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The prevalence of maternal obesity is rising. Pre-pregnancy obesity is associated with later cardiovascular disease in the child and the underlying pathogenesis begins in early life. Therefore, pregnancy and infancy are key periods for potential intervention. The aim of this study was to study the cardiac function in newborns of obese women compared to newborns of normal-weight women, and to determine if exercise intervention during pregnancy could have an effect on cardiac function of newborns to obese women. Fifty-five pregnant women, 51 obese (BMI ≥ 30 kg/m2) and four overweight (BMI 28-30 kg/m2), were randomized to an exercise training group (n = 27) or a control group (standard maternity care, n = 28). From gestational week 14 until delivery participants in the intervention group were offered supervised training sessions three times weekly. In addition, they were told to exercise at home once weekly. All newborns had an echocardiogram performed 1-3 days and 6-8 weeks after delivery. The results were compared with newborns of normal weight women (n = 20, standard maternity care). Newborns of obese women had an impaired systolic and diastolic cardiac function with reduced global strain, strain rate, tissue Doppler velocities and a thicker intraventricular septum at birth and after 6-8 weeks after delivery compared to newborns of normal weight women. Exercise had no statistically significant effect on either of the cardiac function parameters. The mean (± standard deviation) adherence to the exercise protocol was 1.3 ± 0.8 sessions per week for supervised training and 0.8 ± 0.7 sessions per week for home-based exercise training. Newborns of obese women had reduced cardiac function and thicker intraventricular septum compared to newborns of normal weight women. Exercise training during pregnancy had no significant effect, potentially due to a low number of subjects and low adherence to the exercise protocol. ClinicalTrials.gov NCT01243554.

Maternal obesity associates with complications during pregnancy and childbirth. Our aim was to investigate if exercise during pregnancy in overweight/obese women could influence birth weight or other neonatal and maternal outcomes at delivery. This is a secondary analysis of a randomised controlled trial of exercise training in pregnancy for women with body mass index (BMI) ≥ 28 kg/m2. Ninety-one women (31.3 ± 4.3 years, BMI 34.5 ± 4.2 kg/m2) were allocated 1:1 to supervised exercise during pregnancy or to standard care. The exercise group was offered three weekly training sessions consisting of 35 minutes of moderate intensity walking/running followed by 25 minutes of strength training. Data from 74 women (exercise 38, control 36) were analysed at delivery. Birth weight was 3719 ± 695 g in the exercise group and 3912 ± 413 g in the control group (CI -460.96, 74.89, p = 0.16). Birth weight > 4000 g was 35% in the exercise group and 52% in the control group (p = 0.16). Mean gestational age at delivery was 39.1 weeks in the exercise group and 39.5 weeks in the control group (CI -1.33, 0.43, p = 0.31). No significant between-group differences were found in neonatal body size, skinfold thickness, placental weight ratio, or Apgar score. The prevalence of caesarean section was 24% in the exercise group and 17% in the control group (CI 0.20, 2.05, p = 0.57). Mean length of hospital stay was 4.8 days in the exercise group and 4.5 days in the control group (CI -0.45, 1.00, p = 0.45). Offering supervised exercise during pregnancy for overweight and obese women did not influence birth weight or other neonatal and maternal outcomes at delivery. However our trial was limited by low sample size and poor adherence to the exercise protocol, and further research is needed. ClinicalTrials.gov NCT01243554.

