The Role of the Aryl Hydrocarbon Receptor in Vascular Factors Related to Preeclampsia in a Smoking Mouse Model.

Smoking cigarettes is known to lower the risk of preeclampsia. The objective of this study is to evaluate the effect of smoking on the expression of soluble FMS-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), and endoglin (sEng)-1 and the role of the aryl hydrocarbon receptor (AhR) in pregnant mice. We developed a smoking mouse model using a gas-filling system. One or two cigarettes per day were exposed to each of the five pregnant mice for five days a week throughout pregnancy. AhR agonist and antagonist were injected. Serum levels and expression in the placenta of sFlt-1, VEGF, and sEng-1 were analyzed and compared among the cigarette smoke and no-exposure groups after delivery. Compared to the no-smoke exposure group, the serum level of sFlt-1 was significantly decreased in the two-cigarette-exposed group (p < 0.001). When the AhR antagonist was added to the two-cigarette-exposed group, sFlt-1 levels were significantly increased compared to the two-cigarette group (p = 0.002). The levels of sFlt-1 in the AhR antagonist group did not change regardless of two-cigarette exposure (p = 0.064). With the AhR agonist, sFlt-1 decreased significantly compared to the control (p = 0.001) and AhR antagonist group (p = 0.002). The sFlt-1 level was significantly decreased after the injection of the AhR agonist compared to the control group (p = 0.001). Serum levels of VEGF were significantly decreased in the one-cigarette-exposed group compared to the control group; however, there was no difference between the control and the two-cigarette-exposed groups. The placental expression of sFlt-1, VEGF, and sEng were inconsistent. This study offers insights into the potential role of AhR on antiangiogenic sFlt-1 associated with preeclampsia. It may support the invention of a new treatment strategy for preeclampsia using AhR activation.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha-lipoic acid on primary ovarian insufficiency.

Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha-lipoic acid (ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA-related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis, protein-protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein-to-protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top 10 hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple targets and multiple pathways mechanisms.

Prepregnancy Glucose Levels Within Normal Range and Its Impact on Obstetric Complications in Subsequent Pregnancy: A Population Cohort Study.

BACKGROUND: We sought to identify the influence of prepregnancy glucose levels on obstetric complications in subsequent pregnancy. METHODS: Women in Republic of Korea who had given birth between January 1st, 2007 and December 31st, 2010 were enrolled. The database of the Health Insurance Review and Assessment Service and data from a national health screening program for infants and children were used. Subjects were divided into seven groups according to their fasting glucose levels. RESULTS: 59,619 women were included for analysis, and 10.4%, 13.7%, 19.1%, 21.5%, 16.0%, 11.6%, and 7.5% women had glucose levels of < 75, 75-79, 80-84, 85-89, 90-94, 95-100 and > 100 mg/dL. Each 5 mg/dL increase in prepregnancy fasting glucose levels was associated with increased risk of gestational diabetes and macrosomia in subsequent pregnancy. Adjusted risk ratio for gestational diabetes per standard deviation prepregnancy glucose > 100 mg/dL was 2.015 (95% confidence interval, 1.649-2.462) and for macrosomia an adjusted risk ratio 1.389 (95% confidence interval, 1.147-1.682). CONCLUSION: Higher prepregnancy glucose level within normal range was related to gestational diabetes and macrosomia in following pregnancy. Our results may aid in the identification of women at future risk of obstetric complications and may guide to stratify women into normal and intensified care. TWEETABLE ABSTRACT: Higher prepregnancy glucose in normal range is associated with gestational diabetes and macrosomia.

Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma.

Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12-17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9-4.5 × 108 exosomes in 10 µL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 µg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.

A Randomized, Multicenter, Double-Blind, Parallel, Non-Inferiority Clinical Study to Compare the Efficacy and Safety of Unicenta and Melsmon for Menopausal Symptom Improvement.

This study was conducted to evaluate the efficacy and safety of Unicenta in female subjects with menopausal symptoms by analyzing the changes in the Kupperman index (primary endpoint) and hormonal changes (secondary endpoint). It was a randomized, multi-center, double-blind, parallel, non-inferiority clinical study conducted at two different tertiary medical centers. A Unicenta injection was shown to be non-inferior to Melsmon based on the Kupperman index in both the intent-to-treat and per-protocol populations (p = 0.789 and p = 0.826, respectively). Additionally, there were no statistically significant differences in hormone levels (estradiol, follicular-stimulating hormone) or in the evaluation of facial flushes. There was no statistically significant difference in the incidence rate of adverse events between the two groups (p = 0.505). The study demonstrated that Unicenta is not inferior to Melsmon in terms of the change in the Kupperman index after 12 days of injection. The efficacy and safety of Unicenta were shown, resulting in the improvement of menopausal symptoms.

