Diabetic Retinopathy in Pregnancy

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Pregnancy per se is a risk factor for progression of diabetic retinopathy (DR). Achieving good glucose control prior to pregnancy can decrease the risk of development and/or progression of DR (14). The classification of retinopathy during pregnancy is the same as the classification in nonpreg-nant diabetic patients. DR progresses from mild nonproliferative abnormalities with increased vascular permeability, to moderate and severe nonproliferative diabetic retinopathy (NPDR), characterized by vascular closure, to proliferative diabetic retinopathy (PDR), characterized by the growth of new blood vessels on the retina and posterior surface of the vitreous (67, 68).

The gestational effect on progression of DR is not completely understood. Many of the hormonal factors of pregnancy have been considered to increase the risk of development and progression of DR by several biochemical mechanisms that are not yet completely understood. Studies in vitro suggest that the growth factors, insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF), as well as placental growth hormone (pGH) that are produced by the placenta may contribute to retinopathy during pregnancy (62, 69, 70). An early clinical report of four nonpregnant patients with upregulation of IGF-1 prior to onset of retinal deterioration suggested that IGF-1 is a contributor to acceleration of DR (71). However, in a clinical study comparing pregnant diabetic women with nondiabetic pregnant women, it was reported that serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) were lower among pregnant diabetic women than among nondiabetic pregnant controls and/or postpartum indicating that there is not a clear connection between the IGF system and progression of DR during pregnancy (72). It has also been suggested that as blood levels of hormones such as estrogen, progesterone, and human placental lactogen (hPL) increase dramatically in pregnancy, they too may accelerate retinopathy (73).

It has been considered that inflammation during pregnancy contributes to retinopathy. Loukovaara et al. reported that CRP levels are higher among diabetic women with progression of retinopathy and also among those women with poor glycemic control; however, inflammatory markers such as interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) were similar in women with DM1 and nondiabetic women (74).

When retinopathy is present prior to pregnancy, the progression of retinopathy during pregnancy to PDR or within NPDR is common. Several factors have been identified that increase the risk for progression during pregnancy (Table 4).

The severity of retinopathy at the onset of pregnancy is an independent risk factor. In a recent study of pregnant patients with DM1, it was observed that among patients with PDR who had not received laser treatment before pregnancy, 75% showed progression of retinopathy, compared with

Table 4

Factors that Increase the Risk for Progression of Retinopathy during Pregnancy (Adapted from Rahman, 2007 (76))

Retinal status at conception Early onset of diabetes Duration of diabetes

Elevated first trimester A1C or poor glycemic control Rapid normalization of blood glucose Hypertension only 25% of the patients who had PDR and had laser treatment prior to pregnancy (76). These results provide further support for careful preconception evaluation and treatment of women with diabetes mellitus (77).

A retrospective study by Lovestam-Adrian in 1997 addressed the issue whether the short-term risk of progression of DR in pregnant women with DM1 is increased than in nonpregnant women with DM1 and similar diabetes characteristics matched for age and duration of diabetes (78). The patients had been followed for 12 months before, during, and 6 months after pregnancy. The results indicated that progression of retinopathy to potential loss of sight was similar between the pregnancy group and the control group, and pregestational elevated A1C and a rapid decrease in A1C were each significant risk factors for progression of preexisting retinopathy in the groups (78).

The duration of diabetes mellitus is also a significant risk factor for DR. When DM1 has been present more than 5 years, there is a 14% risk for a greater than two-step progression of DR that continues to increase until the risk peaks at approximately 46% between 16 and 20 years duration of DM1 (79, 80). This suggests that women with DM1 onset in childhood and teens have an increased risk for retinopathy during their reproductive years.

