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Current Diabetes Reviews

Author(s): Fabiana Savoia, Giulia Muscettola, Stamatina Iliodromiti and Elena Greco*

DOI: 10.2174/1573399818666220426085843

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Open Questions on Gestational Diabetes Mellitus in Twin Pregnancies

Article ID: e260422204032 Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: The concurrent, recent increase in prevalence of Gestational Diabetes Mellitus (GDM) and twin pregnancy, in combination with the shared risk factors, has led to speculation that multiples are a risk factor for GDM and, GDM may contribute to twin complications. Twin pregnancies have different physiology and greater obstetric risks compared to singletons, including prematurity and growth restriction. However, in twins methods of GDM screening, thresholds for diagnosis and treatment, as well as glycaemic control targets, have been predominantly extrapolated from singletons. Studies investigating the impact of GDM on pregnancy outcomes in twin pregnancies are conflicting.

Objective: To provide a comprehensive, critical overview of evidence on GDM in twin pregnancies with an emphasis on prevalence, methods of screening, thresholds for diagnosis, risk of pregnancy complications and the impact of treatment on perinatal outcomes.

Methods: Review of retrospective and prospective cohort, case-control, and case-series studies on twin pregnancies with GDM published between 1980 and 2021.

Results: Glucose tolerance in twin pregnancies is poorly studied. Specific guidance for screening, diagnosis, and treatment of GDM in twins is lacking. Studies evaluating pregnancy outcomes in twins with GDM are few and heterogeneous. The absolute risk of maternal complications is greater in twins with GDM compared to singletons; conversely, differences in risks between twins with and without GDM may be due to maternal confounders rather than to GDM. Most studies agree on a positive effect of GDM on neonatal outcomes in twins, likely mediated by the hyperglycaemia improving fetal growth. The impact of lifestyle-measures versus medical management on pregnancy outcomes in twins with GDM is unknown.

Conclusion: Larger longitudinal studies evaluating glucose tolerance, pregnancy outcomes and the impact of treatment both in mono and di-chorionic twins with GDM are warranted to gain further insight into the pathophysiology of this condition and guide optimal management.

Keywords: Gestational diabetes, twins, multiple pregnancy, morbidity, outcomes, complications, perinatal

