Comparative impact of pharmacological treatments for gestational diabetes on neonatal anthropometry independent of maternal glycaemic control: A systematic review and meta-analysis


Autoři: Jane L. Tarry-Adkins aff001;  Catherine E. Aiken aff001;  Susan E. Ozanne aff001
Působiště autorů: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom aff001;  Department of Obstetrics and Gynaecology, the Rosie Hospital and NIHR Cambridge Comprehensive Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom aff002
Vyšlo v časopise: Comparative impact of pharmacological treatments for gestational diabetes on neonatal anthropometry independent of maternal glycaemic control: A systematic review and meta-analysis. PLoS Med 17(5): e32767. doi:10.1371/journal.pmed.1003126
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003126

Souhrn

Background

Fetal growth in gestational diabetes mellitus (GDM) is directly linked to maternal glycaemic control; however, this relationship may be altered by oral anti-hyperglycaemic agents. Unlike insulin, such drugs cross the placenta and may thus have independent effects on fetal or placental tissues. We investigated the association between GDM treatment and fetal, neonatal, and childhood growth.

Methods and findings

PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and Cochrane databases were systematically searched (inception to 12 February 2020). Outcomes of GDM-affected pregnancies randomised to treatment with metformin, glyburide, or insulin were included. Studies including preexisting diabetes or nondiabetic women were excluded. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Maternal outcome measures were glycaemic control, weight gain, and treatment failure. Offspring anthropometric parameters included fetal, neonatal, and childhood weight and body composition data. Thirty-three studies (n = 4,944), from geographical locations including Europe, North Africa, the Middle East, Asia, Australia/New Zealand, and the United States/Latin America, met eligibility criteria. Twenty-two studies (n = 2,801) randomised women to metformin versus insulin, 8 studies (n = 1,722) to glyburide versus insulin, and 3 studies (n = 421) to metformin versus glyburide. Eleven studies (n = 2,204) reported maternal outcomes. No differences in fasting blood glucose (FBS), random blood glucose (RBS), or glycated haemoglobin (HbA1c) were reported. No studies reported fetal growth parameters. Thirty-three studies (n = 4,733) reported birth weight. Glyburide-exposed neonates were heavier at birth (58.20 g, 95% confidence interval [CI] 10.10–106.31, p = 0.02) with increased risk of macrosomia (odds ratio [OR] 1.38, 95% CI 1.01–1.89, p = 0.04) versus neonates of insulin-treated mothers. Metformin-exposed neonates were born lighter (−73.92 g, 95% CI −114.79 to −33.06 g, p < 0.001) with reduced risk of macrosomia (OR 0.60, 95% CI 0.45–0.79, p < 0.001) than insulin-exposed neonates. Metformin-exposed neonates were born lighter (−191.73 g, 95% CI −288.01 to −94.74, p < 0.001) with a nonsignificant reduction in macrosomia risk (OR 0.32, 95% CI 0.08–1.19, I2 = 0%, p = 0.09) versus glyburide-exposed neonates. Glyburide-exposed neonates had a nonsignificant increase in total fat mass (103.2 g, 95% CI −3.91 to 210.31, p = 0.06) and increased abdominal (0.90 cm, 95% CI 0.03–1.77, p = 0.04) and chest circumferences (0.80 cm, 95% CI 0.07–1.53, p = 0.03) versus insulin-exposed neonates. Metformin-exposed neonates had decreased ponderal index (−0.13 kg/m3, 95% CI −0.26 to −0.00, p = 0.04) and reduced head (−0.21, 95% CI −0.39 to −0.03, p = 0.03) and chest circumferences (−0.34 cm, 95% CI −0.62 to −0.05, p = 0.02) versus the insulin-treated group. Metformin-exposed neonates had decreased ponderal index (−0.09 kg/m3, 95% CI −0.17 to −0.01, p = 0.03) versus glyburide-exposed neonates. Study limitations include heterogeneity in dosing, heterogeneity in GDM diagnostic criteria, and few studies reporting longitudinal growth outcomes.

