Evidence for uteroplacental malperfusion in fetuses with major congenital heart defects.

AIMS: Fetuses affected by congenital heart defects (CHD) are considered to be at increased risk of fetal growth restriction and intrauterine demise. Whether these risks are a direct consequence of fetal CHD or a result of associated uteroplacental dysfunction is not evident from the data of recent studies. The aim of this study was to investigate the prevalence of uteroplacental dysfunction reflected by abnormal uterine artery Doppler indices and reduced fetal growth in CHD pregnancies. METHODS: This is a retrospective case-control study including singleton pregnancies referred for detailed fetal cardiac assessment subsequently diagnosed with or without CHD. Mid-trimester uterine artery Doppler assessment at 20-24 weeks as well as third trimester fetal biometry and arterial Doppler pulsatility indices (PI) were performed. All fetal biometry were converted into centiles and Doppler values to multiples of median (MoM) to adjust for physiological changes with gestation. RESULTS: The study included 811 pregnancies including 153 cases where the fetus was diagnosed with CHD. Mid-pregnancy uterine artery PI was significantly higher in women with fetal CHD compared to controls (0.90MoM vs 0.83MoM; p = 0.006). In the third trimester, median centiles for fetal head circumference (45.4 vs 57.07; p<0.001), abdominal circumference (51.17 vs 55.71; p = 0.014), estimated fetal weight (33.6 vs 56.7; p<0.001) and cerebroplacental ratio (CPR: 0.84MoM vs 0.95MoM; p<0.001) were significantly lower in fetuses with CHD compared to controls. The percentage of small for gestational age births <10th centile (24.0% vs 10.7%; <0.001) and low CPR <0.6MoM (11.7% vs 2.5%; p<0.001) were significantly higher in the fetal CHD cohort. CONCLUSIONS: Mid-pregnancy uterine artery resistance is increased and subsequent fetal biometry reduced in pregnancies with CHD fetuses. These findings suggest that fetal CHD are associated with uteroplacental dysfunction, secondary to impaired maternal uteroplacental perfusion resulting in relative fetal hypoxaemia and reduced fetal growth

Risk of neonatal care unit admission in small for gestational age fetuses at term: a prediction model and internal validation.

OBJECTIVE: Small for gestational age (SGA) fetuses are at increased risk of admission to the neonatal unit, even at term. We aimed to develop and validate a predictive model for the risk of prolonged neonatal unit admission in suspected SGA fetuses at term. METHODS: A single-center cohort study of singleton pregnancies with SGA fetus, defined as estimated fetal weight (EFW) less than the 10th centile, at term. The variables included known risk factors for neonatal unit admissions: maternal characteristics, EFW, abdominal circumference (AC), fetal Dopplers, gestational age (GA) at delivery, and intrapartum risk factors (meconium, pyrexia). Logistic regression analysis was used for model building and the prediction models were validated internally using bootstrapping. RESULTS: 701 SGA pregnancies at term were included; 5.9% had prolonged neonatal unit admission (> 48 hours). The multivariable model (AUC 0.71; 95% CI: 0.63-0.79) included GA at delivery < 39 weeks (OR 2.76; 95% CI 1.23-6.04, p = 0.011), cerebroplacental ratio (CPR) multiples of median (MoM) (OR 0.21; 95% CI 0.05-0.79, p = 0.023), and EFW below the third centile (OR 2.43; 95% CI 1.26-4.68, p < 0.007). The combined model showed a sensitivity 30.9% (95% CI: 16.6-45.2%) for a fixed 10% false positive rate. CONCLUSION: The prediction model shows good accuracy and good calibration for assessing the risk of neonatal unit admission in suspected SGA fetuses. It has the potential to be used for patient counseling, determining the timing of delivery and the individual risk

Maternal hemodynamics in screen‐positive and screen‐negative women of the ASPRE trial