Effect of Human Amniotic Epithelial Stem Cell Transplantation on Preterm Premature Rupture of Fetal Membrane Using the Amniotic Pore Culture Technique in vitro.

OBJECTIVES: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro. DESIGN: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes. MATERIALS: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study. SETTINGS: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control. METHODS: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05. RESULTS: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 µm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 µm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8). LIMITATIONS: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested. CONCLUSIONS: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine.

Women with multiple gestations have an increased risk of development of hypertension in the future.

BACKGROUND: Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. METHODS: In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. RESULTS: Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. CONCLUSIONS: Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study.

PURPOSE: Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies. STUDY DESIGN: Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C. CONCLUSIONS: In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.

Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics.

BACKGROUND: Obstetric hemorrhage is one of the most common causes of obstetrical morbidity and mortality, and transfusion is the most important management for hemorrhage. The aim of our study was to investigate the pre-pregnancy and pregnancy risk factors for peripartum transfusion. METHODS: Women who delivered a baby from 2010 to 2014 in Korea and participated in the Korean National Health Screening Program for Infants and Children were included. To analyze pre-pregnant risk factors for peripartum transfusion, an additional analysis was done for women who underwent a National Health Screening Examination within 1 year before pregnancy, including maternal waist circumference, body mass index, blood pressure, laboratory tests and history of smoking. Multivariable logistic regression analysis was used to estimate the risk factors for peripartum transfusion. RESULTS: Of the total 1,980,126 women who met the inclusion criteria, 36,868 (1.86%) were transfused at peripartum. In a multivariable regression model, the pregnancy risk factors for peripartum transfusion included maternal age above 35 years [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.32-1.50], preterm birth (OR: 2.39; 95% CI: 2.15-2.65), and maternal hypertension (OR: 2.49; 95% CI: 2.24-2.77). Pre-pregnancy risk factors including fasting glucose level of more than 126 mg/dL (OR: 1.11; 95% CI: 1.02-1.20), current-smoker status (OR: 1.20; 95% CI: 1.06-1.37), and waist-circumference less than 80 cm (OR: 1.18; 95% CI: 1.06-1.30) were independently associated with peripartum blood transfusion. CONCLUSIONS: Several pre-pregnancy and pregnancy risk factors were associated with peripartum blood transfusion. Some identified factors are modifiable before conception, and our study validated peripartum blood transfusion as a form of triage.

Prepregnancy liver enzyme levels and risk of preeclampsia in a subsequent pregnancy: A population-based cohort study.

BACKGROUND & AIMS: Preeclampsia is a serious multisystemic disorder leading to maternal and neonatal adverse outcomes. However, little is known about the early markers of this disease. The aim of this study was to investigate the association between prepregnancy liver function and the development of preeclampsia. METHODS: We enrolled 192 571 Korean women who had their first delivery between January 1, 2008, and December 31, 2014, and had undergone a national health screening examination through the National Health Insurance Corporation during 1-2 years before delivery. RESULTS: Preeclampsia developed in 3973 (2.0%) women. The rate of development of preeclampsia was higher in women with abnormal prepregnancy liver enzyme levels than in those with normal liver enzyme levels before pregnancy. On multivariate analysis, women with abnormal alanine aminotransferase level before pregnancy had a 1.21-fold increased risk of developing preeclampsia than those with normal alanine aminotransferase level before pregnancy, after adjusting for age, family history of hypertension, hepatitis B virus carrier status, smoking, alcohol status, prepregnancy body mass index and blood pressure. Prepregnancy γ-glutamyltransferase and aspartate aminotransferase levels were not associated with the risk of preeclampsia development. CONCLUSION: Abnormal prepregnancy alanine aminotransferase level was associated with the development of preeclampsia in a subsequent pregnancy. Further studies are needed to evaluate whether early intervention for liver function before pregnancy can decrease the risk of preeclampsia.

Cerclage is associated with the increased risk of preterm birth in women who had cervical conization.

BACKGROUND: The aim of this study was to determine the effect of cerclage in women who underwent cervical conization. METHODS: Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2009-2013. Women who had a conization in 2009 and a subsequent first delivery between 2009 and 2013 in Korea were enrolled. RESULTS: Among the women who had conization in 2009, 1075 women had their first delivery between 2009 and 2013. A cerclage was placed in 161 of the women who were treated by conization. The rate of preterm birth was higher in the women who were treated with cerclage following a conization compared with those without cerclage (10.56 vs 4.27, p < 0.01, respectively). The multivariate regression analysis revealed that the women who were treated cerclage following a conization had an increased risk of preterm delivery compared with women without cerclage (odds ratio (OR), 2.6, 95% confidence interval (CI), 1.4-4.9). CONCLUSION: Our study showed that cerclage associated with an increased risk of preterm birth and preterm premature rupture of membranes in women who underwent conization. Further studies are required to clarify the mechanism by which cerclage affects the risk of preterm birth.