During the DCCT it had been observed that in the first year of intensified diabetes management in nonpregnant women with DM1, there was a transient increase of retinopathy, known as "early worsening" that was characterized as development of soft exudates, dilated tortuous intraretinal vessels, or clinically important retinopathy that were noted at the 6- or 12-month follow-up visits (81, 82). In the intensively treated group, the frequency of early worsening was somewhat greater when moderate/severe NPDR was present at the baseline visit (75, 81, 82). In a study comparing Conti-nuous Subcutaneous Insulin Infusion therapy (CSII) to Conventional Insulin Therapy (CIT), the proportion of patients whose retinopathy progressed did not differ significantly between the CSII and CIT groups, and in the majority the deterioration was mild (83). However, two patients in the CSII group who had the highest and most rapidly decreased A1C developed acute ischemic retinopathy that progressed to the proliferative stage in spite of laser treatment (83). Other investigators have also reported that during pregnancy, elevated first trimester A1C followed by rapid improvement of maternal blood glucose increases progression of DR during pregnancy (77, 80). Many investigators have concluded that initial poor glycemic control and rapid institution of strict control during pregnancy are associated with the progression of retinopathy (78, 84, 85). One prospective study with the least progression of retinopathy reported the lowest A1C levels at conception and also the least decrease of A1C during pregnancy (80). Therefore, optimal glycemic control should be achieved prior to conception with planning of pregnancy to allow normalization of blood glucose before conception.

Evaluation of the retina is essential during preconception care of women with preexisting diabetes mellitus. An adequate examination requires the appropriate equipment by an experienced ophthalmologist who understands the risk for progression of retinopathy during pregnancy. A dilated eye exam and baseline retinal photographs are necessary since direct ophthalmoscopic examination alone may not identify DR (86). The frequency of eye examinations during pregnancy should be determined by the initial baseline evaluation of retinopathy and the risk factors associated with pregnancy. Currently, it is recommended that ophthalmologic follow-up continues throughout pregnancy and the postpartum period with photocoagulation initiated for significant neovascularization (67, 87).

Although there are no controlled studies evaluating the risk of retinal hemorrhage during different modes of delivery, it may be recommended to use assisted second-stage labor during vaginal delivery or a cesarean section in order to avoid the valsalva maneuver associated with maternal pushing during labor if the woman has significant retinopathy or risk for retinal hemorrhage.

The prevalence of diabetic nephropathy among patients with DM1 has been reported to rapidly increase after diabetes has been present for 10 years (88). This suggests that in some women with DM2 and early onset of diabetes, renal insufficiency may be present during the reproductive years. With the increase in diagnosis of DM2 among teenagers there is an increase in the potential risk for development of nephropathy in young adults during their reproductive years. Currently, nephropathy complicates between 5 and 10% of pregnancies among women with preexisting diabetes mellitus (89-91). The presence of nephropathy during pregnancy not only increased risks to the mother (preeclampsia, anemia, renal failure), but there are significant risks to the fetus including intrauterine growth restriction, stillbirth, and preterm delivery (92, 93).

Pregnancy and parity do not appear to increase the risk for development of diabetic nephropathy nor do they increase the progression of established diabetic nephropathy (94). Rossing et al. have reported an observational study of 93 diabetic women who were followed over a range of 3-28 years during which 26 of the women became pregnant after developing nephropathy (95). The study demonstrated that pregnancy did not have any long-term effect on renal function or survival, comparing the pregnant diabetic women with those women who did not become pregnant (95). Other studies have demonstrated that among pregnant women with decreased renal function due to either diabetic or nondiabetic causes, there is an increased risk of end-stage renal disease within months to a few years after delivery (96, 97). Although the rates of maternal complications are increased when moderate or severe renal insufficiency is present among pregnant diabetic women, the fetal survival rate remains high (97). Aggressive medical management of renal complications preconception and during pregnancy can reduce both maternal and fetal morbidities and mortality (98-100).

In nonpregnant diabetes mellitus, nephropathy is characterized by albumin excretion in a spot or 24-h urine collection (Table 5).

Table 5

Nephropathy in Nonpregnant Patients with Diabetes Mellitus (Adapted from ADA (29))

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100 Pregnancy Tips

Prior to planning pregnancy, you should learn more about the things involved in getting pregnant. It involves carrying a baby inside you for nine months, caring for a child for a number of years, and many more. Consider these things, so that you can properly assess if you are ready for pregnancy. Get all these very important tips about pregnancy that you need to know.

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