Imdad et al. BMC Public Health 2011, 11(Suppl 3):S18 http://www.biomedcentral.com/1471-2458/11/S3/S18 Page 9 of 13 Table 2 Application of standardized rules to collective mortality and morbidity outcomes to estimate effect of calcium supplementation during pregnancy on maternal mortality Outcome measure Cause specific Maternal Mortality All cause maternal mortality Eclampsia Severe gestational hypertensive related morbidity/mortality* Severe Pre-eclampsia Pre-eclampsia Studies Total Reduction (Relative Events risk) 0 - - (n=1) 7 83% (RR 0.17; 95% CI 0.02, 1.39) (n=1) 42 32% reduction (RR 0.68; 95% CI 0.37, 1.26) (n=1) 376 20 % (RR 0.80; 95 % CI 0.70-0.91) (n=3) 93 (n=10) 558 30% (RR 0.70; 95% CI 0.46, 1.05) 59 % (RR=0.41; 95% CI 0.24- 0.69) GRADE quality of pooled estimate - Low Low Moderate (® low) moderate High Application of standard rules - Rule 1: Do not apply < 50 events Rule 3: Do not apply < 50 events Rule 3 applies “If there is low- or very low-quality evidence of effect on cause-specific mortality, And there is high- or moderate-quality evidence of effect on serious morbidity… Then use the smaller of the two effects.” [47] * Include any one of the following; admission to intensive or special care unit, eclampsia, severe pre-eclampsia, placental abruption, HELLP (hemolysis, elevated liver enzyme and low platelet count) syndrome, renal failure or maternal death. cause mortality was recommended for inclusion in the LiST as effectiveness of calcium supplementation during pregnancy for neonatal outcomes [12]. Table 3 presents the application of CHERG rules applied to collective neonatal mortality and morbidity outcomes. Discussion Role of calcium supplementation during pregnancy in reducing hypertensive disorders has been evaluated before. The review by Hofmeyr et al [8,10] included studies from both developed and developing countries and their pooled estimate had shown that calcium supplementation during pregnancy significantly reduced occurrence of gestational hypertension [RR 0.70, 95% CI 0.57-0.86] and pre-eclampsia [RR 0.48, 95% CI 0.33-0.69]. In the same review, risk of prema- turity was also reduced in calcium supplemented group compared to control however the results were not statistically significant [RR 0.81, 95% CI 0.64-1.03]. On the other hand, a review by Trumbo and Ellwood for US Food and Drug Administration (FDA) has shown that the beneficial effects of calcium supple- mentation during pregnancy cannot be generalized to USA and populations with adequate baseline calcium Table 3 Application of standardized rules for choice of final outcome to estimate effect of calcium supplementation during pregnancy on neonatal mortality Outcome measure All-cause neonatal mortality Preterm Birth Low birth weight (< 2500 g) Small for gestational age 5 3 2 Studies Total Events 1 90 Reduction (Relative risk) 30 % (RR 0.56-0.88) GRADE quality of pooled estimate Moderate (® low) 967 1159 84 12% (RR 0.88; 95% CI 0.78, 0.99) 19 % (RR 0.81; 95 % CI 0.58-1.12] 10 % (RR 0.90; 95 % CI 0.59-1.38) High Moderate Moderate Application of standard rules Rule 1: applies “If there is no evidence of effect on cause-specific mortality, And there is evidence of effect on all-cause mortality… Then translate all-cause into cause-specific, and downgrade the quality score by one level”[47]