On the effectivenessof a personalized approach in the prevention of calcitriol-associated complications of pregnancy and childbirth

Abstract

Aim: to assess vitamin D status (VDS) and frequency distribution of alleles and genotypes BsmI (A> G, rs1544410) polymorphism of the gene encoding VD receptors (VDR) in patients with placental dysfunction (PD) and physiological pregnancy, and to study the possibility of preventing calcitriol -associated complications of pregnancy and childbirth. Methods. At the 1st stage of work made on the principle "case-control", 56 pregnant women with PD (group ІА) and 40 women with physiological pregnancy (group ІB) were examined. At the 2nd stage, 57 women with VD deficiency and the history of pregnancy complicated by PD were undere xamination; 27 of them were observed from the pre-gravid stage (group IIA) and 30 – starting from the 1st trimester of pregnancy (group IIB). The level of 25 (OH) D in the blood was determined by ELISA, and Bsml polymorphism of VDR gene - by PCR. Patients at the 2nd stage in addition to the vitamin-mineral complex received colecalciferol at a dose of 4000 IU per day, after optimization of VD level (3-4 months) it was prescribed at a dose of 2000 IU per day until the end of pregnancy. Results. In pregnant women with PD, VD level was lower than in group IB (31.40 ± 8.6 and 43.54 ± 11.20) ng / ml, (p ≤ 0.05). A heterozygous combination of A / G alleles was diagnosed in 67.8% and in 35% in groups IA and IB, (OR = 3.95; 95% CI 2.19-7.1; χ2 = 20.88, p <0, 01); genotype A / A - in 12.5% and 17.5%, (OR = 0.68; 95% CI 0.31-1.48; χ2 = 1.013, p <0.05); genotype G / G - in 19.6% and in 47.5%, (OR = 0.27; 95% CI 0.15-0.51; χ2 = 16.71, p <0.01). association of average strength between the frequency of AP and genotype A / G, (OR = 3.8; 95% CI 2.1-6.8; χ2 = 20.88; p <0.01), medium-strength feedback - with genotype G / G, (OR = 0.27; 95% CI 0.15-0.51; χ2 = 16.71; p <0.01) In groups IIA and IIB, VD level before treatment was 15.72 ± 2,59 ng / ml and 16.1 ± 1.99 ng / ml, (U = 883; p> 0.05); after 3 months increased by more than 2 times (38.31 ± 3.29 ng / ml and 36.13 ± 2.99 ng / ml; U = 900; p> 0.05). Women who received VDc subsidies at the pregravid preparation stage, had pregnancy accompanied by fewer complications. Early gestosis was diagnosed in 7.4% and 36.7%, (F = 0.00001; p <0.01), violation of fetoplacental perfusion - in 18.5% and 40%, (F = 0.0018; p <0.01); signs of amnionitis - in 18.5% and 33.3%, (F = 0.035; p <0.05); low placentation - in 3.7% and 20%, (F = 0.0008; p <0.01); hyper- or hypotrophy of the placenta - in 7.4% and 36.7% (F = 0.00001; p <0.01), preeclampsia - in 3.7% and 6.7% (F = 0.54; p <0.05). The frequency of cesarean section was significantly higher in group IIB (40% vs 14.8%, F = 0.0018; p <0.01). Conclusion. Women with an aggravated obstetric history need to develop a personalized plan for pregnancy preparation and one of the directions of its management may be the assessment of vitamin D status and, possibly, the determination of Bsml of the VDR gene polymorphism associated with a high risk of developing placental dysfunction. With a deficiency of VDc, its timely subsidy from the stage of gravidar preparation is a pathogenetically determined and promising approach to pre-gravidar, preclinical prevention of perinatal and intrapartum complications. All human studies were conducted in compliance with the rules of the Helsinki Declaration of the World Medical Association "Ethical principles of medical research with human participation as an object of study". Informed consent was obtained from all participants.