Leukocyte Telomere Length Reflects Prenatal Stress Exposure, But Does Not Predict Atopic Dermatitis Development at 1 Year

PURPOSE: Prenatal maternal stress affects offspring's atopic dermatitis (AD) development, which is thought to be mediated by the oxidative stress. We aimed to evaluate the difference in leukocyte telomere length (LTL), a marker for exposure to oxidative stress, according to the prenatal stress exposure and the later AD development. METHODS: From a birth cohort (the COhort for Childhood Origin of Asthma and allergic diseases) that had displayed a good epidemiologic association between the exposure to prenatal stress and AD development in the offspring, we selected 68 pairs of samples from 4 subject groups based on the level of prenatal maternal stress and later AD development. The LTL was measured from both cord blood and 1-year peripheral blood, and their LTLs were compared between subject groups. Finally, the proportion of AD development was examined in the subject groups that are reclassified based on subjects' exposure to prenatal stress and there LTL. RESULTS: Cord-blood LTL was shorter in prenatally stressed infants than in unstressed ones (P = 0.026), which difference was still significant when subjects became 1 year old (P = 0.008). LTL of cord blood, as well as one of the 1-year peripheral blood, was not different according to later AD development at 1 year (P = 0.915 and 0.174, respectively). Shorter LTL made no increase in the proportion of later AD development in either prenatally high-stressed or low-stressed groups (P = 1.000 and 0.473, respectively). CONCLUSIONS: Cord-blood LTL may reflect subjects' exposure to maternal prenatal stress. However, the LTL shortening is not a risk factor of increasing AD development until the age of 1, and a longer investigation may be necessary for validation. Currently, the results doubt the role of LTL shortening as a marker for risk assessment tool for the prenatal stress associated with AD development in the offspring.ope

Prenatal Exposure to Lead and Chromium is Associated with IL-13 Levels in Umbilical Cord Blood and Severity of Atopic Dermatitis: COCOA Study

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.ope

The Effect of SP-6 Acupressure on Labor Pain and Patternof Uterine Contraction

Objective: To evaluate the effect of SP-6 acupressure on labor pain, labor duration, change in serum stress hormone levels, and the pattern of uterine contraction in laboring women. Methods: A total of 66 pregnant women were randomly divided into acupressure group (n=26) and control group (n=40). When cervical dilation reached 3 cm, acupressure group were received with the acupressure of 120 mmHg on the SP-6 points. As for the control group, thumbs were placed on the SP-6 points not applying any pressure. The severity of labor pain interpreted by visual- analogue scale (VAS), labor duration, serum stress hormone levels, and tocodynanometry findings were evaluated and compared between the two groups. Results: The severity of labor pain was significantly reduced in the acupressure group (p=0.007). Average labor durations in acupressure group and control groups were not significantly different (487.5±215.4 vs. 434.6±203.4 mins). Also, no significant differences regarding contraction duration, intensity, interval, rate of rise, area-under-curve, and Montevideo unit of uterine contraction were noted between the groups. No significant changes in the serum stress hormone level were noted in both groups. Conclusion: SP-6 acupressure effectively reduce perceived labor pain in pregnant women during active labor. However, the pain relief following acupressure were not attributable to modification of uterine contraction or changes in stress hormone levels. Though its mechanism is unknown, SP-6 acupressure seems to be a non-invasive, cost-free, and a simple method to reduce labor pain.ope

Postpartum Glucose Testing Rates Following Gestational Diabetes Mellitus and Factors Affecting Testing Non-compliance from Four Tertiary Centers in Korea

The purpose of this study was to investigate postpartum glucose testing rates in patients with gestational diabetes mellitus (GDM) and to determine factors affecting testing non-compliance in the Korean population. This was a retrospective study of 1,686 patients with GDM from 4 tertiary centers in Korea and data were obtained from medical records. Postpartum glucose testing was conducted using a 2-hr 75-g oral glucose tolerance, fasting glucose, or hemoglobin A1C test. Test results were categorized as normal, prediabetic, and diabetic. The postpartum glucose testing rate was 44.9% (757/1,686 patients); and of 757 patients, 44.1% and 18.4% had pre-diabetes and diabetes, respectively. According to the multivariate analysis, patients with a high parity, larger weight gain during pregnancy, and referral from private clinics due to reasons other than GDM treatment were less likely to receive postpartum glucose testing. However, patients who had pharmacotherapy for GDM were more likely to be screened. In this study, 55.1% of patients with GDM failed to complete postpartum glucose testing. Considering the high prevalence of diabetes (18.4%) at postpartum, clinicians should emphasize the importance of postpartum diabetes screening to patients with factors affecting testing noncompliance.ope

Non-alcoholic fatty liver disease in pregnancy, paving the way for adverse pregnancy outcome risk assessment

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Uterine Cervical Change at Term Examined Using Ultrasound Elastography: A Longitudinal Study

