Table 2.
Placental Histopathologic Abnormalities in Pregnancies Affected by Pregestational diabetes
| Authors, Year |
Ref | Study type | Population | Diabetes Type | Blinding of pathologist to diabetes diagnosis ? |
Glycemic control ? |
Placental structure/abnormalities under investigation |
Defined placental variables? | Results | |
|---|---|---|---|---|---|---|---|---|---|---|
| Diabetes | Control | |||||||||
| Fox, 1969 | (8) | Prospective | 48 | 234 | Pregestational diabetes |
Not specified | Not specified | Gross lesions (infarction, perivillous fibrin, calcification, retroplacental hematoma, intervillous thrombi); villous abnormalities (excess syncytial knots, villous fibrosis, excess villous fibrinoid necrosis, trophoblastic basement membrane thickening, excess Langhans cells); abnormalities of fetal stem arteries (fetal artery thrombosis, obliterative endarteritis, calcification) |
No | -No statistically significant difference in gross lesions. - Principal histologic abnormalities in placentas from diabetic women were an obliterative endarteritis of the fetal stem arteries, thickening of the trophoblastic basement membrane and villous fibrinoid necrosis. - Placentas in diabetic women had a higher frequency of villous fibrosis and excess syncytial knot formation. - No consistent pattern of disturbance in villous maturation. |
| Asmussen, 1982 |
(6) | Prospective | 9 | Not specified | White Class D, non-smokers |
Not specified | Well- controlled |
Morphological changes in terminal villi and fetal capillaries |
No | - Terminal villi of diabetic women showed changes in maturation, increased vascularization due to small vessels penetrating into the trophoblast, and glycogen accumulation within the stroma cells and pericytes. - Women with diabetes had 2-3 times as many capillaries per terminal villus compared to controls. |
| Bjork & Persson, 1982 |
(37) | Prospective | 17 | 20 | White Class B, C, D, F (all Insulin- dependent) |
Not specified | Not specified | Syncytial knots; vasculosyncytial membranes; hypovascular villi; intravillous hemorrhage; subsyncytial edema; the frequency of immature villi |
Yes | - Placentas from diabetic women had a higher frequency of hypovascular villi, subsyncytial edema, syncytial knots and immature villi |
| Teasdale, 1983 |
(11) | Prospective | 10 (5 with appropriate for gestational age infants; 5 with large for gestational age infants) |
5 | White Class B (not specified whether insulin- dependent) |
Not specified | Excellent | [Within the parenchyma, defined as the intervillous space, trophoblast layer (cytotrophoblast and syncytiotrophoblast) and the fetal capillaries of both peripheral and stem villi] Volume of intervillous space and fetal capillary bed; the number per unit area, surface densities and surface areas of the villi and their fetal capillaries; the number of syncytiovascular membranes per 100 peripheral villi |
Yes | - Placentas from diabetic women were significantly heavier. - Placenta for appropriate for gestational age infants morphologically similar to control group except for villous vascularization. - The placenta of large for gestational age infants had significantly greater accumulation of non- parenchymal tissue (sum of the decidual and chorionic plates, intercotyledonary septa, fetal vessels, connective tissue of the villi, fibrin deposits, and infarcts) and a moderate increase in parenchymal tissue compared to control group. |
| Bjork & Persson, 1984 |
(17) | Prospective | 13 | 13 | T1DM | Not specified | Not specified | Length and area of villi in three well-defined areas within a cotyledon (central, intermediate and lateral regions) |
Yes | - While normoglycemic controls showed consistent organization of the cotyledon with increasing villous length towards the periphery, villi were of even length through the cotyledon in women with T1DM. - Average surface area of the cotyledon due to increased branching of peripheral villi was significantly greater in women with T1DM. |
| Teasdale, 1985 |
(38) | Prospective | 10 | 5 | White Class C (not specified whether insulin- dependent) |
Not specified | Excellent | [Within the parenchyma, defined as the intervillous space, trophoblast layer (cytotrophoblast and syncytiotrophoblast) and the fetal capillaries of both peripheral and stem villi] Volume of intervillous space and fetal capillary bed; the number per unit area, surface densities and surface areas of the villi and their fetal capillaries; the number of syncytiovascular membranes per 100 peripheral villi |
Yes | - Placentas from diabetic women had significantly greater increase in parenchymal (intervillous space, the trophoblast layer, and fetal capillaries of both the peripheral and stem villi) and non-parenchymal tissue (sum of the decidual and chorionic plates, intercotyledonary septa, fetal vessels, connective tissue of the villi, fibrin deposits, and infarcts). |
