[Vitamin D deficiency in pregnancy and its impact on the fetus, the newborn and in childhood]

Abstract

OBJECTIVE:: Vitamin D deficiency (VDD) in pregnant women and their children is an important health problem with severe consequences for the health of both. Thus, the objectives of this review were to reassess the magnitude and consequences of VDD during pregnancy, lactation and infancy, associated risk factors, prevention methods, and to explore epigenetic mechanisms in early fetal life capable of explaining many of the non-skeletal benefits of vitamin D (ViD).

DATA SOURCE:: Original and review articles, and consensus documents with elevated level of evidence for VDD-related clinical decisions on the health of pregnant women and their children, as well as articles on the influence of ViD on epigenetic mechanisms of fetal programming of chronic diseases in adulthood were selected among articles published on PubMed over the last 20 years, using the search term VitD status, in combination with Pregnancy, Offspring health, Child outcomes, and Programming.

DATA SYNTHESIS:: The following items were analyzed: ViD physiology and metabolism, risk factors for VDD and implications in pregnancy, lactation and infancy, concentration cutoff to define VDD, the variability of methods for VDD detection, recommendations on ViD replacement in pregnant women, the newborn and the child, and the epigenetic influence of ViD.

CONCLUSIONS:: VDD is a common condition among high-risk pregnant women and their children. The routine monitoring of serum 25(OH)D3 levels in antenatal period is mandatory. Early preventive measures should be taken at the slightest suspicion of VDD in pregnant women, to reduce morbidity during pregnancy and lactation, as well as its subsequent impact on the fetus, the newborn and the child.

Keywords: Children; Criança; Fetal programming; Feto; Fetus; Gestação; Lactation; Lactação; Newborn; Pregnancy; Programação fetal; Recém‐nascido; Vitamin D; Vitamina D.

Figure 1. Synthesis and metabolism of vitamin D as well as its action on the regulation of levels of calcium, phosphorus and bone metabolism (Adapted from Holick MF.8). UVB, ultraviolet light B; 25 (OH) D, 25-hydroxyvitamin D; 1,25 (OH) 2D, 1,25-dihydroxyvitamin D; 23-FGF, fibroblast growth factor 23; Ca2 +, calcium ions; HPO42-, phosphorus ions

Figure 2. Non-skeletal functions of 1.25-dihydroxyvitamin D (Adapted from Holick MF.8). VDR, vitamin D receptor; RXR, target region; 1-OHase, 25-hydroxyvitamin D-1a-hydroxylase; 25 (OH) D: 25-hydroxyvitamin D; 1,25 (OH) 2D, 1,25-dihydroxyvitamin D; 24-OHase, 25-hydroxyvitamin D-24-hydroxylase; p21 and p27, genes involved in the control of proliferation, angiogenesis inhibition and cell apoptosis

Figure 3. Regulatory mechanisms of serum levels of calcium and phosphorus. Adapted from Ross AC et al. PTH, parathyroid hormone; Ca²⁺, calcium ion; PO₄ ^3-, phosphate ions; ↑, increase; ↓, decrease

Figura 1. Síntese e metabolismo da vitamina D assim como sua ação na regulação dos níveis de cálcio, fósforo e metabolismo ósseo.8 UVB, raios ultravioleta B; 25(OH)D, 25-hidroxivitamina D; 1,25(OH)2D, 1,25-di-hidroxivitamina D; FGF-23, fator de crescimento de fibroblastos 23; Ca2+, ions cálcio; HPO42-, íons fósforo.

Figura 2. Funções não esqueléticas da 1,25-dihidroxivitamina D. Adaptado de Holick MF et al.8 VDR, receptor da vitamina D; RXR, região alvo; 1-OHase, 25-hidroxivitamina D-1a-hidroxilase; 25(OH)D, 25-hidroxivitamina D; 1,25(OH)2D, 1,25-di-hidroxivitamina D; 24-OHase, 25-hidroxivitamina D-24-hidroxilase; p21 e p27, genes envolvidos no controle da proliferação, inibição da angiogênese e apoptose celulares.

Figura 3. Mecanismos regulatórios dos níveis séricos de cálcio e fósforo. Adaptado de Ross AC et al.7 PTH, hormônio da paratireoide; Ca2+, íon cálcio; PO43-, íons fosfato; ↑, aumento; ↓, redução.