Volume 15, Issue 8 (9-2017)                   IJRM 2017, 15(8): 461-470 | Back to browse issues page

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Elmaraezy A, Ibrahim Abushouk A, Emara A, Elshahat O, Ahmed H, I. Mostafa M. Effect of metformin on maternal and neonatal outcomes in pregnant obese non-diabetic women: A meta-analysis. IJRM. 2017; 15 (8) :461-470
URL: http://journals.ssu.ac.ir/ijrmnew/article-1-851-en.html
1- Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2- Faculty of Medicine, Ain Shams University, Cairo, Egypt , Abdelrahman.Abushouk@med.asu.edu.eg
3- Faculty of Medicine, Zagazig University, Zagazig, Egypt
4- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
Abstract:   (44 Views)
Background: Metformin reduces maternal and neonatal weight gain in gestational diabetes mellitus; however, this effect is poorly investigated in non-diabetic women. Objective: We performed this meta-analysis to investigate the effect of metformin intake during pregnancy on maternal and neonatal outcomes in obese non-diabetic women. Materials and Methods: We searched Medline, EMBASE, and Cochrane CENTRAL for eligible randomized controlled trials addressing the efficacy of metformin in pregnant obese non-diabetic women. Data were extracted and analyzed using RevMan software (Version 5.3). Neonatal birth weight was the key outcome. Secondary outcomes included maternal weight gain, the incidence of preeclampsia, and neonatal adverse effects (miscarriage, stillbirth and congenital anomalies). Results: Pooled data from two RCTs (n=843) showed that metformin caused a significant reduction in maternal gestational weight gain (MD-1.35, 95% CI: [2.08, -0.630]), compared to placebo. The summary effect-estimate did not favor either of the two groups in terms of reduction of neonatal birth weight Z score (MD-0.09, 95% CI: [0.23, 0.06]). Metformin was associated with 41% reduction in the risk of preeclampsia; however, this reduction was not statistically significant [RR 0.59, 95% CI: [0.03, 11.46]). None of the neonatal adverse events including stillbirth [RR 1.14, 95% CI: 0.42, 3.10]) and congenital anomalies (RR= 1.36, 95% CI: [0.58, 3.21]) differed significantly between the two groups. Conclusion: For obese pregnant women, metformin could decrease gestational weight gain with no significant reduction in neonatal birth weight. In light of the current evidence, metformin should not be used to prevent poor pregnancy outcomes in obese non-diabetic women.
Full-Text [PDF 1104 kb]   (19 Downloads)    
Type of Study: Original Article |
Received: 2017/10/1 | Accepted: 2017/10/14 | Published: 2017/10/14

References
1. Chan A, Scott J, Nguyen AM, Sage L. Pregnancy outcome in South Australia 2008. Adelaide: Pregnancy Outcome Unit, SA Health, Government of South Australia, 2009.
2. O'Brien TE, Ray JG, Chan W-S. Maternal body mass index and the risk of preeclampsia: a systematic overview. Epidemiology 2003; 14: 368-374. [DOI:10.1097/01.EDE.0000059921.71494.D1]
3. Wright D, Syngelaki A, Akolekar R, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obste Gynecol 2015; 213: 62. [DOI:10.1016/j.ajog.2015.02.018]
4. Johansson S, Villamor E, Altman M, Bonamy A-KE, Granath F, Cnattingius S. Maternal overweight and obesity in early pregnancy and risk of infant mortality: a population based cohort study in Sweden. BMJ 2014; 349: g6572. [DOI:10.1136/bmj.g6572]
5. Catalano PM, Ehrenberg HM. Review article: The short‐and long‐term implications of maternal obesity on the mother and her offspring. BJOG 2006; 113: 1126-1133. [DOI:10.1111/j.1471-0528.2006.00989.x]
6. Syngelaki A, Bredaki FE, Vaikousi E, Maiz N, Nicolaides KH. Body mass index at 11-13 weeks' gestation and pregnancy complications. Fetal Diagn Ther 2011; 30: 250-265. [DOI:10.1159/000328083]
7. Heslehurst N, Simpson H, Ells LJ, Rankin J, Wilkinson J, Lang R, et al. The impact of maternal BMI status on pregnancy outcomes with immediate short‐term obstetric resource implications: a meta‐analysis. Obes Rev 2008; 9: 635-683. [DOI:10.1111/j.1467-789X.2008.00511.x]
8. Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, Stampfer MJ. Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 1996; 94: 3246-3250. [DOI:10.1161/01.CIR.94.12.3246]
9. Parsons TJ, Power C, Logan S, Summerbelt CD. Childhood predictors of adult obesity: a systematic review. Int J Obes Int J Obes Relat Metab Disord 1999;23 (Suppl.): S1-107
10. Yu Z, Han S, Zhu J, Sun X, Ji C, Guo X. Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PloS One 2013; 8: e61627. [DOI:10.1371/journal.pone.0061627]
11. Chiswick C, Reynolds RM, Denison F, Drake AJ, Forbes S, Newby DE, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 3: 778-786. [DOI:10.1016/S2213-8587(15)00219-3]
12. Galtier-Dereure F, Montpeyroux F, Boulot P, Bringer J, Jaffiol C. Weight excess before pregnancy: complications and cost. Int J Obes Relat Metab Disord 1995; 19: 443-448.
