Pre-conceptional care of women with diabetes
Despite progress in diabetes treatment pregnancies in women with either Type 1 or Type 2 diabetes are still associated with poorer outcomes with respect to healthy nondiabetic women.
A survey conducted in the UK covering a period of 12 years from 1990 to 2002 showed that pregnancy in Type 2 diabetic mothers was associated with an increased risk of infant mortality (2-fold for stillbirth up to 6-fold for death within 1 year) and of congenital malformation (11 times) with respect to nondiabetic mothers in the same geographical area.71
Another study conducted in the Netherlands in the period 199-2000 showed higher rate of perinatal mortality (2.8%), preterm delivery (32.2%), Cesarean section (44.1%) and congenital malformation (8.8%) in pregnant women with Type 1 diabetes related to the referring general population; they also showed an higher incidence of poor outcomes in unplanned pregnancies.72
Elements of an organized program for pre-conceptional care are best based on the various published clinical trials that have been successful in preventing excess spontaneous abortions and major malformations in IDM3,73,74 when a good metabolic control is achieved. The pre-conceptional care is also provided on the basis of a cost-benefit analysis.
The model for diabetes preconception and early pregnancy health care includes four main elements: (1) education of the patient about the interaction between diabetes, pregnancy, and family planning; (2) education in diabetes self-management skills; (3) physician-directed medical care and laboratory testing; and (4) counselling by a mental health professional, when indicated, to reduce stress and improve adherence to the diabetes treatment plan.70
The desired outcome of the preconception phase of care is to lower HbA1c values to a level associated with optimal development during organogenesis. Epidemiological studies indicate that HbA1c test values up to 1% above normal are associated with rates of congenital malformations and spontaneous abortions that are not greater than rates in nondiabetic pregnancies. However, rates of each complication continue to decrease with even lower HbA1c test levels. Thus, the general goal for glycemic management in the preconception period and during the first trimester should be to obtain the lowest HbA1c test level possible without undue risk of hypoglycemia in the mother. In 2003 the ADA stated that the goal for metabolic control in diabetic pregnant should be less than 1% above the upper limit of the normal range.75
To obtain these values, there is need for an appropriate meal plan, self-monitoring of blood glucose (SMBG), self-administration of insulin and self-adjustment of insulin doses, treatment of hypoglycemia (patient and family members), incorporation of physical activity, and development of techniques to reduce stress and cope with denial.70
A complete anamnesis is imperative before planning for pregnancy. This should include, but not be limited to, questioning for duration and type of diabetes (Type 1 or Type 2), acute complications, including history of infections, ketoaci-dosis, and hypoglycemia, chronic complications, including retinopathy, nephropathy, hypertension, atherosclerotic vascular disease, and autonomic and peripheral neuropathy, diabetes management, including insulin regimen, prior or current use of oral glucose-lowering agents, SMBG regimens and results, medical nutrition therapy, and physical activity, concomitant medical conditions and medications, thyroid disease in particular for patients with Type 1 diabetes, menstrual/ pregnancy history; contraceptive use and support system, including family and work environment.70 To minimize the occurrence of malformations, standard care for all women with diabetes who have child-bearing potential should include
(1) counselling about the risk of malformations associated with unplanned pregnancies and poor metabolic control;
(2) use of effective contraception at all times unless the patient is in good metabolic control and actively trying to conceive;70
(3) integration of the patient into the management of her condition; and (4) identification and treatment of complications of diabetes such as retinopathy, nephropathy, and hypertension.76
Diabetic retinopathy, nephropathy, autonomic neuropathy (especially gastroparesis), and coronary artery disease (CAD) can be affected by or can affect the outcome of pregnancy. Thus, physical examination should give particular attention to blood pressure measurement, including testing for orthostatic changes, dilated retinal examination by an ophthalmologist or other eye specialist knowledgeable about diabetic eye disease, and cardiovascular examination for evidence of cardiac or peripheral vascular disease. If found, patients should have screening tests for CAD before attempting pregnancy, to ensure they can tolerate the increased cardiac demands; and a neurological examination, including examination for signs of autonomic neuropathy.
