Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women.

BACKGROUND: The folate metabolism that converts homocysteine to methionine is closely related to the accumulation of homocysteine. Increased homocysteine levels lead to an impaired antithrombotic function of the vascular endothelium and uterine-placental circulation, resulting in abnormal pregnancy outcomes. Previous studies have reported that gene polymorphisms in folate metabolism are associated with the development of preterm birth (PTB) in various populations. OBJECTIVE: we performed a case-control study to evaluate the association between five polymorphisms in folate metabolic genes (MTHFR, MTR, MTRR, TCN2) and PTB. METHODS: In this study, a total of 254 subjects were analyzed (111 patients with PTB and 143 women at ≥ 38 weeks of gestation). Genotype and allele frequency differences between patients and control groups and the Hardy-Weinberg equilibrium were assessed using a Chi-square test. For evaluation indicators, odds ratios (ORs) of 95% confidence intervals (CI) were estimated. In addition, we analyzed the combined genotype frequencies of SNPs of folate-metabolizing genes to measure gene-gene interactions for PTB. RESULTS: Our results showed that the MTR rs1805087 GG (p = 0.031), and TCN2 rs1801198 CG genotype (OR 0.53, 95% CI 0.288-0.980, p = 0.042) were significantly associated with PTB. The MTHFR rs4846049 AA showed a marginal trend toward significance (OR 0.15, 95% CI 0.018-1.205, p = 0.041). In particular, the combined genotypes, including MTHFR rs1537514 CC-MTRR rs1801394 GG, MTHFR rs1537514 CC-TCN2 rs1801198 CG, and MTR rs1805087 AA-TCN2 rs1801198 CG, have significant interactions with PTB (OR 0.49, 95% CI 0.248-0.992, p < 0.05). CONCLUSION: The polymorphisms of folate metabolic genes may have a genetic association with the development of PTB in Korean women. A larger sample set and functional studies are required to further elucidate our findings.

Association between the IL-6, IL-10, and TNFα gene polymorphisms and preterm-birth in Korean women.

BACKGROUND: Preterm birth (PTB) is a major adverse pregnancy outcome and largely contributes to increasing neonatal and maternal mortality. Genetic and environmental factors may play an important role in the development of PTB. Numerous studies have shown that immune genes related to the immune system, such as IL-6, IL-10, and TNFα, are associated with the occurrence of PTB. OBJECTIVE: We examined genetic associations between IL-6 rs1800796, IL-10 rs1800872, and TNFα rs1800630 polymorphisms and PTB in Korean women. METHODS: In this study, 115 PTB patients and 147 controls were analyzed. The genotyping of three SNPs was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Our result showed that the rs1800872 polymorphism was significantly associated with the development of PTB in genotype frequency (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.01-2.90, p = 0.046). We also found a significant association in an analysis of combined genotypes (rs1800796 CC, rs1800872 CA, and rs1800630 CA) (OR 7.43, 95% CI 2.06-26.84, p = 0.001). In a correlation analysis, rs1800630 A allele was significantly related with the increased birth weight (g) within PTB patients (p = 0.005). CONCLUSION: Our results imply possible relationships between the rs1800796, rs1800872, and rs1800630 polymorphisms and the development of PTB.

Genetic Association of Angiotensin-Converting Enzyme (ACE) Gene I/D Polymorphism with Preterm Birth in Korean Women: Case-Control Study and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The ACE gene encodes the angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system. Increased ACE activity may cause abnormal regulation of placental circulation and angiogenesis, resulting in adverse pregnancy outcomes. Previous studies have reported that the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the development of preterm birth (PTB). However, results of the association between ACE gene I/D and PTB are inconsistent in various populations. Therefore, we performed a case-control study and a meta-analysis to evaluate the association between ACE I/D polymorphism and PTB. Materials and Methods: We analyzed a total of 254 subjects (111 patients with PTB and 143 women at ≥38 weeks gestation) for the case-control study. For the meta-analysis, we searched Google Scholar, PubMed, and NCBI databases with the terms "ACE," "angiotensin-converting enzyme," "preterm birth," "preterm delivery," and their combinations. Results: Our results of the case-control study indicated that ACE I/D polymorphism is significantly associated with PTBs in the overdominant genetic model (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.347-0.949, p = 0.029) and that the ID genotype of ACE I/D polymorphism has a protective effect for PTB (OR 0.57, 95% CI 0.333-0.986, p = 0.043). Similarly, the meta-analysis showed that the OR for the ACE gene ID genotype was 0.66 (95% CI 0.490-0.900, p < 0.01). Conclusion: The ACE gene ID genotype has a significant association with PTB and is a protective factor for PTB. A larger sample set and functional studies are required to further elucidate of our findings.

Vaginal sling implant misdiagnosed as rectal subepithelial tumor.

