Diabetes and Pregnancy

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee

David Thompson MD, FRCPC Howard Berger MD Denice Feig MD, MSc, FRCPC Robert Gagnon MD, FRCSC Tina Kader MD, FRCPC Erin Keely MD, FRCPC Sharon Kozak BSN Edmond Ryan MD, FRCPC Mathew Sermer MD, FRCSC Christina Vinokuroff PDt

  • Key Messages
  • Recommendations
  • Figures
  • Highlights
  • Full Text
  • References

Key Messages

Pregestational Diabetes

  • All women with pre-existing type 1 or type 2 diabetes should receive preconception care to optimize glycemic control, assess complications, review medications and begin folate supplementation.
  • Care by an interdisciplinary diabetes healthcare team composed of diabetes nurse educators, dietitians, obstetricians and diabetologists, both prior to conception and during pregnancy, has been shown to minimize maternal and fetal risks in women with pre-existing type 1 or type 2 diabetes.

Gestational Diabetes Mellitus

  • The diagnostic criteria for gestational diabetes mellitus (GDM) remain controversial; however, the committee has chosen a preferred approach and an alternate approach. The preferred approach is to begin with a 50 g glucose challenge test and, if appropriate, proceed with a 75 g oral glucose tolerance test, making the diagnosis of GDM if ≥1 value is abnormal (fasting ≥5.3 mmol/L, 1 hour ≥10.6 mmol/L, 2 hours ≥9.0 mmol/L). The alternate approach is a 1-step approach of a 75 g oral glucose tolerance test, making the diagnosis of GDM if ≥1 value is abnormal (fasting ≥5.1 mmol/L, 1 hour ≥10.0 mmol/L, 2 hours ≥8.5 mmol/L).
  • Untreated GDM leads to increased maternal and perinatal morbidity, while treatment is associated with outcomes similar to control populations.

Highlights of Revisions

  • All recommendations have been updated and reorganized to clarify management considerations for women with pregestational or gestational diabetes in the prepregnancy period, during pregnancy, and in the intrapartum and postpartum periods.
  • New criteria have been added for the screening and diagnosis of GDM (Figures 1 and 2).

Figure 1
Preferred approach for the screening and diagnosis of gestational diabetes.

1hPG, 1-hour plasma glucose; 2hPG, 2-hour plasma glucose; FPG, fasting plasma glucose; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test; PG, plasma glucose.

Figure 2
Alternative approach for the screening and diagnosis of gestational diabetes.

1hPG, 1-hour plasma glucose; 2hPG, 2-hour plasma glucose; FPG, fasting plasma glucose; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test; PG, plasma glucose.

Recommendations

Pregestational Diabetes

Preconception care

  1. 1.All women of reproductive age with type 1 or type 2 diabetes should receive advice on reliable birth control, the importance of glycemic control prior to pregnancy, the impact of BMI on pregnancy outcomes, the need for folic acid and the need to stop potentially embryopathic drugs prior to pregnancy [Grade D, Level 4 (1)].
  2. 2.Women with type 2 diabetes and irregular menses/PCOS who are started on metformin or a thiazolidinedione should be advised that fertility may improve and be warned about possible pregnancy [Grade D, Consensus].
  3. 3.Before attempting to become pregnant, women with type 1 or type 2 diabetes should:
    1. a.Receive preconception counselling that includes optimal diabetes management and nutrition, preferably in consultation with an interdisciplinary pregnancy team to optimize maternal and neonatal outcomes [Grade C, Level 3 (2,3)]
    2. b.Strive to attain a preconception A1C ≤7.0% (or A1C as close to normal as can safely be achieved) to decrease the risk of:
      1. Spontaneous abortion [Grade C, Level 3 (4)]
      2. Congenital anomalies [Grade C, Level 3 (3–6)]
      3. Preeclampsia [Grade C, Level 3 (7,8)]
      4. Progression of retinopathy in pregnancy [Grade A, Level 1, for type 1 diabetes (9) ; Grade D, Consensus, for type 2 diabetes]
    3. c.Supplement their diet with multivitamins containing 5 mg folic acid at least 3 months preconception and continuing until at least 12 weeks postconception [Grade D, Level 4 (10)]. Supplementation should continue with a multivitamin containing 0.4–1.0 mg folic acid from 12 weeks postconception to 6 weeks postpartum or as long as breastfeeding continues [Grade D, Consensus].
    4. d.Discontinue medications that are potentially embryopathic, including any from the following classes:
      • ACE inhibitors and ARBs prior to conception or upon detection of pregnancy [Grade C, Level 3 (11–13)]
      • Statins [Grade D, Level 4 (14)]
  4. 4.Women with type 2 diabetes who are planning a pregnancy should switch from noninsulin antihyperglycemic agents to insulin for glycemic control [Grade D, Consensus]. Women with pregestational diabetes who also have PCOS may continue metformin for ovulation induction [Grade D, Consensus].