[1]
Collins J. Global epidemiology of multiple birth. Reprod Biomed Online 2007; 15 (Suppl. 3): 45-52.
[http://dx.doi.org/10.1016/S1472-6483(10)62251-1] [PMID: 18598609]
[2]
Kiely JL, Kiely M. Epidemiological trends in multiple births in the United States, 1971-1998. Twin Res 2001; 4(3): 131-3.
[http://dx.doi.org/10.1375/twin.4.3.131] [PMID: 11665309]
[3]
Roberts WE, Morrison JC, Hamer C, Wiser WL. The incidence of preterm labor and specific risk factors. Obstet Gynecol 1990; 76(1) (Suppl.): 85S-9S.
[PMID: 2359586]
[4]
Spellacy WN, Handler A, Ferre CD. A case-control study of 1253 twin pregnancies from a 1982-1987 perinatal data base. Obstet Gynecol 1990; 75(2): 168-71.
[PMID: 2300344]
[5]
Luke B, Brown MB, Hediger ML, Misiunas RB, Anderson E. Perinatal and early childhood outcomes of twins versus triplets. Twin Res Hum Genet 2006; 9(1): 81-8.
[http://dx.doi.org/10.1375/twin.9.1.81] [PMID: 16611472]
[6]
ACOG Practice Bulletin No. 180. Gestational diabetes mellitus. Obstet Gynecol 2017; 130(1): e17-37.
[7]
Giannakou K, Evangelou E, Yiallouros P, et al. Risk factors for gestational diabetes: An umbrella review of meta-analyses of observational studies. PLoS One 2019; 14(4)e0215372
[http://dx.doi.org/10.1371/journal.pone.0215372] [PMID: 31002708]
[8]
Benhalima K, Van Crombrugge P, Moyson C, et al. Risk factor screening for gestational diabetes mellitus based on the 2013 WHO criteria. Eur J Endocrinol 2019; 180(6): 353-63.
[http://dx.doi.org/10.1530/EJE-19-0117] [PMID: 31120231]
[9]
González González NL, Goya M, Bellart J, et al. Obstetric and perinatal outcome in women with twin pregnancy and gestational diabetes. J Matern Fetal Neonatal Med 2012; 25(7): 1084-9.
[http://dx.doi.org/10.3109/14767058.2011.622009] [PMID: 21919552]
[10]
Buhling KJ, Henrich W, Starr E, et al. Risk for gestational diabetes and hypertension for women with twin pregnancy compared to singleton pregnancy. Arch Gynecol Obstet 2003; 269(1): 33-6.
[http://dx.doi.org/10.1007/s00404-003-0483-z] [PMID: 12682848]
[11]
Hiersch L, Berger H, Okby R, et al. Incidence and risk factors for gestational diabetes mellitus in twin versus singleton pregnancies. Arch Gynecol Obstet 2018; 298(3): 579-87.
[http://dx.doi.org/10.1007/s00404-018-4847-9] [PMID: 29971559]
[12]
Moses RG, Webb AJ, Lucas EM, Davis WS. Twin pregnancy outcomes for women with gestational diabetes mellitus compared with glucose tolerant women. Aust N Z J Obstet Gynaecol 2003; 43(1): 38-40.
[http://dx.doi.org/10.1046/j.0004-8666.2003.00015.x] [PMID: 12755345]
[13]
Rauh-Hain JA, Rana S, Tamez H, et al. Risk for developing gestational diabetes in women with twin pregnancies. J Matern Fetal Neonatal Med 2009; 22(4): 293-9.
[http://dx.doi.org/10.1080/14767050802663194] [PMID: 19340713]
[14]
Lai FY, Johnson JA, Dover D, Kaul P. Outcomes of singleton and twin pregnancies complicated by pre-existing diabetes and gestational diabetes: A population-based study in Alberta, Canada, 2005-11. J Diabetes 2016; 8(1): 45-55.
[http://dx.doi.org/10.1111/1753-0407.12255] [PMID: 25496644]
[15]
Wang YA, Nikravan R, Smith HC, Sullivan EA. Higher prevalence of gestational diabetes mellitus following assisted reproduction technology treatment. Hum Reprod 2013; 28(9): 2554-61.
[http://dx.doi.org/10.1093/humrep/det270] [PMID: 23814097]
[16]
Retnakaran R, Shah BR. Impact of twin gestation and fetal sex on maternal risk of diabetes during and after pregnancy. Diabetes Care 2016; 39(8): e110-1.
[http://dx.doi.org/10.2337/dc16-0825] [PMID: 27222507]
[17]
Yogev Y, Eisner M, Hiersch L, Hod M, Wiznitzer A, Melamed N. The performance of the screening test for gestational diabetes in twin versus singleton pregnancies. J Matern Fetal Neonatal Med 2014; 27(1): 57-61.
[http://dx.doi.org/10.3109/14767058.2013.799660] [PMID: 23617682]
[18]
Henderson CE, Scarpelli S, LaRosa D, Divon MY. Assessing the risk of gestational diabetes in twin gestation. J Natl Med Assoc 1995; 87(10): 757-8.