As cosmetic procedures receive increasing attention from the media, female genital cosmetic surgery (FGCS) has become quite popular in Korea. The safety and efficacy of these surgeries and procedures have yet to be thoroughly documented. We report a case of a 47-year-old woman who underwent a vaginal sling implantation, which resulted in the misdiagnosis of a rectal subepithelial tumor during endoscopic mucosal resection (EMR). This patient suffered an iatrogenic rectal perforation during the EMR, which necessitated an exploratory operation. The sling implant was removed via the vaginal approach, and a primary repair of the vaginal and rectal walls was performed. The patient subsequently showed no sign of complication at her 6-month follow-up. Patients need to be educated about the importance of reporting a history of FGCS prior to undergoing surgical or endoscopic procedures. Also, physicians have to check the medical history of patient thoroughly to avoid misdiagnoses and unnecessary treatment.

The relationship between spontaneous abortion and female workers in the semiconductor industry.

BACKGROUND: This study investigated the relationship between job type and the risk for spontaneous abortion to assess the reproductive toxicity of female workers in the semiconductor industry. METHODS: A questionnaire survey was administered to current female workers of two semiconductor manufacturing plants in Korea. We included female workers who became pregnant at least 6 months after the start of their employment with the company. The pregnancy outcomes of 2,242 female workers who experienced 4,037 pregnancies were investigated. Personnel records were used to assign the subjects to one of three groups: fabrication process workers, packaging process workers, and clerical workers. To adjust for within-person correlations between pregnancies, a generalized estimating equation was used. The logistic regression analysis was limited to the first pregnancy after joining the company to satisfy the assumption of independence among pregnancies. Moreover, we stratified the analysis by time period (pregnancy in the years prior to 2008 vs. after 2009) to reflect differences in occupational exposure based on semiconductor production periods. RESULTS: The risk for spontaneous abortion in female semiconductor workers was not significantly higher for fabrication and packaging process workers than for clerical workers. However, when we stratified by time period, the odds ratio for spontaneous abortion was significantly higher for packaging process workers who became pregnant prior to 2008 when compared with clerical workers (odds ratio: 2.21; 95% confidence interval: 1.01-4.81). CONCLUSIONS: When examining the pregnancies of female semiconductor workers that occurred prior to 2008, packaging process workers showed a significantly higher risk for spontaneous abortions than did clerical workers. The two semiconductor production periods in our study (prior to 2008 vs. after 2009) had different automated processes, chemical exposure levels, and working environments. Thus, the conditions prior to 2008 may have increased the risk for spontaneous abortions in packaging process workers in the semiconductor industry.

Genetic variations of MTHFR gene and their association with preterm birth in Korean women.

BACKGROUND AND OBJECTIVE: The MTHFR gene encodes the methylenetetrahydrofolate reductase known to be involved in the homocysteine-methionine pathway. It has been reported that the deficiency of MTHFR activity may cause hyperhomocysteinemia which results in adverse pregnancy outcomes. Previous studies reported a correlation between the MTHFR gene polymorphisms (677 T/C and 1298 A/C) and lower MTHFR activity and its association with preterm birth in various populations. Since these results were conflicting, we analyzed the genetic association of MTHFR gene 677 T/C and 1298 A/C polymorphisms with preterm birth in Korean women. MATERIALS AND METHODS: The subjects for case-control study were collected a total of 226 Korean women (98 preterm-birth patients and 128 controls). Genotype frequency differences between the case and the control were assessed using chi-square tests. Mann-Whitney t-test was used to estimate the effects of 1298 A/C genotype on clinicopathological characteristics (systolic blood pressure, diastolic blood pressure, birth weight, and gestational age at delivery) in preterm-birth patients. RESULTS: Our results showed that the MTHFR 677 C/T polymorphism was significantly associated with preterm-birth patients in the analysis of genotype frequency (P=0.044) and the over-dominant model (OR=0.54; 95% CI, 0.320-0.920; P=0.023). The recessive model showed a marginal trend toward significance (OR=0.47; 95% CI, 0.220-1.010; P=0.046). The 1298 A/C polymorphism was also associated with reduced preterm-birth risk in the recessive model (P=0.032). In the correlation analysis, the 1298 C allele was significantly associated with increasing of gestational age at delivery in preterm-birth patients (P=0.034). CONCLUSIONS: Our findings suggested that the MTHFR gene 677 C/T and 1298 A/C polymorphisms might have protective effects for preterm birth in the Korean women.

Uterine arteriovenous malformation with positive serum beta-human chorionic gonadotropin: Embolization of both uterine arteries and extra-uterine feeding arteries.

The incidence of uterine arteriovenous malformation (AVM) is rare. However, it is clinically significant in that it can cause life-threatening vaginal bleeding. We report a case of a large uterine AVM with positive serum beta-human chorionic gonadotropin. A presumptive diagnosis was made; a uterine AVM accompanied by, early pregnancy or retained product of conception. Because this uterine AVM was extensive, transcatheter arterial embolization of both uterine arteries and extra-uterine feeding arteries was performed. Three months after undergoing transcatheter arterial embolization, complete resolution of the uterine AVM was confirmed without major complication.

