IL-33 and Soluble ST2 Are Associated With Recurrent Spontaneous Abortion in Early Pregnancy

Normal pregnancy is related to the successful transition from type 1 cellular immunity to type 2 cellular immunity. Therefore, this study aimed to investigate whether there is abnormal expression of cytokines in the process of inducing Recurrent spontaneous abortion (RSA). Interleukin (IL)-33 is a new member of the IL-1 family, and ST2, as IL-33’s receptor, induced the production of type 2 cytokines. In this study, blood samples were collected from 19 non-pregnant women of normal childbearing age, 28 normal pregnant women, and 33 women with RSA. The serum concentrations of IL-33 and ST2 were detected by flow cytometry. Our results showed that the serum concentrations of IL-33 and ST2 in the RSA group were significantly higher than those in the healthy control group (IL-33: P < 0.05; ST2: P < 0.0001), and IL-33 and ST2 had a higher level in the process of RSA predictive value. In addition, this study initially found that the serum concentrations of IL-33 and ST2 were not significantly correlated with the number of weeks of pregnancy, and there was a lower correlation between IL-33 and ST2 during RSA. This result may be related to the small number of cases. This study is the first time to correlate the changes in serum concentrations of IL-33 and ST2 with RSA, which may be a novel biomarker for the prediction and treatment of RSA.

Toxoplasmosis impact on prematurity and low birth weight

Background Toxoplasma gondii, one of the most common parasites, causes toxoplasmosis, one of the most frequent zoonotic diseases worldwide. T. gondii infects about one-third of the world’s population. T. gondii infection is generally considered a major risk for spontaneous abortion, prematurity and low birth weight in the animal sphere. Less commonly, a toxoplasma serological profile is correlated with the particular data of delivery. Acute T. gondii infection during pregnancy often leads to spontaneous abortion and/or a severe injury of the eyes, brain, and other structures of the foetus. Latent T. gondii infection of pregnant women could lead to less obvious but important changes during pregnancy, including the end product of pregnancy and the timing of labour. This study aimed to contribute to the current knowledge by comparing serological T. gondii profiles of pregnant women with prematurity and low birth weights of newborns. Material and methods A retrospective study design was adopted. The study participants included a cohort of 1733 pregnant women who consecutively gave birth to their children and underwent regular antenatal biochemical screening between the 14th and 16th weeks of pregnancy. Prematurity was defined as the liveborn preterm delivery in gestational age of pregnancy <37 weeks. Low birth weight was defined as weight at birth of ≤2499 grams. The complement-fixation test (CFT) provided serological profiles for toxoplasmosis that expresses the overall levels of toxoplasma immunoglobulins of all classes. Enzyme-linked immunosorbent assay (ELISA) tests for IgG and IgM were used simultaneously. IgM positivity helped to differentiate acute from the latent stage of toxoplasmosis. Birth data, especially the week of delivery and fetal weight, were evaluated accordingly. Results Of the 1733 pregnant women, 25% were diagnosed as latent toxoplasma positive, and 75% as toxoplasma negative. There were 87 premature deliveries versus 1646 timely births. We observed 88 low birth weights and 1645 normal fetal weights. We found a statistically significant association between latent toxoplasmosis and prematurity, χ2(1) = 5.471, p = .019 and between latent toxoplasmosis and low birth weight of newborns, χ2(1) = 7.663, p = .006. There was a 1.707 times higher risk of prematurity for toxoplasma-positive women, while the risk for low birth weight was 1.861 times higher. The strength of both tests of association was mild. We tested the correlation between the levels of CFT titres and week of delivery and weight of newborns. No association was found between the level of latent toxoplasmosis and the week of delivery and fetal weight. Conclusion Latent toxoplasmosis was associated with premature birth rate and lower birth weight of newborns. The odds of premature delivery was 1.7 and low birth weight 1.9 times higher in women with latent toxoplasmosis compared to toxoplasma negative women. Even though the strength of the association in our large sample is relatively mild, the combination of latent toxoplasmosis with other adverse factors could cause serious harm. Whole CFT and specific IgG levels of latent toxoplasmosis are not linked to the severity of prematurity or low birth weight in newborns.

