Adenosine A2A-receptor blockade abolishes the roll-off respiratory response to hypoxia in awake lambs

Adenosine (ADO) receptor antagonists (aminophylline, caffeine) blunt the respiratory roll-off response to hypoxia in the newborn. This study was designed to determine the ADO receptor subtype involved in the respiratory depression. Chronically catheterized lambs of 7–16 days of age breathed via face mask a gas mixture with a fraction of inspired O2 of 0.21 (normoxia) or 0.07 (hypoxia), while being infused intravascularly with 9-cyclopentyl-1,3-dipropylxanthine (DPCPX; ADO A1-receptor antagonist, n = 8), ZM-241385 (ADO A2A-receptor antagonist, n = 7), or vehicle. Ventilation was measured at 20°C by a turbine transducer flowmeter. In normoxia [arterial PO2 (PaO2) of ∼83 Torr], infusion of vehicle did not alter cardiorespiratory measurements, whereas hypoxia (PaO2 of ∼31 Torr, 15 min) elicited biphasic effects on mean arterial pressure (transient increase), heart rate (HR; diminishing tachycardia), and minute ventilation. In the latter, hypoxia increased ventilation to a peak value of ∼2.5 times control within the first 3 min, which was followed by a significant (P < 0.05) decline to ∼50% of the maximum increment over the subsequent 7 min. ZM-241385 abolished the hypoxic ventilatory roll-off and blunted the rate of rise in HR without affecting mean arterial pressure or rectal temperature responses. In normoxia, DPCPX increased ventilation and mean arterial pressure but did not change HR. Compared with vehicle, DPCPX did not significantly affect cardiorespiratory responses to hypoxemia (PaO2 of ∼31 Torr, 10 min). It is concluded that 1) ADO A2A receptors are critically involved in the ventilatory roll-off and HR responses to hypoxia, and 2) ADO A1 receptors, which are tonically active in cardiorespiratory control in normoxia, appear to have little impact on hypoxic ventilatory depression.ope

태아 심장종양의 산전 진단과 산후 결과

Objective: The objective of this study was to evaluate the ultrasonographic appearance of suspected fetal cardiac tumor and their evolution until delivery and in the postnatal period, and to document the associated problems including tuberous sclerosis. Methods: We retrospectively reviewed the medical records of all cases born in Yonsei University Health System, Seoul, Korea, between September 1996 and August 2006, and diagnosed as fetal cardiac tumor prenatally. Results: 10 cases were found in all medical records. The mean age of the mothers on delivery was 30.2±2.4 and the mean gestational age on diagnosis was 30.6±5.4 weeks. The cardiac tumors were single in five cases and multiple in the other five cases. The size ranged from 7 to 34mm. Most of the tumors were located in right ventricle (RV, n=9), left ventricle (LV, n=6), but they also located in interventricular septum (IVS, n=4), right atrium (RA, n=1). In one case, fetal arrhythmia was found, which was normalized in two days after birth, and in another case, mild intracardiac flow obstruction was noted. The duration of postnatal follow-up ranged from 2 months to 36 months (mean, 18.9±13.1 months). In most cases the tumor masses decreased after birth (n=6), but had no change in utero (n=5). Three of them were diagnosed as tuberous sclerosis after birth, and none of them needed surgical intervention. Conclusion: Fetal cardiac tumors and their effect on the fetal cardiac function could be well evaluated by two-dimensional and Doppler echocardiography. The fetal cardiac tumors may have little effect on the fetal well being both prenatally and postnatally from the cardiovascular standpoint in most affected fetuses, but are important in the early diagnosis of tuberous sclerosis and in suggesting careful follow-up and management.ope

