Calcium supplement in pregnancy for prevention of preeclampsia: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Huijuan ^1,2,3,4 , YAO Liang ^5,6 , YAN Peijing ⁷ , LI Meixuan ^1,2,3,4 , XUN Yangqin ^1,2,3,4 , LU Cuncun ^2,3,4 ,  YANG Kehu ^1,2,3,4 ,  ZHANG Dengxia ⁸

1. School of Public Health, Lanzhou University, Lanzhou, 730000, P.R.China;
2. Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, P.R.China;
3. Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, P.R.China;
4. Evidence-based Social Sciences Research Center, Lanzhou University, Lanzhou, 730000, P.R.China;
5. Chinese Medicine Faculty of Hongkong Baptist University, HongKong, 999077, P.R.China;
6. Institution of Clinical Research and Evidence Based Medicine, The Gansu Provincial Hospital, Lanzhou, 730000, P.R.China;
7. Gansu Provincial Hospital, Lanzhou, 730000, P.R.China;
8. The Second Changzhou Hospital, Nanjing Medical University, Changzhou, 213003, P.R.China;

Corresponding author：

YANG Kehu, Email: kehuyangebm2006@126.com; ZHANG Dengxia, Email: 13919255870@163.com

Keywords：

Preeclampsia; Calcium supplement; Pregnancy-induced-hypertension; Calcium dose; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.201804013

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objectives To investigate calcium supplement in pregnancy for prevention of preeclampsia and relevant outcomes. Methods The Cochrane Library, PubMed, EMbase, CBM, WanFang Data, VIP and CNKI databases were searched online to collect randomized controlled trials (RCTs) of calcium supplement in pregnancy for prevention of preeclampsia and relevant outcomes from inception to July 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed by RevMan 5.3 software. Results A total of 33 RCTs involving 29 234 subjects were included. The results of meta-analysis showed that: compared with control group, the calcium supplement group was associated with lower preeclampsia (RR=0.48, 95%CI 0.38 to 0.62, P<0.000 01) and gestational hypertension (RR=0.65, 95%CI 0.55 to 0.77,P<0.000 01) incidence. The incidence of premature delivery, intrauterine growth retardation and severe preeclampsia in calcium supplement group was lower than that in placebo group, and the neonatal weight in calcium was higher than that in placebo group. However, there was no significant difference in the pregnancy cycle between the two groups. Conclusions Current evidence shows that calcium supplement is associated with lower risk of preeclampsia and gestational hypertension. Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusion.

Citation： LI Huijuan, YAO Liang, YAN Peijing, LI Meixuan, XUN Yangqin, LU Cuncun, YANG Kehu, ZHANG Dengxia. Calcium supplement in pregnancy for prevention of preeclampsia: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2018, 18(10): 1070-1079. doi: 10.7507/1672-2531.201804013 Copy