Objective: To investigate whether there is an association between serum thyroid-stimulating hormone (TSH) within the normal range and body mass index (BMI). Design and subjects: The study was performed in 6164 subjects (2813 males) who attended the fifth Tromsø study in 2001, and in 1867 subjects (873 males) that attended both the fourth Tromsø study in 1994/1995 as well as the fifth Tromsø study. Measurements: Height, weight, and serum TSH were measured in all subjects, and smoking status was recorded. Results: Smokers and nonsmokers were analyzed separately. In the fifth Tromsø study, serum TSH was positively and significantly associated with BMI in the nonsmokers. Within the normal TSH range (defined as the 2.5–97.5 percentile), nonsmoking males in the highest TSH quartile had a mean BMI 0.4 kg/m 2 higher compared to those in the lower quartile, whereas the difference for nonsmoking women was 1.4 kg/m 2 . Similarly, in nonsmokers in the longitudinal study, there was a significant and positive association between delta serum TSH (serum TSH in 2001 minus serum TSH in 1994) and delta BMI in those with serum TSH within the normal range both in 1994 and 2001. In these subjects, the quartile with the highest delta serum TSH had a mean increase in BMI from 1994 to 2001 that was 0.3 kg/m 2 higher compared to those in the quartile with the lowest delta serum TSH. For the smokers, relations between serum TSH and BMI were not statistically significant. Conclusion: In nonsmokers there is a positive association between serum TSH within the normal range and BMI.

IntroductionGestational diabetes mellitus (GDM) is associated with increased risk for type 2 diabetes in the mother and cardiometabolic diseases in the child. The preconception period is an optimal window to adapt the lifestyle for improved outcomes for both mother and child. Our aim is to determine the effect of a lifestyle intervention, initiated before and continued throughout pregnancy, on maternal glucose tolerance and other maternal and infant cardiometabolic outcomes.Methods and analysisThis ongoing randomised controlled trial has included 167 females aged 18–39 years old at increased risk for GDM who are contemplating pregnancy. The participants were randomly allocated 1:1 to an intervention or control group. The intervention consists of exercise (volume is set by a heart rate-based app and corresponds to ≥ 1 hour of weekly exercise at ≥ 80% of individual heart rate maximum), and time-restricted eating (≤ 10 hours/day window of energy intake). The primary outcome measure is glucose tolerance in gestational week 28. Maternal and offspring outcomes are measured before and during pregnancy, at delivery, and at 6–8 weeks post partum. Primary and secondary continuous outcome measures will be compared between groups based on the ‘intention to treat’ principle using linear mixed models.Ethics and disseminationThe Regional Committees for Medical and Health Research Ethics in Norway has approved the study (REK 143756). The anonymised results will be submitted for publication and posted in a publicly accessible database of clinical study results.Trial registration numberClinical trial gov NCT04585581.

Background In this pilot study, we investigated continuous cerebral blood flow velocity measurements to explore cerebrovascular hemodynamics in infants with congenital heart disease undergoing cardiac surgery. Methods A non-invasive transfontanellar cerebral Doppler monitor (NeoDoppler) was used to monitor 15 infants (aged eight days to nine months) during cardiac surgery with cardiopulmonary bypass. Numerical and visual analyses were conducted to assess trends and events in Doppler measurements together with standard monitoring equipment. The mean flow index, calculated as the moving Pearson correlation between mean arterial pressure and time averaged velocity, was utilized to evaluate dynamic autoregulation. Two levels of impaired autoregulation were defined (Mean flow index >0.3/0.45), and percentage of time above these limits were calculated. Results High quality recordings were achieved during 90.6% of the monitoring period. There was a significant reduction in time averaged velocity in all periods of cardiopulmonary bypass. All patients showed a high percentage of time with impaired dynamic autoregulation, with Mean flow index >0.3 and 0.45: 73.71% ± 9.06% and 65.16% ± 11.27% respectively. Additionally, the system promptly detected hemodynamic events. Conclusion Continuous transfontanellar cerebral Doppler monitoring could become an additional tool in enhancing cerebral monitoring in infants during cardiac surgery. Impact This pilot study demonstrates the feasibility of continuous transfontanellar Doppler monitoring of cerebral blood flow velocities during cardiac surgery in infants. It also demonstrates a high proportion of time with impaired cerebral autoregulation during cardiac surgery based on the Mean flow index. Continuous transfontanellar Doppler could become a useful tool to improve cerebral monitoring and provide new pathophysiological insight.

