Pregestational diabetes

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 monitoring during pregnancy

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.

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