Preeclampsia and neonatal outcomes in pregnancies with maternal congenital heart disease: A nationwide cohort study from Norway.

INTRODUCTION: The prevalence of congenital heart disease (CHD) among women of reproductive age is rising. We aimed to investigate the risk of preeclampsia and adverse neonatal outcomes in pregnancies of mothers with CHD compared to pregnancies of mothers without heart disease. MATERIAL AND METHODS: In a nationwide cohort of pregnancies in Norway 1994-2014, we retrieved information on maternal heart disease, the course of pregnancy, and neonatal outcomes from national registries. Comparing pregnancies with maternal CHD to pregnancies without maternal heart disease, we used Cox regression to estimate the adjusted hazard ratio (aHR) for preeclampsia and log-binomial regression to estimate the adjusted risk ratio (aRR) for adverse neonatal outcomes. The estimates were adjusted for maternal age and year of childbirth and presented with 95% confidence intervals (CIs). RESULTS: Among 1 218 452 pregnancies, 2425 had mild maternal CHD, and 603 had moderate/severe CHD. Compared to pregnancies without maternal heart disease, the risk of preeclampsia was increased in pregnancies with mild and moderate/severe maternal CHD (aHR1.37, 95% CI 1.14-1.65 and aHR 1.62, 95% CI 1.13-2.32). The risk of preterm birth was increased in pregnancies with mild maternal CHD (aRR 1.33, 95% CI 1.15-1.54) and further increased with moderate/severe CHD (aRR 2.49, 95% CI 2.03-3.07). Maternal CHD was associated with elevated risks of both spontaneous and iatrogenic preterm birth. The risk of infants small-for-gestational-age was slightly increased with mild maternal CHD (aRR 1.12, 95% CI 1.00-1.26) and increased with moderate/severe CHD (aRR 1.63, 95% CI 1.36-1.95). The prevalence of stillbirth was 3.9 per 1000 pregnancies without maternal heart disease, 5.6 per 1000 with mild maternal CHD, and 6.8 per 1000 with moderate/severe maternal CHD. Still, there were too few cases to report a significant difference. There were no maternal deaths in women with CHD. CONCLUSIONS: Moderate/severe maternal CHD in pregnancy was associated with increased risks of preeclampsia, preterm birth, and infants small-for-gestational-age. Mild maternal CHD was associated with less increased risks. For women with moderate/severe CHD, their risk of preeclampsia and adverse neonatal outcomes should be evaluated together with their cardiac risk in pregnancy, and follow-up in pregnancy should be ascertained.

Conscious Self-Regulation as a Meta-Resource of Academic Achievement and Psychological Well-Being of Young Adolescents.

Background: The role of conscious self-regulation in determining students' psychological well-being and academic performance is considered in the context of the fundamental problem of the regularities of young adolescents' development. Objective: To reveal the role of meta-resources of conscious self-regulation in determining young adolescents' psychological well-being and academic performance. Design: Sample: 500 students in 4th- to 6th grade (10-12) in general schools, 149 of whom participated in a three-year longitudinal study. The Self-Regulation Profile of Learning Activity and the Well-Being Manifestation scales were used. Results: Conscious self-regulation and academic performance increase significantly in fifth grade and decrease in sixth grade. On the contrary, psychological well-being is characterized by a systemic positive dynamic. A typological analysis identified the levels of psychological well-being of students growing, stable, and declining during the transition period. It was found that the general level of conscious self-regulation made a significant positive contribution and is a universal resource for students' psychological well-being and academic performance. Special regulatory resources for academic performance are described, depending on the trajectory of changes in psychological well-being. Increased well-being is determined by the regulatory competencies of Planning and Evaluation of results and its stability by Planning, Modelling, Flexibility, and Responsibility. The general level of self-regulation, regulatory competencies, Planning, Programming and Responsibility mediate in the relationship between student psychological well-being and academic performance. A longitudinal study found that self-regulation has a long-term positive effect on student psychological well-being and academic performance. Conclusion: Conscious self-regulation is a meta-resource that makes a significant contribution to both the psychological well-being and academic performance. Mediator and prognostic effects of self-regulation on these properties create a psychological basis for practical work.