[PMID: 7473851]
[19]
Cho HJ, Shin JS, Yang JH, et al. Perinatal outcome in twin pregnancies complicated by gestational diabetes mellitus: A comparative study. J Korean Med Sci 2006; 21(3): 457-9.
[http://dx.doi.org/10.3346/jkms.2006.21.3.457] [PMID: 16778389]
[20]
Morikawa M, Yamada T, Akaishi R, et al. Prevalence of hyperglycaemia in singleton versus twin pregnancy. Diabetes Metab Res Rev 2015; 31(2): 198-203.
[http://dx.doi.org/10.1002/dmrr.2586] [PMID: 25066690]
[21]
Hazan Y, Blickstein I. Diabetes and multiple pregnancies Textbook of Diabetes and Pregnancy. London: Martin Dunitz 2003; pp. 502-7.
[22]
Okby R, Weintraub AY, Sergienko R, Eyal S. Gestational diabetes mellitus in twin pregnancies is not associated with adverse perinatal outcomes. Arch Gynecol Obstet 2014; 290(4): 649-54.
[http://dx.doi.org/10.1007/s00404-014-3272-y] [PMID: 24823995]
[23]
McGrath RT, Hocking SL, Scott ES, Seeho SK, Fulcher GR, Glastras SJ. Outcomes of twin pregnancies complicated by gestational diabetes: A meta-analysis of observational studies. J Perinatol 2017; 37(4): 360-8.
[http://dx.doi.org/10.1038/jp.2016.254] [PMID: 28079866]
[24]
Poulain C, Duhamel A, Garabedian C, et al. Outcome of twin pregnancies associated with glucose intolerance. Diabetes Metab 2015; 41(5): 387-92.
[http://dx.doi.org/10.1016/j.diabet.2014.12.005] [PMID: 25636580]
[25]
Hod M, Asatiani N, Elphick A, et al. Twinning project: Israel and Georgia--the birth of a diabetes-in-pregnancy centre in Georgia. Diabet Med 1999; 16(8): 645-9.
[http://dx.doi.org/10.1046/j.1464-5491.1999.00114.x] [PMID: 10477208]
[26]
Luo ZC, Simonet F, Wei SQ, Xu H, Rey E, Fraser WD. Diabetes in pregnancy may differentially affect neonatal outcomes for twins and singletons. Diabet Med 2011; 28(9): 1068-73.
[http://dx.doi.org/10.1111/j.1464-5491.2011.03366.x] [PMID: 21679236]
[27]
Simões T, Queirós A, Correia L, Rocha T, Dias E, Blickstein I. Gestational diabetes mellitus complicating twin pregnancies. J Perinat Med 2011; 39(4): 437-40.
[http://dx.doi.org/10.1515/jpm.2011.048] [PMID: 21728916]
[28]
Cheng AY. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Introduction. Can J Diabetes 2013; 37 (Suppl. 1): S1-3.
[http://dx.doi.org/10.1016/j.jcjd.2013.01.009] [PMID: 24070926]
[29]
Schwartz DB, Daoud Y, Zazula P, et al. Gestational diabetes mellitus: Metabolic and blood glucose parameters in singleton versus twin pregnancies. Am J Obstet Gynecol 1999; 181(4): 912-4.
[http://dx.doi.org/10.1016/S0002-9378(99)70324-8] [PMID: 10521752]
[30]
Xiong QF, Yu ZH, Zhang AL, Zhu XH. Impact of maternal age on perinatal outcomes in twin pregnancies: A systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2022; 26(1): 99-109.
[PMID: 35049025]
[31]
Dimitris MC, Kaufman JS, Bodnar LM, Platt RW, Himes KP, Hutcheon JA. Gestational diabetes in twin versus singleton pregnancies with normal weight or overweight pre-pregnancy body mass index: The mediating role of mid-pregnancy weight gain. Epidemiology 2022; 33(2): 278-86.
[http://dx.doi.org/10.1097/EDE.0000000000001454] [PMID: 34907972]
[32]
Spellacy WN, Buhi WC, Birk SA. Carbohydrate metabolism in women with a twin pregnancy. Obstet Gynecol 1980; 55(6): 688-91.
[PMID: 6992002]
[33]
Dwyer PL, Oats JN, Walstab JE, Beischer NA. Glucose tolerance in twin pregnancy. Aust N Z J Obstet Gynaecol 1982; 22(3): 131-4.
[http://dx.doi.org/10.1111/j.1479-828X.1982.tb01425.x] [PMID: 6959610]
[34]
Moodley SP, Jialal I, Moodley J, Naicker RS, Marivate M. Carbohydrate metabolism in African women with twin pregnancy. Diabetes Care 1984; 7(1): 72-4.
[http://dx.doi.org/10.2337/diacare.7.1.72] [PMID: 6368153]
[35]
Naidoo L, Jailal I, Moodley J, Desai R. Intravenous glucose tolerance tests in women with twin pregnancy. Obstet Gynecol 1985; 66(4): 500-2.
[PMID: 3900835]
[36]
Ihara M, Mitao M, Yamasaki H, et al. Analysis of glucose tolerance in twin gestations using an oral glucose load. Horm Metab Res 2002; 34(6): 338-40.
