Reference Ranges for Arterial Oxygen Saturation, Heart Rate, and Cerebral Oxygen Saturation during Immediate Postnatal Transition in Neonates Born Extremely or Very Preterm.

OBJECTIVE: To define percentile charts for arterial oxygen saturation (SpO2), heart rate (HR), and cerebral oxygen saturation (crSO2) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome. STUDY DESIGN: We conducted a secondary-outcome analysis of neonates born preterm included in the Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth III (COSGOD III) trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. crSO2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute. RESULTS: A total of 207 neonates born preterm with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) g were eligible for analyses. The 10th percentile of SpO2 at minute 2, 5, 10, and 15 was 32%, 52%, 83%, and 85%, respectively. The 10th percentile of HR at minute 2, 5, 10, and 15 was 70, 109, 126, and 134 beats/min, respectively. The 10th percentile of crSO2 at minute 2, 5, 20, and 15 was 15%, 27%, 59%, and 63%, respectively. CONCLUSIONS: This study provides new centile charts for SpO2, HR, and crSO2 for neonates born extremely or very preterm with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Young hearts, early risks: novel cardiovascular biomarkers in former very preterm infants at kindergarten age.

BACKGROUND: Preterm birth is associated with long-term cardiovascular morbidity and mortality. In adults, fibroblast growth factor-23 (FGF-23), α-Klotho, and secretoneurin have all garnered attention as cardiovascular biomarkers, but their utility in pediatric populations has not yet been ascertained. The aim of this pilot study was to evaluate these novel cardiovascular biomarkers and their association with indicators of cardiovascular impairment in the highly vulnerable population of former very preterm infants. METHODS: Five- to seven-year-old children born at < 32 weeks' gestation were eligible for the study. Healthy same-aged children born at term served as controls. Biomarkers were quantified in fasting blood samples, and echocardiographic measurements including assessment of aortic elastic properties were obtained. RESULTS: We included 26 former very preterm infants and 21 term-born children in the study. At kindergarten age, former very preterm infants exhibited significantly higher plasma concentrations of biologically active intact FGF-23 (iFGF-23; mean 43.2 pg/mL vs. 29.1 pg/mL, p = 0.003) and secretoneurin (median 93.8 pmol/L vs. 70.5 pmol/L, p = 0.046). iFGF-23 inversely correlated with distensibility of the descending aorta. CONCLUSION: In preterm-born children, iFGF-23 and secretoneurin both offer prospects as valuable cardiovascular biomarkers, potentially allowing for risk stratification and timely implementation of preventive measures. IMPACT: Former very preterm infants have increased plasma concentrations of the novel cardiovascular biomarkers intact fibroblast growth factor-23 (iFGF-23) and secretoneurin at kindergarten age. Increases in iFGF-23 concentrations are associated with decreased distensibility of the descending aorta even at this early age. Monitoring of cardiovascular risk factors is essential in individuals with a history of preterm birth. Both iFGF-23 and secretoneurin hold promise as clinically valuable biomarkers for risk stratification, enabling the implementation of early preventive measures.

Cardiac biomarkers and left ventricular systolic function in former very preterm infants and term controls at preschool age.

Introduction: Due to improvements in perinatal care, survival rates of preterm infants have improved during the last decades. However, these infants remain at risk of developing cardiovascular sequelae later in life. This study aimed to investigate the cardiac biomarkers and left ventricular systolic function in former preterm infants in comparison with term controls at preschool age. Methods: The study included children aged 5-7 years old born below 32 weeks of gestational age. The control group consisted of same-age children born at term. Basic data of study participants were collected using questionnaires and follow-up databases. During the study visit, we recorded anthropometric data and blood pressure readings, determined high-sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentrations, and calculated fractional shortening (FS) and left ventricular mass (LVM). Results: Term-born (n = 25; median gestational age, 40.1 weeks) compared with preterm-born infants (n = 80; median gestational age 29.6 weeks) showed no significant differences in the median concentration of hs-cTnT [median, 3.5 (IQR 3.5; 3.5) vs. 3.5 (3.5; 3.5) ng/L, p = 0.328] and the median concentration of NT-pro-BNP [median, 91.0 (IQR 40.8; 150.3) vs. 87.5 (50.1; 189.5) ng/L, p = 0.087]. FS and LVM/LVMI were not significantly different between the two groups. Conclusion: At preschool age, we observed no significant differences in cardiac biomarkers and left ventricular systolic function in preterm infants. Further studies are warranted to explore the potential of cardiac biomarkers as a prognostic tool for subclinical cardiac alterations after preterm birth.

Two-year neurodevelopmental outcome in extremely preterm-born children: The Austrian Preterm Outcome Study Group.

AIM: The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. METHODS: All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. RESULTS: 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. CONCLUSION: In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.

Amplitude-integrated electroencephalography showed no differences in cerebral activity between preterm singletons and twins in the first 4 weeks of life.