Altered brain dynamics index levels of arousal in complete locked-in syndrome.

Complete locked-in syndrome (CLIS) resulting from late-stage amyotrophic lateral sclerosis (ALS) is characterised by loss of motor function and eye movements. The absence of behavioural indicators of consciousness makes the search for neuronal correlates as possible biomarkers clinically and ethically urgent. EEG-based measures of brain dynamics such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) have been shown to have explanatory power for consciousness and may provide such neuronal indices for patients with CLIS. Here, we validated PLE and LZC (calculated in a dynamic way) as benchmarks of a wide range of arousal states across different reference states of consciousness (e.g., awake, sleep stages, ketamine, sevoflurane). We show a tendency toward high PLE and low LZC, with high intra-subject fluctuations and inter-subject variability in a cohort of CLIS patients with values graded along different arousal states as in our reference data sets. In conclusion, changes in brain dynamics indicate altered arousal in CLIS. Specifically, PLE and LZC are potentially relevant biomarkers to identify or diagnose the arousal level in CLIS and to determine the optimal time point for treatment, including communication attempts.

Bacterial Communities of Lamiacea L. Medicinal Plants: Structural Features and Rhizosphere Effect.

Bacterial communities associated with medicinal plants are an essential part of ecosystems. The rhizosphere effect is rather important in the cultivation process. The purpose of the study was to analyze the rhizosphere effect of oregano (Origanum vulgare L.), peppermint (Mentha piperita L.), thyme (Thymus vulgaris L.), creeping thyme (Thymus serpillum L.) and sage (Salvia officinalis L.). To estimate the quantity of 16S bacteria ribosomal genes, qPCR assays were used. To compare bacterial communities' structure of medicinal plants rhizosphere with bulk soil high-throughput sequencing of the 16S rRNA targeting variable regions V3-V4 of bacteria was carried out. The highest bacterial abundance was associated with T. vulgaris L., M. piperita L. and S. officinalis L., and the lowest was associated with the O. vulgare L. rhizosphere. Phylum Actinobacteriota was predominant in all rhizosphere samples. The maximum bacterial α-diversity was found in S. officinalis L. rhizosphere. According to bacterial ß-diversity calculated by the Bray-Curtis metric, T. vulgaris L. root zone significantly differed from bulk soil. The rhizosphere effect was positive to the Myxococcota, Bacteroidota, Verrucomicrobiota, Proteobacteria and Gemmatimonadota.

Conscious Self-regulation, Motivational Factors, and Personality Traits as Predictors of Students' Academic Performance: A Linear Empirical Model.

Background: The theoretical basis of this study was the resource approach (Morosanova 2014, 2017), in which the conscious self-regulation of learning activity is understood as a meta-resource for students, allowing them to consciously and independently set learning goals and manage their achievement. This approach made it possible to create models of direct and mediate contributions of self-regulation and school engagement not only to academic performance, but also to other motivational and personal competencies. Objective: Our study aimed to investigate the impact of conscious self-regulation, school engagement, motivation, and personality on academic achievement, while taking into account the effects of mediation. Design: A quantitative research design was applied, using data collected from more than 1524 students from the 5th to 11th grades in Russian schools and applying Structural Equation Modelling (SEM). Results: The results allowed us to construct a statistical model of predictors of students' academic achievement. The model was verified on the total sample, as well as samples differing in gender and age. The results show that conscious self-regulation is central to non-cognitive predictors of academic achievement. For the first time, a study has revealed and described the reciprocal relationship between self-regulation, academic motivation, school engagement, and academic performance. The resulting model demonstrates that behavioral and cognitive engagement make a significant contribution to academic performance, while emotional and social engagement do not find significant links with it, although they determine other areas of school life. Conclusion: Our paper investigates the nature and strength of the effects of major non-cognitive predictors of academic achievement. The study results substantiated the resource role of conscious self-regulation not only for students' academic performance, but also for their academic motivation, school engagement, and attitude toward learning. The predictor model of academic achievement we developed will provide a foundation for combining existing heterogeneous concepts into a single integrated model and clarify the contradictions between them.

