Imdad et al. BMC Public Health 2011, 11(Suppl 3):S18 http://www.biomedcentral.com/1471-2458/11/S3/S18 Data abstraction and quality assessment All the included trials were assessed for methodologi- cal quality and outcomes of interest using a standar- dized form [12]. Data were abstracted for study design, study site, methods of sequence generation, allocation concealment, attrition and primary outcomes of inter- est. Individual studies were evaluated according to CHERG adaptation of GRADE technique [12,13]. In this method of qualitative evaluation, all RCTs received an initial score of ‘high’ and an observational study as ‘low’. The study scores were adjusted depending on limitations of the study design. Trials with a final grade of ‘high’ or ‘moderate’ and ‘low grade’ were included in the analysis with exclusion of studies with a final grade of ‘very low’ [12]. Quantitative data synthesis The primary outcomes assessed were maternal mortal- ity, gestational hypertension (± proteinuria), pre-eclamp- sia, severe pre-eclampsia and eclampsia. Data on neonatal outcomes like neonatal mortality, preterm birth, low birth weight and birth of small-for-gestational age were also extracted. Pooled analyses were conducted where data were available from more than one study for an outcome. The results are presented as risk ratios (RR) and 95% confidence intervals (CIs). The assessment of statistical heterogeneity among trials was done by visual inspection i.e. the overlap of the confidence inter- vals among the studies, and by the Chi square (P-value) of heterogeneity in the meta-analyses. A low P value (less than 0.10) or a large chi-squared statistic relative to its degree of freedom was considered as providing evidence of heterogeneity. The I2 values were also looked into and I2 values greater than 50% were taken as substantial and high heterogeneity. In situations of substantial or high heterogeneity being present, causes were explored by sensitivity analysis and random effects model were used. Although random model is not a sub- stitute for a thorough investigation of heterogeneity, it takes an ‘average’ effect from all the included studies compared to fixed models that take the exact contribu- tion from the individual studies [16].It is thus preferred in case of significant heterogeneity in pooled estimate. All analyses were conducted using software Rev Man version 5 [17]. We did a subgroup analysis based on a priori hypothesis that calcium supplementation during pregnancy would be more effective in reducing hyper- tensive disorders in pregnant women who are at increased risk for developing gestational hypertensive disorders. Participants were defined as being at a higher risk of developing hypertension in pregnancy in case of teenage pregnancy, women with previous pre-eclampsia, and women with positive roll over test and/or positive angiotension II sensitivity test [10]. We applied CHERG Page 3 of 13 rules to collective maternal and neonatal mortality and morbidity outcomes related to maternal hypertensive disorders [12]. The purpose of this exercise was to get a point estimate for effectiveness of calcium supplementa- tion during pregnancy in reducing maternal and neona- tal mortality due to hypertensive disorders. Results Trial flow Literature search of electronic databases, and papers from hand searches yielded a total number of 1402 titles after removal of duplicates (Figure 1). Initially 29 studies were considered for inclusion in the review. Out of these seven studies were excluded due to insufficient data on outcomes of interest [18-24]. Three studies were excluded due to very low grade quality [25-27]. In two trials, calcium was supplemented as therapeutic intervention and not as preventive [28,29]. Two studies were excluded because calcium was supplemented in combination, either with linoleic acid [30] or L-aspartate [31] and it was not possible to separate out their effect from calcium supplementation. Five studies were excluded because they were conducted in developed countries [32-36].Finally 10 studies that met our inclu- sion criteria were included in the review [37-46]. Study characteristics All the included studies were randomized controlled trials with comparison group receiving a placebo in all except in two studies in which participants of compari- son group were simply observed as controls [45,46]. Table 1 presents characteristics of included studies. The starting period of calcium supplementation in all the included studies was before 20-32 weeks of gestation and continued till delivery. In three of the included stu- dies [39,40,42], the participants were defined as being at a higher risk of developing hypertension in pregnancy (pregnant teenage girls, women with previous pre- eclampsia or women with positive roll over test). The dose of calcium ranged from 0.5 g/day to 2 g/day. Five of the included studies were from Asia [38,42,43,45,46] and four from South America [37,39-41]. One large multicentre trial was conducted by World Health Orga- nization (WHO) in Argentina, Egypt, India, Peru, South Africa and Vietnam [44]. Quantitative data synthesis Maternal mortality Data on cause specific maternal mortality (i.e. due to gestational hypertensive disorders) were not available in any of the included studies. The outcome of all-cause maternal death was reported by only one study [44], with 1 death occurring in the intervention group and 6 deaths in the control group (RR 0.17; 95% CI 0.03-0.76).