Systematic Review of Effects for S-Adenosyl-L-Methionin on Improving the Pregnancy Outcomes of Intrahepatic Cholestasis of Pregnancy_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Tao ¹ , LIU Shu yun ¹ , XU Liang zhi ¹² , XING Ai yun ¹ , LIU Guan jian ²

1 Department of Obstetrics and Gynecology; West China Women and Children Hospital; Sichuan University; Chengdu 610041; China2 Chinese Cochrane Center; West China Hospital; Sichuan University; Chengdu 610041; China;

Corresponding author：

Keywords：

S-adenosyl-l-methionine; Intrahepatic choletasis of pregnancy; Systematic review

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective 　To assess the efficacy and safety of S-adenosyl-l-methionine (SAMe) for outcome improvement of intrahepatic cholestasis of pregnancy.
Methods 　Randomized controlled trials (RCT) and quasi-randomized controlled trials were identified from MEDLINE (1983 to 2003), The Cochrane Library (Issue 4,2003), EMBASE (1980 to 2003), China Hospital Digital Library (CHDL) and Wanfang data (1994 to 2003). We also handsearched the relative references. Two researchers evaluated the quality of the trials and extracted the data independently. RevMan software 4.2 was used for meta-analysis.
Results 　Eight studies involving 424 pregnant women were included. The following data were the results of meta-analysis of SAMe for improvements: ① Reducing cesarean-section ratio: no significant difference was seen between SAMe and placebo groups with OR 1.00, 95%CI 0.23 to 4.33 and P= 1.00; significant differences were seen SAMe versus dexamethasone and SAMe versus Dianglining with OR 0.44, 95%CI 0.23 to 0.85 and P=0.01; OR 0.28 95%CI 0.10 to 0.75 and P=0.01 respectively。② Prolonging the period of pregnancy: SAMe had no significant difference compared with placebo groups with WMD=0.70, 95%CI －0.69 to 2.10, P=0.32. SAMe was more effective than dexamethasone, Ganyinling and Qianglining on prolonging the period of pregnancy with WMD=1.10，95%CI 0.46 to 1.74, P=0.000 07; WMD=2.50，95%CI 1.86 to 3.14, P≤0.000 01; WMD=2.20，95%CI 1.61 to 2.79, P≤0.000 01 respectively；③ Increasing the weight of the newborn: meta-analysis showed that SAMe group had not significant difference compared with placebo group on increasing the weight of the newborn with WMD=-26.27，95%CI -338.35 to 285.82, P=0.87. Significant differences were seen between SAMe and dexamethasone, SAMe and Ganyiling, SAMe and Qiangling with WMD=386.86，95%CI 134.41 to 603.31, P=0.002; WMD=410.00,95%CI 321.10 to 498.90, P≤0.000 01 respectively. ④ Fetal distress: There was no significant difference compared with dexamethasone and Kuhuang groups on decreasing the fetal distress with OR=0.47, 95%CI 0.14 to 1.16, P=0.23; OR=0.44, 95%CI 0.10 to 1.97, P=0.29 respectively; ⑤ Decreasing pollution of amniotic fluid: no significant differences were seen in SAMe versus dexamethasone, SAMe versus ursoddeoxycholic and SAMe versus Kuhuang with OR=0.46, 95%CI 0.21 to 1.02, P=0.06; OR=0.68, 95%CI 0.20 to 2.31, P=0.53; OR=0.82 95%CI 0.24 to 2.81,P=0.75 recpectively. ⑥ Newborn stifile: SAMe group had no significant difference compared with dexamethasone and Kuhuang groups on decreasing the Newborn stifile with OR=0.19, 95%CI 0.01 to 4.06, P=0.29; OR=0.31, 95%CI 0.08 to 1.13, P=0.08 respectively. Compared with Qianglining group, SAMe group had better effect on reducing ratio of newborn stifile with OR=0.09, 95%CI 0.02 to 0.42, P=0.002. ⑦ Improving Apgar scores: no significant differences were seen between SAMe and placebo, dexamethasone and ursoddeoxycholic with OR=0.25, 95%CI 0.02 to 3.04, P=0.28; OR=2.09, 95%CI 0.70 to 6.27, P=0.19; OR=1.22, 95%CI 0.35 to 4.19, P=0.75 respectively. Six RCTs mentioned the side effects of S-adenosy-l-methionine, only one RCT reported mild gastrointestinal irritation.
Conclusions 　SAMe is partly effective on improving the pregnancy outcomes of intrahepatic choletasis of pregnancy, such as reducting cesarean-section ratio, prolonging the period of pregnancy and increasing the weight of the newborn. The specified efficacy and safety of SAMe require rigorously designed, randomized, double-blind and placebo-controlled trials to offer evidence.

Citation： WANG Tao,LIU Shu yun,XU Liang zhi,XING Ai yun,LIU Guan jian. Systematic Review of Effects for S-Adenosyl-L-Methionin on Improving the Pregnancy Outcomes of Intrahepatic Cholestasis of Pregnancy. Chinese Journal of Evidence-Based Medicine, 2005, 05(2): 130-135. doi: Copy

1.	曹泽毅. 《中华妇产科学》[M]. 第1版, 北京: 人民卫生出版社, 1999. p. 500～507.
2.	艾英, 刘淑芸. 妊娠期肝内胆汁淤积症的药物治疗[J]. 中国实用妇科与产科杂志, 2002;18(1): 55～56.
3.	王家良, 刘鸣. 循征医学[M]. 北京: 人民卫生出版社, 2001. p. 177～188.
4.	谭友文, 庄红仙. 腺苷蛋氨酸对妊娠肝内胆汁淤积症的临床观察[J]. 中国实用妇科与产科杂志, 2001;17(6): 343～345.
5.	周晓宇, 赵蔚, 朱仲建. 思美泰治疗妊娠肝内胆汁淤积症的疗效观察[J]. 浙江临床医学, 2002;4(1): 51～52.
6.	李珉. 思美泰治疗妊娠肝内胆汁淤积症30例疗效观察[J]. 苏州大学学报(医学版), 2003;23(3): 366～367.
7.	王亚儿, 陈丽萍. 思美泰治疗妊娠肝内胆汁淤积症[J]. 现代实用医学, 2003;15(6): 379～380.
8.	徐春佳, 陈晓芸. 思美泰联合地塞米松治疗妊娠肝内胆汁淤积症的临床观察[J]. 贵州医药, 2003;27(2): 118～119.
9.	马健婷. 腺苷蛋氨酸联合熊去氧胆酸治疗妊娠肝内胆汁淤积症21例[J]. 临床医药, 2003;12(6):64～65.
10.	Cao ZY. Chinese Obstetrics and Gynecology[M]. 1st edition. Beijing:People,medical publishing house, 1999. p. 500-507.
11.	Ai Y, Liu SY. The medicines in treatment of Intrahepatic cholestasis of pregnancy[J]. Journal of Chinese Practical Obsterics and Gynecology, 2002;18(1): 55-56.
12.	Wang JL, Liu M. Evidence-Based Medicine[M]. Beijing: People,medical publishing house, 2001. p. 177-188.
13.	Jadad AR, Moore A, Carroll D. Assessing the quality of reports of randomized clinical trials: Is blinding necessary[J]. Control Clinical Trials, 1996;17(1): 1-12 .
14.	Bonessio L, Ciardo A, Spina V, Morini A. Intrahepatic cholestasis in pregnancy[J]. Clin Ter, 1996;147(7-8): 377-384.
15.	Ribalta J, Reyes H, Gonzalez MC. S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results[J]. Hepatology, 1991;13(6): 1 084-1 089.
16.	Frezza M, Pozzato G, Chiesa L. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration[J]. Hepatology, 1984;4(2): 274-278.