The Dynamics of the Interrelationships between Conscious Self-regulation, Psychological Well-being and School-related Subjective Well-being in Adolescents: A Three-year Cross-lagged Panel Study.

Background: Recently, research on psychological well-being and its dynamics and predictors in adolescence, has gained special attention, due to the importance of well-being for mental and physical health, as well as for success in different activities. Self-regulation (SR) is considered a significant resource for maintaining psychological and school-related subjective well-being. Objective: The purpose of our study was to identify the role of conscious SR in maintaining pupils' satisfaction with school life, and to assess the contribution of conscious SR to the development of psychological well-being in adolescence. Design: Two three-year longitudinal studies were carried out on samples of young adolescents in Russian schools (N = 148; N = 132; 10-13 years). The studies utilized methods for assessing conscious SR, psychological well-being (PWB), and school-related subjective well-being (SWB), the latter being the cognitive component of life satisfaction. Results: Our research revealed differences in the dynamics of PWB and SWB levels in adolescents during their transition from primary to basic secondary school. It also identified the specifics of longitudinal relationships between conscious SR, PWB, and SWB in adolescence. We showed that there was a reciprocal relationship between them. However, the most significant cross-longitudinal effects were established between SR and school-related SWB. These effects changed over time: at the beginning, well-being acted as a significant factor of self-regulation, while later self-regulation acted as a significant resource for maintaining adolescent well-being in the subsequent years. Conclusion: School-related SWB is characterized by the most pronounced trajectory of change, while PWB is characterized by greater stability and insignificant growth. Our three-year longitudinal study demonstrated that the link between self-regulation and well-being is consistently reproduced. Conscious self-regulation is a significant resource for both the psychological and school subjective well-being of adolescents.

Are intrinsic neural timescales related to sensory processing? Evidence from abnormal behavioral states.

The brain exhibits a complex temporal structure which translates into a hierarchy of distinct neural timescales. An open question is how these intrinsic timescales are related to sensory or motor information processing and whether these dynamics have common patterns in different behavioral states. We address these questions by investigating the brain's intrinsic timescales in healthy controls, motor (amyotrophic lateral sclerosis, locked-in syndrome), sensory (anesthesia, unresponsive wakefulness syndrome), and progressive reduction of sensory processing (from awake states over N1, N2, N3). We employed a combination of measures from EEG resting-state data: auto-correlation window (ACW), power spectral density (PSD), and power-law exponent (PLE). Prolonged neural timescales accompanied by a shift towards slower frequencies were observed in the conditions with sensory deficits, but not in conditions with motor deficits. Our results establish that the spontaneous activity's intrinsic neural timescale is related to the neural capacity that specifically supports sensory rather than motor information processing in the healthy brain.

Antihypertensive activity of a new c-Jun N-terminal kinase inhibitor in spontaneously hypertensive rats.

c-Jun N-terminal kinases (JNKs) are involved in the myocardial and aortic remodeling, increased arterial tone, and arterial blood pressure elevation associated with hypertension. The aim of the present study was to investigate the antihypertensive effect of a new JNK inhibitor, 1H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), on spontaneously hypertensive rats (SHRs). Experiments were performed using normotensive Wistar-Kyoto (WKY) rats and SHRs. Experimental groups of SHRs received IQ-1S intragastrically for 6 weeks in daily doses of 5 and 50 mg/kg; experimental groups of WKY rats received 50 mg/kg IQ-1S according to the same regimen. The IQ-1S administration regimen induced decreases in systolic blood pressure, mean arterial blood pressure, total peripheral resistance, blood viscosity, hematocrit, myocardial cell cross-sectional area, and aortic wall thickness in SHRs vs untreated SHRs. There were no significant differences in systolic blood pressure values between the control and experimental groups of WKY rats during the treatment period. A concentration-dependent decrease in the tone of carotid arterial rings isolated from SHRs was observed after JNK inhibitor application in vitro. Application of the JNK inhibitor diminished endothelin-1 secretion by human umbilical vein endothelial cells in vitro. The main mechanisms of the antihypertensive effect of IQ-1S included the attenuation of blood viscosity due to decreased hematocrit, a vasodilatory effect on arterial smooth muscle cells, and a decrease in endothelin-1 production by endothelial cells.