Conclusions

Maternal randomisation to glyburide resulted in heavier neonates with a propensity to increased adiposity versus insulin- or metformin-exposed groups. Metformin-exposed neonates were lighter with reduced lean mass versus insulin- or glyburide-exposed groups, independent of maternal glycaemic control. Oral anti-hyperglycaemics cross the placenta, so effects on fetal anthropometry could result from direct actions on the fetus and/or placenta. We highlight a need for further studies examining the effects of intrauterine exposure to antidiabetic agents on longitudinal growth, and the importance of monitoring fetal growth and maternal glycaemic control when treating GDM. This review protocol was registered with PROSPERO (CRD42019134664/CRD42018117503).

Klíčová slova:

Anthropometry – Birth weight – Diabetes mellitus – Insulin – Metaanalysis – Neonates – Pregnancy – Weight gain


Zdroje

1. Melchior H, Kurch-Bek D, Mund D. The prevalence of gestational diabetes. Dtsch Artztebl Int. 2017;144: 412–8.

2. International Diabetes Federation. IDF diabetes atlas. 8th edition. Brussels: International Diabetes Federation; 2017.

3. Farrar D. Hyperglycemia in pregnancy: prevalance, impact and management challenges. Int J Womens Health 2016;8: 519–27. doi: 10.2147/IJWH.S102117 27703397

4. Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab. 2015;66: 14–20.

5. Sridhar SB, Ferrara A, Ehrlich SF, Brown SD, Hedderson MM. Risk of large-for-gestational-age newborns in women with gestational diabetes by race and ethnicity and body mass index categories. Obstet Gynecol. 2013;121: 1255–62. https://doi.org/10.1097/AOG.0b013e318291b15c 23812460

6. Mitanchez D. Foetal and neonatal complications in gestational diabetes: perinatal morbidity, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal complications. Diabetes Metab. 2010;36: 617–27. doi: 10.1016/j.diabet.2010.11.013 21163425

7. Cordero L, Paetow P, Landon MB, Nankervis CA. Neonatal outcomes of macrosomic infants of diabetic and non-diabetic mothers. J Neonatal Perinat Med. 2015;8: 105–12.

8. Weissmann-Brenner A, Simchen MJ, Zilberberg E, Kalter A, Weisz B, Achiron R, et al. Maternal and neonatal outcomes of large for gestational age pregnancies. Acta Obstet Gynecol Scand. 2012;91: 844–49. https://doi.org/10.1111/j.1600-0412.2012.01412.x 22471810

9. Krishnaveni GV, Yajnik CS. Foetal programming in a diabetic pregnancy: long term implications for the offspring. Curr Sci. 2017;113: 1321–6.

10. Damm P, Houshmand-Oeregaard A, Kelstrup L, Lauenborg J, Mathiesen ER, Clausen TD. Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia. 2016;59: 1396–99. doi: 10.1007/s00125-016-3985-5 Epub 2016 May 12. 27174368

11. Mendez-Figueroa H, Schuster M, Maggio L, Pedroza C, Chauhan SP, Paglia MJ. Gestational Diabetes Mellitus and Frequency of Blood Glucose Monitoring: A Randomized Controlled Trial. Obstet Gynecol. 2017;130: 163–70. doi: 10.1097/AOG.0000000000002101 28594772

12. Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358: 1991–2002. https://doi.org/10.1056/NEJMoa0707943 18463375

13. Nicholson W, Baptiste-Roberts K. Oral hypoglycaemic agents during pregnancy: The evidence for effectiveness and safety. Best Pract Res Clin Obstet Gynaecol. 2011;25: 51–63. https://doi.org/10.1016/j.bpobgyn.2010.10.018 21251886

14. Management of Diabetes in Pregnancy. Diabetes Care 2017;40(Suppl. 1): S114–S119. doi: 10.2337/dc17-S016 27979900

15. Committee on Practice Bulletins: Obstetrics. Practice Bulletin No.180: gestational diabetes mellitus. Obstet Gynecol 2017;130: e17–37. doi: 10.1097/AOG.0000000000002159 28644336

16. Clinical Practice Guidelines: Diabetes and Pregnancy Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013;37: S168–S183.

17. Society for Maternal-Fetal Medicine W, DC. SMFM Statement: Pharmacological treatment of gestational diabetes. Am J Obstet Gynecol. 2018;218: B2–B4.