Laboratory evaluation should focus on assessment and detection of diabetic complications that may affect or be affected by pregnancy: serum creatinine and urinary excretion of total protein and/or albumin (albumin-to-creatinine ratio or 24-h excretion rate).
Pregnancy seems not to be correlated with the development of diabetic retinopathy in women who did not have retinopathy before pregnancy.77 Nevertheless pregnancy is associated with a significant progress towards more severe degrees of retinopathy in those who have pre-proliferative or proliferative retinopathy before pregnancy. All women who present proliferative retinopathy should undergo laser therapy before initiating a pregnancy.78 Different studies showed a rapid worsening of retinopathy in diabetic mothers when a strict metabolic control is obtained in a short time.79-81 Intervention in women with severe pre-proliferative or proliferative retinopathy should be tailored to achieve gradual metabolic control in preconception care.
Diabetic nephropathy complicates 5-10% of pregnancies in women with Type 1 diabetes82 leading to an increased risk of fetal abnormalities, perinatal mortality, and mother morbidity.
Patients with protein excretion >190 mg/24 h have been shown to be at increased risk for hypertensive disorders during pregnancy. Patients with protein excretion >400 mg/24 h also are at risk for intrauterine growth retardation during later pregnancy. No specific treatments are indicated, but patients should be counselled about these risks. Since patients should not take angiotensin-converting enzyme (ACE) inhibitors during pregnancy, these assessments should be carried out after cessation of these drugs.
Women with incipient renal failure (serum creatinine >265.2 |mol/L or creatinine clearance <50 mL/min) should be counselled that pregnancy may induce a permanent worsening of renal function in >40% of patients. In subjects with less severe nephropathy, renal function may worsen transiently during pregnancy, but permanent worsening occurs at a rate no different from the background. Therefore, it should not serve as a contraindication to conception and pregnancy. As mentioned above, the presence of proteinuria in excess of 190 mg/24 h before or during early pregnancy is associated with a tripling of the risk of hypertensive disorders in the second half of pregnancy. ACE inhibitors for treatment of microalbuminuria should be discontinued in women who are attempting to become pregnant.
The presence of autonomic neuropathy, particularly manifested by gastroparesis, urinary retention, hypoglycemic unawareness or orthostatic hypotension may complicate the management of diabetes in pregnancy. These complications should be identified, appropriately evaluated, and treated before conception. Peripheral neuropathy, especially compartment syndromes such as carpal tunnel syndrome, may be exacerbated by pregnancy.
Measurement of serum thyroid stimulating hormone and/or free thyroxin level in women with Type 1 diabetes because of the 5-10% coincidence of hyper- or hypothyroidism and then other tests as indicated by physical examination or history. Successful preconception care programs have used the following pre- and postprandial glycemic goals: (1) before meals, values for capillary whole-blood glucose of 70-100 mg/dL (3.9-5.6 mmol/L) or capillary plasma glucose 80-110 mg/dL (4.4-6.1 mmol/L) 2 h; and (2) after meals, values for capillary whole-blood glucose of <140 mg/dL (<7.8 mmol/L) at 2 h or capillary plasma glucose <155 mg/dL (<8.6 mmol/L) at 2 h.75 Implement the treatment plan and monitor HbA1c levels at intervals of 1-2 weeks until stable. Then, counsel the patient about the risk associated with her level. If she does not achieve a low-risk level of <1% above the upper limit of normal, consider modification of the treatment regimen, including addition of postprandial glucose mon-itoring.11 Glycemic goals may need to be modified according to the patient's recognition of hypoglycemia and the risk of severe neuroglycopenia. Outpatient management is the appropriate forum for achieving preconception glycemic goals. Once the patient has achieved stable glycemic control (assessed by the
HbAlc test) that is as good as she can achieve, then she can be counselled about the risk of malformations and spontaneous abortions. If the risk as well as the status of maternal diabetic complications and any coexisting medical conditions are acceptable, then contraception can be discontinued. If conception does not occur within 1 year, the patient's fertility should be assessed.