17.	Floreani A, Paternoster D, Melis A, Grella PV. S-adenosyl-l-methionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial[J]. Eur J Obstet Gynecol Reprod Biol,1996 ;67(2):109-113.
18.	Frezza M, Tritapepe R, Pozzato G, Di Padova C. Prevention of S-adenosyl-l-methionine of estrogen-induced hepatobiliary toxicity in susceptible women[J]. Am J Gastroenterol,1988;83(10): 1 098-1 102.
19.	Nicastri PL, Diaferia A, Tartagni M, Loizzi P, Fanelli M. A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy[J]. Br J Obstet Gynaecol, 1998 ;105(11): 1 205-1 207.
20.	Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study[J]. Gastroenterology, 1990;99(1): 211-215.
21.	Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis[J]. Drugs,1990;40 (Suppl 3): 111-123.
22.	Tan XW, Zhuang XH. The clinical observation of s-adenosyl-L-methionine for Intrahepatic cholestasis of pregnancy[J]. Journal of Chinese Practical Obsterics and Gynecology, 2001;17(6): 343-345.
23.	Zhou XY ,Zhang W, Zhu ZJ. The clinical efficacy of s-adenosyl-L-methionine for the treatment of Intrahepatic cholestasis of pregnancy[J]. Zhejiang Clinical Medicine Journal, 2002;4(1): 51-52.
24.	Li M. The clinical efficacy of s-adenosyl-L-methionine Therapy in the 30 cases of intrahepatic cholestasis of pregnancy[J]. Journal of Suzhou University(Medicine Journal), 2003;23(3): 366-367.
25.	Wang YE, Chen LP. s-adenosyl-L-methionine in treatment of Intrahepatic cholestasis of pregnancy[J]. Journal of Modern Medicine, 2003;15(6): 379-380.
26.	Xu CJ, Chen XY. The clinical observation of S-adenosyl-L-methionine combinated with dexamethasone for the treatment of Intrahepatic cholestasis of pregnancy[J]. Guizhou Medicine Journal, 2003;27(2): 118-119.
27.	Ma JT. The clinical efficacy of s-adenosyl-L-methionine combinated with ursoddeoxycholic Therapy in the 21 cases of Intrahepatic cholestasis of pregnancy[J]. Journal of Clinical Medicine, 2003;12(6): 64-65.