18. National Institute for Health and Care Excellence. Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. NICE guideline [NG3]. London: National Institute for Health and Care Excellence; 2015 [cited 2020 Feb 1]. https://www.nice.org.uk/guidance/ng3

19. Ministry of Health. Diabetes in Pregnancy: Quick reference guide for health professionals on the screening, diagnosis and treatment of gestational diabetes in New Zealand. Wellington: Ministry of Health; 2014.

20. Nankervis A, Conn J. Gestational diabetes mellitus. Negiotiating the confusion. Australian Family Physician. 2013;42: 528–31. 23971059

21. Cho HY, Jung I, Kim SJ. The association between maternal hyperglycaemia and peritnatal outcomes in gestational diabetes mellitus patients: A retrospective cohort study. Medicine (Baltimore) 2016;95: e4712.

22. Charles B, Norris R, Xiao X, Hague W. Population pharmacokinetics of metformin in late pregnancy. Ther Drug Monit. 2006;28: 67–72. doi: 10.1097/01.ftd.0000184161.52573.0e 16418696

23. Eyal S, Easterling TR, Carr D, Umans JG, Miodovnik M, Hankins GD, et al. Pharmacokinetics of metformin during pregnancy. Drug Metab Disposition. 2010;38: 833–40. https://doi.org/10.1124/dmd.109.031245 20118196

24. Vanky E, Zahlsen K, Spigset O, Carlsen SM (2005) Placental passage of metformin in women with polycystic ovary syndrome. Fertil Steril. 2005;83: 1575–8. doi: 10.1016/j.fertnstert.2004.11.051 15866611

25. Hebert MF, Ma X, Naraharisetti SB, Krudys KM, Umans JG, Hankins GD et al. Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice. Clin Pharmacol Ther 2009;85: 607–14. doi: 10.1038/clpt.2009.5 Epub 2009 Mar 18. 19295505

26. Pollex EK, Feig DS, Koren G. Oral hypoglycemic therapy: understanding the mechanisms of transplacental transfer. J Matern Fetal Neonatal Med. 2010;23: 224–8. doi: 10.3109/14767050903550881 20064105

27. Kimber-Trojnar Ż, Marciniak B, Patro-Malysza J, Skorzynska-Dziduszko K, Poniedzialek-Czajkowska E, Mierzynski R et al. Is glyburide safe in pregnancy? Curr Pharm Biotechnol. 2014;15: 100–112. doi: 10.2174/1389201015666140330200254 24720590

28. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Int Med. 2009;151: 264–9. https://doi.org/10.7326/0003-4819-151-4-200908180-00135 19622511

29. Tarry-Adkins JL, Aiken CE, Ozanne SE. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: a systematic review and meta-analysis. PLoS Med 2019. 16: e1002848. doi: 10.1371/journal.pmed.1002848 eCollection 2019 Aug. 31386659

30. Arshad R, Khanam S, Shaikh F, Karim N. Feto-maternal outcomes and Glycemic control in Metformin versus insulin treated Gestational Diabetics. Pak J Med Sci. 2017;33: 1182–7. https://doi.org/10.12669/pjms.335.13286 29142561

31. Ashoush S, El-Said M, Fathi H, Abdelnaby M. Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus. J Obstet Gynaecol Res. 2016;42: 640–7. https://doi.org/10.1111/jog.12950 26992090

32. Mirzamoradi M, Heidar Z, Faalpoor Z, Naeiji Z, Jamali R.Comparison of glyburide and insulin in women with gestational diabetes mellitus and associated perinatal outcome: a randomised clinical trial. Acta Med Iran. 2015;53: 97–103. 25725178

33. Ijas H, Vaarasmaki M, Morin-Papunen L, Keravuo R, Ebeling T, Saarela T, et al. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG. 2011;118: 880–5. https://doi.org/10.1111/j.1471-0528.2010.02763.x 21083860

34. Tertti K, Ekblad U, Koskinen P, Vahlberg T, Ronnemaa T. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes, Obesity Metab. 2013;15: 246–51. https://doi.org/10.1111/dom.12017 23020608

35. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med, 2000; 343: 1134–8. doi: 10.1056/NEJM200010193431601 11036118.