Interactive Effects of Maternal Vitamin D Status and Socio-Economic Status on the Risk of Spontaneous Abortion: Evidence from Henan Province, China

Background: Maternal vitamin D deficiency might generate adverse reproductive outcomes, and socio-economic inequalities in micronutrient-related diseases have often been found. This study aimed to explore the interactive effects of maternal vitamin D status and socio-economic status (SES) on risk of spontaneous abortion. Methods: A population-based case–control study was conducted including 293 women with spontaneous abortion and 498 control women in December 2009 and January, 2010 in Henan Province, China. Information on pregnancy outcomes, maternal demographic, lifestyle and exposure factors and blood samples were collected at the same time. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. SES index was constructed with principal component analysis by aggregating women’s and their husbands’ education level and occupation, and household income and expenditure. Interactive effects were assessed on a multiplicative scale with ratio of the odds ratio (ROR). Results: Compared to those with high SES and vitamin D sufficiency, women with vitamin D deficiency and low SES index had an increased risk of spontaneous abortion (aOR: 1.99; 95% CI: 1.23–3.23). The ROR was 2.06 (95% CI: 1.04–4.10), indicating a significant positive multiplicative interaction. Conclusions: Maternal low SES may strengthen the effect of vitamin D deficiency exposure on spontaneous abortion risk in this Chinese population.

Clinical and statistical assessment of the reproductive health of fertilized women in the Tyumen region and the risks of miscarriage in Western Siberia

Introduction. Loss of pregnancy remains an extremely acute public health problem today. Live birth accounts for only 30% of gestational outcomes, all other pregnancies that occur end in reproductive losses: 30% – implantation, 30% – postimplantation, 10% – spontaneous miscarriages. In conditions of declining birth rates, reducing reproductive losses is the most important element of the state’s demographic policy.Аim. Тo assess the reproductive health of women of fertile age in the Tyumen region, registered in antenatal clinics and other medical institutions in connection with pregnancy, as well as the risks associated with an increase in the frequency of diseases endemic for the West Siberian region.Materials and methods. The study used data from federal statistical observation. Statistical analysis of the data was carried out using the statistical program Statistica (version 13.0). Quantitative features are described by absolute and relative (percent) indicators. The difference is considered significant at p < 0.05. Results. Despite the increase in the number of women of reproductive age, fertility rates are declining both in the Tyumen region and in the Ural Federal District, as well as in Russia as a whole. The 5-year dynamics of registered pregnancies in the Tyumen region correlates with the dynamics of the birth rate. The incidence of HIV and hepatitis C among pregnant women for five years and for each of the given nosologies exceeds 1% of the number of patients admitted under the supervision of health care facilities. At the same time, since 2018, the incidence of ectopic pregnancy associated with HIV has significantly increased (p >< 000.1). These data also indicate an increased risk of spontaneous abortion in HIV-infected pregnant women (p >< 000.1). From 2016 to 2019, there has been a steady increase in the incidence of ectopic pregnancies and spontaneous abortion in primary pregnant women. The situation has improved somewhat in 2020. Noteworthy is the high share of medical abortion in birth control. Сonclusions. Despite the increase in the number of women of reproductive age, fertility rates are declining both in the Tyumen region and in the Ural Federal District, as well as in Russia as a whole. The 5-year dynamics of registered pregnancies in the Tyumen region correlates with the dynamics of the birth rate. >< 0.05.Results. Despite the increase in the number of women of reproductive age, fertility rates are declining both in the Tyumen region and in the Ural Federal District, as well as in Russia as a whole. The 5-year dynamics of registered pregnancies in the Tyumen region correlates with the dynamics of the birth rate. The incidence of HIV and hepatitis C among pregnant women for five years and for each of the given nosologies exceeds 1% of the number of patients admitted under the supervision of health care facilities. At the same time, since 2018, the incidence of ectopic pregnancy associated with HIV has significantly increased (p < 000.1). These data also indicate an increased risk of spontaneous abortion in HIV-infected pregnant women (p >< 000.1). From 2016 to 2019, there has been a steady increase in the incidence of ectopic pregnancies and spontaneous abortion in primary pregnant women. The situation has improved somewhat in 2020. Noteworthy is the high share of medical abortion in birth control. Сonclusions. Despite the increase in the number of women of reproductive age, fertility rates are declining both in the Tyumen region and in the Ural Federal District, as well as in Russia as a whole. The 5-year dynamics of registered pregnancies in the Tyumen region correlates with the dynamics of the birth rate. >< 000.1). These data also indicate an increased risk of spontaneous abortion in HIV-infected pregnant women (p < 000.1). From 2016 to 2019, there has been a steady increase in the incidence of ectopic pregnancies and spontaneous abortion in primary pregnant women. The situation has improved somewhat in 2020. Noteworthy is the high share of medical abortion in birth control. Сonclusions. Despite the increase in the number of women of reproductive age, fertility rates are declining both in the Tyumen region and in the Ural Federal District, as well as in Russia as a whole. The 5-year dynamics of registered pregnancies in the Tyumen region correlates with the dynamics of the birth rate. >< 000.1). From 2016 to 2019, there has been a steady increase in the incidence of ectopic pregnancies and spontaneous abortion in primary pregnant women. The situation has improved somewhat in 2020. Noteworthy is the high share of medical abortion in birth control.Сonclusions. Despite the increase in the number of women of reproductive age, fertility rates are declining both in the Tyumen region and in the Ural Federal District, as well as in Russia as a whole. The 5-year dynamics of registered pregnancies in the Tyumen region correlates with the dynamics of the birth rate.