Assessment and management of complications

  1. 5.Women should undergo an ophthalmological evaluation by an eye care specialist [Grade A, Level 1, for type 1 (9,15) ; Grade D, Level 4, for type 2 (16)].
  2. 6.Women should be screened for chronic kidney disease prior to pregnancy (see Chronic Kidney Disease chapter, p. S129) [Grade D, Level 4, for type 1 diabetes (17) ; Grade D, Consensus, for type 2 diabetes]. Women with microalbuminuria or overt nephropathy are at increased risk for development of hypertension and preeclampsia [Grade A, Level 1 (17,18)] and should be followed closely for these conditions [Grade D, Consensus].

Management in pregnancy

  1. 7.Pregnant women with type 1 or type 2 diabetes should:
    1. a.Receive an individualized insulin regimen and glycemic targets typically using intensive insulin therapy [Grade A, Level 1B, for type 1 (19,20) ; Grade A, Level 1, (20) for type 2]
    2. b.Strive for target glucose values:
      • Fasting PG <5.3 mmol/L
      • 1-hour postprandial <7.8 mmol/L
      • 2-hour postprandial <6.7 mmol/L [Grade D, Consensus]
    3. c.Be prepared to raise these targets if needed because of the increased risk of severe hypoglycemia during pregnancy [Grade D, Consensus]
    4. d.Perform SMBG, both pre- and postprandially, to achieve glycemic targets and improve pregnancy outcomes [Grade C, Level 3 (3)]
  2. 8.Women with pregestational diabetes may use aspart or lispro in pregnancy instead of regular insulin to improve glycemic control and reduce hypoglycemia [Grade C, Level 2, for aspart (21) ; Grade C, Level 3, for lispro (22,23)].
  3. 9.Detemir [Grade C, Level 2 (24)] or glargine [Grade C, Level 3 (25)] may be used in women with pregestational diabetes as an alternative to NPH.

Intrapartum glucose management

  1. 10.Women should be closely monitored during labour and delivery, and maternal blood glucose levels should be kept between 4.0 and 7.0 mmol/L in order to minimize the risk of neonatal hypoglycemia [Grade D, Consensus].
  2. 11.Women should receive adequate glucose during labour in order to meet their high-energy requirements [Grade D, Consensus].

Postpartum

  1. 12.Women with pregestational diabetes should be carefully monitored postpartum as they have a high risk of hypoglycemia [Grade D, Consensus].
  2. 13.Metformin and glyburide may be used during breastfeeding [Grade C, Level 3 (26) for metformin; Grade D, Level 4, for glyburide (27)].
  3. 14.Women with type 1 diabetes in pregnancy should be screened for postpartum thyroiditis with a TSH test at 6–8 weeks postpartum [Grade D, Consensus].
  4. 15.All women should be encouraged to breastfeed since this may reduce offspring obesity, especially in the setting of maternal obesity [Grade C, Level 3 (28)].

Gestational Diabetes

Diagnosis

  1. 16.All pregnant women should be screened for GDM at 24–28 weeks of gestation [Grade C, Level 3 (29)].
  2. 17.If there is a high risk of GDM based on multiple clinical factors, screening should be offered at any stage in the pregnancy [Grade D, Consensus]. If the initial screening is performed before 24 weeks of gestation and is negative, rescreen between 24 and 28 weeks of gestation. Risk factors include:
    • Previous diagnosis of GDM
    • Prediabetes
    • Member of a high-risk population (Aboriginal, Hispanic, South Asian, Asian, African)
    • Age ≥35 years
    • BMI ≥30 kg/m 2
    • PCOS, acanthosis nigricans
    • Corticosteroid use
    • History of macrosomic infant
    • Current fetal macrosomia or polyhydramnios [Grade D, Consensus]
  3. 18.The preferred approach for the screening and diagnosis of GDM is the following [Grade D, Consensus]:
    • a.Screening for GDM should be conducted using the 50 g GCT administered in the nonfasting state with PG glucose measured 1 hour later [Grade D, Level 4 (30)]. PG ≥7.8 mmol/L at 1 hour will be considered a positive screen and will be an indication to proceed to the 75 g OGTT [Grade C, Level 2 (31)]. PG ≥11.1 mmol/L can be considered diagnostic of gestational diabetes and does not require a 75 g OGTT for confirmation [Grade C, Level 3 (32)].
    • b.If the GCT screen is positive, a 75 g OGTT should be performed as the diagnostic test for GDM using the following criteria:
      • ≥1 of the following values:
        • Fasting ≥5.3 mmol/L
        • 1 hour ≥10.6 mmol/L
        • 2 hours ≥9.0 mmol/L [Grade B, Level 1 (33)]
  4. 19.An alternative approach that may be used to screen and diagnose GDM is the 1-step approach [Grade D, Consensus]:
    1. a.A 75 g OGTT should be performed (with no prior screening 50 g GCT) as the diagnostic test for GDM using the following criteria [Grade D, Consensus]:
      • ≥1 of the following values:
        • Fasting ≥5.1 mmol/L
        • 1 hour ≥10.0 mmol/L
        • 2 hours ≥8.5 mmol/L [Grade B, Level 1 (33)]

Management during pregnancy

  1. 20.Women with GDM should:
    1. a.Strive for target glucose values:
      1. i.Fasting PG <5.3 mmol/L [Grade B, Level 2 (34)]
      2. ii.1-hour postprandial <7.8 mmol/L [Grade B, Level 2 (35)]
      3. iii.2-hour postprandial <6.7 mmol/L [Grade B, Level 2 (34)]
    2. b.Perform SMBG, both fasting and postprandially, to achieve glycemic targets and improve pregnancy outcomes [Grade B, Level 2 (35)].
    3. c.Avoid ketosis during pregnancy [Grade C, Level 3 (36)].
  2. 21.Receive nutrition counselling from a registered dietitian during pregnancy [Grade C, Level 3 (37)] and postpartum [Grade D, Consensus]. Recommendations for weight gain during pregnancy should be based on pregravid BMI [Grade D, Consensus].
  3. 22.If women with GDM do not achieve glycemic targets within 2 weeks from nutritional therapy alone, insulin therapy should be initiated [Grade D, Consensus].
  4. 23.Insulin therapy in the form of multiple injections should be used [Grade A, Level 1 (20)].
  5. 24.Rapid-acting bolus analogue insulin may be used over regular insulin for postprandial glucose control, although perinatal outcomes are similar [Grade B, Level 2 (38,39)].
  6. 25.For women who are nonadherent to or who refuse insulin, glyburide [Grade B, Level 2 (40–45)] or metformin [Grade B, Level 2 (46)] may be used as alternative agents for glycemic control. Use of oral agents in pregnancy is off-label and should be discussed with the patient [Grade D, Consensus].

Intrapartum glucose management

  1. 26.Women should be closely monitored during labour and delivery, and maternal blood glucose levels should be kept between 4.0 and 7.0 mmol/L in order to minimize the risk of neonatal hypoglycemia [Grade D, Consensus].
  2. 27.Women should receive adequate glucose during labour in order to meet their high-energy requirements [Grade D, Consensus].

Postpartum

  1. 28.Women with GDM should be encouraged to breastfeed immediately after delivery in order to avoid neonatal hypoglycemia [Grade D, Level 4 (47)] and to continue for at least 3 months postpartum in order to prevent childhood obesity [Grade C, Level 3 (48)] and reduce risk of maternal hyperglycemia [Grade C, Level 3 (49)].
  2. 29.Women should be screened with a 75 g OGTT between 6 weeks and 6 months postpartum to detect prediabetes and diabetes [Grade D, Consensus].

Abbreviations:
A1C, glycated hemoglobin; ACE, angiotension-converting enzyme; ARB, angiotensin II receptor blocker; BMI, body mass index; GCT, glucose challenge test; OGTT,  oral glucose tolerance test; PCOS, polycystic ovarian syndrome; PG, plasma glucose; SMBG, self-monitoring of blood glucose; TSH, thyroid-stimulating syndrome.

References

  1. Murphy HR, Roland JM, Skinner TC, et al. Effectiveness of a regional prepregnancy care program in women with type 1 and type 2 diabetes: benefits beyond glycemic control. Diabetes Care 2010;33:2514-20.
  2. Wahabi HA, Alzeidan RA, Bawazeer GA, et al. Preconception care for diabetic women for improving maternal and fetal outcomes: a systematic review and meta-analysis. BMC Pregnancy Childbirth 2010;10:63.
  3. Ray JG, O’Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. QJM 2001;94:435-44.
  4. Inkster ME, Fahey TP, Donnan PT, et al. Poor glycated hemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes mellitus: systematic review of observational studies. BMC Pregnancy Childbirth 2006;6:30.
  5. Suhonen L, Hiilesmaa V, Teramo K. Glycemic control during early pregnancy and fetal malformations in women with type 1 diabetes mellitus. Diabetologia 2000;43:79-82.
  6. Guerin A, Nisenbaum R, Ray JG. Use of maternal GHb concentration to estimate the risk of congenital anomalies in the offspring of women with pre-pregnancy diabetes. Diabetes Care 2007;30:1920-5.
  7. Hiilesmaa V, Suhonen L, Teramo K. Glycaemic control is associated with preeclampsia but not with pregnancy-induced hypertension in women with type 1 diabetes mellitus. Diabetologia 2000;43:1534-9.
  8. Hsu CD, Tan HY, Hong SF, et al. Strategies for reducing the frequency of preeclampsia in pregnancies with insulin-dependent diabetes mellitus. Am J Perinatol 1996;13:265-8.
  9. The Diabetes Control and Complications Trial Research Group. Effect of pregnancy on microvascular complications in the Diabetes Control and Complications Trial. Diabetes Care 2000;23:1084-91.
  10. Wilson RD. Pre-conception vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can 2007;29:1003-26.
  11. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006; 354:2443-51.
  12. Li DK, Yang C, Andrade S, et al. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 2011;343:d5931.
  13. Walfisch A, Al-maawali A, Moretti ME, et al. Teratogenicity of angiotensin converting enzyme inhibitors or receptor blockers. J Obstet Gynaecol 2011;31: 465-72.
  14. Edison RJ, Muenke M. Central nervous system and limb anomalies in case reports of first-trimester statin exposure. N Engl J Med 2004;350:1579-82.
  15. The Diabetes Control and Complications Trial Research Group. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998;116:874-86.
  16. Rasmussen KL, Laugesen CS, Ringholm L, et al. Progression of diabetic retinopathy during pregnancy in women with type 2 diabetes. Diabetologia 2010; 53:1076-e83.
  17. Jensen DM, Damm P, Ovesen P, et al. Microalbuminuria, preeclampsia, and preterm delivery in pregnancy women with type 1 diabetes: results from a nationwide Danish study. Diabetes Care 2010;33:90-4.
  18. Nielsen LR, Damm P, Mathiesen ER. Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy? Diabetes Care 2009;32:38-44.
  19. The Diabetes Control and Complications Trial Research Group. Pregnancy outcomes in the Diabetes Control and Complications Trial. Am J Obstet Gynecol 1996;174:1343-53.
  20. Nachum Z, Ben-Shlomo I, Weiner E, et al. Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. BMJ 1999;319:1223-7.
  21. Mathiesen ER, Kinsley B, Amiel SA, et al. Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women. Diabetes Care 2007;30:771-6.
  22. Chico A, Saigi I, Garcia-Patterson A, et al. Glycemic control and perinatal outcomes of pregnancies complicated by type 1 diabetes: influence of continuous subcutaneous insulin and lispro insulin. Diabetes Tech Ther 2010; 12:937-45.
  23. Durnwald CP, Landon MB. A comparison of lispro and regular insulin for the management of type 1 and type 2 diabetes in pregnancy. J Matern Fetal Neonatal Med 2008;21:309-13.
  24. Mathiesen ER, Hod M, Ivanisevic M, et al. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care 2012; 35:2012-7.
  25. Pollex E, Moreti ME, Koren G, Feig DS. Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis. Ann Pharmacother 2011;45:9-16.
  26. Glueck CJ, Wang P, Kobayashi S, et al. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002;77:520e5.
  27. Feig DS, Briggs GG, Kraemer JM, et al. Transfer of glyburide and glipizide into breast milk. Diabetes Care 2005;28:1851-5.
  28. Mayer-Davis EJ, Rifas-Shiman SL, Zhou L, et al. Breast-feeding and risk for childhood obesity: does maternal diabetes or obesity status matter? Diabetes Care 2006;29:2231-7.
  29. Griffin ME, Coffey M, Johnson H, et al. Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med 2000;17:26-32.
  30. Rey E, Hudon L, Michon N, et al. Fasting plasma glucose versus glucose challenge test: screening for gestational diabetes and cost effectiveness. Clin Biochem 2004;37:780-4.
  31. Sermer M, Naylor CD, Gare DJ, et al. Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project. Am J Obstet Gynecol 1995;173:146-56.
  32. Cheng YW, Esakoff TF, Block-Kurbisch I, et al. Screening or diagnostic: markedly elevated glucose loading test and perinatal outcomes. J Matern Fetal Neonatal Med 2006;19:729-34.
  33. HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;35:1991-2002.
  34. de Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med 1995;333:1237-41.
  35. Rey E, Monier D, Lemonnier MC. Carbohydrate intolerance in pregnancy: incidence and neonatal outcomes. Clin Invest Med 1996;19:406-15.
  36. Rizzo T, Metzger BE, Burns WJ, et al. Correlations between antepartum maternal metabolism and child intelligence. N Engl J Med 1991;325:911-6.
  37. Anderson K, Barbeau M-C, Blagrave P, et al. Recommendations for nutrition best practice in the management of gestational diabetes mellitus. Can J Diet Pract Res 2006;67:206-8.
  38. Mecacci F, Carignani L, Cioni R, et al. Maternal metabolic control and perinatal outcome in women with gestational diabetes treated with regular or lispro insulin: comparison with non-diabetic pregnant women. Eur J Obstet Gynecol Reprod Biol 2003;111:19-24.
  39. Pettitt DJ. Comparison of an insulin analog, insulin aspart, and regular human insulin with no insulin in gestational diabetes mellitus. Diabetes Care 2003;26: 183-6.
  40. Langer O, Conway DL, Berkus MD, et al. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-8.
  41. Chmait R, Dinise T, Moore T. Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus. J Perinatol 2004;24:617-22. 187.
  42. Elliott BD, Schenker S, Langer O, et al. Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer. Am J Obstet Gynecol 1994;171:653. 188.
  43. Kahn BF, Davies JK, Lynch AM, et al. Predictors of glyburide failure in the treatment of gestational diabetes. Obstet Gynecol 2006;107:1303-9.
  44. Bertini AM, Silva JC, Taborda W, et al. Perinatal outcomes and the use of oral hypoglycemic agents. J Perinat Med 2005;33:519-23.
  45. Jacobson GF, Ramos GA, Ching JY, et al. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J Obstet Gynecol 2005;193:118-24.
  46. Rowan JA, Hague WM, Gao W, et al. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003-15.
  47. ChertokI RA, Raz I, Shoham I, et al. Effects of early breastfeeding on neonatal glucose levels of term infants born to women with gestational diabetes. J Hum Nuti Diet 2009;22:166-9.
  48. Schaefer-Graf UM, Hartmann R, Pawliczak J, et al. Association of breast-feeding and early childhood overweight in children from mothers with gestational diabetes mellitus. Diabetes Care 2006;29:1105-7.
  49. Gunderson EP, Hedderson MM, Chiang V, et al. Lactation intensity and postpartum maternal glucose tolerance and insulin resistance in women with recent GDM: the SWIFT cohort. Diabetes Care 2012;35:50-6.

 

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