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Clinical-biological and genetic changes in vitamin D status in pre- and postnatal periods of child's development

Author: Voloc Alexandru
Degree:doctor habilitat of medicine
Speciality: 14.00.09 - Pediatrics
Scientific consultant: Michèle Garabédian
doctor în științe medicale și biologice, doctor de stat, director de cercetări de I clasă, profesor.,
Institution: Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova


The thesis was presented on the 23 December, 2016
Approved by NCAA on the 16 February, 2017


Adobe PDF document1.35 Mb / in romanian


CZU 616.391:577.161.2-053.1/.2

Adobe PDF document 5.66 Mb / in romanian
217 pages


prenatal and postnatal prevention of vitamin D deficiency, vitamin D status, Klotho gene, VDR, haplotype, lactase gene LCT.


The field of study: pediatrics.

Goal: Evaluation of the impact of vitamin D deficiency on phospho-calcic metabolism and bone health in correlation with genetic factors in children and adolescents, ways of correction.

The study objectives: Evaluation of the impact of vitamin D deficiency on the clinicalphysiological and genetic status in children and adolescents. Study of manifestations of vitamin D deficiency depending on the ontogenetic period of child development (in utero, early and late postnatal), season and climatic and geographic area (Moldova, France, Algeria, Martinique, Ingushetia). Comparative analysis of inferior limbs deformities and biochemical parameters in association with vitamin D values in children and adolescents from Moldova and France. Detecting the impact of genetic factors on calcium metabolism, bone health, physical development, through the prism of 3 gene polymorphism: VDR, Klotho and LCT in association with serum level of vitamin D in children and adolescents of different ages. Development of diagnostic algorithm of hypocalcaemia to optimize early diagnosis. Elaboration of therapeutic management of vitamin D deficiency aiming to improve specific treatment and prophylaxis.

Methodology: two types of study: clinical controlled study with randomized selection of pregnant women and newborns, and a cohort study.

Scientific novelty and originality: For the first time in the Republic of Moldova we have conducted a multicentric international study to assess multiple aspects of vitamin D deficiency, applying a specific vitamin D deficiency prevention strategy, in-depth study of genetic polymorphism of different genes with an impact on bone mass and density. We have studied the influence of calcium/dairy products intake on bone health by testing the LCT lactase gene polymorphism.

Scientific problem solved through this research lies in estimating the clinical-physiological and genetic pattern of vitamin D deficiency in pre- and postnatal child development through the prism of determining the correlation between vitamin D status, calcium intake with VDR genotype and Klotho gene polymorphism in children and adolescents for an abjective diagnosis and efficient treatment of hypocalcaemia conditions.

Theoretical value: Highlighting pathogenetic links leading to clinical and laboratory picture of bone demineralization is an essential baseline in broadening the existing knowledge in bone deformities.

Practical value of the research: A new concept of pre- and postnatal specific prevention of neonatal hypocalcaemia and vitamin D deficiency rickets was developed by optimizing the therapeutic management, thus improving the quality of life in children and adults in the long term.

Implementation of international multicentric scientific results: The result of the study were implemented in Department of Pediatrics of the SMPU "N. Testemitanu", Regional Hospital Centre of Franceville, University Centers in Angondge, Koula-Moutou, Owendo and Libreville (Equatorial Africa).