36. Bertini AM, Silva JC, Taborda W, Becker F, Lemos Bebber FR, Zucco Viesi JM et al. Perinatal outcomes and the use of oral hypoglycemic agents. J Perinat Med. 2005;33: 519–523. doi: 10.1515/JPM.2005.092 16318615

37. Silva JC, Bertini AM, Taborda W, Becker F, Bebber FR, Aquim GM et al. Glibenclamide in the treatment for gestational diabetes mellitus in a compared study to insulin. Arq Bras Endocrinol Metabol. 2007;51:541–6. doi: 10.1590/s0004-27302007000400007 17684614

38. Silva JC, Pacheco C, Bizato J, de Souza BV, Ribeiro TE, Bertini AM. Metformin compared with glyburide for the management of gestational diabetes. Int J Gynaecol Obstet. 2010;111: 37- doi: 10.1016/j.ijgo.2010.04.028 20542272

39. Silva JC, Fachin DR, Coral ML, Bertini AM. Perinatal impact of the use of metformin and glyburide for the treatment of gestational diabetes mellitus. J Perinat Med. 2012;40: 225–8. doi: 10.1515/jpm-2011-0175 22505499

40. Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, Akbari S. Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Diabetes Res Clin Pract. 2012;98: 422–9. https://doi.org/10.1016/j.diabres.2012.09.031 23068960

41. Borg H.S, Ezat S. Metformin Opposed to Insulin in the Management of Gestational Diabetes. Res Obstet Gynecol. 2016;4: 17–26.

42. Somani PS, Sahana PK, Chaudhuri P, Sengupta N. Treatment of gestational diabetes mellitus: Insulin or metformin? J Evol Med Dent Sci. 2016;5: 4423–9.

43. 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: 2003–15. https://doi.org/10.1056/NEJMoa0707193 18463376

44. Spaulonci CP, Bernardes LS, Trindade TC, Zugaib M, Francisco RP. Randomised trial of metformin vs insulin in the management of gestational diabetes. Am J Obstet Gynecol 2013;209: e1–e7.

45. Saleh HS, Abdelsalam WA, Mowafy HE, Abd ElHameid AA. Could Metformin Manage Gestational Diabetes Mellitus instead of Insulin? Int J Reprod Med. 2016;2016: 3480629. https://doi.org/10.1155/2016/3480629 27597988

46. R Core Team. R: a language and environment for statistical computing. Version 3.5.1. Vienna: R Foundation for Statistical Computing; 2018. https://www.R-project.org/.

47. Ijas H, Vaarasmaki M, Saarela T, Keravuo R, Raudaskoski T. A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. BJOG. 2015;122: 994–1000. https://doi.org/10.1111/1471-0528.12964 25039582

48. Tertti K, Laine K, Ekblad U, Rinne V, Ronnemaa T. The degree of fetal metformin exposure does not influence fetal outcome in gestational diabetes mellitus. Acta Diabetol. 2014;51: 731–8. https://doi.org/10.1007/s00592-014-0570-6 24633859

49. Tertti K, Toppari J, Virtanen HE, Sadov S, Ronnemaa T. Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes. Review Diabet Stud. 2016;13: 59–65.

50. Senat MV, Affres H, Letourneau A, Coustols-Valat M, Cazaubiel M, Legardeur et al. Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial. JAMA 2018;319: 1773–1780. doi: 10.1001/jama.2018.4072 29715355

51. Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU)—Body composition at 2 years of age. Diabetes Care. 2011;34: 2279–84. https://doi.org/10.2337/dc11-0660 21949222

52. Rowan JA, Rush EC, Plank LD, Lu J, Obolonkin V, Coat S, et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7–9 years of age. BMJ Open. 2018;6: e000456. doi: 10.1136/bmjdrc-2017-000456 29682291

53. Lain KY, Garabedian MJ, Daftary A, Jeyabalan A. Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared with insulin. Am J Obstet Gynecol, 2009;200: e1–e6. doi: 10.1016/j.ajog.2009.02.038 19375570

54. Moore LE, Briery CM, Clokey D, Martin RW, Williford NJ, Bofill JA et al. Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. J Reprod Med. 2007;52: 1011–5. 18161398

55. Moore LE, Clokey D, Rappaport VJ, Curet LB. Metformin compared with glyburide in gestational diabetes: a randomized controlled trial. Obstet Gynecol. 2010;115: 55–9. doi: 10.1097/AOG.0b013e3181c52132 20027034

56. Hassan JA, Karim N, Sheikh Z. Metformin prevents macrosomia and neonatal morbidity in gestational diabetes. Pak J Med Sci. 2012;28: 384–9.

