Ishaque et al. BMC Public Health 2011, 11(Suppl 3):S3 http://www.biomedcentral.com/1471-2458/11/S3/S3 Herpes simplex infections have also been described as a cause of fetal death [54]. However, Herpes simplex viruses rarely, if ever, cause stillbirth, likely because the virus rarely causes an intrauterine infection. Neonatal infections are acquired during fetal passage through an infected birth canal. There is a paucity of evidence with regards to the significance of Herpes virus in causing stillbirths. Also, whether treatment and prevention have a significant positive impact on adverse pregnancy out- comes remains elusive. Tables 1 - 4 outline the quality grading of the overall evidence of all the interventions considered in this review and described below in the same order. Discussion Syphilis remains a major cause of avoidable perinatal death in many countries despite being treatable, and despite the WHO recommendation that all pregnant women be tested as part of routine antenatal care. Most studies report syphilis to have a relative risk of stillbirth in the range of 2 to 5; however, a Tanzanian study reported a relative risk of 18 for women with active syphilis [55]. In some areas of sub-Saharan Africa, about 25% to 50% of all stillbirths were associated with syphilis [56]. Syphilis also contributes to stillbirths in other areas of the world including Russia, Asia and South America [57]. The findings of a meta-analysis by Blencowe et al. correlate with the above observations and shows that treatment of syphilis during pregnancy can significantly reduce syphilis related stillbirths by up to 80 % [23]. This estimate has been recommended for inclusion in the LiST model with a quality grade of ‘low’ (Table 1). The overall evidence was graded as ‘low’ as all the included studies in the meta-aalysis were observational studies. Malaria in pregnancy is an important preventable cause of maternal and perinatal morbidity and mortality [7]. The WHO advocates a three-pronged approach to control malaria in pregnancy that includes the use of ITNs, IPTp and case management of parasitemia with artemisin-based therapies, especially in areas where malaria is endemic [58]. Our meta-analysis suggests that malaria prevention interventions in pregnancy (IPTp or ITNs) can reduce stillbirths by 22% in malaria endemic Page 7 of 12 countries (RR = 0.78; 95% CI: 0.59 – 1.03). While this effect is only marginally significant (and thus graded as that of ‘moderate’ quality in table 4), there is other evi- dence to suggest that such interventions could be highly effective in improving maternal and birth outcomes [58-61]. This is supported by the fact that IPTp has been shown to significantly reduce placental malaria, as well as maternal anemia [60], which are associated with adverse pregnancy outcome. The pandemic of human immunodeficiency virus (HIV) in pregnancy is one of the major health problems today [63]. Maternal HIV infection may increase the risk of stillbirth [64]. A study from Zambia has reported an inverse relationship between decreasing CD4 cell counts in HIV seropositive women and stillbirth (P =0.000) [65]. Our pooled analysis however failed to show a statistically significant reduction in stillbirth when antiretrovirals for pregnant women were com- pared to placebo (RR = 0.93; 95% CI 0.45 – 1.92) and thus no recommendations have been made for LiST regarding this intervention. Results of our review are consistent with the results from a Cochrane Review by Volmink et al [66]. Data was not pooled in this Cochrane review however none of the six included trials showed a significant impact of antiretrovirals in preg- nancy on stillbirth [66]. Pooled analysis from a review by Suksomboon et al. [67], that included five rando- mized trials, showed a non-significant impact on still- birth (RR=1·11 95% CI 95% 0·48- 2·56). Bacterial vaginosis in pregnant women is common, ranging from 14% to 21% in Western countries and 13.6–18% in Asian countries [68]. However, very few perinatal deaths have been reported in relation to maternal bacterial vaginosis [68]. Mc Donald reports a non-significant association of the treatment of bacterial vaginosis in pregnancy with reduction in perinatal mor- tality [34]. Our meta-analysis of four studies (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (Figure 4). Whether treat- ment of bacterial vaginosis will reduce stillbirths is unknown and would need to be validated by future trials. Applying the CHERG Rules for Evidence Review, studies included for bacterial vaginosis and perinatal Table 1 Quality assessment of trials of interventions for infections (syphilis) in pregnancy Quality Assessment Summary of Findings Design Limitations Consistency No of studies (ref) 8 Syphilis and stillbirth: LOWoutcome specific quality Observational studies none Some heterogeneity and 5 out of 8 studies show benefit Directness No of events Generalizability to Generalizability to Intervention Control Relative population of intervention of Risk (95% interest interest CI) Yes Yes Not available Not available 0.20 (0.12 - 0.34)