[http://dx.doi.org/10.1055/s-2002-33263] [PMID: 12173075]
[37]
Rebarber A, Dolin C, Fields JC, et al. Screening approach for gestational diabetes in twin pregnancies. Am J Obstet Gynecol 2014; 211(6): 639.e1-5.
[http://dx.doi.org/10.1016/j.ajog.2014.08.030] [PMID: 25439813]
[38]
Jung YJ, Kwon JY, Cho HY, Park YW, Kim YH. Comparison of the performance of screening test for gestational diabetes in singleton versus twin pregnancies. Obstet Gynecol Sci 2015; 58(6): 439-45.
[http://dx.doi.org/10.5468/ogs.2015.58.6.439] [PMID: 26623406]
[39]
Liu X, Chen Y, Zhou Q, Shi H, Cheng WW. Utilization of International Association of Diabetes and Pregnancy Study Groups criteria vs. a two-step approach to screening for gestational diabetes mellitus in Chinese women with twin pregnancies. Diabet Med 2015; 32(3): 367-73.
[http://dx.doi.org/10.1111/dme.12636] [PMID: 25407306]
[40]
Dinham GK, Henry A, Lowe SA, et al. Twin pregnancies complicated by gestational diabetes mellitus: A single centre cohort study. Diabet Med 2016; 33(12): 1659-67.
[http://dx.doi.org/10.1111/dme.13076] [PMID: 26802478]
[41]
Kim Y, Hong SY, Kim SY, et al. Obstetric and neonatal outcomes of gestational diabetes mellitus in twin pregnancies according to changes in its diagnostic criteria from national diabetes data group criteria to carpenter and coustan criteria: A retrospective cohort study. BMC Pregnancy Childbirth 2022; 22(1): 9.
[http://dx.doi.org/10.1186/s12884-021-04361-9] [PMID: 34979991]
[42]
Sibai BM, Hauth J, Caritis S, et al. Hypertensive disorders in twin versus singleton gestations. Am J Obstet Gynecol 2000; 182(4): 938-42.
[http://dx.doi.org/10.1016/S0002-9378(00)70350-4] [PMID: 10764477]
[43]
Hiersch L, Berger H, Okby R, et al. Gestational diabetes mellitus is associated with adverse outcomes in twin pregnancies. Am J Obstet Gynecol 2019; 220(1): 102.e1-8.
[http://dx.doi.org/10.1016/j.ajog.2018.10.027] [PMID: 30595142]
[44]
Suzuki S, Igarashi M. Risk factors for preeclampsia in Japanese twin pregnancies: Comparison with those in singleton pregnancies. Arch Gynecol Obstet 2009; 280(3): 389-93.
[http://dx.doi.org/10.1007/s00404-009-0932-4] [PMID: 19151988]
[45]
Guillén MA, Herranz L, Barquiel B, Hillman N, Burgos MA, Pallardo LF. Influence of gestational diabetes mellitus on neonatal weight outcome in twin pregnancies. Diabet Med 2014; 31(12): 1651-6.
[http://dx.doi.org/10.1111/dme.12523] [PMID: 24925592]
[46]
Tward C, Barrett J, Berger H, et al. Does gestational diabetes affect fetal growth and pregnancy outcome in twin pregnancies? Am J Obstet Gynecol 2016; 214(5): 653.e1-8.
[http://dx.doi.org/10.1016/j.ajog.2015.11.006] [PMID: 26596233]
[47]
Sheehan ACM, Umstad MP, Cole S, Cade TJ. Does gestational diabetes cause additional risk in twin pregnancy? Twin Res Hum Genet 2019; 22(1): 62-9.
[http://dx.doi.org/10.1017/thg.2018.72] [PMID: 30661509]
[48]
Mourad M, Too G, Gyamfi-Bannerman C, Zork N. Hypertensive disorders of pregnancy in twin gestations complicated by gestational diabetes. J Matern Fetal Neonatal Med 2019; 16: 1-5.
[PMID: 31096815]
[49]
Hung TH, Hsieh TT, Shaw SH, Seong CK, Chen S. Risk factors and adverse maternal and perinatal outcomes for women with dichorionic twin pregnancies complicated by gestational diabetes mellitus: A retrospective cross-sectional study. J Diabetes Investig 2020.
[PMID: 33064935]
[50]
Shah BR, Retnakaran R, Booth GL. Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care 2008; 31(8): 1668-9.
[http://dx.doi.org/10.2337/dc08-0706] [PMID: 18487472]
[51]
Barchilon-Tiosano L, Sheiner E, Wainstock T, Sergienko R, Okby-Cronin R. Long-term risk for maternal cardiovascular morbidities in twin pregnancies complicated with gestational diabetes mellitus - a retrospective cohort study. J Matern Fetal Neonatal Med 2019; 1-5.
[PMID: 31581869]
[52]
Okby R, Shoham-Vardi I, Sergienko R, Sheiner E. Twin pregnancy: Is it a risk factor for long-term cardiovascular disease? J Matern Fetal Neonatal Med 2016; 29(10): 1626-30.