Recurrent Risk of Preterm Birth in the Third Pregnancy in Korea.

BACKGROUND: Although preterm delivery is the most common cause of infant morbidity and mortality, an obvious cause cannot be found in most cases. Preterm delivery is known to be the most important risk factor for preterm birth in a subsequent pregnancy. We aimed to evaluate the recurrence rate of premature births for subsequent pregnancies in women with a history of a preterm birth. METHODS: Study data were collected from the Korea National Health Insurance (KNHI) claims database and data from a national health-screening program for infants and children. We enrolled women who had their first delivery between January 1, 2007 and December 31, 2007 and a subsequent delivery before 2014. RESULTS: Preterm delivery had a significant higher risk of preterm birth in a subsequent singleton pregnancy. The risk of preterm birth at second pregnancy was 2.2% in women whose first delivery at ≥ 37 weeks and 18.6% in women whose first delivery at < 37 weeks (relative risks [RR], 8.64; 95% confidence interval [CI], 7.94-9.40). In the analysis of the third pregnancy, we compared women with an initial term birth followed by preterm birth and women with an initial preterm birth followed by a subsequent term birth. A history of a just preceding preterm birth at < 37 weeks was the most relevant factor for recurrence of preterm delivery in a subsequent pregnancy (26.6%, RR, 4.01; 95% CI, 2.45-6.58). CONCLUSION: We found that the prognosis of a third pregnancy was more closely related to the outcome of the second pregnancy to that of the first pregnancy.

The safety of progestogen in the prevention of preterm birth: meta-analysis of neonatal mortality.

BACKGROUND: The safety of preventive progestogen therapy for preterm birth remains to be established. This meta-analysis aimed to evaluate the effects of preventive progestogen therapy on neonatal mortality. METHODS: Randomized controlled trials (RCTs) on the preventive use of progestogen therapy, published between October 1971 and November 2015, were identified by searching MEDLINE/PubMed, EMBASE, Scopus, ClinicalTrials.gov, Cochrane Library databases, CINAHL, POPLINE, and LILACS using "progesterone" and "preterm birth" as key terms. We conducted separate analyses according to the type of progestogen administered and plurality of the pregnancy. RESULTS: Twenty-two RCTs provided data on 11,188 neonates. Preventive progestogen treatment in women with a history of preterm birth or short cervical length was not associated with increased risk of neonatal death compared to placebo in all analyzed progestogen types and pregnancy conditions. The pooled relative risks (95% confidence interval) of neonatal mortality were 0.69 (0.31-1.54) for vaginal progestogen in singleton pregnancies, 0.6 (0.33-1.09) for intramuscular progestogen in singleton pregnancies, 0.96 (0.51-1.8) for vaginal progestogen in multiple pregnancies, and 0.96 (0.49-1.9) for intramuscular progestogen in multiple pregnancies. CONCLUSIONS: The results of this meta-analysis suggest that administration of preventive progestogen treatment to women at risk for preterm birth does not appear to negatively affect neonatal mortality in single or multiple pregnancies regardless of the route of administration.

Placental thickness-to-estimated foetal weight ratios and small-for-gestational-age infants at delivery.

This study aimed to determine the correlation between the placental thickness-to-estimated foetal weight ratio on midterm ultrasonography and small-for-gestational-age (SGA) infants. In this retrospective study, the placental thickness at the umbilical cord insertion site was measured and adjusted for foetal body weight at 18-24 weeks gestation. Investigators compared the data of women who delivered SGA infants (birth weight <10th percentile) with those of women who delivered non-SGA infants. Among the 1281 women in this study, those who delivered SGA infants were younger and less likely to be obese. Women with higher placental thickness-to-estimated foetal weight ratios delivered more SGA infants. In logistic regression analysis, a higher placental thickness-to-estimated foetal weight ratio remained associated with SGA infants. Since the placental thickness-to-estimated foetal weight ratio in midterm pregnancy was associated with infant body weight at delivery, this ratio could be an effective, adjunctive screening marker for predicting SGA status.

Congenital varicella syndrome: A systematic review.