13. Oteng-Ntim E, Varma R, Croker H, Poston L, Doyle P. Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis. BMC Med 2012; 10: 47. [DOI:10.1186/1741-7015-10-47]
14. Poston L, Bell R, Croker H, Flynn AC, Godfrey KM, Goff L, et al. Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial. Lancet 2015; 3: 767-777. [DOI:10.1016/S2213-8587(15)00227-2]
15. Renault KM, Nørgaard K, Nilas L, Carlsen EM, Cortes D, Pryds O, et al. The Treatment of Obese Pregnant Women (TOP) study: a randomized controlled trial of the effect of physical activity intervention assessed by pedometer with or without dietary intervention in obese pregnant women. Am J Obstet Gynecol 2014; 210: 134. [DOI:10.1016/j.ajog.2013.09.029]
16. Scholl TO, Sowers M, Chen X, Lenders C. Maternal glucose concentration influences fetal growth, gestation, and pregnancy complications. Am J Epidemiol 2001; 154: 514-520. [DOI:10.1093/aje/154.6.514]
17. Lowe LP, Metzger BE, Dyer AR, Lowe J, McCance DR, Lappin TRJ, et al. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care 2012; 35: 574-580. [DOI:10.2337/dc11-1687]
18. Cassina M, Donà M, Di Gianantonio E, Litta P, Clementi M. First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update 2014; 20: 656-669. [DOI:10.1093/humupd/dmu022]
19. Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med 2009; 26: 798-802. [DOI:10.1111/j.1464-5491.2009.02780.x]
20. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. New Engl J Med 2008; 358: 2003-2015. [DOI:10.1056/NEJMoa0707193]
21. Vanky E, Salvesen KÅ, Heimstad R, Fougner KJ, Romundstad P, Carlsen SM. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum Reprod 2004; 19: 1734-1740. [DOI:10.1093/humrep/deh347]
22. Fougner KJ, Vanky E, Carlsen SM. Metformin has no major effects on glucose homeostasis in pregnant women with PCOS: results of a randomized double‐blind study. Scand J Clin Lab Invest 2008; 68: 771-776. [DOI:10.1080/00365510802254620]
23. Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, et al. Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus. New Engl J Med 2016; 374: 434-443. [DOI:10.1056/NEJMoa1509819]
24. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of interventions. The Cochrane Collaboration; 2008. [DOI:10.1002/9780470712184]
25. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014; 14: 135. [DOI:10.1186/1471-2288-14-135]
26. Terrin N, Schmid CH, Lau J, Olkin I. Adjusting for publication bias in the presence of heterogeneity. Stat Med 2003; 22: 2113-2126. [DOI:10.1002/sim.1461]
27. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634. [DOI:10.1136/bmj.315.7109.629]
28. Lazurova I, Dravecka I, Kraus V, Petrovicova J. Metformin versus sibutramine in the treatment of hyperinsulinemia in chronically anovulating women. Bratisl Lek Listy 2004; 105: 207-210.
29. Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000; 85: 2767-2774. [DOI:10.1210/jcem.85.8.6738]
30. De Oliveira Baraldi C, Lanchote VL, de Jesus Antunes N, Carvalho TM de JP, Moisés ECD, Duarte G, et al. Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome. Eur J Clin Pharmacol 2011; 67: 1027-1033. [DOI:10.1007/s00228-011-1053-0]
31. De Oliveira Baraldi C, Moisés ECD, Carvalho TM de JP, de Jesus Antunes N, Lanchote VL, Duarte G, et al. Effect of type 2 diabetes mellitus on the pharmacokinetics of metformin in obese pregnant women. Clin Pharmacokinetics 2012; 51: 743-749. [DOI:10.1007/s40262-012-0008-7]
32. Hughes RCE, Gardiner SJ, Begg EJ, Zhang M. Effect of pregnancy on the pharmacokinetics of metformin. Diabetic Med 2006; 23: 323-326. [DOI:10.1111/j.1464-5491.2005.01769.x]
33. Ghazeeri GS, Nassar AH, Younes Z, Awwad JT. Pregnancy outcomes and the effect of metformin treatment in women with polycystic ovary syndrome:an overview. Acta Obstet Gynecol Scand 2012; 91: 658-678. [DOI:10.1111/j.1600-0412.2012.01385.x]
34. Sivalingam VN, Myers J, Nicholas S, Balen AH, Crosbie EJ. Metformin in reproductive health, pregnancy and gynaecological cancer: established and emerging indications. Hum Reprod Update 2014; 20: 853-868. [DOI:10.1093/humupd/dmu037]
35. Hong Y-C, O'Boyle CP, Chen I-C, Hsiao C-T, Kuan J-T. Metformin-associated lactic acidosis in a pregnant patient. Gynecol Obstet Invest 2008; 66: 138-141. [DOI:10.1159/000132463]
36. Shigiyama F, Kumashiro N, Rikitake T, Usui S, Saegusa M, Kitamura M, et al. A case of lean polycystic ovary syndrome with early stage of type 1 diabetes successfully treated with metformin [Rapid Communication]. Endocrine J 2016; 63: 193-198. [DOI:10.1507/endocrj.EJ15-0548]
37. Vanky E, Stridsklev S, Heimstad R, Romundstad P, Skogøy K, Kleggetveit O, et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab 2010; 95: 448-455. [DOI:10.1210/jc.2010-0853]
38. Salvesen KÅ, Vanky E, Carlsen SM. Metformin treatment in pregnant women with polycystic ovary syndrome-is reduced complication rate mediated by changes in the uteroplacental circulation? Ultrasound Obstet Gynecol 2007; 29: 433-437. [DOI:10.1002/uog.3965]
39. Catov JM, Bodnar LM, Ness RB, Barron SJ, Roberts JM. Inflammation and dyslipidemia related to risk of spontaneous preterm birth. Am J Epidemiol 2007; 166: 1312-1319. [DOI:10.1093/aje/kwm273]
40. Greer IA, Lyall F, Perera T, Boswell F, Macara LM. Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction? Obstet Gynecol 1994; 84: 937-940.
41. Guven MA, Coskun A, Ertas IE, Aral M, Zencırcı B, Oksuz H. Association of maternal serum CRP, IL-6, TNF-α, homocysteine, folic acid and vitamin b12 levels with the severity of preeclampsia and fetal birth weight. Hypertens Pregnancy 2009; 28: 190-200. [DOI:10.1080/10641950802601179]
42. Charles B, Norris R, Xiao X, Hague W. Population pharmacokinetics of metformin in late pregnancy. Therapeutic Drug Monitor 2006; 28: 67-72. [DOI:10.1097/01.ftd.0000184161.52573.0e]
43. Glueck CJ, Goldenberg N, Wang P, Sieve L, Loftspring M, Sherman A. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone, and development of gestational diabetes: prospective longitudinal study of women with polycystic ovary syndrome from pre-conception through pregnancy. J Invest Med 2004; 52: S378.
44. Schwartz R, Gruppuso PA, Petzold K, Brambilla D, Hiilesmaa V, Teramo KA. Hyperinsulinemia and macrosomia in the fetus of the diabetic mother. Diabetes Care 1994; 17: 640-648. [DOI:10.2337/diacare.17.7.640]
45. Catalano PM, Hauguel-De Mouzon S. Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am J Obstet Gynecol 2011; 204: 479-487. [DOI:10.1016/j.ajog.2010.11.039]
46. El Husseny MW, Mamdouh M, Shaban S, Ibrahim AA, Zaki MM, Ahmed OM, et al. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity. J Diabetes Res 2017; 2017: 8095926. [DOI:10.1155/2017/8095926]
47. Salomäki H, Heinäniemi M, Vähätalo LH, Ailanen L, Eerola K, Ruohonen ST, et al. Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring. PloS One 2014; 9: e115778. [DOI:10.1371/journal.pone.0115778]

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