Diabetes mellitus is one of the most common diseases. The incidence of diabetes in recent decades has been increasing worldwide. Due to the effectiveness of insulin therapy and the use of a rational physiological diet, the majority of women with diabetes have normalized reproductive function. However, practice shows that diabetes and pregnancy have a negative effect on each other. With diabetes, there is a violation of all types of metabolism (carbohydrate, protein and fat), microcirculation, and immune status. This leads to the development of severe trophic disorders in the organs and tissues of patients, vascular and neurological complications. Obvious diabetes complicates from 0.2 to 3%, and gestational diabetes – from 2 to 12% of pregnancies and there is a tendency to increase this indicator.
Of all endocrine extragenital diseases, diabetes has the most adverse effects on the health of the mother, fetus and newborn. The course of diabetes during pregnancy is characterized by lability, instability of compensation, with this pathology, a large number of obstetric complications occur .
So, but according to a number of maternity hospitals in the city of Lugansk, 200 births account for one birth in a patient with diabetes mellitus. However, the morphological rearrangement in the placenta-fetus system is not well understood. In this regard, the goal of our study was clinical and morphological studies in case of diabetes in the mother.
The object of the study was 75 pregnant women with diabetes mellitus of varying severity and duration, the outcome of their birth and the condition of the newborn. The majority of the examined (n = 62 pregnant women) were patients with insulin-dependent diabetes mellitus (IDDM). Significantly fewer (6) were patients with non-insulin-dependent diabetes mellitus (NIDDM). A separate group consisted of 7 patients whose diabetes mellitus was first detected during a real pregnancy – gestational diabetes. The control group consisted of 10 somatically healthy, pre-pregnant women with uncomplicated pregnancy and childbirth, giving birth to live and viable children.
Morphofunctional analysis of placentas was performed in 62 puerperas with IDDM and in 10 women with physiological pregnancy. Macroscopic evaluation included weighing and measuring, analyzing the shape, color, attachment of the umbilical cord, structure, type of blood supply, determining the presence of white and red heart attacks, caverns, intervillous blood clots, calcifications, and hematomas. Immediately after birth, 3 pieces of 1 mm in size were cut from the placenta for light, transmission, and scanning electron microscopy. For electron microscopy, the pieces were fixed in a three-component fixing mixture: 0.25% solution of glutaraldehyde, 2% solution of formaldehyde freshly prepared from paraformaldehyde and 5% DMSO solution in 0.1 M phosphate buffer pH 7.2. After washing in a 0.25 M sucrose solution with the addition of 3 mM MgSO
4, the pieces were fixed in osmium tetroxide and poured into epon-eraldite, as usual . Ultrathin sections were prepared on an LKB ultratome (Sweden) and viewed in a JEM-100CX electron microscope (Japan).
When studying the course of pregnancy in women with diabetes mellitus, it was noteworthy that the most common complications of a real pregnancy were nephropathy (61.6%), the threat of abortion (41%), polyhydramnios (24.6%). Ketoacidosis during pregnancy occurred in 54.7%. In almost all cases, chronic fetal hypoxia was noted. During pregnancy, a combination of various types of complications was observed.
Of the concomitant pathologies for diabetes in pregnant women, obesity (31.5%), urinary tract infections (24.6%), thyroid gland hyperplasia (21.9%), myopia (17.8%), and hypertension were most common ( 9.5%), myocardial dystrophy (8.2%). Among complications of diabetes in pregnant women, diabetic angiopathy occurred in 41% of cases, diabetic retinopathy in 17.8%, and diabetic polyneuropathy in 24.8%. 11 women were disabled for the underlying disease. In 39 cases, the delivery ended with a caesarean section, the delivery through the natural birth canal occurred in 24 cases, and with antenatal fetal death in 10 women in labor, a fruit-destroying operation was performed.
In 39 observed women, the pregnancy ended in the birth of a live and viable baby, antenatal fetal death took place in 12 women, postnatal death of the newborn occurred in 22. Two women suffering from IDDM underwent termination of pregnancy for medical reasons up to 22 weeks.