Metabolic and weight targets for diabetic pregnant women are similar to those presented for GDM. Close attention should be paid to the management of insulin doses considering that during pregnancy insulin need progressively increases from the first to the third trimester and that it inversely reduces in the immediate postpartum period. A recent study confirmed also in Type 1 diabetic pregnancy the superiority of 1 h postprandial blood glucose measurements in respect to the pre-prandial monitoring in reducing the risk of maternal and fetal complications.12 Hypoglycemia occurs more frequently during pregnancy in women with Type 1 diabetes, some evidences correlate maternal hypoglycemia with adverse fetal consequences. Thus although tight glycemic control is desirable during pregnancy efforts should be made to avoid blood glucose below 3.9 mmol/L.83 Therefore it will be very important to provide educational support for self-management both for the home blood glucose monitoring and for the insulin self-adjustment. Moreover, strict control of blood pressure should be guaranteed. According to the recent classification by the Joint National Committee (JNCV) four levels of blood pressure control are defined.84 The first stage corresponds to blood pressure of 140-159/90-99 mmHg and indicates the lowest degree of severity. However, due to the fact that diabetic pregnant women have a higher risk of hypertensive disorder some authors suggested starting anti-hypertensive treatment when blood pressure levels are above 135/85 mmHg. The contraindication of treatment with ACE inhibitors during pregnancy has to be reinforced due to the higher risk of fetal malformation. Diuretics and beta blockers should also be avoided during pregnancy. One of the greatest risks for the diabetic mother is the worsening of a pre-existing diabetic retinopathy. In the case of development of proliferative lesions laser treatment can be used during pregnancy. Hospitalization is not an elective choice for pregnant diabetics but it should be considered only in case of severe complications like ketoacidosis, hypoglycemic coma or pre-eclampsia.
Also, for the diabetic pregnant patient Cesarean section should be avoided whenever possible. It is vice versa recommended in the following cases: pre-eclampsia, malformations, abnormal fetal presentation, advanced age of the mother, and previous Cesarean section.
1. Hawthorne G, Robson S, Ryall EA, et al. Prospective population based 2. Casson IF, Clarke CA, Howard CV, et al. Outcomes of pregnancy in survey of outcome of pregnancy in diabetic women: results of the insulin dependent diabetic women: results of a five year population
Northern Diabetic Pregnancy Audit, 1994. BMJ 1997; 315: 279-81. cohort study. BMJ 1997; 31 5: 275-8.
3. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care 1996; 19: 514-41.
4. Persson B, Hanson U, Lunell NO. Diabetes mellitus and pregnancy. In: Alberti, Zimmet, DeFronzo, eds. International Textbook of Diabetes Mellitus. Chichester: John Wiley; 1997.
5. Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 1998; 21(suppl. 2): B161-7.
6. Carr SB. Screening for gestational diabetes mellitus. Diabetes Care 1998; 21(suppl 2): B14-8.
7. Orsini Federici M, Mosca A, Testa R, et al., for the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, and the Italian Society of Laboratory Medicine. National survey on the execution of the oral glucose tolerance test (OGTT) in a representative cohort of Italian laboratories. Clin Chem Lab Med 2006; 44: 568-73.
8. HAPO Study Cooperative Research Group. The Hyperglycemia and Adverse Pregnancy Outcome Study. Int J Gynecol Obstet 2002; 78: 69-77.
9. International Diabetes Federation - European Region. Guidelines for diabetes care. A desktop guide to type 2 diabetes mellitus. Walter Wirtz Druck Verlag, Germany, August 1998.
10. Homko CJ, Sivan E, Reece EA. Is self-monitoring of blood glucose necessary in the management of gestational diabetes mellitus? Diabetes Care 1998; 21(suppl 2): B118-22.
