistic effect between them [24], the data were pooled irrespec- tive of method used. The combined results show 22% reduction in stillbirths (RR = 0.78; 95% CI: 0.59 – 1.03) (Figure 2). A subgroup analysis of three trials [25-27] that evaluated the impact of IPTp with sulfadoxine-pyri- methamine vs. placebo showed no effect on stillbirth (RR = 0.96; 95% CI: 0.62 – 1.50; fixed model) or perina- tal mortality (RR = 0.78; 95% CI: 0.52 – 1.17; fixed model). Pooled results of three studies that used ITNs in pregnancy yielded a statistically significant association with reduced fetal loss (RR 0.67, 95% CI 0.47 to 0.97) compared to controls. HIV Our pooled meta-analysis of 6 studies [28-33] failed to show a statistically significant reduction in stillbirth when the use of anti-retrovirals in pregnancy was compared to control (RR 0.93 95% CI 0.45 – 1.92) (See Figure 3). Bacterial vaginosis Our pooled analysis combining four studies [34-37] showed a non-significant impact of treatment of bacter- ial vaginosis on perinatal mortality (OR 0.88 95% CI 0.50 – 1.55). Sub-group analysis showed similar results with the use of oral (OR 0.96 95% CI 0.53 – 1.73) and vaginal (OR 0.35 95% CI 0.05 – 2.52) antibiotics (Fig 4). There are no data on Still Births.