1.	袁松, 唐中. 尿蛋白定量在先兆子痫诊断中的研究进展. 国际检验医学杂志, 2017, 38(2): 235-236.
2.	苏普玉. 孕 20 周内母体甲状腺功能与不良妊娠结局、婴幼儿体格生长及神经精神发育关系的前瞻性队列研究. 合肥: 安徽医科大学, 2012.
3.	阮利红, 贾桂花, 方政慧. 微小 RNA 在子痫前期中的研究进展. 中国妇幼保健, 2013, 28(32): 5406-5407.
4.	Goldberg GR, Jarjou LM, Cole TJ, et al. Randomized, placebo-controlled, calcium supplementation trial in pregnant Gambian women accustomed to a low calcium intake: effects on maternal blood pressure and infant growth. Am J Clin Nutr, 2013, 98(4): 972-982.
5.	Sparling TM, Henschke N, Nesbitt RC, et al. The role of diet and nutritional supplementation in perinatal depression: a systematic review. Matern Child Nutr, 2017, 13(1): 10.
6.	Belizán JM, Villar J. The relationship between calcium intake and edema-, proteinuria-, and hypertension-getosis: an hypothesis. Am J Clin Nutr, 1980, 33(10): 2202-2210.
7.	Bautista LE. Calcium and linoleic acid supplements in the prevention of preeclampsia. Colomb Med (Cali), 2016, 47(1): 68.
8.	Alzate A, Herrera-Medina R, Pineda LM. Preeclampsia prevention: a case-control study nested in a cohort. Colomb Med (Cali), 2015, 46(4): 156-161.
9.	An LB, Li WT, Xie TN, et al. Calcium supplementation reducing the risk of hypertensive disorders of pregnancy and related problems: A meta-analysis of multicentre randomized controlled trials. Int J Nurs Pract, 2015, 21(Suppl 2): 19-31.
10.	Patrelli TS, Dall'asta A, Gizzo S, et al. Calcium supplementation and prevention of preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med, 2012, 25(12): 2570-2574.
11.	Moghadam BL, Aliyan MN, Author A, et al. Calcium supplementation in pregnancy and neonatal outcomes. Iran J Reprod Med, 2011, 9(S1): 77-78.
12.	Hofmeyr GJ, Belizán JM, von Dadelszen P, et al. Low-dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary. BJOG, 2014, 121(8): 951-957.
13.	Samimi M, Kashi M, Foroozanfard F, et al. The effects of vitamin D plus calcium supplementation on metabolic profiles, biomarkers of inflammation, oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia. J Hum Nutr Diet, 2016, 29(4): 505-515.
14.	Aghamohammadi A, Zafari M. Calcium supplementation in pregnancy and prevention of hypertensive disorders in elderly women. Scienceasia, 2015, 41(4): 259.
15.	Khan A, Mandal SK, Pal A. Role of high dose calcium in the prevention of preeclampsia. Bangladesh J Obstet Gynaecol, 2013, 28(2): 66-70.
16.	Asemi Z, Tabassi Z, Heidarzadeh Z, et al. Effect of calcium-vitamin D supplementation on metabolic profiles in pregnant women at risk for pre-eclampsia: a randomized placebo-controlled trial. Pak J Biol Sci, 2012, 15(7): 316-324.
17.	Nenad S, Olivera KV, Goran R, et al. P32. Did calcium management prevent preeclampsia? Pregnancy Hypertens, 2011, 1(3-4): 287.
18.	Kumar A, Devi SG, Batra S, et al. Calcium supplementation for the prevention of pre-eclampsia. Int J Gynaecol Obstet, 2009, 104(1): 32-36.
19.	Villar J, Abdel-Aleem H, Merialdi M, et al. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Am J Obstet Gynecol, 2006, 194(3): 639-649.
20.	Herrera JA, Shahabuddin AK, Ersheng G, et al. Calcium plus linoleic acid therapy for pregnancy-induced hypertension. Int J Gynaecol Obstet, 2005, 91(3): 221-227.
21.	Taherian AA, Taherian A, Shirvani A. Prevention of preeclampsia with low-dose aspirin or calcium supplementation. Arch Iran Med, 2002, 5(3): 151-156.
22.	Wanchu M, Malhotra S, Khullar M. Calcium supplementation in pre-eclampsia. J Assoc Physicians India, 2001, 49: 795-798.