Hilma Holm and colleagues report genome-wide association studies to electrocardiographic measures of heart rate, PR interval, QRS duration and QT interval. Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 × 10 −7 ). We identified one locus for heart rate ( MYH6 ), four for PR interval ( TBX5 , SCN10A , CAV1 and ARHGAP24 ) and four for QRS duration ( TBX5 , SCN10A , 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between TBX5 and CAV1 and atrial fibrillation ( P = 4.0 × 10 −5 and P = 0.00032, respectively), between TBX5 and advanced atrioventricular block ( P = 0.0067), and between SCN10A and pacemaker implantation ( P = 0.0029). We also replicated previously described associations with the QT interval.

Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear. We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses. Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow. Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs . Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1β, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays. After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004). No plasma differences in the rest of the inflammatory markers were noted across groups. However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1β and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1β compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). , incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03). A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. experiments may imply bone marrow to be the primary IL-6 source.

Background Today, there are conflicting descriptions of how neonates respond to tilt. Examining physiologic responses of cerebral blood flow velocities (BFVs) in challenging situations like a tilt requires equipment that can cope with positional changes. We aimed to characterize how healthy term neonates respond to mild cerebral hemodynamic stress induced by a 90° tilt test using the recently developed NeoDoppler ultrasound system. Methods A small ultrasound probe was fixated to the neonatal fontanel by a cap, and measured cerebral BFV in healthy neonates during and after a 90° head-up tilt test, five min in total, at their first and second day of life. Unsupervised k -means cluster analysis was used to characterize common responses. Results Fifty-six ultrasound recordings from 36 healthy term neonates were analyzed. We identified five distinct, immediate responses that were related to specific outcomes in BFV, heart rate, and pulsatility index the next two min. Among 20 neonates with two recordings, 13 presented with different responses in the two tests. Conclusions Instant changes in cerebral BFV were detected during the head-up tilt tests, and the cluster analysis identified five different hemodynamic responses. Continuous recordings revealed that the differences between groups persisted two min after tilt. Impact NeoDoppler is a pulsed-wave Doppler ultrasound system with a probe fixated to the neonatal fontanel by a cap that can measure continuous cerebral blood flow velocity. Healthy neonates present with a range of normal immediate cerebral hemodynamic responses to a 90° head-up tilt, categorized in five groups by cluster analysis. This paper adds new knowledge about connection between immediate responses and prolonged responses to tilt. We demonstrate that the NeoDoppler ultrasound system can detect minute changes in cerebral blood flow velocity during a 90° head-up tilt.

Purpose: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study. Patients and Methods: Using the Tromso Study Cardiovascular Disease Register for 2013-2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test. Results: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8-99.2) and a sensitivity of 88.2% (95% CI 82.0-92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6-98.8) and the sensitivity was 85.6% (95% CI 79.0-90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1-98.9) and a sensitivity of 91.5% (95% CI 85.995.4). Conclusion: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromso Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area. Keywords: cardiovascular diseases, data quality, registers, data collection, quality control

Objectives: Gestational diabetes mellitus (GDM), particularly when combined with overweight or obesity, is associated with adverse neonatal outcomes such as high birth weight and increased adiposity. We determined the effect of a preconception lifestyle intervention initiated before and continued throughout pregnancy on neonatal, birth-related, and body composition outcomes at birth and 6–8 weeks of age in children of participants in the BEFORE THE BEGINNING randomized controlled trial. Methods: People (N = 167) at increased risk of GDM and planning pregnancy were randomly allocated 1:1 to intervention or control. The intervention included time-restricted eating and exercise training. Time-restricted eating involved consuming all energy within ≤10 h/day, ≥5 days per week, and the amount of exercise was set using a heart rate-based physical activity metric (Personal Activity Intelligence, PAI), with the goal of ≥100 weekly PAI points. The main outcome of interest in this report was the proportion of infants with birth weight > 4.0 kg. Results: Among 106 live births, 21% (11/53) of infants in the intervention group and 28% (15/53) in the control group had birth weight > 4 kg (p = 0.367). Mean birth weight did not differ significantly between groups (mean difference −159.3 g, 95% confidence interval −375.7 to 57.2, p = 0.148). No significant between-group differences were found for additional neonatal, birth-related, or early postnatal body composition outcomes. Conclusions: In this secondary analysis, we found no evidence of effects of a preconception lifestyle intervention on the risk of macrosomia or neonatal body composition.