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Preeclampsia is an obstetric complication that is becoming a major cause of maternal and perinatal morbidity and mortality. The rate of preeclampsia in diabetes mellitus is 3 to 5-fold higher than in the population. Heparin is used for prevention of preeclampsia due to its experimentally shown important role in the trophoblast invasion and differentiation, as well as its influence on the production of proangiogenic factors. The paper gives a clinical case report that broadens our understanding on the preeclampsia pathophysiology and possibilities of its prevention. A 30-year old patient with no past history of serious physical illnesses had her two previous pregnancies with severe preeclampsia of early onset (arterial hypertension, massive proteinuria, thrombocytopenia, renal and hepatic insufficiency). Both babies were born extremely preterm (24 to 25 weeks of gestation) and died. Her hereditary background included type 2 diabetes in her maternal grandmother. At early terms of both pregnancies she had her fasting venous plasma glucose of 3.8 to 4.6 mmol/L (normal, < 5.1 mmol/L). Oral glucose tolerance test which had to be performed at 24 to 28 weeks of gestation, according to the protocol, was not performed. While planning for the third pregnancy, her body mass index was 29 kg/m 2 , with normal values of the blood pressure and renal function, no proteinuria and no evidence of the anti-phospholipid syndrome. In the 1 st trimester, she had her fasting venous plasma glucose of 4.4 mmol/L. From the early term of her pregnancy, the patient was administered low molecular weight heparin; from the week 15, she was started with antihypertensive medications due to gestational arterial hypertension. Manifest diabetes was diagnosed at week 24 to 25 based on the results of the oral glucose tolerance test (4.96–10.42–11.46 mmol/L). With diet treatment, she had her postprandial glycaemia of up to 8.9 mmol/L, causing the initiation of basal-bolus insulin therapy from week 25 of gestation (0.4 U/kg), with achievement of good glucose control. At week 16, she had her sFlt1/PlGF level of 44 (high risk of preeclampsia). Molecular genetic assessment identified a HNF4A gene mutation, associated with MODY1. From week 34, she had moderate preeclampsia and fetal growth delay. An elective cesarean section was performed at week 38, with a healthy boy of 2300 g and 48 cm. After delivery, her diabetes was controlled by diet. The baby had an identical mutation. Thus, one cannot exclude a genetically determined link between complications of previous pregnancies and manifest diabetes diagnosed during the current pregnancy. Diagnosis of MODY1 in a pregnant patient would require the earliest initiation insulin treatment to prevent fetal macrosomia and neonatal hypoglycemia, as well as to prevent preeclampsia. The reason of successful outcome of this pregnancy could be related to heparin administration at the early terms of pregnancy that allowed for appropriate implantation and placenta formation, as well as for timely good glucose control.

Reproductive disorders in women with pre-gestational diabetes mellitus lead not only to poorer fertility, but to complicated course and poor outcomes of pregnancy for mother and fetus. Compared to general population, patients with pre-gestational diabetes mellitus have higher frequencies of ovulation delay, ovarian dysfunction and infertility, and if they become diabetic before their puberty, they have later menarche and earlier menopause. All this is caused by functional disorders of hypothalamic-hypophyseal-adrenal axis and ovarian insufficiency with significant decrease in progesterone levels. Pre-conceptional existence of diabetes mellitus is associated with high probability of menstrual cycle disorders, infertility, and in case of pregnancy – with its complicated course (congenital malformations, miscarriage, fetoplacental insufficiency, pre-eclampsia). The risk of these abnormalities is increased in case of late diabetic complications and poor glucose control. Babies born to diabetic mothers, beyond fetopathy and fetoplacental insufficiency, suffer from long term central nervous system disorders that may lead to problems in social adaptation. There are no effective treatments for advanced clinical pre-eclampsia and uncontrolled fetoplacental insufficiency that necessitates the pregnancy to be terminated in the interests of mother or fetus. Due to this, in women with pre-gestational diabetes it is reasonable to implement preventive measures including those aimed at the main components of pathophysiology of a number of obstetric complications. In particular, to correct potential complications of pregnancy in women with diabetes mellitus, administration of active forms of folinic acid and normalization of eicosanoid balance with oral polyunsaturated ω-3 fatty acids is indicated during pregnancy planning and during gestation.

The authors made a clinicoanatomic analysis of fetal death in a 32-year-old diabetic gravida at 34-35 weeks gestational age. Fetal autopsy identified the characteristic signs of fetopathy: macrosomy, cardiomegaly, hepatomegaly, and brain weight reduction. Histological analysis revealed minute foci of leukomalacia with glial proliferation in the cerebral hemispheres; adipose and hyaline drop degeneration of cardiomyocytes in the heart, that of hepatocytes in the liver, the proximal renal tubular epithelial cells; hemorrhages in the respiratory portions of the lung. The pancreas displayed inflammation foci, hypertrophy and hyperplasia of the islets of Langerhans. Immunohistochemical studies identified cells with enlarged nuclei among the beta and alpha-cells. The placenta showed a large mass with pronounced changes. It has been demonstrated that steroid diabetes may lead to the development of diabetic fetopathy and placental changes, which are typical of maternal diabetes.