Adverse Events During Pregnancy Associated With Entecavir and Adefovir: New Insights From a Real-World Analysis of Cases Reported to FDA Adverse Event Reporting System

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring.Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP).Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value &gt;2, and lower limit of 95% confidence interval (CI)&gt; 1.Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively.Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice.

The effect of post-abortion care (PAC) on anxiety in women with spontaneous abortion based on MicroRNA-21 expression, cortisol level, and Fordyce happiness pattern

Abortion is one of the most common complications in pregnancy, and the cause of its occurrence in many cases remains unknown. The high prevalence and consequences of anxiety in women with spontaneous abortion could highlight the importance and role of post-abortion care (PAC). Detection and identification of biomarkers related to abortion and anxiety can effectively diagnose and prevent complications. Among the known biomarkers, microRNAs and the cortisol level have high potential. Therefore, the present study evaluated the effect of post-abortion care (PAC) on anxiety in women with spontaneous abortion based on MicroRNA-21 expression, cortisol level, and Fordyce happiness pattern. In this randomized clinical trial, 72 women with spontaneous abortion were studied and randomly divided into two groups of intervention (n = 36) and control (n = 36). Data were collected through a demographic questionnaire and HADS. To assess PAC, the intervention group was consulted in 8 sessions of 60 minutes in the first 72 hours after abortion. Meetings were held twice a week for four weeks. Both groups were followed up immediately after and one month after the intervention. To evaluate biological factors, 4ml of blood sample was obtained from the subjects. Blood cortisol levels were measured by the Cortisol Competitive Human ELISA Kit (Thermo-Fisher, USA), and microRNA-21 evaluation was performed by Real-time PCR technique. Data were analyzed using SPSS16 software. Results showed that before the intervention, there was no significant difference in the mean score of anxiety between the control and intervention groups (P> 0.05); But at the time immediately and one month after the intervention, there was a significant difference in the mean score of anxiety (p <0.001). The results of biological factors evaluation showed that in the intervention group, serum cortisol levels and microRNA-21 expression decreased significantly (p <0.05). In general, PAC based on the happiness pattern can control the anxiety of women with spontaneous abortion. Therefore, it is recommended as an effective and non-invasive intervention in preventing women's psychological problems after spontaneous abortion.

Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation

Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA.