Study: Vitamin D in miscarriage prevention

Reference

samimi m, foroozanfard f, amini f, et al. Effect of a vitamin D supplementation in inexplicable recurrent spontaneous abortions: a double-blind, randomized control study. glob j health sci . 2017; 9 (3): 95-102.

Study goal

Investigation of the effects of a vitamin D supplementation in inexplicable recurrent spontaneous abortions (URSA)

Design

double -blind, randomized control study

participant

The investigators recruited 80 women aged 18 to 35 who were transferred to pregnancy to an obstetric and gynecological clinic in Iran. All participants had experienced at least 2 consecutive or 3 non -successive spontaneous miscarriages for unknown cause and pregnancy by the same partner in all past and current pregnancies. The participants had no other contributors, including uterine anomalies, thrombophilia, genetic diseases, endocrine disorders, chemical stress in the workplace or sensitivity/allergy to progesterone or vitamin D3.

study parameters evaluated

In the patients, the serum vitamin D and interleukin (IL) -23 levels were measured at the start of the course and again when the study was completed. Loss of pregnancy was regarded as a spontaneous abort from the beginning of the study to the 20th week of pregnancy.

primary result measurements

The incidence of spontaneous miscarriage at some point in time between the beginning of the study and the 20th week of pregnancy was examined, as was the serum levels of IL-23 at the beginning of pregnancy and again at the time of the spontaneous miscarriage or the 20th week of pregnancy.

Intervention

The intervention group (n = 40) received 400 IE vitamin D3 in tablet form every day. The control group (n = 40) received an identical placebo without D3. Both groups received 400 mg vaginal progesterone per day. The patients also received folic acid and iron preparations at least 1 month before pregnancy.

important knowledge

Before the study started, the serum vitamin D levels were 11.65 ± 3.76 ng/ml in the intervention group and 11.53 ± 2.39 ng/ml in the control group ( p = 0.86). At the end of the study, the values ​​had changed to 13.21 ± 3.47 ng/ml or 11.08 ± 2.76 ng/ml ( p = 0.004). Before the study started, the IL-23 levels were 20.69 ± 3.01 pg/ml in the intervention group and 21.52 ± 4.37 pg/ml in the control group ( p = 0.33) and at the end of the study they were 18.4 ± 3.78 pg/ml or 23.16 ± 4.74 p. ( p <0.001). There was an opposite relationship between vitamin D and IL-23 levels ( p = 0.004). The number of spontaneous abortions during the study period was 5 (12.8 %) or 13 (34.2 %) in the intervention and control group (OR: 3.53; 95 %confidence interval [CI]: 1.12-11.2; p = 0.03).

Taking into account disruptive factors such as age, gravidity, number of abortions and IL-23 levels, the vitamin D3 levels were statistically not significant (OR: 3.53; 95 %-KI: 1.12–11.2; p = 0.03). However, the serum il-23 levels and the incidence of abortions were statistically significant (odds ratio [or]: 1,63; 95 % KI: 1.26–2.11; p <0.001). Based on their analysis, the researchers came to the conclusion that vitamin D3 lowers the frequency of abortions by the causal path with IL-23. They also point out that other biological confounders should be taken into account.

practice implications

This study complements the growing number of research results that show the role of vitamin D3 in the event of infertility and recurring miscarriages. This study specifically examined the relationship between the serum vitamin D3 mirrors and the IL-23 levels and the rate of unexplained recurrent spontaneous abortions (URSA).

Ursa is a complex illness that affects 2 % to 4 % of women worldwide and is defined by the American Society of Reproductive Medicine as 2 or more consecutive spontaneous miscarriages before the 20th week of pregnancy. Low or high body mass index (BMI), alcohol consumption, severe lifting and night shift work identified. ^{2 In the case of URSA, several contributions were recognized, including uterus anomalies, endocrine disorders, genetic disorders, coagulation disorders and environmental factors, although the cause of most cases of Ursa is unknown remains.}

According to the American Pregnancy Association, 40 % to 60 % of North Americans, including pregnant women, have a vitamin D deficiency.

It was previously shown that vitamin D levels reduce the frequency of miscarriages in the first trimester; However, there was no connection between low vitamin D and a miscarriage in the second trimester. ^{3 Women with Ursa and low vitamin D mirrors have greater likelihood of antiphospholipide antibodies, antinuclear antibodies, thyro-operated oxide antibodies and increased natural killer cells (NK) than women with normal Vitamin D status. 4 What indicates an immunomodulating role in the fetomatic interface. The presence of vitamin D receptors and enzymes, which are responsible for vitamin D hydroxylation, and the identification of a localized vitamin D3 synthesis in human placenta and decidua 5 further highlight the potential mechanism between vitamin D status and persistent pregnancy.}

Until recently, research on recurring miscarriages focused on the T-helper-Typ-1 (TH1)/Th2 paradigm. In this paradigm, the motherly tolerance of fetal alloantigen is explained by the prevailing TH2 immunity during pregnancy, which overrides the TH1 immunity and thus protects the fetus from a TH1 cell attack. (Tregs). ^{6 There are now several studies that indicate an increased TH17/TREG relationship with URSA, which creates an inhospitable environment for the survival of the fetus. showed that both TH17 and IL-23 were higher in the serum and in the placenta of women with Ursa compared to normal women in early pregnancy.}

vitamin D3 was extensively examined for its immune -modulating effects, including its ability to suppress cytokin production by TH17. The presence of IL-23, which is secreted by activated type 1 macrophages and dendritic cells, promotes the development of TH17 and the resulting cytokines, including IL-17. Vitamin D reduces the differentiation of TH17/TREG intermediate cells to TH17 cells, possibly through their high concentration of vitamin D receptors. ^{9 This shift changes the expression of many genes, including the GEN for IL-17, which may reduce the TH17-induced inflammation path.}

Several studies focus on the vitamin D3 serum mirror at the time of miscarriage, but so far none has shown the effects of a vitamin D supplement on the pregnancy outcome at URSA. The dosage used in the current study was 400 IE, which is under the therapeutic area in almost all regions of the world, whereby the recommendations of different organizations from 600 IE to 4,000 IE vary greatly for pregnant women. Minimum levels of 20 ng/ml were, although there was a statistical decrease in IL-23 levels, which the authors attribute to the vitamin D supplementation. The authors do not respond to the ongoing vitamin D deficiency in the intervention group or state whether they would expect improved results if the serum levels were increased to the normal range. In view of the positive result of the study, with a lower than the therapeutic dosage of vitamin D3 paired with the existing vitamin D deficiency status of the test subjects, one could speculate that the use of therapeutic vitamin D3 levels could lead to the serum levels are brought back into an adequate area.

In a recently carried out study, 300,000 IE vitamin D3 were administered by injection in a single bolus dose after lymphocyte immunotherapy (LIT), a controversial treatment of URSA. The researchers showed a reduction in the TH17/TREG ratio according to vitamin D3 supplementation and showed a promising trend for a better pregnancy result in the treatment group. The study was published before all women who had reached pregnancy, so that no data on the frequency of miscarriage were available.

According to the American Pregnancy Association, 40 % to 60 % of North Americans, including pregnant women, have a vitamin D deficiency. ^{12 In view of the fact that vitamin D3 is a cost-effective and easily accessible vitamin with a variety of health advantages, including general health, fertility and exit of pregnancy, it is very useful To ensure the patient's vitamin D status before conception to not only prevent miscarriage, but also a broad spectrum of avoidable diseases and suffering.}