Objective To compare maternal hemodynamics and perinatal outcome, in pregnancies that do not develop pre‐eclampsia (PE) or deliver a small‐for‐gestational‐age (SGA) neonate, between those identified at 11–13 weeks' gestation as being screen positive or negative for preterm PE, by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and pregnancy associated plasma protein‐A. Methods This was a prospective longitudinal cohort study of maternal cardiovascular function, assessed using a bioreactance method, in women undergoing first‐trimester screening for PE. Maternal hemodynamics and perinatal outcome were compared between screen‐positive and screen‐negative women who did not have a medical comorbidity, did not develop PE or pregnancy‐induced hypertension and delivered at term a live neonate with birth weight between the 5th and 95th percentiles. A multilevel linear mixed‐effects model was used to compare the repeated measures of cardiac variables, controlling for maternal characteristics. Results The screen‐negative group (n = 926) had normal cardiac function changes across gestation, whereas the screen‐positive group (n = 170) demonstrated static or reduced cardiac output and stroke volume and higher mean arterial pressure and peripheral vascular resistance with advancing gestation. In the screen‐positive group, compared with screen‐negative women, birth‐weight Z‐score was shifted toward lower values, with prevalence of delivery of a neonate below the 35th, 30th or 25th percentile being about 70% higher, and the rate of operative delivery for fetal distress in labor also being higher. Conclusion Women who were screen positive for impaired placentation, even though they did not develop PE or deliver a SGA neonate, had pathological cardiac adaptation in pregnancy and increased risk of adverse perinatal outcome

Maternal haemodynamics in Hypertensive Disorders of Pregnancy under antihypertensive therapy (HyperDiP): study protocol for a prospective observational case-control study

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are associated with a high incidence of maternal and perinatal morbidity and mortality. HDP, in particular pre-eclampsia, have been determined as risk factors for future cardiovascular disease. Recently, the common hypothesis of pre-eclampsia being a placental disorder was challenged as numerous studies show evidence for short-term and long-term cardiovascular changes in pregnancies affected by HDP, suggesting a cardiovascular origin of the disease. Despite new insights into the pathophysiology of HDP, concepts of therapy remain unchanged and evidence for improved maternal and neonatal outcome by using antihypertensive agents is lacking. METHODS AND ANALYSIS: A prospective observational case-control study, including 100 women with HDP and 100 healthy controls, which will assess maternal haemodynamics using the USCOM 1A Monitor and Arteriograph along with cardiovascular markers (soluble fms-like kinase 1/placental-like growth factor, N-terminal pro-B type natriuretic peptide) in women with HDP under antihypertensive therapy, including a follow-up at 3 months and 1 year post partum, will be conducted over a 50-month period in Vienna. A prospective, longitudinal study of cardiovascular surrogate markers conducted in Oslo will serve as a comparative cohort for the Vienna cohort of haemodynamic parameters in pregnancy including a longer follow-up period of up to 3 years post partum. Each site will provide a dataset of a patient group and a control group and will be assessed for the outcome categories USCOM 1A measurements, Arteriograph measurements and Angiogenic marker measurements. To estimate the effect of antihypertensive therapy on outcome parameters, ORs with 95% CIs will be computed. Longitudinal changes of outcome parameters will be compared between normotensive and hypertensive pregnancies using mixed-effects models. ETHICS AND DISSEMINATION: Ethical approval has been granted to all participating centres. Results will be published in international peer-reviewed journals and will be presented at national and international conferences

Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension.

Background Women with chronic hypertension face a 5- to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty-seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt-1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P<0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P<0.001 for both) compared with women who delivered for other reasons. SFlt-1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications (P<0.05). Half of women with angiogenic imbalance (sFlt-1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0-2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval

Data Archived for Events in the Caucasus for the CauSINCollaboration Project

The Causin project is a joint effort between the countries in the Caucasus region to develop a Probabilistic Seismic Hazard Analysis. To that end, we have compiled a database of all available network data in the region. The information contained in the database is from four countries: Armenia, Georgia, Azerbaijan, and Turkey and from the Incorporated Research Institutions for Seismology (IRIS). Table 1 lists the networks from which data were obtained. Figure 1 shows the locations of stations, and Figure 2 shows ray paths for event locations of the archived data. An ongoing effort in the region is the Caucasus Seismic Information Network (CauSIN) is an international scientific project enabling the countries and scientists of the region to: better understand the seismicity of the greater Caucasus; develop new monitoring networks to support the scientific understanding; provide access to seismic data from local networks in the participating countries; and develop a probabilistic seismic hazards assessment for the region enabling the governments in the region to better mitigate the damaging effects from large earthquakes. In parallel with this effort, training has been conducted on modern techniques for probabilistic hazards assessment. CauSIN is also an ongoing effort to promote cooperation in the geosciences between Georgia, Armenia, Azerbaijan, European Union and the United States. The DOE supports the American team from New England Research, Inc. (NER), Massachusetts Institute of Technology (MIT), Boston College, and Lawrence Livermore National Laboratory (LLNL)

Gas and seismicity within the Istanbul seismic gap

Understanding micro-seismicity is a critical question for earthquake hazard assessment. Since the devastating earthquakes of Izmit and Duzce in 1999, the seismicity along the submerged section of North Anatolian Fault within the Sea of Marmara (comprising the “Istanbul seismic gap”) has been extensively studied in order to infer its mechanical behaviour (creeping vs locked). So far, the seismicity has been interpreted only in terms of being tectonic-driven, although the Main Marmara Fault (MMF) is known to strike across multiple hydrocarbon gas sources. Here, we show that a large number of the aftershocks that followed the M 5.1 earthquake of July, 25th 2011 in the western Sea of Marmara, occurred within a zone of gas overpressuring in the 1.5–5 km depth range, from where pressurized gas is expected to migrate along the MMF, up to the surface sediment layers. Hence, gas-related processes should also be considered for a complete interpretation of the micro-seismicity (~M < 3) within the Istanbul offshore domain

Suicidal tendencies and attitude towards freedom to choose suicide among Lithuanian schoolchildren: results from three cross-sectional studies in 1994, 1998, and 2002

BACKGROUND: Suicidal behaviour is increasingly becoming a phenomenon associated with young people and an important public health issue in Lithuania. However, there are very few studies evaluating impact of young peoples' attitudes towards suicide to their suicidal behaviour. A better understanding of the relations among the variables associated with suicidal ideation and threats in the normal population of adolescents may eventually result in a better understanding of the more serious forms of adolescent suicidal behaviour. The aim of the present study was to evaluate prevalence of suicidal tendencies among Lithuanian schoolchildren and to estimate its association with an attitude towards suicide in 1994 – 2002. METHODS: Three country representative samples of schoolchildren, aged 11, 13 and 15, were surveyed in 1994 (n = 5428), 1998 (n = 4513), and 2002 (n = 5645) anonymously in conformity with the methodology of the World Health Organization Cross – National study on Health Behaviour in School-aged Children (HBSC). RESULTS: About one third of respondents reported about suicidal ideation, plans or attempts to commit suicide. In the study period of eight years, the percentage of adolescents who reported sometime suicidal ideation decreased but the percentage of adolescents who declared serious suicidal behaviour remained on the same high level (8.1%, 9.8% and 8.4% correspondingly in 1994, 1998 and 2002). Moreover, the number of suicidal attempts changed from 1.0% in 1994 to 1.8% in the year 1998 and to 1,7% in the year 2002. The schoolchildren's attitude towards suicide became more agreeable: 36.6%, 41.9% and 62.5% of respondents, correspondingly in 1994, 1998 and 2002, answered that they agree with a person's freedom to make a choice between life and suicide. A multiple logistic regression analysis with low level of suicidality and high level of suicidality versus non suicidal behaviour as dependent variables for gender, age, year of the survey and attitude towards freedom to choose suicide as independent variables approved a significant association between studied covariates over the entire study period. CONCLUSION: Suicidal tendencies are quite frequent among Lithuanian adolescents. An increasing number of schoolchildren are expressing an agreeable attitude towards suicide. The approving attitude towards suicide among adolescents correlates with suicidal ideation and behaviour