11. De Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. New Engl J Med 1995; 333: 1237-41.
12. Manderson G, Patterson C, Hadden R, et al. Preprandial versus postprandial blood glucosemonitoring in type 1 diabetic pregnancy: A randomized controlled clinical trial. Am J Obstet Gynecol 2003; 189: 507-12.
13. Gabbe S, Graves R. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003; 102: 857-68.
14. Weisz B, Shrim A, Homko C, et al. One hour versus two hours postprandial glucose measurement in gestational diabetes: a prospective study. J Perinatol 2005; 25: 241-4.
1 5. Chen R, Yogev Y, Ben-Haroush A, et al. Continuous glucose monitoring for the evaluation and improved control of gestational diabetes mellitus. J Matern Fetal Neonatal Med 2003; 14: 256-60.
16. Buhling KJ, Winkel T, Wolf C, et al. Optimal timing for postprandial glucose measurement in pregnant women with diabetes and a non-diabetic pregnant population evaluated by the Continuous Glucose Monitoring System (CGMS). J Perinat Med 2005; 33: 1 25- 31.
17. American Diabetes Association. Gestational diabetes mellitus. Position Statements. Diabetes Care 2004; 2 7: S88-S90.
1 8. Gunton JE, McElduff A. Hemoglobinopathies and HbAlc measurement. Diabetes Care 2000; 23: 1 197-8.
19. Madsen H, Ditzel J, Hansen P. Hemoglobin Alc determinations in diabetic pregnancy. Diabetes Care 1981; 4: 541-6.
20. Cefalu WT, Prather KL, Chester DL. Total serum glycosolated proteins in detection and monitoring of gestational diabetes. Diabetes Care 1990; 1 3: 872-5.
21. Gin H, Vambergue A, Vasseur C, et al. Could blood ketone monitoring be a tool for managing gestational diabetes mellitus? Diabetes Care 2006; 29: 743.
22. Hoffman L, Nolan C, Wilson JD, Oats JJN, Simmons D. Gestational diabetes mellitus - management guidelines The Australasian Diabetes in Pregnancy Society. MJA 1998; 169: 93-7.
23. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2001; 24(suppl 1): 77.
24. Franz MJ, Horton ES, Bantle JP, et al. Nutrition principles for the management of diabetes and related complications [Technical review]. Diabetes Care 1994; 1 7: 490-518.
25. American Diabetes Association. Standards of Medical care in diabetes - 2007. Diabetes Care 2007; 30: S4-S41.
26. American Diabetes Association. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 2003; 26(suppl. 1): S51-S61.
27. Luke B, Murtaugh MA. Dietetic treatment. In: Reece EA, Coustan DR eds. Diabetes Mellitus in Pregnancy. New York: Churchill Livingstone; 1998.
28. Lapolla A, Botta RM, Vitacolonna E. Diabete in gravidanza. Diabete 2001; 13: 269-83.
29. Crowther C, Hiller J, Moss J, et al., for the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86.
30. Buchanan TA, Kjos Sl, Schafer U, et al. Utility of foetal measurements in the management of gestational diabetes mellitus. Diabetes Care 1998; 21(suppl 2): B99-B106.
31. J Jovanovic L, Ilic S, Pettitt DJ, et al. Metabolic and immunologic effects of insulin lispro ingestational diabetes. Diabetes Care 1999; 22: 1422- 7.
32. Persson B, Swahn ML, Hjertberg R, et al. Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus. Diabetes Res Clin Pract 2002; 58: 115-21.
33. Owens D, Vora J. Insulin aspart: a review. Expert Opin Drug Metab Toxicol 2006; 2: 793-804.
34. Pettitt DJ, Ospina P, Kolaczynski JW, Jovanovic L. Comparison of an insulin analog, insulin aspart, and regular human insulin with no insulin in gestational diabetes mellitus. Diabetes Care 2003; 26: 183-6.
35. Jovanovic L. Achieving euglycaemia in women with gestational diabetes mellitus: current options for screening, diagnosis and treatment. Drugs 2004; 64: 1401-17.