Self-Regulation and Psychological Well-Being in Early Adolescence: A Two-Wave Longitudinal Study.

This paper addresses the question of whether self-regulation capacities are a significant psychological resource of schoolchildren's psychological well-being. The study contributes to the search of significant predictors of the students' psychological well-being. Moscow secondary schools pupils (N = 239) participated in a two-wave longitudinal study, the procedure being made in the 4th grade and repeated in the 5th grade, six months after the first measurement. The results are presented describing the dynamics of manifestations of the psychological well-being and the conscious self-regulation of the schoolchildren during their transition from the primary to the middle school. Using the cross-lagged panel analysis allowed concluding that the level of conscious self-regulation of the learning activity of the 4th graders significantly predicts their psychological well-being not only in the 4th grade, but also in the 5th grade. The study revealed the specific regulatory predictors characteristic of different manifestations of the schoolchildren' psychological well-being. The obtained results highlight the significance of research on the conscious self-regulation of learning activities as a resource for pupils' psychological well-being, which is predictive for its maturation in the subsequent ages.

Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats.

c-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5'-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage. In rats with IQ-1S administration, the LCBF was significantly higher (by 60%) compared with that in the GCI control. Treatment with IQ-1S also decreases blood viscosity and endothelial dysfunction. A concentration-dependent decrease (IC50 = 0.8 ± 0.3 µM) of tone in isolated carotid arterial rings constricted with phenylephrine was observed after IQ-1S application in vitro. We also found that IQ-1S decreased the intensity of the lipid peroxidation in the brain tissue in rats with GCI. 2.2-Diphenyl-1-picrylhydrazyl scavenging for IQ-1S in acetonitrile and acetone exceeded the corresponding values for ionol, a known antioxidant. Overall, these results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant/antiradical IQ-1S activity.

The Relationship between the Conscious Self-Regulation of Schoolchildren's Learning Activity, Their Test Anxiety Level, and the Final Exam Result in Mathematics.

This article presents the results of a study on the relationship between conscious self-regulation of learning activity, test anxiety and performance in the Unified State Exam in mathematics in a sample of Russian students (N = 231). The Self-Regulation Profile of Learning Activity Questionnaire (SRPLAQ, 2015) and Spielberger's Test Anxiety Inventory (TAI) (Russian adaptation, 2004) were used to measure self-regulation and anxiety, respectively. The study also took into account the students' results for the Unified State Exam in mathematics. The study revealed a negative correlation for the test anxiety indicators with both the exam results and regulatory characteristics. The cluster analysis identified groups of students that differed in their level of self-regulation development, anxiety indicators, and the math exam result. It appears that students who have the lowest exam results are characterized not only by high test anxiety rates, but also by lower self-regulation levels. The regression analysis within the groups showed that a higher exam result is largely associated with a person's regulatory resources. Examination success is based not so much on the ability to cope with adverse functional states, but on the maturity and stability of an integrated system of conscious self-regulation, which determines students' effectiveness in achieving educational goals.

Paternal characteristics associated with maternal periconceptional use of folic acid supplementation.

