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癇診斷中的研究進展. 國際檢驗醫學雜志, 2017, 38(2): 235-236.
2.	蘇普玉. 孕 20 周內母體甲狀腺功能與不良妊娠結局、嬰幼兒體格生長及神經精神發育關系的前瞻性隊列研究. 合肥: 安徽醫科大學, 2012.
3.	阮利紅, 賈桂花, 方政慧. 微小 RNA 在子癇前期中的研究進展. 中國婦幼保健, 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.	李雪蘭, 茍文麗. 補鈣預防妊高征及對血小板細胞內游離鈣濃度的影響. 西安醫科大學學報, 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.	叢克家, 遲紹霖, 劉桂榮. 妊娠期補鈣對降低妊高征的作用. 中華醫學雜志, 1995, 108(1): 57-59.
32.	叢克家, 遲紹霖, 劉桂榮. 鈣與妊高征. 中華婦產科雜志, 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.	陳玉琪. 孕期補鈣在妊娠期高血壓預防方面的作用. 臨床合理用藥雜志, 2018, 11(2): 76-77.
41.	謝瓊英. 孕期補鈣預防高危孕婦妊娠期高血壓疾病的臨床觀察. 廣東微量元素科學, 2017, 24(4): 51-53.
42.	王帆. 抗氧化藥物對妊娠期高血壓疾病預測陽性孕婦的治療效果及對血流動力學的影響. 中國計劃生育學雜志, 2017, 25(1): 47-50.
43.	郭琳瓊, 吉婷, 劉星. 鈣劑聯合小劑量阿司匹林對子癇前期的預防效果. 陜西醫學雜志, 2017, 46(6): 803-804.
44.	李冉, 李巍. 營養教育和鈣補充對孕中期鈣缺乏和妊娠并發癥的影響. 中國優生與遺傳雜志, 2017, 25(11): 95-96.
45.	曹明月. 圍產期加強保健并及時補鈣對妊娠高血壓綜合征的預防效果觀察. 實用婦科內分泌電子雜志, 2017, 4(1): 102, 106.
46.	炎性指標鈣網蛋白水平在先兆子癇母體循環中升高, 在胎兒循環中不升高. 世界核心醫學期刊文摘 (婦產科學分冊), 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.	郝艷華, 程明剛, 陳文萍, 等. 妊高征孕婦血清鈣、鎂和尿酸測定的臨床意義. 實用醫學雜志, 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: 妊娠中毒癥の病態に基づく発癥予知·予防法について (妊娠中毒癥: 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. 先兆子癇患者體內的抗體通過激活血管緊張素受體刺激細胞內鈣離子動員增加. 世界核心醫學期刊文摘 (心臟病學分冊): 2005, (2): 27.
51.	連玉巍. 補充鈣劑預防妊娠期高血壓的臨床效果. 醫藥前沿, 2015, 5(3): 45-46.

1. 袁松, 唐中. 尿蛋白定量在先兆子癇診斷中的研究進展. 國際檢驗醫學雜志, 2017, 38(2): 235-236.
2. 蘇普玉. 孕 20 周內母體甲狀腺功能與不良妊娠結局、嬰幼兒體格生長及神經精神發育關系的前瞻性隊列研究. 合肥: 安徽醫科大學, 2012.
3. 阮利紅, 賈桂花, 方政慧. 微小 RNA 在子癇前期中的研究進展. 中國婦幼保健, 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. 李雪蘭, 茍文麗. 補鈣預防妊高征及對血小板細胞內游離鈣濃度的影響. 西安醫科大學學報, 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. 叢克家, 遲紹霖, 劉桂榮. 妊娠期補鈣對降低妊高征的作用. 中華醫學雜志, 1995, 108(1): 57-59.
32. 叢克家, 遲紹霖, 劉桂榮. 鈣與妊高征. 中華婦產科雜志, 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. 陳玉琪. 孕期補鈣在妊娠期高血壓預防方面的作用. 臨床合理用藥雜志, 2018, 11(2): 76-77.
41. 謝瓊英. 孕期補鈣預防高危孕婦妊娠期高血壓疾病的臨床觀察. 廣東微量元素科學, 2017, 24(4): 51-53.
42. 王帆. 抗氧化藥物對妊娠期高血壓疾病預測陽性孕婦的治療效果及對血流動力學的影響. 中國計劃生育學雜志, 2017, 25(1): 47-50.
43. 郭琳瓊, 吉婷, 劉星. 鈣劑聯合小劑量阿司匹林對子癇前期的預防效果. 陜西醫學雜志, 2017, 46(6): 803-804.
44. 李冉, 李巍. 營養教育和鈣補充對孕中期鈣缺乏和妊娠并發癥的影響. 中國優生與遺傳雜志, 2017, 25(11): 95-96.
45. 曹明月. 圍產期加強保健并及時補鈣對妊娠高血壓綜合征的預防效果觀察. 實用婦科內分泌電子雜志, 2017, 4(1): 102, 106.
46. 炎性指標鈣網蛋白水平在先兆子癇母體循環中升高, 在胎兒循環中不升高. 世界核心醫學期刊文摘 (婦產科學分冊), 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. 郝艷華, 程明剛, 陳文萍, 等. 妊高征孕婦血清鈣、鎂和尿酸測定的臨床意義. 實用醫學雜志, 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: 妊娠中毒癥の病態に基づく発癥予知·予防法について (妊娠中毒癥: 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. 先兆子癇患者體內的抗體通過激活血管緊張素受體刺激細胞內鈣離子動員增加. 世界核心醫學期刊文摘 (心臟病學分冊): 2005, (2): 27.
51. 連玉巍. 補充鈣劑預防妊娠期高血壓的臨床效果. 醫藥前沿, 2015, 5(3): 45-46.

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