[PMID: 26429152]
[53]
Piper JM, Xenakis EM, Langer O. Delayed appearance of pulmonary maturation markers is associated with poor glucose control in diabetic pregnancies. J Matern Fetal Med 1998; 7(3): 148-53.
[http://dx.doi.org/10.1002/(SICI)1520-6661(199805/06)7:3<148:AID-MFM9>3.0.CO;2-K] [PMID: 9642613]
[54]
Berkowitz K, Reyes C, Saadat P, Kjos SL. Fetal lung maturation. Comparison of biochemical indices in gestational diabetic and nondiabetic pregnancies. J Reprod Med 1997; 42(12): 793-800.
[PMID: 9437594]
[55]
Foeller ME, Zhao S, Szabo A, Cruz MO. Neonatal outcomes in twin pregnancies complicated by gestational diabetes compared with non-diabetic twins. J Perinatol 2015; 35(12): 1043-7.
[http://dx.doi.org/10.1038/jp.2015.133] [PMID: 26513454]
[56]
Luo ZC, Zhao YJ, Ouyang F, Yang ZJ, Guo YN, Zhang J. Diabetes and perinatal mortality in twin pregnancies. PLoS One 2013; 8(9)e75354
[57]
Klein K, Mailath-Pokorny M, Leipold H, Krampl-Bettelheim E, Worda C. Influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies. Twin Res Hum Genet 2010; 13(4): 393-7.
[http://dx.doi.org/10.1375/twin.13.4.393] [PMID: 20707711]
[58]
Chakravarthy MV, Zhu Y, Wice MB, et al. Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age. Diabetes 2008; 57(10): 2698-707.
[http://dx.doi.org/10.2337/db08-0404] [PMID: 18591393]
[59]
Bouvier D, Forest JC, Blanchon L, et al. Risk factors and outcomes of preterm premature rupture of membranes in a cohort of 6968 pregnant women prospectively recruited. J Clin Med 2019; 8(11): 1987.
[http://dx.doi.org/10.3390/jcm8111987] [PMID: 31731659]
[60]
McElrath TF, Norwitz ER, Robinson JN, Tanasijevic MJ, Lieberman ES. Differences in TDx fetal lung maturity assay values between twin and singleton gestations. Am J Obstet Gynecol 2000; 182(5): 1110-2.
[http://dx.doi.org/10.1067/mob.2000.105437] [PMID: 10819842]
[61]
Leveno KJ, Quirk JG, Whalley PJ, Herbert WN, Trubey R. Fetal lung maturation in twin gestation. Am J Obstet Gynecol 1984; 148(4): 405-11.
[http://dx.doi.org/10.1016/0002-9378(84)90716-6] [PMID: 6695997]
[62]
Ghai V, Vidyasagar D. Morbidity and mortality factors in twins. An epidemiologic approach. Clin Perinatol 1988; 15(1): 123-40.
[http://dx.doi.org/10.1016/S0095-5108(18)30730-9] [PMID: 3286088]
[63]
Friedman SA, Schiff E, Kao L, Kuint J, Sibai BM. Do twins mature earlier than singletons? Results from a matched cohort study. Am J Obstet Gynecol 1997; 176(6): 1193-6.
[http://dx.doi.org/10.1016/S0002-9378(97)70334-X] [PMID: 9215173]
[64]
Tshiyombo TD, Oulton MR. Comparative effects of chronic exposure to glucose or sodium butyrate on surfactant development in fetal rabbits. J Perinat Med 2001; 29(6): 476-85.
[http://dx.doi.org/10.1515/JPM.2001.067] [PMID: 11776678]
[65]
Engle MJ, Langan SM, Sanders RL. The effects of insulin and hyperglycemia on surfactant phospholipid synthesis in organotypic cultures of type II pneumocytes. Biophys Acta 1983; 753(1): 6-13.
[http://dx.doi.org/10.1016/0005-2760(83)90091-7]
[66]
Bourbon JR, Farrell PM. Fetal lung development in the diabetic pregnancy. Pediatr Res 1985; 19(3): 253-67.
[http://dx.doi.org/10.1203/00006450-198503000-00001] [PMID: 3885150]
[67]
Fox NS, Gerber RS, Saltzman DH, et al. Glycemic control in twin pregnancies with gestational diabetes: Are we improving or worsening outcomes? J Matern Fetal Neonatal Med 2015; 1-5. Early Online
[http://dx.doi.org/10.3109/14767058.2015.1087498] [PMID: 25938874]
[68]
Akiba Y, Miyakoshi K, Ikenoue S, et al. Glycemic and metabolic features in gestational diabetes: Singleton versus twin pregnancies. Endocr J 2019; 66(7): 647-51.
[http://dx.doi.org/10.1507/endocrj.EJ18-0575] [PMID: 31019153]
[69]
Fox NS, Rebarber A, Klauser CK, Roman AS, Saltzman DH. Intrauterine growth restriction in twin pregnancies: Incidence and associated risk factors. Am J Perinatol 2011; 28(4): 267-72.
[http://dx.doi.org/10.1055/s-0030-1270116] [PMID: 21128199]