vitD3 Level in Cases of Recuurent Pregnancy Loss Clinical Trial
Official title:
Assesment of Vit D3 Level in Cases of Unexplaind Pregnancy Loss in Assiut
Assesment of Vit D3 leve in cases of unexplained recurrent pregnancy loss in assiut
Recurrent pregnancy loss is defined as two or more consecutive pregnancy loss before 20
weekse of gestation (1). It affects about 1-5% of women of reproductive age. This not only
causes significant physical and mental problems in families, but also a heavy economic burden
on families and health systems (2, 3) Recurrent pregnancy loss (RPL) is a syndrome caused by
multiple etiologies such as anatomical, endocrine, genetic, infectious, immunological,
thrombotic and unexplained etiologies hence an investigation of underlying etiologies is
often complicated When the conventional investigation scheme is applied, up to 60% of women
with RPL remain unexplained (4). Recent studies have indicated that immune inflammatory and
thrombotic conditions are two major under-lying pathologies for RPL (5). Approximately 20% of
women with RPL have autoimmune conditions, such as antiphospholipid antibody
(APA)(6),antinuclear antibody (ANA), anti-thyroperoxidase antibody and anti-thyroglobulin
antibody(7,8).
Immune function in pregnancy From initial implantation of the conceptus, the maternal uterine
endometrium undergoes decidualisation to support placental development and function. The
resulting decidua is a tissue formed from the maternal endometrium, originating from
epithelial and stromal cells, and is characterised by invasion from the extraembryonic
fetal-derived trophoblasts and close 'cell-cell juxtaposition' of these different tissues The
principal function of the decidua is to facilitate early fetal-maternal exchange of
nutrients, gases and waste, while also acting as a secretory source of steroid hormones,
cytokines and growth factors (9).However, the decidua also plays a key role in protecting
pregnancy against maternal immune surveillance(10) .
Cellular infiltration is a key feature of immune function within decidua, and leukocytes
comprise at least 40% of the total decidual stromal cell population(11) . The leukocyte
subtypes present include decidual (uterine) natural killer (uNK) cells, macrophage subtypes,
CD4C and CD8C T-lymphocytes (including T-regulatory cells (Tregs) and antigen-presenting
cells (APCs) such as dendritic cells (DCs)(12) . There has been renewed interest in the role
vitamin D, as key regulators of decidual immune cell function and its roles in fetal-maternal
immune tolerance (13) .
- 3 - Vitamin D and autoimmunity Vitamin D, a steroid hormone, is well known to be involved
in calcium and phosphate homeostasis and bone metabolism (14).The target organs for the
non-classical actions of the vitamin D include immune systems, pancreatic b-cells, the heart
and cardiovascular system, the brain and reproductive tissues. Tissue responses to vitamin D
include regulation of hormone secretion modulation of immune responses, and a control of
cellular proliferation and differentiation (15). Vitamin D was also reported to inhibit
proliferation of T helper 1 (Th1) cells and limit their production of cytokines, such as
interferon gamma (IFN-g), interleukin-2 (IL-2) and tumor necrosis factor-alpha
(TNF-a).Conversely, vitamin D induces T helper 2 (Th2) cytokines, such as IL-4, IL-5, IL-6,
IL-9, IL-10 and IL-13 (16). Furthermore, in many studies vitamin D has been presented as a
modifiable environmental factor for Th1-mediated autoimmune disease and appears to be
important for susceptibility to and severity of the disease (17). Vitamin D also regulates B
cell immunity. It down-regulates the proliferation and differentiation of B lymphocytes and
inhibits IgG production (16).
Vitamin D deficiency in pregnant women is associated with increased risk of obstetrical
complications such as pre-eclampsia (18), bacterial vaginosis associated preterm delivery
(19), gestational diabetes mellitus (20) and small-for-gestational age births (21).
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