23.	Niromanesh S, Laghaii S, Mosavi-Jarrahi A. Supplementary calcium in prevention of pre-eclampsia. Int J Gynaecol Obstet, 2001, 74(1): 17-21.
24.	李雪兰, 苟文丽. 补钙预防妊高征及对血小板细胞内游离钙浓度的影响. 西安医科大学学报, 2000, 21(1): 46-48.
25.	Herrera JA, Arevalo-Herrera M, Herrera S. Prevention of preeclampsia by linoleic acid and calcium supplementation: a randomized controlled trial. Obstet Gynecol, 1998, 91(4): 585-590.
26.	Almirante CY. Calcium supplementation during pregnancy in the prevention of EPH Gestosis. Prenatal Neonat Med, 1998, 3(1): 24.
27.	López-Jaramillo P, Delgado F, Jácome P, et al. Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant teenagers. Obstet Gynecol, 1997, 90(2): 162-167.
28.	Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. N Engl J Med, 1997, 337(2): 69-76.
29.	Purwar M, Kulkarni H, Motghare V, et al. Calcium supplementation and prevention of pregnancy induced hypertension. J Obstet Gynaecol Res, 1996, 22(5): 425-430.
30.	Sanchez-Ramos L, Briones DK, Kaunitz AM, et al. Prevention of pregnancy-induced hypertension by calcium supplementation in angiotensin II-sensitive patients. Obstet Gynecol, 1994, 84(3): 349-353.
31.	丛克家, 迟绍霖, 刘桂荣. 妊娠期补钙对降低妊高征的作用. 中华医学杂志, 1995, 108(1): 57-59.
32.	丛克家, 迟绍霖, 刘桂荣. 钙与妊高征. 中华妇产科杂志, 1993, 28(11): 657-659.
33.	Villar J, Repke JT. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Am J Obstet Gynecol, 1990, 163(4 Pt 1): 1124-1131.
34.	Lopez-Jaramillo P, Narvaez M, Felix C, et al. Dietary calcium supplementation and prevention of pregnancy hypertension. Lancet, 1990, 335(8684): 293.
35.	López-Jaramillo P, Narváez M, Weigel RM, et al. Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population. Br J Obstet Gynaecol, 1989, 96(6): 648-655.
36.	Villar J, Repke J, Belizan JM, et al. Calcium supplementation reduces blood pressure during pregnancy: results of a randomized controlled clinical trial. Obstet Gynecol, 1987, 70(3 Pt 1): 317-322.
37.	Marya RK, Rathee S, Manrow M. Effect of calcium and vitamin D supplementation on toxaemia of pregnancy. Gynecol Obstet Invest, 1987, 24(1): 38-42.
38.	Belizán JM, Villar J, Gonzalez L, et al. Calcium supplementation to prevent hypertensive disorders of pregnancy. N Engl J Med, 1991, 325(20): 1399-1405.
39.	Crowther CA, Hiller JE, Pridmore B, et al. Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group. Aust N Z J Obstet Gynaecol, 1999, 39(1): 12-18.
40.	陈玉琪. 孕期补钙在妊娠期高血压预防方面的作用. 临床合理用药杂志, 2018, 11(2): 76-77.
41.	谢琼英. 孕期补钙预防高危孕妇妊娠期高血压疾病的临床观察. 广东微量元素科学, 2017, 24(4): 51-53.
42.	王帆. 抗氧化药物对妊娠期高血压疾病预测阳性孕妇的治疗效果及对血流动力学的影响. 中国计划生育学杂志, 2017, 25(1): 47-50.
43.	郭琳琼, 吉婷, 刘星. 钙剂联合小剂量阿司匹林对子痫前期的预防效果. 陕西医学杂志, 2017, 46(6): 803-804.
44.	李冉, 李巍. 营养教育和钙补充对孕中期钙缺乏和妊娠并发症的影响. 中国优生与遗传杂志, 2017, 25(11): 95-96.
45.	曹明月. 围产期加强保健并及时补钙对妊娠高血压综合征的预防效果观察. 实用妇科内分泌电子杂志, 2017, 4(1): 102, 106.
46.	炎性指标钙网蛋白水平在先兆子痫母体循环中升高, 在胎儿循环中不升高. 世界核心医学期刊文摘 (妇产科学分册), 2005, (11): 12-13.Braekke K, Holthe MR, Harsem NK, et a1.
47.	Nardulli G, Proverbio F, Limongi FG, et al. Preeclampsia and calcium adenosine triphosphatase activity of red blood cell ghosts. Am J Obstet Gynecol, 1994, 171(5): 1361-1365.
48.	郝艳华, 程明刚, 陈文萍, 等. 妊高征孕妇血清钙、镁和尿酸测定的临床意义. 实用医学杂志, 2005, 21(9): 952-953.
49.	伊藤昌, 松井和, 坂本卓, 等. Angiotensin IIに対する血管反応性の基礎と臨床: 妊娠中毒症の病態に基づく発症予知·予防法について (妊娠中毒症: その病態論的アプローチ). 日本産科婦人科學會雜誌, 1988, 40(8): 991-999.
50.	Thway TM, Shlykov SG, Day MC, 等. 先兆子痫患者体内的抗体通过激活血管紧张素受体刺激细胞内钙离子动员增加. 世界核心医学期刊文摘 (心脏病学分册): 2005, (2): 27.
51.	连玉巍. 补充钙剂预防妊娠期高血压的临床效果. 医药前沿, 2015, 5(3): 45-46.