36. Gottlieb PA, Frias JP, Peters KA, Chillara B, Garg SK. Optimizing insulin therapy in pregnant women with type 1 diabetes mellitus. Treat Endocrinol 2002; 1: 235-40.
37. Price N, Bartlett C, Gillmer M. Use of insulin glargine during pregnancy: a case-control pilot study. Br J Obstet Gynaecol 2007.
38. Graves D, White J, Kirk J. The use of insulin glargine with gestational diabetes mellitus. diabetes care 2006; 29: 471-2.
39. Langer O. Maternal glycaemic criteria for insulin therapy in gestational diabetes mellitus. Diabetes Care 1998; 21(suppl 2): B91-8.
40. Jovanovic L, Peterson CM. The art and science of maintenance of normoglycemia in pregnancies complicated by type 1 diabetes mellitus. Endocr Pract 1996; 2: 130-42.
41. Nachum Z, Ben-Shlomo I, Weiner E, Shalev E. Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. BMJ 1999; 31 9: 1223-7.
42. Simmons D, Thompson CF, Conroy C, Scott DJ. Pumps in pregnancies complicated by type 2 diabetes and gestational diabetes in a multiethnic community. Diabetes Care 2001; 24: 2078-82.
43. Carta Q, Meriggi E, Trossarelli GF, et al. Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy. Diabet Metab 1986; 12: 121-9.
44. Kremer C, Duff P. Glyburide for the treatment of gestational diabetes. Am J Obstet Gynecol 2004; 190; 1438-9.
45. Langer O, Yogev Y, Xenakis E, Rosenn B. Insulin and glyburide therapy: Dosage, severity level of gestational diabetes, and pregnancy outcome. Am J Obstet Gynecol 2005; 192; 134-9.
46. Elliot B, Langer O, Schussling F. A model of human placental drug transfer. Am J Obstet Gynecol 1997; 1 76: 527-30.
47. Cefalo RC. A comparison of glyburide and insulin in women with gestational diabetes mellitus. Obstet Gynecol Survey 2001; 56: 126-7.
48. Kirschbaum TH. Medical complications of pregnancy. In: Yearbook of Obstetrics, Gynecology, and Women's Health. St. Louis, MO: Mosby; 2002, pp. 103-6.
49. Vanky E, Salvesen KA, Heimstad R, et al. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Human Reprod 2004; 19: 1 734-40.
50. Brock B, Smidt K, Ovesen P, Schmitz O, Rungby J. Is metformin therapy for polycystic ovary syndrome safe during pregnancy? Basic Clin Pharmacol Toxicol 2005; 96: 410- 2.
51. Jovanovic L. Controversies in the diagnosis and treatment of gestational diabetes. Cleve Clin J Med 2000; 67: 481-8.
52. Jovanovic L, Kessler A, Peterson GM. Human maternal and fetal response to graded exercise. J Appl Physiol 1985; 56: 1 719-22.
53. Collings C, Curet IB. Fetal heart rate response to maternal exercise. Am J Obstet Gynecol 1985; 151: 498-501.
54. Erkkola R. The physical work capacity of the expectant mother and its effect on pregnancy, labor and newborn. Int J Gynecol Obstet 1976; 14: 153-9.
55. Veille JC, Hohimer RA, Burry K, Speroff L. The effect of exercise on uterine activity in the last eight weeks of pregnancy. Am J Obstet Gynecol 1985; 151: 727-30.
56. Durak EP, Jovanovic-Peterson L, Peterson CM. Comparative evaluation of uterine response to exercise on five aerobic machines. Am J Obstet Gynecol 1990; 162: 754-6.
57. Jovanovic L. American Diabetes Association's Fourth International Workshop-Conference on Gestational Diabetes Mellitus: summary and discussion. Therapeutic interventions. Diabetes Care 1998; 21(suppl. 2): B131-7.