BACKGROUND: Maternal predictors of folic acid (FA) supplementation use to reduce offspring risk of neural tube defects are well known, while paternal determinants for maternal FA use are less known. Such knowledge is important to increase women's compliance to recommended periconceptional FA use. METHODS: In a nation-wide study of 683,785 births registered in the Medical Birth Registry of Norway during 1999-2010, the associations between paternal characteristics (age, education, occupation, country of origin) and maternal FA use were estimated by relative risks (RR) with 95% confidence intervals (CI), using log-binomial regression. RESULTS: Maternal FA use before and during pregnancy (adequate FA use) was found in 16% of the births. The association between paternal age and adequate FA use was inversely U-shaped; adjusted RRs for adequate FA use were 0.35 (95% CI 0.28-0.43) and 0.72 (95% CI 0.71-0.74) for paternal age < 20 and ≥ 40 years, respectively, comparing age 30-34 years. Compulsory education (1-9 years) among fathers was compared to tertiary education; the RR was 0.69 (95% CI 0.68-0.71) for adequate FA use. The lower risk of adequate FA use for paternal compulsory education was present in all categories of maternal education. Occupation classes other than "Higher professionals" were associated with decreased risk of adequate FA use, compared with the reference "Lower professionals". RR for adequate FA use was 0.58 (95% CI 0.56-0.60) comparing fathers from "Low/middle-income countries" with fathers born in Norway. CONCLUSION: Adequate FA use in the periconceptional period was lower when fathers were younger or older than 30-34 years, had shorter education, had manual or self-employed occupations, or originated from low/middle-income countries. Partners may contribute to increase women's use of periconceptional FA supplementation.

Effect of p-tyrosol on hemorheological parameters and cerebral capillary network in young spontaneously hypertensive rats.

BACKGROUND: Many pathological mechanisms are involved in the development of arterial hypertension; disturbance of the rheological properties of blood and microvascular rarefaction are among those mechanisms. OBJECTIVE: The effect of p-tyrosol (Tyr) on hemorheological parameters and microvascularization in the cerebral cortex of spontaneously hypertensive rats (SHRs) at the stage of blood pressure rising (5-11 weeks) was studied. METHODS: Blood viscosity (BV), plasma viscosity (PV), hematocrit, erythrocyte aggregation and deformability, the oxygen transport capacity index (OTCI), and the capillary network in the cerebral cortex after the course of treatment of Tyr (50 mg/kg daily i.g. for 6 weeks) were studied. Control normotensive Wistar-Kyoto (WKY) rats and control SHRs received an equivalent amount of 1% starch mucilage. RESULTS: In comparison with WKY rats, disturbances of rheological blood parameters and a decrease in OTCI were revealed in control SHRs at the 11 weeks of life. By the end of the experiment, brain microvascular rarefaction was observed in the control SHRs (the average density of the capillary bed was reduced due to a decrease in the number of capillaries with a diameter of 3-7 µm). In SHRs rats treated with Tyr, BV and PV, the indices of erythrocyte aggregation were lower, and OTCI was higher in comparison with control SHRs. The density of the capillary network and the number of capillaries of 3-7 µm in the cerebral cortex of SHRs rats receiving Tyr were significantly higher than the corresponding values in control SHRs. CONCLUSION: When Tyr is administered to young SHRs during the development of hypertension, it limits the development of hyperviscosity syndrome, improves the oxygen transport capacity and eliminates microvascular rarefaction in the cerebral cortex.

Case series: Slowing alpha rhythm in late-stage ALS patients.

The alpha peak frequency (APF) of the human electroencephalogram (EEG) is a reliable neurophysiological marker for cognitive abilities. In these case series, we document a shift of the APF towards the lower end of the EEG spectrum in two completely locked-in ALS patients. In not completely locked-in ALS patients, the alpha rhythm lies within the common frequency range. We discuss potential implications of this shift for the largely unknown cognitive state of completely locked-in ALS patients.

Effects of pentoxifylline on hemodynamic, hemorheological, and microcirculatory parameters in young SHRs during arterial hypertension development.