Aortic dissection accompanied by preeclampsia in a postpartum young woman.

Aortic dissection is very rare in obstetrics, but it is a fatal disease. A 37-weeks primigravida woman with dyspnea and pitting edema presented to our emergency room. The patient was diagnosed with preeclampsia and underwent an emergency cesarean section under spinal anesthesia. The patient complained of severe dyspnea after the cesarean section, and the chest computed tomography scan was done. With the finding of aortic dissection, cardiopulmonary arrest occurred 5 hours after the cesarean section, and the patient died without reaction to cardio-pulmonary resuscitation. If a patient with preeclampsia complains of severe dyspnea or chest pain, aortic dissection needs to be suspected and a diagnosis should not be delayed.

Comparison of needle aspiration and vacuum-assisted biopsy in the ultrasound-guided drainage of lactational breast abscesses.

PURPOSE: The purpose of this study was to compare needle aspiration and vacuum-assistedbiopsy in the ultrasound-guided treatment of lactational breast abscesses. METHODS: Between January 2005 and December 2014, a total of 74 patients presented withlactational breast abscesses. Thirty of these patients underwent treatment with antibioticsalone, while the remaining 44 lactating women with breast abscesses were treated withneedle aspiration (n=25) or vacuum-assisted biopsy (n=19). Age, duration of lactation, abscess diameter, pus culture results, the number of interventions, the healing time, and the cure rate were reviewed and compared between these two groups. The Student's t test and the chi-square test were used to compare the variables. RESULTS: No significant difference was found in the cure rate between the needle aspirationgroup (22/25, 88%) and the vacuum-assisted biopsy group (18/19, 94.7%) (P=0.441). However, the mean healing time was significantly shorter in the vacuum-assisted biopsy group (6.7 days) than in the needle aspiration group (9.0 days) (P=0.001). CONCLUSION: Vacuum-assisted biopsy is a viable option for the management of lactational breast abscesses and was found to lead to a shorter healing time than needle aspiration. However, further study is necessary to establish the clinical efficacy of vacuum-assisted biopsy in the management of lactational breast abscesses.

Practice patterns in the management of threatened preterm labor in Korea: A multicenter retrospective study.

OBJECTIVE: This study aimed to examine clinical practice patterns in the management of pregnant women admitted with threatened preterm labor (TPL) in Korea. METHODS: Data from women admitted with a diagnosis of TPL were collected from 22 hospitals. TPL was defined as regular uterine contractions with or without other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and cervical changes. Data on general patient information, clinical characteristics at admission, use of tocolytics, antibiotics, and corticosteroids, and pregnancy outcomes were collected using an online data collections system. RESULTS: A total of 947 women with TPL were enrolled. First-line tocolysis was administered to 822 (86.8%) patients. As a first-line tocolysis, beta-agonists were used most frequently (510/822, 62.0%), followed by magnesium sulfate (183/822, 22.3%), calcium channel blockers (91/822, 11.1%), and atosiban (38/822, 4.6%). Of the 822 women with first-line tocolysis, second-line tocolysis were required in 364 (44.3%). Of 364 with second-line, 199 had third-line tocolysis (37.4%). Antibiotics were administered to 29.9% of patients (284/947) with single (215, 22.7%), dual (26, 2.7%), and triple combinations (43, 4.5%). Corticosteroids were administered to 420 (44.4%) patients. Betamethasone was administered to 298 patients (71.0%), and dexamethasone was administered to 122 patients (29.0%). CONCLUSION: Practice patterns in the management of TPL in Korea were quite various. It is needed to develop standardized practice guidelines for TPL management.

3D microenvironment of collagen hydrogel enhances the release of neurotrophic factors from human umbilical cord blood cells and stimulates the neurite outgrowth of human neural precursor cells.

The umbilical cord blood (UCB) cells have been reported to secrete therapeutic signals, including a series of neurotrophic factors. This suggests the cell source provides suitable therapeutic environments for nerve regeneration that ultimately finds a possible cell therapy for nerve tissue. In this study, we observe a collagen hydrogel provides human UCB cells a proper 3D environment that stimulates the release of various neurotrophic factors. When compared to 2D culture, the 3D hydrogel culture significantly enhanced the expression of a series of neurotrophic factors, including neurotrophins, nerve growth factor, brain-derived neurotrophic factor, and ciliary neurotrophic factor as verified by the gene and protein analysis. To confirm the effects of neurotrophic factors secretion, we allowed an indirect interaction of the UCB-environment with human neural precursor cells (hNPCs). Results showed significantly enhanced neurite outgrowth of hNPCs. Collectively, our findings demonstrate that the collagen-based 3D hydrogel provides excellent environment for UCB-derived cells to release neurotrophic factors that will be ultimately useful for the neural repair and regeneration purposes.