Polyhydramnios in pregnant women are one of the most frequent pathologies in obstetrics, which is caused by an increase in the use of ultrasound screening of pregnant women and ranges from 1–3 to 8%. The aim of the study was to evaluate changes in blood biochemical parameters, biophysical profile of the fetus and the health status of newborns in pregnant women with polyhydramnios during the prophylactic therapy of this pathology and to estimate the frequency of polyhydramnios occurrence under the influence of preventive therapy in pregnant women at risk of polyhydramnios. We examined 120 pregnant women at gestational age from 20 to 38 weeks between the ages of 20 and 39 years: 1 group consisted of 30 healthy pregnant women, 2 group — 90 pregnant women with chronic polyhydramnios, which was divided into two subgroups: 40 pregnant women without fetal distress in 1 subgroup and 50 pregnant women with fetal distress in 2 subgroups. 1 subgroup of pregnant women received prophylactic Magnerot, Tivortin, Larnamine, Lymphomyosot and vitamin D3. The 2nd subgroup of pregnant women received traditional treatment according to the clinical protocol of the Ministry of Health of Ukraine №900 dated December 27, 2006, №782 dated December 29, 2005. Prenatal diagnosis was carried out by the method of enzyme-linked immunosorbent assay: the metabolite level of vitamin D-25 OH(D) was determined, anti-inflammatory cytokines IL–10, IL–6, vascular endothelial growth factor VEGF, malonic aldehyde, carbonyl groups of proteins, superoxide dismutase, serum protein content. Conducted ultrasound examination of the fetus and dopplerometry of uterine-placental vessels, cardiotocography of the fetus, evaluated the biophysical profile of the fetus. The significance of the difference between the compared groups was determined using Student's t test. In pregnant women with chronic polyhydramnios, a decrease in endogenous glutathione antioxidant reserves, a decrease in the activity of the superoxide dismutase antioxidant enzyme, an increase in the activity of the pro-oxidant enzyme xanthine oxidase and the presence of cytokine imbalance have been found. It is shown that among all biochemical changes in the body of pregnant women with chronic polyhydramnios, vitamin D deficiency, inflammation and disturbance of angiogenesis play the most important role in the development of fetal distress. Pregnant women at high risk of polyhydramnios who received the proposed preventive therapy for fetal distress, improved fetoplacental blood flow, decreased the percentage of placental dysfunction by 1.8 times, fetal distress — by 1.5 times, premature birth — by 2 times, decreased asphyxia in newborns 1.7 times, the rate of perinatal morbidity in newborns decreased 1.9 times, compared with the group of pregnant women receiving traditional therapy. Thus, the positive effect of preventive therapy of pathology of pregnant women with polyhydramnios was confirmed clinically and biochemically.