Varicella-zoster virus (VZV) is a teratogen that can cross the placenta and cause the congenital varicella syndrome (CVS), which is characterised by multi-system anomalies. There have been 130 reported cases of CVS from 1947 to 2013. The estimated incidence of CVS was 0.59% and 0.84% for women infected with VZV during the entire pregnancy and for those infected the first 20 weeks of pregnancy, respectively. Nine cases were reported at 21-27 weeks of gestation and one case was identified at 36 weeks. Herpes zoster caused CVS in two cases. Regarding treatment, varicella zoster immunoglobulin treatment, irrespective of gestational age, should be considered in addition to antiviral drugs for women who have been exposed to or infected with virus.

Prior cesarean section is associated with increased preeclampsia risk in a subsequent pregnancy.

BACKGROUND: To evaluate the impact of a prior cesarean section on preeclampsia risk in a subsequent pregnancy. METHODS: Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2006-2010. Patients who had their first delivery in 2006 and subsequent delivery between 2007 and 2010 in Korea were enrolled. The overall incidence of preeclampsia during the second pregnancy was estimated and to evaluate the risk of preeclampsia in the second pregnancy, a model of multivariate logistic regression analysis was performed with preeclampsia as the final outcome RESULTS: The risk of preeclampsia in any pregnancy was 2.17%; the risk in the first pregnancy was 2.76%, and that in the second pregnancy was 1.15%. During the second pregnancy, the risk of preeclampsia was 13.30% for women who had developed preeclampsia in their first pregnancy and 0.85% for those who had not. In the entire population, prior cesarean section was associated with preeclampsia risk in their subsequent pregnancy (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.13-1.41). Among women with and without preeclampsia in their first pregnancy, a prior cesarean section was associated with preeclampsia risk in their second pregnancy (OR, 1.35; 95% CI, 1.09-1.67; OR, 1.23; 95% CI, 1.08-1.40, respectively). CONCLUSIONS: Our study showed that cesarean section in a first pregnancy was associated with increased preeclampsia risk in the second pregnancy. These results provide physicians with a preeclampsia risk evaluation method for a second pregnancy that they may aid counseling in patients.

The neuroprotective effect of magnesium sulfate in preterm fetal mice.

OBJECTIVE: To investigate the use of magnesium sulfate (MgSO4) as a neuroprotective agent in a mouse model of inflammation-associated and noninflammation-associated preterm birth. METHODS: On embryonic day 15 of gestation, lipopolysaccharide (LPS) and mifepristone (RU486) were used, respectively, to create mouse models of inflammation and noninflammation-associated preterm birth. After intraperitoneal injection of LPS, RU486, or normal saline solution (NS), dams were randomized to intraperitoneal MgSO4 or NS injection. From the 6 treatment groups (NS+NS, LPS+NS, NS+MgSO4, LPS+MgSO4, RU486+NS and RU486+MgSO4), fetal brains were collected for Western blot analysis and neuronal cultures. Protein expression of S100B was assessed, and immunohistochemistry was performed to detect NeuN. The numbers of NeuN-labeled cells were counted using confocal laser scanning microscopy. RESULTS: The expression of S100B significantly differed among the groups and was decreased in the LPS+MgSO4 group compared to the LPS+NS group. The expression of S100B did not differ between the RU486+NS and RU486+MgSO4 groups. NeuN-labeled cells were increased in the LPS+MgSO4 group compared with the LPS+NS group. NeuN-labeled cells were decreased in the RU486+MgSO4 group compared with the RU486+NS group. CONCLUSIONS: We observed that prenatal treatment with MgSO4 was associated with decreased expression of S100B and increased numbers of NeuN-labeled cells in an inflammation-associated preterm mouse model but not in a noninflammation-associated preterm mouse model. Our results suggest that prenatal treatment of MgSO4 reduces inflammation-associated brain injury in fetal mice.

Use of the angle of progression on ultrasonography to predict spontaneous onset of labor within 7 days.

OBJECTIVE: To investigate the relationship between angle of progression (AoP) on ultrasonography at 37-40 weeks' gestation and delivery within 7 days. METHODS: This prospective study was conducted between January 2013 and May 2013 at Korea University Guro Hospital, Korea. Nulliparous women between 37/0 and 40/3 weeks' gestation with a singleton fetus, intact membrane, and cephalic presentation from January 2013 to May 2013 were enrolled. To evaluate the cervical parameters of cervical length and AoP, transvaginal and transperineal ultrasonography were performed, respectively. We then assessed the relationship between cervical parameters and onset of labor within 7 days by multivariate logistic regression analysis. RESULTS: Women who underwent spontaneous onset of labor within 7 days had a significantly shorter cervical length and AoP than those who underwent labor after 7 days. Logistic regression analysis showed that a larger AoP was an independent predictor of spontaneous labor within 7 days. CONCLUSIONS: A larger AoP was significantly associated with spontaneous onset of labor within 7 days. These findings may be useful for counseling patients regarding the management of term pregnancies.