정상 산모와 태아 발육 지연이 있는 산모에서 모체 혈청과 제대혈 prealbumin의 임상적 의의

Objectives: (a) To assess the changes in maternal serum prealbumin levels during normal gestation, (b) to compare the paired maternal serum and fetal cord blood prealbumin levels of normal and intrauterine growth restricted pregnancies, and (c) to determine the relationship between the maternal serum and cord blood prealbumin levels and fetal birth weight. Methods: Maternal serum prealbumin levels were measured in: (a) Normal pregnant women in the first (n=25), second (n=20) and third (n=25) trimester with appropriate for gestational age (AGA) fetuses; and (b) pregnant women with intrauterine growth restriction (IUGR) at delivery (n=15). Corresponding fetal cord blood prealbumin levels from the AGA group in the third trimester (n=25) and the IUGR group (n=15) were obtained during delivery. The prealbumin concentrations were quantified by immunoturbidmetric assay. Results: There was no significant correlation between the gestational weeks and maternal serum prealbumin levels during normal gestation. However, the maternal serum prealbumin concentrations from the third trimester were significantly lower than those of 1st and 2nd trimester. Furthermore, there was no significant difference between the maternal serum and cord blood prealbumin level of the control and those of IUGR group of third trimester. Moreover, there was no significant relationship between fetal and maternal level of prealbumin and fetal birthweight for both normal and IUGR pregnancies. Conclusion: Maternal serum and fetal cord blood prealbumin level was not an independent predictor of birth weight or fetal growth restriction. The failure to demonstrate a positive relationship may be due to the complex physiologic changes associated with pregnancy.ope

Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth

Ureaplasma and Prevotella infections are well-known bacteria associated with preterm birth. However, with the development of metagenome sequencing techniques, it has been found that not all Ureaplasma and Prevotella colonizations cause preterm birth. The purpose of this study was to determine the association between Ureaplasma and Prevotella colonization with the induction of preterm birth even in the presence of Lactobacillus. In this matched case-control study, a total of 203 pregnant Korean women were selected and their cervicovaginal fluid samples were collected during mid-pregnancy. The microbiome profiles of the cervicovaginal fluid were analyzed using 16S rRNA gene amplification. Sequencing data were processed using QIIME1.9.1. Statistical analyses were performed using R software, and microbiome analysis was performed using the MicrobiomeAnalyst and Calypso software. A positive correlation between Ureaplasma and other genera was highly related to preterm birth, but interestingly, there was a negative correlation with Lactobacillus and term birth, with the same pattern observed with Prevotella. Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth, although Ureaplasma and Prevotella are associated with preterm birth. Balanced colonization between Lactobacillus and Ureaplasma and Prevotella is important to prevent preterm birth.ope

Maternal total cell-free DNA in preeclampsia with and without intrauterine growth restriction

Elevation of total cell-free DNA (cfDNA) in patients with preeclampsia is well-known; however, whether this change precedes the onset of symptoms remains inconclusive. Here, we conducted a nested case-control study to determine the elevation of cfDNA levels in women who subsequently developed preeclampsia. Methylated HYP2 (m-HYP2) levels were determined in 68 blood samples collected from women with hypertensive disorders of pregnancy, along with 136 control samples, using real-time quantitative PCR. The measured m-HYP2 levels were converted to multiples of the median (MoM) values for correction of maternal characteristics. The m-HYP2 levels and MoM values in patients with preeclampsia were significantly higher than in controls during the third trimester (P < 0.001, both), whereas those for women who subsequently developed preeclampsia did not differ during the second trimester. However, when patients with preeclampsia were divided based on the onset-time of preeclampsia or 10th percentile birth weight, both values were significantly higher in women who subsequently developed early-onset preeclampsia (P < 0.05, both) and preeclampsia with small-for-gestational-age (SGA) neonate (P < 0.01, both) than controls. These results suggested that total cfDNA levels could be used to predict early-onset preeclampsia or preeclampsia with SGA neonate.ope

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.ope

MicroRNA-548 Regulates High Mobility Group Box 1 Expression in Patients With Preterm Birth and Chorioamnionitis

High mobility group box 1 (HMGB1) is a prototypic alarmin and plays an important role in the pathogenesis of inflammatory process in spontaneous preterm birth. This study was conducted to compare the levels of HMGB1 in amniotic fluid and amnion membranes in women with chorioamnionitis/intra-amniotic inflammation to the levels in healthy controls. We also aimed to elucidate the involvement of microRNA-548 (miR-548) in regulating HMGB1 expression and its function in human amniotic epithelial cells (hAECs). A bioinformatics analysis predicted the binding of HMGB1 by the miR-548 cluster. A repressed and forced expression assay in hAECs was performed to investigate the causal relationship between the miR-548 cluster and HMGB1. The levels of HMGB1 in amniotic fluid and amnion membranes were significantly higher in patients with intra-amniotic inflammation/chorioamnionitis than in those without inflammation. The miR-548 was significantly under-expressed in amnion membranes from patients with chorioamnionitis than in normal term controls. Repressed expression of miR-548 up-regulated HMGB1 expression in hAECs and increased its release from hAECs. Moreover, forced expression of miR-548 suppressed HMGB1 and inflammatory cytokines in hAECs, which increased when treated with lipopolysaccharide. These results suggest miR-548 can alter the inflammatory responses in hAECs, and might be involved in the pathogenesis of preterm birth by regulating HMGB1.ope

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.ope

Comparison of placental endothelin-1 (ET-1) expression under hypoxic condition between normal versus preeclamptic pregnancy

Objective: To evaluate endothelin-1 (ET-1) expression in the villous explants from normal and preeclamptic (PE) placentae under hypoxic condition. Methods: Villous explants from normal (n=5) and PE (n=4) placentae were obtained. To obtain hypoxic culture condition, villous explants were cultured in hypoxic chamber or treated with deferoxamine (DFO). ET-1 mRNA expressions in villous explants were evaluated by RT-PCR following 0, 24, and 48 h of culture in hypoxic chamber, and 0, 2, 4, 6 h following DFO treatment. ET-1 protein levels in media were measured by enzyme immunoassay. Results: After 24 and 48 hours of incubation of villous explants from normal and PE placentae in hypoxic chamber, ET-1 mRNA and protein levels were increased in both groups, however, ET-1 production seemed to be more exaggerated in the villous explants from PE placentae. During 6 h of DFO exposure, ET-1 mRNA level was increased in the villous explants from PE placenta comparing to those from normal placentae (p<0.05). Interestingly, the increase of ET-1 mRNA expression in the villous explants from PE placentae was more exaggerated than those from normal placentae. Concordantly, increments of protein level between 0 to 2 h and 2 to 4 h were significantly higher in villous explants from PE placentae (p<0.05). Conclusion: ET-1 mRNA and protein were increased in villous explants from PE placentae compared to those from normal placentae under hypoxic condition. Furthermore, villous explants from PE placentae showed upregulated ET-1 expression upon hypoxic stimulation. This enhanced sensitivity to hypoxia may contribute to ET-1 overexpression in PE placenta in vivo and it needs further investigation for clarification.ope

The Clinical Usefulness of Predictive Models for Preterm Birth with Potential Benefits: A KOrean Preterm collaboratE Network (KOPEN) Registry-Linked Data-Based Cohort Study

Background: Preterm birth is strongly associated with increasing mortality, incidence of disability, intensity of neonatal care required, and consequent costs. We examined the clinical utility of the potential preterm birth risk factors from admitted pregnant women with symptomatic preterm labor and developed prediction models to obtain information for prolonging pregnancies. Methods: This retrospective study included pregnant women registered with the KOrean Preterm collaboratE Network (KOPEN) who had symptomatic preterm labor, between 16 and 34 gestational weeks, in a tertiary care center from March to November 2016. Demographics, obstetric and medical histories, and basic laboratory test results obtained at admission were evaluated. The preterm birth probability was assessed using a nomogram and decision tree according to birth gestational age: early preterm, before 32 weeks; late preterm, between 32 and 37 weeks; and term, after 37 weeks. Results: Of 879 registered pregnant women, 727 who gave birth at a designated institute were analyzed. The rates of early preterm, late preterm, and term births were 18.16%, 44.02%, and 37.83%, respectively. With the developed nomogram, the concordance index for early and late preterm births was 0.824 (95% CI: 0.785-0.864) and 0.717 (95% CI: 0.675-0.759) respectively. Preterm birth was significantly more likely among women with multiple pregnancy and had water leakage due to premature rupture of membrane. The prediction rate for preterm birth based on decision tree analysis was 86.9% for early preterm and 73.9% for late preterm; the most important nodes are watery leakage for early preterm birth and multiple pregnancy for late preterm birth. Conclusion: This study aims to develop an individual overall probability of preterm birth based on specific risk factors at critical gestational times of preterm birth using a range of clinical variables recorded at the initial hospital admission. Therefore, these models may be useful for clinicians and patients in clinical decision-making and for hospitalization or lifestyle coaching in an outpatient setting.ope