When analyzing the body weight of newborns whose mothers suffered from IDDM, a table of percentile levels was used depending on the gestational age. It is noteworthy that 47.5% of newborns were with normal body weight, 35.5% with degree I-III malnutrition and only 17% with signs of macrosomia. Among all the children born, the symptom complex of diabetic fetopathy was detected in 91.6%, the risk of developing diabetic fetopathy – in 8.2%. In observations ending in antenatal fetal death, diabetic fetopathy was found to be 100%.
A separate group consisted of 7 newborns who needed additional treatment in the intensive care unit,
and then were transferred to the neonatal pathology department for the second stage of nursing. These children were admitted to the intensive care unit on the second day (4), the third day (1), the fifth day (1), and the eleventh day (1). Premature birth was in 6 cases and most often in the period of 35-36 weeks. (2), 37 weeks (2). Through the birth canal, birth occurred in two, and a caesarean section was performed in 5 cases. All women showed insulin-dependent diabetes mellitus. Medium severity – in 3 women, severe – in 4. Pregnancy proceeded with the effects of ketoacidosis in 4 cases. Assessment of the condition of newborns on the Apgar scale was 3-6 points in 4 cases, 7 points – in 3. Prematurity of the I degree was determined in 4 children, III degree – in two. When studying the percentile body weight estimate of newborns in the intensive care unit, normal body weight was in 4, exceeded the gestational norm in 3 newborns. The blood glucose level at birth in the group in premature infants averaged 2.89 mmol / L, on the first day – 4.26 mmol / L. Upon admission to the intensive care unit, all children were examined.
When studying laboratory data, the presence of hypoproteinemia (49.4 g / l) draws attention, the blood sugar level was 3.37 mmol / l. Diabetic fetopathy was detected in all seven cases. When studying planlets in women with diabetes mellitus, it was noted that the placenta mass predominantly corresponded to the gestational age. In such placentas, paracentral cord attachment, white and red heart attacks, and calcifications were observed more often than in the control group.
Microscopically on the fetal surface, a number of changes characteristic of the placenta pathology were observed. Thus, an increase in the area of deposition of fibrinoid, as well as areas of necrosis on the maternal surface, was noted. First of all, vascular pathology attracted attention. Along with vasospasm, sclerosis of the wall of most of them was noted. However, the most characteristic changes are noted in the villous tree. At the same time, the percentage ratio of all types of pathologically altered villi in the chorion increased significantly. This applies equally to the stem, intermediate, terminal parts of the villus tree. So, instead of unchanged villi, which occupy up to 80-90% of the area in the control group, the proportion of sclerosed (Fig. 1), edematous and fibrinoid-modified villi increased. In cases with dead fruits, their content reached 90%.
Electron microscopy of terminal villi showed significant changes in the placental barrier. At the same time, the thickness of syncytiotrophoblast was less in women with diabetes than in the control group and in some areas, especially in cases of a combination of diabetes and gestosis of the second half of pregnancy, its desquamation was observed with exposure of the basement membranes of the capillaries. In the preserved areas, the number of microvilli was less
than in the control group, and they were also smaller in size. Their shape is changed (Fig. 2). Syncytiotrophoblast nuclei were predominantly irregular in shape with expansion of karyolemma and nuclear pores. Some of them were necrotic (Fig. 3). The nucleolus was often in an active state, in favor of which its “basket” form testified. The presence of a large amount of diffuse chromatin in the cytoplasm, and only an insignificant part of it was in a condensed state, testifies to the active functioning of the nucleus in diabetes mellitus. The collagen content in the villi is significantly increased.
In cases with fetal death, an increase in the number of nuclei in a state of karyopiknosis and karyorexis is observed. When studying the cytoplasm, attention is drawn to the increased vacuolization of some villi and sclerosis of others with a sharp increase in the amount of collagen in them. In addition, in the cells of terminal villi, in contrast to those of women in the control group, there is a decrease in the number of cytoplasmic organelles, consisting mainly of mitochondria, enlarged with destroyed cristae, and the expansion of the endoplasmic reticulum; decrease in the number of both ribosomes and polysomes. In the placenta of women who had stillbirths, practically no cytoplasmic organelles are observed, and the surviving ones are mainly in an altered state.