Epidemiology of spontaneous pregnancy loss in Kazakhstan: A national population-based cohort analysis during 2014-2019 using the national electronic healthcare system.

INTRODUCTION: Spontaneous pregnancy loss (SPL) is a common health problem that affects 1:10 of childbearing women, and is linked with physical and psychological complications. As the number of nationwide studies on the incidence of SPL is few, especially from middle-income countries, in this study we investigated the epidemiology, complications and outcomes of SPL before 22 weeks of gestation by analyzing large-scale healthcare data from the Unified Nationwide Electronic Healthcare System (UNEHS) in Kazakhstan. MATERIAL AND METHODS: A population-based study among women who experienced SPL in any healthcare setting of the Republic of Kazakhstan during the period of 2014-2019. The International Classification of Diseases (ICD) 10th edition and ICD 9th edition's procedural codes were utilized to retrieve data using relevant diagnostic and procedural codes. RESULTS: In total, 207 317 records of women who have experienced an SPL before 22 weeks of gestation were analyzed from all Kazakhstani regions. The estimated prevalence of SPL was 8.7%, with a 20% decline over a 6-year period. The SPL cases ratio comprises on average 6.2 per 1000 reproductive-age women. Incomplete miscarriage (ICD-10 code "O03.4") was the most common type (37.8%), followed by blighted ovum (ICD-10 code "O02.0"; 34.1%) and missed abortion (ICD-10 code "O02.1"; 13.5%). The most common management methods were dilation and curettage of the uterus (ICD-9 code "69.0"; 84.7%) and aspiration curettage of the uterus (ICD-9 code "65.0"; 15%), whereas medical management was rarely performed (2.6%). CONCLUSION: The information available in UNEHS adequately identifies types of miscarriages and treatment methods. Although the prevalence of SPL before 22 weeks of gestation is decreasing, management of miscarriages requires closer attention.

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box.

Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

Biological Role of Folic Acid in Pregnancy and Possible Therapeutic Application for the Prevention of Preeclampsia.

The rationale and importance of folic acid supplementation during pregnancy for fetal congenital defect prevention are accepted worldwide. Moreover, a sufficient plasma concentration of folates can reduce the incidence of spontaneous abortions, and support the normal expansion of placental blood vessels, ensuring physiological placental blood flow, thus promoting appropriate fetal growth and development. Furthermore, there is emerging evidence that long-term supplementation with folic acid can effectively prevent preeclampsia. Preeclampsia is unique to the human species in complications during pregnancy, which contributes to maternal and perinatal mortality worldwide. In the pathogenesis of preeclampsia abnormal placental invasion, the excess of antiangiogenic factors and maternal-placental syndrome play a key role. Increased blood levels of homocysteine during pregnancy are associated with the risk of preeclampsia. Moreover, hyperhomocysteinemia has been proposed to be an independent risk factor for preeclampsia. Folate supplementation helps to decrease elevated levels of homocysteine; thus, the role of folic acid supplementation in pregnancy is even more important. Multiple reports suggest that folate administration decreases the level of serum homocysteine and, therefore, reduce the risk and severity of preeclampsia. However, the association between folic acid supplementation and the decreased risk of preeclampsia has been investigated with controversial conclusions. Currently, the optimal dose of folic acid that is effective for preeclampsia prevention remains uncertain. In this review, we aim to summarize the accumulated knowledge on the role of folic acid in the pathogenesis of preeclampsia, and the possible impact of folate supplementation on the decreased risk of preeclampsia.

Depression, Anxiety, and Stress in Kazakhstani Women with Recurrent Pregnancy Loss: A Case-Control Study.

Background: Recurrent pregnancy loss (RPL) is associated with increased incidence and severity of depression, anxiety, and stress, and screening for these comorbidities following miscarriages is beneficial for women with RPL who are planning future pregnancies. This study aims to investigate depression, anxiety, and stress among Kazakhstani women with RPL. Methods: This was a case−control study involving 70 women with confirmed RPL and 78 ethnically matched control women. Depression, anxiety, and stress were evaluated using the Depression Anxiety Stress Scales (DASS)-21 instrument. Linear regression and correlation analysis were used in assessing the association of RPL with symptoms of depression, and/or anxiety, and/or stress, after adjusting for key covariates. Results: Women with RPL were found to have significantly higher mean scores for depression (p < 0.001), anxiety (p < 0.001), and stress (p < 0.001) symptoms. Mild−moderate stress and mild−moderate and severe−extreme depression and anxiety symptoms were more frequent in the RPL group than in the control group. Regression analysis demonstrated that RPL was the only significant variable associated with anxiety, depression, and stress symptoms. Conclusion: The results of this study suggest that women with RPL are more likely to experience heightened symptoms of depression, anxiety, and stress. Proper psychological counseling is recommended for women with RPL, as well as their spouses.

Association of Human forkhead box protein 3 (FOXP3) gene polymorphisms with idiopathic recurrent pregnancy loss among Kazakhstani women.

BACKGROUND: Recurrent pregnancy loss (RPL) is major pregnancy complication, with poorly defined cause.Forkhead Box P3 (FOXP3) is a transcription factor that supports Treg activation and development and attenuates immune responses. As FOXP3 production is genetically determined, we tested the association of FOXP3 gene variants with RPL. METHODS: A retrospective case-control study, performed between April 2019 and February 2020. Study subjects comprised 62 RPL cases and 60 control women. Genotyping of the four FOXP3 variants rs2294021 (T > C), rs2232365 (G > A), rs3761548 (C > A), and rs141704699 (C > T) was done by real-time PCR, with defined clusters. Logistic odds ratios (ORs) of RPL risk were estimated with 95% confidence interval (CI) after adjustment; statistical significance set at P < 0.05. RESULTS: Minor allele frequency (MAF) of rs2294021 was significantly lower [P < 0.001; OR(95% CI) = 0.25(0.11-0.55)], while rs2232365 MAF was significantly higher [P = 0.045; OR(95% CI) = 1.85(1.05-3.28)] in cases, hence assigning RPL-protection and -susceptibility to these variants, respectively. Increased RPL risk was seen in rs2232365 homozygous minor allele carrying genotype [OR(95% CI) = 5.14(1.01-26.15)], while reduced RPL risk was noted in rs2294021 heterozygous [OR(95% CI) = 0.30(0.11-0.80)], and homozygous minor allele [OR(95% CI) = 0.10(0.01-0.83)] genotype carriers. Moderate linkage disequilibrium analysis was seen between the tested variants. Increased frequency of TACC, and reduced frequency of CGAC haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection to these haplotypes, respectively. CONCLUSION: These results suggest that FOXP3 variants and haplotypes are associated with idiopathic RPL, suggesting the likely contribution of Treg to RPL.