58. Zamorski MA, Biggs WS. Management of suspected foetal macrosomia. Am Fam Physician 2001; 63: 302-5.
59. Coustan DR, for the American College of Obstetricians and Gynecologists Committee on Practice Bulletins - Obstetrics. Gestational Diabetes. ACOG practice bulletin #30. Washington: ACOG; 2001.
60. Coustan DR. Delivery time, mode and management. In: Reece EA, Coustan DR, eds. Diabetes Mellitus in Pregnancy. New York: Churchill Livingstone; 1998.
61. Hod M, Bar J, Peled Y, et al. Antepartum management protocol. Timing and mode of delivery in gestational diabetes. Diabetes Care 1998; 21(suppl. 2): B113-7.
62. Persson B, Hanson U. Neonatal morbidities in gestational diabetes mellitus. Diabetes Care 1998; 21(suppl. 2): B79-B84.
63. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes. Diabetes Care 2002; 25: 1862-8.
64. Dalfrä MG, Lapolla A, Masin M, et al. Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus. Diabet Metab 2001; 27: 675-80.
65. Dornhorst A, Rossi M. Risk and prevention of type 2 diabetes in women with gestational diabetes. Diabetes Care 1998; 21(suppl. 2): B43-9.
66. Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes. Diabet Med 2004; 21: 103-13.
67. Wah N, Cheung T, Helmink D. Gestational diabetes. The significance of persistent fasting hyperglycemia for the subsequent development of diabetes mellitus. J Diabet Comp 2006; 20: 21-5.
68. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26(suppl. 1): S5-20.
69. American Diabetes Association. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2002; 25(suppl. 1): S5-20.
70. American Diabetes Association. Preconception care of women with diabetes. Diabetes Care 2002; 25(suppl. 1): S82-4.
71. Dunne F, Brydon P, Smith K, Gee H. Pregnancy in women with Type 2 diabetes: 12 years. outcome data 1990-2002. Diabet Med 2003; 20: 734-8.
72. Evers M, de Valk H, Visser G. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ 2004; 328; 915-20.
73. Rosenn B, Miodovnik M, Combs CA, Khoury J, Siddiqi TA. Glycaemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus. Obstet Gynecol 1994; 84: 515-20.
74. Willhoite MB, Bennert HW, Palomaki GE, et al. The impact of preconception counselling on pregnancy outcomes. The experience of the Maine Diabetes in Pregnancy Program. Diabetes Care 1 993; 16: 450-5.
75. American Diabetes Association. Preconception care of women with diabetes. Diabetes Care 2003; 26(suppl. 1): S91-3.
76. Elixhauser A, Weschler JM, Kitzmiller JL, et al. Cost-benefit analysis of preconception care for women with established diabetes mellitus. Diabetes Care 1 993; 16: 1146-57.
77. Star J, Carpenter MW. The effect of pregnancy on the natural history of diabetic retinopathy and nephropathy. Clin Perinatol 1988; 25: 887-916.
78. Chan WC, Lim LT, Quinn MJ, et al. Management and outcome of sight-threatening diabetic retinopathy in pregnancy. Eye 2004; 18: 826-32.
79. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998; 116: 874-6.
80. Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood glucose control on later complications of type 1 diabetes. Lancet 1 993; 341: 1306-9.
81.Jampol LM, Phelps R, Sakol P, et al. Diabetic retinopathy during pregnancy: Role of regulation of hyperglycemia. Ophthalmol Vis Sci 1986; 27: 4.
82. Gordon M, Landon MB, Samuels P, Hissrich S, Gabbe SG. Perinatal outcome and long-term follow-up associated with modern management of diabetic nephropathy. Obstet Gynecol 1996; 87: 401-9.
83. ter Braak E, Evers I, Erkelens D, Visser G. Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences. Diabetes Metab Res Rev 2002; 18: 96-105.
84. The Fifth Report of the Joint National Committee on Detection and Treatment of High Blood Pressure. Arch Intern Med 1993; 1 53: 1 54.
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