Imdad et al. BMC Public Health 2011, 11(Suppl 3):S18 http://www.biomedcentral.com/1471-2458/11/S3/S18 Background Hypertension in pregnancy stand alone or with protei- nuria is one of the leading causes of maternal mortality and morbidity in the world [1]. Hypertensive disorders are the second most common cause of maternal deaths worldwide [2] and account for more than 40,000 mater- nal deaths annually [3]. These disorders are also asso- ciated with adverse perinatal outcomes such as stillbirth, preterm and small for gestational age babies [4-6]. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy [4,7]. Many trials have been conducted to observe the protec- tive effect of preventive calcium supplementation in pregnant women [8]. There is substantial data that sup- ports that calcium supplementation in pregnancy is associated with reduction in gestational hypertensive disorder [9,10], although the impact varies according to the baseline calcium intake of the population and pre- existing risk factors [8,11]. A previous review by Hofmyer et al. has shown that calcium supplementation during pregnancy had a signif- icant effect in reducing risk of gestational hypertension and pre-eclampsia [10]. This effect was more prominent in those studies where participants had low baseline cal- cium intake compared to that of adequate calcium intake [10]. Another review by Trumbo et al. had shown that beneficial effects of calcium supplementation can- not be generalized to USA population and suggested that beneficial effects could only be shown in popula- tions whose baseline calcium intake is inadequate [11]. The objective of this review was to evaluate the effect of calcium supplementation during pregnancy in redu- cing maternal hypertensive disorders and related mater- nal and neonatal mortality and morbidity in developing countries. This paper is a part of series of papers for Lives Saved Tool (LiST) model. An intervention is cur- rently included in the LiST if there is substantial evi- dence that it decrease maternal mortality, neonatal/child mortality and/or stillbirths [12]. This process is guided by qualitative assessment of available evidence according to Grading of Recommendations, Assessment, Develop- ment and Evaluation (GRADE) criteria [13] and quanti- tative inputs according to Child Health Epidemiology Reference Group (CHERG) guidelines [12]. For more details of the review methods, the adapted GRADE approach or the LiST model, see the methods and results section and other articles in this supplement. Methods Searching To identify studies that evaluated the effect of calcium supplementation during pregnancy for prevention of Page 2 of 13 gestational hypertensive disorders, a comprehensive search of PubMed, Cochrane Library and WHO regional databases was carried out using different terms for cal- cium and gestational hypertensive disorders. Following search strategy was used for PubMed; (“Calcium” AND “pregnancy”) AND (“Hypertension” OR “pre-eclampsia” OR “blood pressure” OR “neonatal death” OR “preterm “OR “low birth weight”). The search was limited to “ran- domized trial” and “humans”. Studies were considered for inclusion irrespective of language or status of publi- cation. The date of last search was March 22, 2010. Additional studies were obtained through hand search of references from identified studies and previous reviews. Inclusion/exclusion criteria All published randomized controlled trials (RCTs) in which pregnant women received calcium supplementa- tion as compared to control (placebo or no interven- tion) were included. Observational studies were not considered for inclusion as we expected to have rea- sonable number of RCTs for inclusion in the review. Trials which included participants diagnosed with hypertension prior to pregnancy were excluded. Sup- plementation started with calcium before 32 weeks of pregnancy at the latest. As per objectives of LiST model, all the included studies were from developing countries [12]. The developing countries were defined as countries with Gross National Income per capita (GNI) below US$11,905, according to World Bank [14]. High blood pressure was taken as defined by authors mostly as diastolic blood pressure equal to or greater than 90 mmHg, or an increase in systolic blood pressure of 30 mmHg or more, or in diastolic blood pressure of 15 mmHg or more from the base- line. Pre-eclampsia was defined as high blood pressure plus significant proteinuria (as defined by authors). Ideally, a proteinuria of 1+ or greater by dipstick test- ing, equal to or greater than 300 mg per 24 hours, or equal to or greater than 500mg per liter is taken as significant proteinuria [15]. Gestational hypertension was defined as high blood pressure developed during pregnancy ± proteinuria (not significant enough to define as pre-eclampsia). Definition of severe pre- eclampsia was also followed as defined by authors usually as systolic blood pressure ≥ 160 and/or diasto- lic blood pressure ≥110 or more on 2 occasions 4 hours apart plus proteinuria (3+ on urine dipstick) [15]. Eclampsia was defined as the development of convulsions and/or unexplained coma during preg- nancy or postpartum in patients with signs and symp- toms of preeclampsia after 20 weeks pre-partum and before 48 hours postpartum [15].