1. 袁松, 唐中. 尿蛋白定量在先兆子痫诊断中的研究进展. 国际检验医学杂志, 2017, 38(2): 235-236.
2. 苏普玉. 孕 20 周内母体甲状腺功能与不良妊娠结局、婴幼儿体格生长及神经精神发育关系的前瞻性队列研究. 合肥: 安徽医科大学, 2012.
3. 阮利红, 贾桂花, 方政慧. 微小 RNA 在子痫前期中的研究进展. 中国妇幼保健, 2013, 28(32): 5406-5407.
4. Goldberg GR, Jarjou LM, Cole TJ, et al. Randomized, placebo-controlled, calcium supplementation trial in pregnant Gambian women accustomed to a low calcium intake: effects on maternal blood pressure and infant growth. Am J Clin Nutr, 2013, 98(4): 972-982.
5. Sparling TM, Henschke N, Nesbitt RC, et al. The role of diet and nutritional supplementation in perinatal depression: a systematic review. Matern Child Nutr, 2017, 13(1): 10.
6. Belizán JM, Villar J. The relationship between calcium intake and edema-, proteinuria-, and hypertension-getosis: an hypothesis. Am J Clin Nutr, 1980, 33(10): 2202-2210.
7. Bautista LE. Calcium and linoleic acid supplements in the prevention of preeclampsia. Colomb Med (Cali), 2016, 47(1): 68.
8. Alzate A, Herrera-Medina R, Pineda LM. Preeclampsia prevention: a case-control study nested in a cohort. Colomb Med (Cali), 2015, 46(4): 156-161.
9. An LB, Li WT, Xie TN, et al. Calcium supplementation reducing the risk of hypertensive disorders of pregnancy and related problems: A meta-analysis of multicentre randomized controlled trials. Int J Nurs Pract, 2015, 21(Suppl 2): 19-31.
10. Patrelli TS, Dall'asta A, Gizzo S, et al. Calcium supplementation and prevention of preeclampsia: a meta-analysis. J Matern Fetal Neonatal Med, 2012, 25(12): 2570-2574.
11. Moghadam BL, Aliyan MN, Author A, et al. Calcium supplementation in pregnancy and neonatal outcomes. Iran J Reprod Med, 2011, 9(S1): 77-78.
12. Hofmeyr GJ, Belizán JM, von Dadelszen P, et al. Low-dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary. BJOG, 2014, 121(8): 951-957.
13. Samimi M, Kashi M, Foroozanfard F, et al. The effects of vitamin D plus calcium supplementation on metabolic profiles, biomarkers of inflammation, oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia. J Hum Nutr Diet, 2016, 29(4): 505-515.
14. Aghamohammadi A, Zafari M. Calcium supplementation in pregnancy and prevention of hypertensive disorders in elderly women. Scienceasia, 2015, 41(4): 259.
15. Khan A, Mandal SK, Pal A. Role of high dose calcium in the prevention of preeclampsia. Bangladesh J Obstet Gynaecol, 2013, 28(2): 66-70.
16. Asemi Z, Tabassi Z, Heidarzadeh Z, et al. Effect of calcium-vitamin D supplementation on metabolic profiles in pregnant women at risk for pre-eclampsia: a randomized placebo-controlled trial. Pak J Biol Sci, 2012, 15(7): 316-324.
17. Nenad S, Olivera KV, Goran R, et al. P32. Did calcium management prevent preeclampsia? Pregnancy Hypertens, 2011, 1(3-4): 287.
18. Kumar A, Devi SG, Batra S, et al. Calcium supplementation for the prevention of pre-eclampsia. Int J Gynaecol Obstet, 2009, 104(1): 32-36.
19. Villar J, Abdel-Aleem H, Merialdi M, et al. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Am J Obstet Gynecol, 2006, 194(3): 639-649.
20. Herrera JA, Shahabuddin AK, Ersheng G, et al. Calcium plus linoleic acid therapy for pregnancy-induced hypertension. Int J Gynaecol Obstet, 2005, 91(3): 221-227.
21. Taherian AA, Taherian A, Shirvani A. Prevention of preeclampsia with low-dose aspirin or calcium supplementation. Arch Iran Med, 2002, 5(3): 151-156.
22. Wanchu M, Malhotra S, Khullar M. Calcium supplementation in pre-eclampsia. J Assoc Physicians India, 2001, 49: 795-798.