The aim of the study was to investigate if there are changes in elastographic parameters in the cervix at term around the time of delivery and if there are differences in the parameters between women with spontaneous labor and those without labor (labor induction). Nulliparous women at 36 weeks of gestation eligible for vaginal delivery were enrolled. Cervical elastography was performed and cervical length were measured using the E-CervixTM system (WS80A Ultrasound System, Samsung Medison, Seoul, Korea) at each weekly antenatal visit until admission for spontaneous labor or labor induction. E-Cervix parameters of interest included elasticity contrast index (ECI), internal os strain mean level (IOS), external os strain mean level (EOS), IOS/EOS strain mean ratio, strain mean level, and hardness ratio. Regression analysis was performed using days from elastographic measurement at each visit to admission for delivery and the presence or absence of labor against cervical length, and each E-Cervix parameter fitted to a linear model for longitudinal data measured repeatedly. A total of 96 women were included in the analysis, (spontaneous labor, n = 39; labor induction, n = 57). Baseline characteristics were not different between the two groups except for cesarean delivery rate. Cervical length decreased with advancing gestation and was different between the two groups. Most elastographic parameters including ECI, IOS, EOS, strain mean, and hardness ratio were significantly different between the two groups. In addition, ECI, IOS, and strain mean values significantly increased with advancing gestation. Our longitudinal study using ultrasound elastography indicated that E-cervix parameters tended to change linearly at term near the time of admission for delivery and that there were differences in E-Cervix parameters according to the presence or absence of labor.ope

Obstetrics & Gynecology Science, on the runway

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Integrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells

Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells. We identified 61 downregulated genes with hypermethylation, including CD74, VAV1, TLR8, and NCF4, as well as 21 upregulated genes with hypomethylation, including ECSCR, MCAM, PGF, and ARHGEF15. Interestingly, gene ontology analysis showed that downregulated genes with hypermethylation were enriched in immune-related functions, and upregulated genes with hypomethylation were enriched in the developmental process and angiogenesis, indicating the important roles of DNA methylation in regulating differentiation. We performed polymerase chain reaction analyses and bisulfite sequencing of representative genes (CD74, VAV1, ECSCR, and MCAM) to verify the negative correlation between DNA methylation and gene expression. Further, inhibition of DNA methyltransferase and demethylase activities using 5'-aza-dc and shRNAs, specific for TET1 and TET2 mRNAs, respectively, revealed that DNA methylation was the main regulator of the reversible expression of functionally important genes. Collectively, our findings implicate DNA methylation as a critical regulator of gene expression during umbilical cord blood derived mononuclear cells to endothelial cell differentiation.ope

A Predictive Model for Large-for-Gestational-Age Infants among Korean Women with Gestational Diabetes Mellitus Using Maternal Characteristics and Fetal Biometric Parameters

Background: With increasing incidence of gestational diabetes mellitus (GDM), newborn infants with perinatal morbidity, including large-for-gestational-age (LGA) or macrosomia, are also increasing. The purpose of this study was to develop a prediction model for LGA infants with GDM mothers. Methods: This was a retrospective case-control study of 660 women with GDM and singleton pregnancies in four tertiary care hospitals from 2006 to 2013 in Korea. Biometric parameters were obtained at diagnoses of GDM and within two weeks before delivery. These biometric data were all transformed retrospectively into Z-scores calculated using a reference. Interval changes of values between the two periods were obtained. Multivariable logistic and stepwise backwards regression analyses were performed to develop the most parsimonious predictive model. The prediction model included pre-pregnancy body mass index (BMI), head circumference (HC), Z-score at 24 + 0 to 30 + 6 weeks' gestation, and abdominal circumference (AC) Z-score at 34 + 0 to 41 + 6 weeks within 2 weeks before delivery. The developed model was then internally validated. Results: Our model's predictive performance (area under the curve (AUC): 0.925) was higher than estimated fetal weight (EFW) within two weeks before delivery (AUC: 0.744) and the interval change of EFW Z-score between the two periods (AUC: 0.874). It was internally validated (AUC: 0.916). Conclusions: A clinical model was developed and internally validated to predict fetal overgrowth in Korean women with GDM, which showed a relatively good performance.ope

Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3 +/Pod +/CD11b + Cells) in Patient with Preeclampsia

The abnormal development or disruption of the lymphatic vasculature has been implicated in metabolic and hypertensive diseases. Recent evidence suggests that the offspring exposed to preeclampsia (PE) in utero are at higher risk of long-term health problems, such as cardiovascular and metabolic diseases in adulthood, owing to in utero fetal programming. We aimed to investigate lymphangiogenic activities in the lymphatic endothelial progenitor cells (LEPCs) of the offspring of PE. Human umbilical cord blood LEPCs from pregnant women with severe PE (n = 10) and gestationally matched normal pregnancies (n = 10) were purified with anti-vascular endothelial growth factor receptor 3 (VEGFR3)/podoplanin/CD11b microbeads using a magnetic cell sorter device. LEPCs from PE displayed significantly delayed differentiation and reduced formation of lymphatic endothelial cell (LEC) colonies compared with the LEPCs from normal pregnancies. LECs differentiated from PE-derived LEPCs exhibited decreased tube formation, migration, proliferation, adhesion, wound healing, and 3D-sprouting activities as well as increased lymphatic permeability through the disorganization of VE-cadherin junctions, compared with the normal pregnancy-derived LECs. In vivo, LEPCs from PE showed significantly reduced lymphatic vessel formation compared to the LEPCs of the normal pregnancy. Gene expression analysis revealed that compared to the normal pregnancy-derived LECs, the PE-derived LECs showed a significant decrease in the expression of pro-lymphangiogenic genes (GREM1, EPHB3, VEGFA, AMOT, THSD7A, ANGPTL4, SEMA5A, FGF2, and GBX2). Collectively, our findings demonstrate, for the first time, that LEPCs from PE have reduced lymphangiogenic activities in vitro and in vivo and show the decreased expression of pro-lymphangiogenic genes. This study opens a new avenue for investigation of the molecular mechanism of LEPC differentiation and lymphangiogenesis in the offspring of PE and subsequently may impact the treatment of long-term health problems such as cardiovascular and metabolic disorders of offspring with abnormal development of lymphatic vasculature.ope