Introduction

Gestational diabetes mellitus (GDM) is glucose intolerance with first re cognition during pregnancy.1 2 to 5% of Indian women are affected2,3 with a prevalence rate of 10 to 14.3%.⁴ This prevalence varied in respect to different geographical locations, ethnicity and level of glucose tolerance within the population. Kayal A and co-authors have reported a prevalence of 16.2% in urban and 9.9%. in rural areas.2,4 A random survey in various cities showed 3.8% in Kashmir i women, 12% in Bangalore, 15% in Trivandrum, 17.5% in Ludhiana, 18.8% in Erode and 21% in Alwaye.5 The incidence is expected to raise by 20% indicating 1every 5 pregnant mother's likely to have GDM.4 The risk factors are glucosuria, maternal age above 30years, obesity, family history of diabetes, GDM or glucose int olerance in previous pregnancy and a previous macrosomic baby.6 GDM is associated with increased perinatal morbidity, macrosomia, neonatal hypoglycemia, hyperbilirubinaemia, shoulder dystocia and respiratory distress syndrome. The Gross and light morphologic changes in placenta are consistent with dysmaturity and immaturity of the trophoblast tissue.7,8,9,10,11 This study was undertaken with the objective to study the morphologic changes in the placenta of GDM as documented in the literature and correlate them with maternal age and parity order.

Materials and Methods

A prospective study was conducted in the pathology department of a teaching hospital from June 2014 to May 2015 after obtaining permission from the Institutional Ethical Committee. The total sample size were 80 placenta of term pregnancy. 40 placenta from cases diagnosed as GDM formed the study group. Remaining 40 from normal pregnancy was the control group. The exclusion criteria included cases of Type 1 and 2 diabetes, GDM with hypertension, other toxemia s of pregnancy, chronic illness or a metabolic disorder in the mother. A writ ten informed consent was obtained. The clinical details and other investigation reports were noted from hospital case sheets. The clinicopathologic correlation for individual case was analysed. The morphologic findings were documented as per the standard proforma. The placental weight in grams and size in cms was noted. The membranes were examined for any colour change and or surface irregularity. Using swiss roll technique they were rolled with the amnion surface inward and formalin fixed The maternal surface was observed for the number of cotyledons and infarcts or any colour change. The fetal surface was looked for vascular pattern or other abnormal changes. O ne cm. serial sections were cut, formalin fixed and processed. The 5-micron thick sections were stained with haematoxylin and osin. Special stains periodic acid schiff (PAS) stain and phosphotungstic acid haematoxylin (PTAH) were done to demonstrate the trophoblast basement membrane thickening and fibrin deposition respectively. The umbilical cord length was measured in cms and observed for its position of insertion, number of vessels, knots or any other changes. It was cut 5cms away from sit e of insertion. Serially sectioned and formalin fixed The data was collected and tabulated in Microsoft excel sheet. The percentages were calculated for purpose of comparison.

Results

In the present study majority of placenta in GDM group 37(92.5%) weighed >500gms. and 02(5%) in control group with a p-value<0.001 (Table 1). The mean weight of the placenta was 629.4gms and 383.25gms. in both groups respectively.

In the GDM group an increased mean diameter of placenta at 21.37cm. was significant with 13.51 cm. in the control group.

The mean number of cotyledons among GDM group was 21.08 and control group at 13.73. In one GDM case upto 28 cotyledons was noted. The p value < 0.001 (Table 2)

The eccentric insertion of umbilical cord was commonest, followed by central insertion and marginal insertion in GDM cases. Comparable finding was observed in control group (Table 3)

Histomorphological study showed chorangiosis as the commonest lesion in GDM placenta 30 (75%) and in the control

group 01 (2.5%). Increased syncytial knots was common in 29 (72.5%) GDM cases and 1 (2.5%) case in the control group. Villous edema was noted in 28 (70%) GDM and 4 (10%) in control cases. The consistent finding of trophoblast basement membrane thickening (BMT) among GDM group was identified in 24 (60%) and in control group in 2 (5%) cases. PAS stain showed positivity for BMT. Villous stromal fibrosis was observed among 24 (60%) of GDM and 01 (2.5%) in control cases. Fibrin deposition was frequently seen in 22(55%) and 2(5%) in GDM and normal groups respectively. PTAH showed positivity in these cases. Fibrinoid necrosis noted in 10(25%) in GDM and 01(2.5%) in the study group. Increased numbers of Hofbauer cell in the intravillous stroma was found in 2 cases of GDM placenta only. (Table 4) depicting the observed findings.

Majority of GDM 15(37.5%) cases were diagnosed in the maternal age group (25-29) years and few 5(12.5%) cases in >3 5 years (Table 5).

Figure 1

Gross photograph showing maternal surface with increased number of cotyledons

Figure 2

Photomicrograph showing chorangiosis (H&E stain, 10x).

Figure 3

Photomicrograph showing increased syncytial knots (H&E stain 10x).

