提示: 手机请竖屏浏览!

在无糖尿病的肥胖孕妇中应用二甲双胍与安慰剂的对比
Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus


Argyro Syngelaki ... 糖尿病 围产医学和儿科 • 2016.02.04

摘要


背景

肥胖与不良妊娠结局的风险增加相关。对生活方式进行干预的研究未显示妊娠结局改善。二甲双胍能改善胰岛素敏感性,且合并妊娠糖尿病的孕妇服用二甲双胍后体重增加较不服用者少。

 

方法

在这项双盲、安慰剂对照的试验中,我们随机指定体质指数(BMI,以千克为单位的体重除以米为单位的身高平方)大于35的无糖尿病孕妇,随机分成2组,从孕12~18周开始,分别每天服用3.0 g二甲双胍或安慰剂直至分娩(每组各225名孕妇)。体质指数在入组时计算(即孕12~18周)。主要结局是新生儿出生体重的Z值中位数降低0.3个标准差(相当于使大于胎龄新生儿的出生率降低50%,范围从20%到10%)。次要结局是孕妇妊娠期体重增加、妊娠糖尿病与先兆子痫的发病率以及不良新生儿的出生率。我们通过计算机生成的随机数字进行随机分组,根据意向性治疗原则对结果进行分析。

 

结果

在试验过程中共有50名孕妇撤回知情同意,余下202名孕妇在二甲双胍组,198名孕妇在安慰剂组。新生儿出生体重的Z值中位数未见显著的组间差异(二甲双胍组中位数0.05[四分位间距,-0.71~0.92],安慰剂组中位数0.17[四分位间距,-0.62~0.89])。二甲双胍组中孕妇妊娠期体重增加的中位数(4.6 kg[四分位间距,1.3~7.2])低于安慰剂组(6.3 kg [四分位间距,2.9~9.2],两者比较P<0.001),先兆子痫发病率也是如此(3.0%对11.3%;比值比,0.24;95%可信区间0.10~0.61;P=0.001)。二甲双胍组中副作用发生率高于安慰剂组。妊娠糖尿病、大于胎龄新生儿以及不良新生儿结局的发生率均未见显著组间差异。

 

结论

在体质指数>35的无糖尿病孕妇中,孕期服用二甲双胍可以减少妊娠期体重增加幅度,但不影响新生儿出生体重(由胎儿医学基金会[Fetal Medicine Foundation]资助;ClinicalTrials.gov注册号为NCT01273584;EudraCT注册号为2008-005892-83)。





作者信息

Argyro Syngelaki, Ph.D., Kypros H. Nicolaides, M.D., Jyoti Balani, M.D., Steve Hyer, M.D., Ranjit Akolekar, M.D., Reena Kotecha, M.D., Alice Pastides, M.D., and Hassan Shehata, M.D.
From the Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital (A.S., K.H.N., R.A., R.K., A.P.), and the Departments of Endocrinology (J.B., S.H.) and Maternal Medicine (H.S.), Epsom and St. Helier University Hospitals NHS Trust, London, and the Department of Fetal Medicine, Medway Maritime Hospital, Gillingham, Kent (R.A.) — all in the United Kingdom. Address reprint requests to Dr. Shehata at the Department of Maternal Medicine, Epsom and St. Helier University Hospitals NHS Trust, London SM5 1AA, United Kingdom, or at hassan.shehata@nhs.net.

 

参考文献

1. Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384:766-781

2. Heslehurst N, Rankin J, Wilkinson JR, Summerbell CD. A nationally representative study of maternal obesity in England, UK: trends in incidence and demographic inequalities in 619 323 births, 1989–2007. Int J Obes (Lond) 2010;34:420-428

3. American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 549: obesity in pregnancy. Obstet Gynecol 2013;121:213-217

4. Catalano PM, Ehrenberg HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 2006;113:1126-1133

5. Sebire NJ, Jolly M, Harris JP, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord 2001;25:1175-1182

6. Johansson S, Villamor E, Altman M, Bonamy AK, 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-g6572

7. 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-e61627

8. Mamun AA, O’Callaghan M, Callaway L, Williams G, Najman J, Lawlor DA. Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: evidence from a birth cohort study. Circulation 2009;119:1720-1727

9. 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 Obstet Gynecol 2015;213:62.e1-62.10

10. 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

11. García-Patterson A, Aulinas A, María MÁ, et al. Maternal body mass index is a predictor of neonatal hypoglycemia in gestational diabetes mellitus. J Clin Endocrinol Metab 2012;97:1623-1628

12. 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;10:47-47

13. Thangaratinam S, Rogozinska E, Jolly K, et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012;344:e2088-e2088

14. Rogozińska E, Chamillard M, Hitman GA, Khan KS, Thangaratinam S. Nutritional manipulation for the primary prevention of gestational diabetes mellitus: a meta-analysis of randomised studies. PLoS One 2015;10:e0115526-e0115526

15. Renault KM, Nørgaard K, Nilas L, Carlsen EM, Cortes D, Pryds O, Secher NJ. 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.e1-134.e9

16. Dodd JM, Turnbull D, McPhee AJ, et al. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial. BMJ 2014;348:g1285-g1285

17. Poston L, Bell R, Croker H, et al. Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol 2015;3:767-777

18. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003-2015

19. 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

20. Martyn JA, Kaneki M, Yasuhara S. Obesity-induced insulin resistance and hyperglycemia: etiologic factors and molecular mechanisms. Anesthesiology 2008;109:137-148

21. Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991-2002

22. 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

23. World Health Organization, Department of Noncommunicable Disease Surveillance. Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization, 1999 (http://apps.who.int/iris/handle/10665/66040).

24. Poon LC, Volpe N, Muto B, Syngelaki A, Nicolaides KH. Birthweight with gestation and maternal characteristics in live births and stillbirths. Fetal Diagn Ther 2012;32:156-165

25. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;20:IX-XIV

26. Kiel DW, Dodson EA, Artal R, Boehmer TK, Leet TL. Gestational weight gain and pregnancy outcomes in obese women: how much is enough? Obstet Gynecol 2007;110:752-758

27. Truong YN, Yee LM, Caughey AB, et al. Weight gain in pregnancy: does the Institute of Medicine have it right? Am J Obstet Gynecol 2015;212:362.e1-362.e8

28. Barton JR, Joy SD, Rhea DJ, Sibai AJ, Sibai BM. The influence of gestational weight gain on the development of gestational hypertension in obese women. Am J Perinatol 2015;32:615-620

29. Vanky E, Salvesen KA, 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

30. Vanky E, Stridsklev S, Heimstad R, 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:E448-55

31. 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

32. Salvesen KA, 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

33. Chiswick C, Reynolds RM, Denison F, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2015;3:778-786

服务条款 | 隐私政策 | 联系我们