57. Khan RMA, Mukhtar A, Khawar A. Comparison of metformin with insulin in the management of gestational diabetes. Medical Forum Monthly. 2017;28: 105–9.

58. Mukhopadhyay P, Bag T, Kyal A, Saha DP, Khalid N. Oral hypoglycemic glibenclamide: Can it be a substitute to insulin in the management of gestational diabetes mellitus? A comparative study. JSAFOG. 2012;4: 28–31.

59. Tempe A, Mayanglambam RD. Glyburide as treatment option for gestational diabetes mellitus. J Obstet Gynaecol Res. 2013;39: 1147–52. doi: 10.1111/jog.12042 23718748

60. Pollex EK, Feig DS, Lubetsky A, Yip PM, Koren G. Insulin glargine safety in pregnancy. Diabetes Care. 2010;33: 29–33. doi: 10.2337/dc09-1045 19808914

61. Suffecool K, Rosenn B, Niederkofler EE, Kiernan UA, Foroutan J, Antwi K, et al. Insulin determir does not cross human placenta. Diabetes Care. 2015;38: e20–e21. doi: 10.2337/dc14-2090 25614695

62. Schwartz RA, Rosenn B, Aleksa K, Koren G. Glyburide transport across the human placenta. Obstet Gynecol. 2015;125: 583–8. doi: 10.1097/AOG.0000000000000672 25730219

63. Fowden AL, Hughes P, Comline RS. The effects of insulin on the growth rate of the sheep fetus during late gestation. Q J Exp Physiol. 1989;74: 703–714. doi: 10.1113/expphysiol.1989.sp003322 2687925

64. Lee N, Hebert MF, Prasad B, Easterling TR, Kelly EJ, Unadkat JD, et al. Effect of gestational age on mRNA and protein expression of polyspecific organic cation transporters during pregnancy. Drug Metab Dispos. 2013;41: 2225–32. https://doi.org/10.1124/dmd.113.054072 24101703

65. Lee N, Hebert MF, Wagner DJ, Easterling TR, Liang CJ, Rice K, et al. Organic cation transporter 3 facilitates fetal exposure of metformin during pregnancy. Mol Pharmacol. 2018;94: 1125–31. doi: 10.1124/mol.118.112482 30012584

66. Howell JJ, Hellberg K, Turner M, Talbott G, Kolar MJ, Ross DS, et al. Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex. Cell Metab. 2017;25: 463–471. https://doi.org/10.1016/j.cmet.2016.12.009 28089566

67. Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, et al. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011;71: 4366–72. https://doi.org/10.1158/0008-5472.CAN-10-1769 21540236

68. Jansson N, Rosario FJ, Gaccioli F, Lager S, Jones HN, Roos S, et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab. 2013;98: 105–13. https://doi.org/10.1210/jc.2012-2667 23150676

69. Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348: 607–14. 10839993

70. Hay WW Jr, Meznarich HK, DiGiacomo JE, Hirst K, Zerbe G. Effects of insulin and glucose concentrations on glucose utilization in fetal sheep. Pediatr Res. 1988;23: 381–7. doi: 10.1203/00006450-198804000-00008 3287321

71. Reynolds RM, Denison FC, Juszczak E, Bell JL, Penneycard J, Strachan MWJ, et al. Glibenclamide and MetfoRmin versus standard care in gEstational diabetes (GRACES): a feasibility open label randomised trial. BMC Pregnancy Childbirth. 2017;17: 1–9.

72. Moucheraud C, Lenz C, Latkovic M, Wirtz VW. The costs of diabetes treatment in low-and middle income countries: a systematic review. BMJ Glob Health. 2019;4: e001258. https://doi.org/10.1136/bmjgh-2018-001258 30899566

Štítky
Interní lékařství

Článek vyšel v časopise

PLOS Medicine


2020 Číslo 5

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×