The most common form of hypertension in young adults is isolated diastolic hypertension. Diastolic arterial pressure is determined by the total peripheral resistance and depends on both vascular hindrance and blood viscosity. The aim of our work was to study the efficiency of pentoxifylline (PTX) in young spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. The effects of a treatment course with PTX (100 mg/kg/day p.o. for 6 weeks, from 5 to 11 weeks old) on the mean, systolic, and diastolic blood pressure (BP); stroke volume; cardiac output; total peripheral resistance (TPR); whole blood viscosity (BV); plasma viscosity; hematocrit; RBC aggregation and deformability; local cerebral blood flow (lCBF); and microvascularization of the visual cortex were studied in SHRs in comparison with control SHRs and Wistar Kyoto rats. PTX-treated SHRs had significantly lower systolic, diastolic, and mean BP (by 24%, 26%, and 15%, respectively) and BV (by 5-9%) and a higher erythrocyte deformability index (by 1.5-2%), lCBF (by 42%), average diameter of capillaries (by 11%), density of the capillary network (by 23%), and percentage of capillaries with a diameter of 3-7 µm in comparison with control SHRs. In conclusion, PTX exerted positive effects on the hemodynamic, hemorheological, and microcirculatory parameters in SHRs during the development of arterial hypertension.

Absence of EEG correlates of self-referential processing depth in ALS.

Self-referential processing is a key cognitive process, associated with the serotonergic system and the default mode network (DMN). Decreased levels of serotonin and reduced activations of the DMN observed in amyotrophic lateral sclerosis (ALS) suggest that self-referential processing might be altered in patients with ALS. Here, we investigate the effects of ALS on the electroencephalography correlates of self-referential thinking. We find that electroencephalography (EEG) correlates of self-referential thinking are present in healthy individuals, but not in those with ALS. In particular, thinking about themselves or others significantly modulates the bandpower in the medial prefrontal cortex in healthy individuals, but not in ALS patients. This finding supports the view of ALS as a complex multisystem disorder which, as shown here, includes dysfunctional processing of the medial prefrontal cortex. It points towards possible alterations of self-consciousness in ALS patients, which might have important consequences for patients' self-conceptions, personal relations, and decision-making.

Self-regulation of brain rhythms in the precuneus: a novel BCI paradigm for patients with ALS.

OBJECTIVE: Electroencephalographic (EEG) brain-computer interfaces (BCIs) hold promise in restoring communication for patients with completely locked-in stage amyotrophic lateral sclerosis (ALS). However, these patients cannot use existing EEG-based BCIs, arguably because such systems rely on brain processes that are impaired in the late stages of ALS. In this work, we introduce a novel BCI designed for patients in late stages of ALS based on high-level cognitive processes that are less likely to be affected by ALS. APPROACH: We trained two ALS patients via EEG-based neurofeedback to use self-regulation of theta or gamma oscillations in the precuneus for basic communication. Because there is a tight connection between the precuneus and consciousness, precuneus oscillations are arguably generated by high-level cognitive processes, which are less likely to be affected by ALS than processes linked to the peripheral nervous system. MAIN RESULTS: Both patients learned to self-regulate their precuneus oscillations and achieved stable online decoding accuracy over the course of disease progression. One patient achieved a mean online decoding accuracy in a binary decision task of 70.55% across 26 training sessions, and the other patient achieved 59.44% across 16 training sessions. We provide empirical evidence that these oscillations were cortical in nature and originated from the intersection of the precuneus, cuneus, and posterior cingulate. SIGNIFICANCE: Our results establish that ALS patients can employ self-regulation of precuneus oscillations for communication. Such a BCI is likely to be available to ALS patients as long as their consciousness supports communication.

Mortality and complications in 3495 children with isolated ventricular septal defects.