23. Niromanesh S, Laghaii S, Mosavi-Jarrahi A. Supplementary calcium in prevention of pre-eclampsia. Int J Gynaecol Obstet, 2001, 74(1): 17-21.
24. 李雪兰, 苟文丽. 补钙预防妊高征及对血小板细胞内游离钙浓度的影响. 西安医科大学学报, 2000, 21(1): 46-48.
25. Herrera JA, Arevalo-Herrera M, Herrera S. Prevention of preeclampsia by linoleic acid and calcium supplementation: a randomized controlled trial. Obstet Gynecol, 1998, 91(4): 585-590.
26. Almirante CY. Calcium supplementation during pregnancy in the prevention of EPH Gestosis. Prenatal Neonat Med, 1998, 3(1): 24.
27. López-Jaramillo P, Delgado F, Jácome P, et al. Calcium supplementation and the risk of preeclampsia in Ecuadorian pregnant teenagers. Obstet Gynecol, 1997, 90(2): 162-167.
28. Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. N Engl J Med, 1997, 337(2): 69-76.
29. Purwar M, Kulkarni H, Motghare V, et al. Calcium supplementation and prevention of pregnancy induced hypertension. J Obstet Gynaecol Res, 1996, 22(5): 425-430.
30. Sanchez-Ramos L, Briones DK, Kaunitz AM, et al. Prevention of pregnancy-induced hypertension by calcium supplementation in angiotensin II-sensitive patients. Obstet Gynecol, 1994, 84(3): 349-353.
31. 丛克家, 迟绍霖, 刘桂荣. 妊娠期补钙对降低妊高征的作用. 中华医学杂志, 1995, 108(1): 57-59.
32. 丛克家, 迟绍霖, 刘桂荣. 钙与妊高征. 中华妇产科杂志, 1993, 28(11): 657-659.
33. Villar J, Repke JT. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Am J Obstet Gynecol, 1990, 163(4 Pt 1): 1124-1131.
34. Lopez-Jaramillo P, Narvaez M, Felix C, et al. Dietary calcium supplementation and prevention of pregnancy hypertension. Lancet, 1990, 335(8684): 293.
35. López-Jaramillo P, Narváez M, Weigel RM, et al. Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population. Br J Obstet Gynaecol, 1989, 96(6): 648-655.
36. Villar J, Repke J, Belizan JM, et al. Calcium supplementation reduces blood pressure during pregnancy: results of a randomized controlled clinical trial. Obstet Gynecol, 1987, 70(3 Pt 1): 317-322.
37. Marya RK, Rathee S, Manrow M. Effect of calcium and vitamin D supplementation on toxaemia of pregnancy. Gynecol Obstet Invest, 1987, 24(1): 38-42.
38. Belizán JM, Villar J, Gonzalez L, et al. Calcium supplementation to prevent hypertensive disorders of pregnancy. N Engl J Med, 1991, 325(20): 1399-1405.
39. Crowther CA, Hiller JE, Pridmore B, et al. Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group. Aust N Z J Obstet Gynaecol, 1999, 39(1): 12-18.
40. 陈玉琪. 孕期补钙在妊娠期高血压预防方面的作用. 临床合理用药杂志, 2018, 11(2): 76-77.
41. 谢琼英. 孕期补钙预防高危孕妇妊娠期高血压疾病的临床观察. 广东微量元素科学, 2017, 24(4): 51-53.
42. 王帆. 抗氧化药物对妊娠期高血压疾病预测阳性孕妇的治疗效果及对血流动力学的影响. 中国计划生育学杂志, 2017, 25(1): 47-50.
43. 郭琳琼, 吉婷, 刘星. 钙剂联合小剂量阿司匹林对子痫前期的预防效果. 陕西医学杂志, 2017, 46(6): 803-804.
44. 李冉, 李巍. 营养教育和钙补充对孕中期钙缺乏和妊娠并发症的影响. 中国优生与遗传杂志, 2017, 25(11): 95-96.
45. 曹明月. 围产期加强保健并及时补钙对妊娠高血压综合征的预防效果观察. 实用妇科内分泌电子杂志, 2017, 4(1): 102, 106.
46. 炎性指标钙网蛋白水平在先兆子痫母体循环中升高, 在胎儿循环中不升高. 世界核心医学期刊文摘 (妇产科学分册), 2005, (11): 12-13.Braekke K, Holthe MR, Harsem NK, et a1.
47. Nardulli G, Proverbio F, Limongi FG, et al. Preeclampsia and calcium adenosine triphosphatase activity of red blood cell ghosts. Am J Obstet Gynecol, 1994, 171(5): 1361-1365.
48. 郝艳华, 程明刚, 陈文萍, 等. 妊高征孕妇血清钙、镁和尿酸测定的临床意义. 实用医学杂志, 2005, 21(9): 952-953.
49. 伊藤昌, 松井和, 坂本卓, 等. Angiotensin IIに対する血管反応性の基礎と臨床: 妊娠中毒症の病態に基づく発症予知·予防法について (妊娠中毒症: その病態論的アプローチ). 日本産科婦人科學會雜誌, 1988, 40(8): 991-999.
50. Thway TM, Shlykov SG, Day MC, 等. 先兆子痫患者体内的抗体通过激活血管紧张素受体刺激细胞内钙离子动员增加. 世界核心医学期刊文摘 (心脏病学分册): 2005, (2): 27.
51. 连玉巍. 补充钙剂预防妊娠期高血压的临床效果. 医药前沿, 2015, 5(3): 45-46.

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