Figure 4

Photomicrograph showing stromal fibrosis (H &E stain (10x).

Figure 5

Photomicrograph showing thickening of trophoblast basement membrane (PAS stain 10x)

Figure 6

Photomicrograph showing intravillous fibrin deposits (PTAH Stain 10x).

Discussion

GDM is associated with significant histomorphologic variations in the placenta. In the present study the mean weight of placenta in GDM group was 629.4gms while in control group was 383.3gms and found to be significant. This observation was comparable with various studies (Table 6).

The mean number of cotyledons were increase d to 21.07 in GDM cases. In one case 28 cotyledons were counted. Similar observation s were reported by other authors as shown in (Table 7).

The mean diameter of placenta e was calculated to be 21.37cms and 13.51cms in GDM and control group respectively. Comparative result was reported by Muhammad Ashfaq and authors with a mean diameter of 18.95cms and 14.26cms in GDM and control group respectively.14 Muhammad Ali Qureshi and co-authors noted 34.5cms. mean diameter in GDM. and 21.1 cms in control group.13

Analysis with onset of GDM with reference to maternal age showed majority of cases in (25-29) (37.5%), followed by in (20-24) (30%) and (30-34) (20%) age group in yrs. respectively. The mean age was 27.43 yrs. Pankaj Saini and co-authors observed maximum cases of GDM in the age group (25-29)yrs. (47.5%).15 An incidence of occurrence of GDM in 67.5% among multiparous and 32.% in primiparousmother"s respectively was seen. Author Vijayasheela observed a comparable incidence of 72% in multiparous and 28% in primiparous women.17

In our study the commonest insertion of umbilical cord was eccentric (25 cases) followed by central (13 cases) and marginal in 2 cases with similar correlation in the control group. Soma Saha and co-authors also noted that cord insertion was commonly eccentric, then central and marginal.18

In the present study histomorphology revealed increased chorangiosis as the commonest finding in upto 30 (75%) GDM cases but only in one (2.5%) in the control group. Memon S studied 50 placenta of GDM and found significant association with chorangiosis.19 Madazli and co-authors study on 22 GDM cases found chorangiosis along with villous immaturity and ischemia.20

We noted increased syncytial knots in upto 29 (72.5%) GDM group and 1 (2.5%) in the control group. Vermaand co-authors in 20 GDM cases observed syncytial knots, fibrinoid necrosis, villous edema, villous fibrosis and capillary proliferation.8 Amal T and authors observed increased syncytial knots in 12 cases of GDM.21

The villous edema was a consistent significant finding present in 28 (70%.) GDM group and 4 (1 0%) in control group. In Soma Saha and co-authors study of total 130 placenta, the GDM cases showed significant changes like villous edema, fibrin deposition, calcification and congestion of blood vessels.18

We noticed a significant villous basement membrane thickening in 24 (60%) GDM and 2 (5%) in normal placenta. PAS stain showed positivity. Lavinia Gheorman and co-authors in their study on two cases of GDM noted the presence of basement membrane thickening, villous immaturity, villous edema, chorangiosis, intra and extravillous fibrinoid and a deposit of glycogen.11

In the present study villous stromal fibrosis in 24 (60%) in GDM and 1 (2.5%) in control was noted.. The p-value was significant. Verma and co-authors studied 20 GDM cases and observed significant varying lesions like villous fibrosis, syncytial knots, fibrinoid necrosis, villous edema and capillary proliferation.9

Intra and intervillous fibrin deposition in 22 (55%) of our GDM group and in 2 (5%) case s in control group and was found to be significant. PTAH showed positivity for both intravillous and intervillous fibrin deposition. Lavinia Gheorman and other authors noted intra and extravillous fibrin deposition, villous immaturity, villous edema, presence of basement membrane thickening, chorangiosis, and deposit of glycogen.10

Fibrinoid necrosis was seen in our 10 (25 %) GDM placenta and 01 (2.5%) in control placenta. Authors Amal T and others also noted fibrinoid necrosis in 12 GDM cases.21

We observed increased number of Hofbauer cells in the intravillous stroma in 2 placenta from GDM. Amal T and co-authors have reported frequent increased presence of Hafbauer cells in 12 GDM cases.21

Conclusion

In our study 0f placenta in 40 cases diagnosed as GDM showed a significant in creased incidence of morphologic changes in comparison to term placenta from normal pregnancy. The observed gross changes in GDM were increased weight in gms., diameter in cms., and number of cotyledons. Light microscopic changes were chorangiosis, increased syncytial knots, villous fibrosis, intra and intervillous fibrinde position, basement membrane thickening, fibrinoid necro sis and villous edema. The above findings correlated with various studies by other authors. So an aim towards an effective euglycemic control would decrease the associated perinatal morbidity.

Source of funding

None.

Conflict of interest

None declared.

Acknowledgement

Regards to Dr. Mythrei M U & Dr Suma H V, postgraduate students of Pathology, MIMS, Mandya for the kind support.