Vitamin D deficiency during pregnancy: Effects, treatment and the outcomes
The aim of this study is to evaluate vitamin D deficiency in pregnant women and its impact on pregnancy course, the best way of management, and the outcome of this management
Bone metabolism in humans is associated with a complex steroid hormone system which comprises of vitamin D (Harvey, et al. 2014). Many reports have suggested the potential benefits of vitamin D across therapeutic areas including vascular health, placental function, metabolism, and immune function (McAree, et al. 2013).
Data based on biological and clinical findings suggest the key role of vitamin D in women reproductive health. However, there is not much evidence to highlight the correlation of vitamin D and adverse pregnancy outcomes. Researchers also contradict the hypothesis of adverse pregnancy outcomes and vitamin D deficiency. The lack of evidence and contradictory information is due to small sample sizes, significant heterogeneity in populations, inadequate control for confounding, and significant heterogeneity in exposure measurement. Till date, healthcare professionals are unable to define vitamin D deficiency and its correlation to pregnancy outcomes. However, it is suggested to pool data from a series of observation studies in order to analyse and evaluate vitamin D deficiency and pregnancy outcomes. Many studies have also show the importance of vitamin D in reproductive health but do not define or provide evidence that vitamin D could cure pregnancy complications. Furthermore, there is limited information on the cure of multifactorial aetiologies of pregnancy due to vitamin D supplementation. Current guidelines and recommendations on daily allowance of vitamin D for pregnant women of 600 IU should be followed until clear evidence on daily recommended allowance is defined (Kaushal & Magon 2013).
This paper provides an overview of vitamin D deficiency in pregnancy its effects and the probable treatment and management strategies to assess better health outcomes.
Objective: This review will summarize the latest scientific evidence of the effect of maternal vitamin D deficiency, the management and the maternal and foetal outcomes.
Pregnancy outcomes: A critical analysis and systemic review on the levels of vitamin D and adverse pregnancy outcomes concluded that the association of vitamin D levels and pregnancy outcomes (complications) such as diabetes and preeclampsia needs to be investigated and remains inconclusive (Urrutia, & Thorp 2012). In a similar analysis, 5 studies were reviewed based on a nested case-control design wherein dietary quality and intake of vitamin D was assessed. However, due to the small cluster size, the results of these studies could be confounding. Based on these 5 studies it can be stated that dietary intake and quality is associated with adverse pregnancy outcomes. These studies also indicate the correlation of vitamin D deficiency in pregnancy outcomes (Urrutia, & Thorp 2012).
Many research studies and scientist have been investigating the link between vitamin D supplementation and pregnancy outcomes. They have also been identifying the association of vitamin D levels and pregnant women and perinatal outcomes (Urrutia, & Thorp 2012).Based on current evidence, vitamin D deficiency can have an impact on reproductive health and pregnancy based on the following factors identified across various studies:
Gestational Hypertension/Preeclampsia
In the case of immune modulation and human placenta, vitamin D and its receptors are known to be active which suggests a role of vitamin D deficiency and preeclampsia (Thorne-Lyman & Fawzi. 2012). A cohort study has supported this hypothesis based on vitamin D exposure in women through randomization of vitamin D supplements. Researchers observed that vitamin D exposure in women is associated with less preeclampsia. In a systematic review in 2012, high levels of vitamin D were reported to have less preeclampsia and lower hypertension based on assessment at delivery and diagnosis (De-Regil, et al. 2012).
Gestational Diabetes
Vitamin D deficiency has been associated with type 2 diabetes in non-pregnant women. There is no clear understanding on the relationship between vitamin D deficiency and gestational diabetes. However, many case-control studies have been reviewed from 3 countries to assess vitamin D levels and gestational diabetes. The results of these studies are mixed and supportive studies are required to make conclusions (Alzaim & Wood. 2013).
Birth Weight
Since Vit. D is involved in bone metabolism, researchers have hypothesized its deficiency with low birth weight (Khalessi, et al. 2015). There is no conclusive data on vit. D deficiency and low birthweight, both at delivery or first trimester vit. D levels. However a large scale cohort study in Amsterdam (3730 women) was found to have low birth weights in women with severe vit. D deficiency at early pregnancy (Khalessi, et al. 2015).
Preterm Delivery
Vitamin D is also known to be associated with increased markers of inflammation which is suggestive of its role in the prevention of preterm birth. There are few studies that have provided vital information on vit. D and preterm delivery. However, a recent study on 40 cases of women who suffer from preterm birth were linked with chorioamnionitis which concludes link of vit. D and preterm delivery (Bodnar, et al. 2015).
Caesarean delivery
Vit. D deficiency and rickets have been linked with pelvic deformities followed by a correlation with an increased risk for obstructed delivery. A study on 300 women confirmed that vit. D deficiency was linked with a higher rate of caesarean delivery (levels <37.5ng/L). This study confirmed the risk of caesarean delivery and vit D. deficiency (Scholl et al. 2012).
Scientific reasoning: In pregnancy, there is an increase in the demand of vitamins, including vitamin D, recent studies found that low maternal vitamin D status is associated with an increased risk of adverse pregnancy outcomes
Vit. D receptors (VDR) and 1αhydroxylase are found in active reproductive tissues. However, researchers are yet to explore the effects of these receptors and make conclusive statements on their roles in the tissues. In a pregnant mice model, VDR was expressed in the placenta, ovarian follicular tissue, and decidual which is suggestive of the hypothesis that vit. D could have a role in the physiological aspects of pregnancy (Shin, et al. 2010).
A genetic analysis based on gene expression profiles was carried out by a group of researchers in pregnant women. (Wagner, et al. 2012). Two groups, women with low levels of vit. D (<25.5ng/ml) and high levels of vit. D (>31.7ng/ml) were evaluated. It was observed that over 300 genes in women with high levels of vit. D were expressed. These genes were associated with varying functions that could impact pregnancy outcomes such as immune function, carbohydrate metabolism, and angiogenesis (Wagner, et al. 2012).
In a recent study, vit. D is known to alter pregnancy outcomes which is linked with the modulation of immune response. In an in-vitro study, human trophoblast cells were treated with vit. D which altered the innate immune response. In a murine model, the trophoblast cells were found to have an increased inflammatory response in 1αhydroxylase and VDR knockout mice. Further analysis with treatment of widl type cells with vit. D supplements suppressed inflammatory responses. This indicates the key biological role of vit D in pregnancy. Lastly, in a study with human syncytiotrophoblastic cells, a reduction in the levels of oxidative stess markers was observed due to high dose of vit. D (Reichetzeder, et al. 2014). Thus, it can be concluded that vitamin D deficiency has an impact on pregnancy outcome and that vit. D supplementation is required to prevent adverse pregnancy outcomes.
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