1. 曹泽毅. 《中华妇产科学》[M]. 第1版, 北京: 人民卫生出版社, 1999. p. 500～507.
2. 艾英, 刘淑芸. 妊娠期肝内胆汁淤积症的药物治疗[J]. 中国实用妇科与产科杂志, 2002;18(1): 55～56.
3. 王家良, 刘鸣. 循征医学[M]. 北京: 人民卫生出版社, 2001. p. 177～188.
4. 谭友文, 庄红仙. 腺苷蛋氨酸对妊娠肝内胆汁淤积症的临床观察[J]. 中国实用妇科与产科杂志, 2001;17(6): 343～345.
5. 周晓宇, 赵蔚, 朱仲建. 思美泰治疗妊娠肝内胆汁淤积症的疗效观察[J]. 浙江临床医学, 2002;4(1): 51～52.
6. 李珉. 思美泰治疗妊娠肝内胆汁淤积症30例疗效观察[J]. 苏州大学学报(医学版), 2003;23(3): 366～367.
7. 王亚儿, 陈丽萍. 思美泰治疗妊娠肝内胆汁淤积症[J]. 现代实用医学, 2003;15(6): 379～380.
8. 徐春佳, 陈晓芸. 思美泰联合地塞米松治疗妊娠肝内胆汁淤积症的临床观察[J]. 贵州医药, 2003;27(2): 118～119.
9. 马健婷. 腺苷蛋氨酸联合熊去氧胆酸治疗妊娠肝内胆汁淤积症21例[J]. 临床医药, 2003;12(6):64～65.
10. Cao ZY. Chinese Obstetrics and Gynecology[M]. 1st edition. Beijing:People,medical publishing house, 1999. p. 500-507.
11. Ai Y, Liu SY. The medicines in treatment of Intrahepatic cholestasis of pregnancy[J]. Journal of Chinese Practical Obsterics and Gynecology, 2002;18(1): 55-56.
12. Wang JL, Liu M. Evidence-Based Medicine[M]. Beijing: People,medical publishing house, 2001. p. 177-188.
13. Jadad AR, Moore A, Carroll D. Assessing the quality of reports of randomized clinical trials: Is blinding necessary[J]. Control Clinical Trials, 1996;17(1): 1-12 .
14. Bonessio L, Ciardo A, Spina V, Morini A. Intrahepatic cholestasis in pregnancy[J]. Clin Ter, 1996;147(7-8): 377-384.
15. Ribalta J, Reyes H, Gonzalez MC. S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results[J]. Hepatology, 1991;13(6): 1 084-1 089.
16. Frezza M, Pozzato G, Chiesa L. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration[J]. Hepatology, 1984;4(2): 274-278.
17. Floreani A, Paternoster D, Melis A, Grella PV. S-adenosyl-l-methionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial[J]. Eur J Obstet Gynecol Reprod Biol,1996 ;67(2):109-113.
18. Frezza M, Tritapepe R, Pozzato G, Di Padova C. Prevention of S-adenosyl-l-methionine of estrogen-induced hepatobiliary toxicity in susceptible women[J]. Am J Gastroenterol,1988;83(10): 1 098-1 102.
19. Nicastri PL, Diaferia A, Tartagni M, Loizzi P, Fanelli M. A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy[J]. Br J Obstet Gynaecol, 1998 ;105(11): 1 205-1 207.
20. Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study[J]. Gastroenterology, 1990;99(1): 211-215.
21. Almasio P, Bortolini M, Pagliaro L, Coltorti M. Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis[J]. Drugs,1990;40 (Suppl 3): 111-123.
22. Tan XW, Zhuang XH. The clinical observation of s-adenosyl-L-methionine for Intrahepatic cholestasis of pregnancy[J]. Journal of Chinese Practical Obsterics and Gynecology, 2001;17(6): 343-345.
23. Zhou XY ,Zhang W, Zhu ZJ. The clinical efficacy of s-adenosyl-L-methionine for the treatment of Intrahepatic cholestasis of pregnancy[J]. Zhejiang Clinical Medicine Journal, 2002;4(1): 51-52.
24. Li M. The clinical efficacy of s-adenosyl-L-methionine Therapy in the 30 cases of intrahepatic cholestasis of pregnancy[J]. Journal of Suzhou University(Medicine Journal), 2003;23(3): 366-367.
25. Wang YE, Chen LP. s-adenosyl-L-methionine in treatment of Intrahepatic cholestasis of pregnancy[J]. Journal of Modern Medicine, 2003;15(6): 379-380.
26. Xu CJ, Chen XY. The clinical observation of S-adenosyl-L-methionine combinated with dexamethasone for the treatment of Intrahepatic cholestasis of pregnancy[J]. Guizhou Medicine Journal, 2003;27(2): 118-119.
27. Ma JT. The clinical efficacy of s-adenosyl-L-methionine combinated with ursoddeoxycholic Therapy in the 21 cases of Intrahepatic cholestasis of pregnancy[J]. Journal of Clinical Medicine, 2003;12(6): 64-65.

Chinese Journal of Evidence-Based Medicine

Systematic Review of Effects for S-Adenosyl-L-Methionin on Improving the Pregnancy Outcomes of Intrahepatic Cholestasis of Pregnancy

Abstract Full text Figures/Tables Video References Cited by

Format

Content