| Boyd et al., 1986 |
(7) | Prospective | 14 | 22 | T1DM | Not specified | Moderate to good glycemic control |
Volume and surface areas of parenchymal tissue (consisting of villi, including fetal capillaries, and the maternal intervillous space) and non-parenchymal tissue (chorionic and decidual plates, fetal vessels of diameter >0.1 cm and intercotyledonary septa); villous surface area |
Yes | - Placentas from diabetic women had significantly increased volume of parenchymal tissue and decreased volume of non- parenchymal tissue. - Placentas from diabetic women had significantly increased villous surface area, with the mean value being 17.3 m2 compared to 11.4 m2 of the normoglycemic women. |
| Jirkovska, 1991 |
(30) | Prospective | 13 | 14 | T1DM | Not specified |
Good | Thickness of capillary basement membrane |
Yes | - Placentas of women with T1DM had increased number of capillaries in the terminal villi - Placenta of women with T1DM had significantly thinner capillary basement membrane |
| Mayhew et al., 1993 |
(39) | Prospective | 11 | 34 | White Class D with benign retinopathy (no proliferative retinopathy or other serious complications) |
Yes | Good | Volumes of the following tissue compartments: intervillous space (excluding fibrin deposits), peripheral villi, villous trophoblast, villous stroma, fetal capillaries and non-parenchymal tissue (comprising decidual and chorionic plates and intercotyledonary septa); total lengths and exchange surface areas of villi and fetal capillaries |
Yes | - Placentas in women with diabetes were 17% heavier. - Volume of fetal capillaries was 45% greater in women with diabetes and 30% larger in males. - Compared to Cesarean deliveries, vaginal deliveries had greater stromal diffusion distance (measured from the fetal aspect of trophoblast to the liminal aspect of capillary endothelium). |
| Mayhew, 2002 |
(31) | Prospective | 34 | 34 | T1DM | Not specified | Good | Volume, surface areas and lengths of peripheral villi and their capillaries |
Yes | - Placentas of women with T1DM had increased volume of fetal capillaries (19-45% greater) that is attributed to the increases in the combined length (12-47% greater) of capillaries and not to alteration of vessel cross- sectional area or perimeter. |
| Evers et al., 2003 |
(32) | Prospective | 71 | 38 | T1DM | Yes | Excellent or good in 82% of women |
Lymphohistiocytic villitis; ischemia; infarction; presence of nucleated fetal red blood cells; villous fibrinoid necrosis; degree of villous immaturity; chorangiosis; hydropic villi; fetal vessel thrombosis/avascular villi |
Yes | - Placentas of women with diabetes were significantly heavier. - Placentas of women with diabetes had increased incidence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity, and chorangiosis. - Placenta of women with large for gestational age infants had a higher incidence of histological abnormalities compared to those of women with appropriate for gestational age infants. |
| Maly et al., 2005 |
(33) | Prospective | 10 | 13 | T1DM | Not specified | Good | Volume and surface area of placental villi and capillaries |
Yes | - Placentas of women with diabetes had more than 5-fold decrease in villous vascular volume |
| Jauniaux et al., 2006 |
(12) | Prospective | 12 | 10 | T1DM | Not specified | 5 patients with poor glycemic control |
Volume and surface area of placental villi and capillaries |
Yes | - Placentas of women with diabetes had a significant increase in fetal and placental weights, placental volume, volumes of the intervillous space and the trophoblast found in diabetic group compared to controls. |
| Nelson et al., 2009 |
(34) | Prospective | 88 | 39 | T1DM | Not specified | Not specified | Volume and surface areas of placental villi and capillaries |
Yes | - Placentas of women with diabetes were significantly heavier. - Placentas of women with diabetes had a significant increase in the intervillous space volume but villous, non- parenchymal, trophoblast and capillary volumes did not differ. |
| Jirkovska et al., 2012 |
(35) | Prospective | 17 | 14 | T1DM | Not specified | Not specified | Spatial arrangement of villous capillary bed and quantitative measures of capillary branching pattern |
Yes | - Placentas from mothers with T1DM had changed size and course of capillaries, altered structure of the villous stroma and enhanced sprouting angiogenesis in the terminal villi. |
| Higgins et al., 2012 |
(36) | Prospective | 74 (9 women with T2DM; 65 women with T1DM) |
77 | Pregestational diabetes |
Yes | Not specified | Delayed villous maturation |
Yes | - Placental diagnosis of delayed villous maturation was significantly increased in women with pregestational diabetes (28.4%) compared to controls (14.3%). |