BACKGROUND: Ventricular septal defects (VSDs) are the most common congenital heart defects (CHDs). Previous studies indicate an increased risk of endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension, arrhythmias and sudden death in patients with isolated VSDs. The present nationwide cohort study reports mortality and cardiac complications requiring hospitalisation or intervention in children with isolated VSDs. METHODS AND RESULTS: Medical information concerning all 943 871 live births in Norway in 1994-2009 was retrieved from the Medical Birth Registry of Norway, the Cardiovascular Disease in Norway project, the Oslo University Hospital's Clinical Registry of Congenital Heart Defects and the Norwegian Cause of Death Registry. Isolated VSDs were identified in 3495 children without known chromosomal aberrations or extracardiac malformations. Surgical or catheter-based treatment of VSD was performed in 181 (5.2%) cases. Twelve (0.3%) children with VSDs died before 2013. There was no operative mortality, and no excess mortality in children with isolated VSDs compared with children without VSDs (adjusted HR 0.8 (0.5 to 1.4), p=0.48). The following conditions were recorded as possible cardiac complications of the VSDs: endocarditis in 3 children (0.9‰), aortic regurgitation in 12 children (3.4‰), left ventricular outflow tract obstructions in no children (0.0‰), pulmonary hypertension in 1 child (0.3‰) and arrhythmias in 16 children (4.6‰). CONCLUSIONS: The entire group of children with isolated VSDs had a favourable prognosis without excess mortality. Cardiac complications requiring hospitalisation or intervention, including endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension and arrhythmias, were infrequent during childhood. TRIAL REGISTRATION NUMBER: NCT02026557.

Supplemental folic acid in pregnancy and childhood cancer risk.

BACKGROUND: We investigated the association between supplemental folic acid in pregnancy and childhood cancer in a nation-wide study of 687 406 live births in Norway, 1999-2010, and 799 children diagnosed later with cancer. METHODS: Adjusted hazard ratios (HRs) compared cancer risk in children by approximated periconceptional folic acid levels (folic acid tablets and multivitamins (0.6 mg), only folic acid (0.4 mg), only multivitamins (0.2 mg)) and cancer risk in unexposed. RESULTS: Any folic acid levels were not associated with leukemia (e.g., high-level folic acid HR 1.25; 95% CI 0.89-1.76, PTrend 0.20), lymphoma (HR 0.96; 95% CI 0.42-2.21, PTrend 0.51), central nervous system tumours (HR 0.68; 95% CI 0.42-1.10, PTrend 0.32), neuroblastoma (HR 1.05; 95% CI 0.53-2.06, PTrend 0.85), Wilms' tumour (HR 1.16; 95% CI 0.52-2.58, PTrend 0.76), or soft-tissue tumours (HR 0.77; 95% CI 0.34-1.75, PTrend 0.90). CONCLUSIONS: Folic acid supplementation was not associated with risk of major childhood cancers.

Trends in Mortality of Congenital Heart Defects.

OBJECTIVE: The aim of the present nationwide cohort study was to describe trends in 1-year mortality in live-born children with congenital heart defects in Norway 1994-2009 and to assess whether changes in the proportion of terminated pregnancies and altered operative mortality have influenced these trends. METHODS: Medical information concerning all 954 413 live births, stillbirths, and late-term abortions in Norway, 1994-2009, was retrieved from the Medical Birth Registry of Norway, the Cardiovascular Disease in Norway project, the Oslo University Hospital's Clinical Registry for Congenital Heart Defects and the Norwegian Cause of Death Registry. Survivors were followed through 2012. RESULTS: The 1-year cumulative mortality proportion during the study period was 17.4% for children with severe congenital heart defects and 3.0% for children with nonsevere congenital heart defects. The 1-year cumulative mortality proportion among live born children with severe congenital heart defects decreased 3.6% (95% CI: -5.4, -1.5) per year. The total mortality of severe congenital heart defects was unchanged when including stillbirths and late-term abortions with severe congenital heart defects. The proportion of stillbirths or terminated pregnancies with severe congenital heart defects among all pregnancies with severe congenital heart defects, was on average 8.8% over the entire period with an annually increase of 16.6% (11.4, 18.0). The mean operative mortality in children with severe congenital heart defects was 8.4% and decreased by 9.0% (-11.9, -5.9) per year. CONCLUSIONS: The 1-year mortality of severe congenital heart defects among live births, 1994-2009, declined in Norway. The downward trend in mortality may be explained by a more frequent use of termination of affected pregnancies, and the reduced operative mortality of severe congenital heart defects.