AIM: Genetic influences on cerebral activity have been described previously, but data are scarce in preterms. We aimed to investigate whether a genetic influence causes amplitude-integrated electroencephalography (aEEG) signals to differ between singletons and twin preterm newborns. METHODS: This was a retrospective single-centre study conducted at Innsbruck Medical University Hospital, Austria. Preterm infants born before 32 weeks of gestation between 6 November 2010 and 6 December 2022 were eligible for the study. The aEEG was analysed for the total maturation score, its component scores and the number of sleep-wake cycles per hour. RESULTS: We enrolled 240 preterm twin infants (57.5% male) with a mean gestational age of 30 (range: 24-32) weeks and a mean birth weight of 1324 (range: 600-2116) grams. We compared 240 singleton matched preterms. No differences were found between preterm singletons and twin preterm infants regarding the total maturation and component scores, or the number of sleep-wake cycles. aEEG showed no difference between monozygotic and dizygotic twins. CONCLUSION: Compared to singletons, twin infants born preterm showed no differences in aEEG signals in the first 4 weeks of life. Future studies should include more complex non-invasive functional neuroimaging methods to gain more insight into this important topic.

Early Brain Activity in Very Preterm Infants of Mothers with Gestational Diabetes Mellitus: A Pilot Study.

INTRODUCTION: Neurological consequences of preterm infants born to mothers with gestational diabetes mellitus (GDM) are unclear. In this pilot study, we investigated the effect of GDM on brain activity in very preterm infants. METHODS: Preterm infants <32 gestational weeks of mothers with GDM compared to gestational age- and sex-matched controls born between 2011 and 2018 were included. Amplitude-integrated electroencephalography (aEEG) was assessed for total maturation and individual component scores according to Burdjalov and colleagues, the dominating visual background, and the presence of sleep-wake cycles per hour in the first 72 h of life and weekly at days 7, 14, 21, and 28. RESULTS: We included 47 infants of mothers with GDM and 94 control infants. Both the aEEG total maturation score and its individual component scores, as well as the percentage of continuous background pattern, increased equally during the first 4 weeks after birth in both groups. GDM-exposed infants showed a slightly but significantly higher number of sleep-wake cycles per hour. CONCLUSION: We found normal maturation of brain activity in the first 4 weeks after birth in very preterm infants born to mothers with GDM, not differing from a very preterm control group. The higher number of sleep-wake cycles per hour in GDM-exposed infants could indicate transiently enhanced maturation. Further studies on brain activity and brain development in very preterm infants of mothers with GDM are needed to validate our results.

Determinants of non-alcoholic fatty liver disease in young people: Maternal, neonatal, and adolescent factors.

AIM: To assess the impact of maternal, neonatal, and adolescent factors on the development of non-alcoholic fatty liver disease (NAFLD) in a cohort of 14- to 19-year-old adolescents. METHODS: This study is part of the Early Vascular Ageing in the YOUth study, a single-center cross-sectional study conducted in western Austria. Maternal and neonatal factors were extracted from the mother-child booklet, adolescent factors were evaluated by a face-to-face interview, physical examination, and fasting blood analyses. Liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan® (Echosense, Paris, France). The association of maternal, neonatal, and adolescent factors with CAP values was analyzed using linear regression models. RESULTS: In total, 595 adolescents (27.2% male) aged 17.0 ± 1.3 years were included. 4.9% (n = 29) showed manifest NAFLD with CAP values above the 90th percentile. Male sex (p < 0.001), adolescent triglyceride levels (p = 0.021), Homeostatic Model Assessment for Insulin Resistance index and BMI z-score (p < 0.001, each) showed a significant association with liver fat content in the multivariable analysis. Maternal pre-pregnancy BMI was associated with CAP values after adjustment for sex, age, and birth weight for gestational age (p < 0.001), but this association was predominantly mediated by adolescent BMI (indirect effect b = 1.18, 95% CI [0.69, 1.77]). CONCLUSION: Components of the metabolic syndrome were the most important predictors of adolescent liver fat content. Therefore, prevention of NAFLD should focus on lifestyle modification in childhood and adolescence.

Comparison of body mass index and fat mass index to classify body composition in adolescents-The EVA4YOU study.

The objectives of this study were to develop age- and sex-specific reference percentiles for fat mass index (FMI) and fat-free mass index (FFMI) in adolescents aged 14 to 19 years and to determine differences in overweight/obesity classification by FMI and body mass index (BMI). The EVA4YOU study is a single-center cross-sectional study conducted in western Austria. Cardiovascular risks including anthropometric measurements and bioelectrical impedance analysis were assessed in adolescents (mean age 17 years). FMI and FFMI were calculated as the ratio of fat mass (FM) and fat-free mass (FFM) to the square of height and compared to study population-specific BMI percentiles. One thousand four hundred twenty-two adolescents were included in the analysis. Girls had a significantly higher mean FM and FMI and a significantly lower mean FFM, FFMI (p < 0.001, each), and mean BMI (p = 0.020) than boys. Body composition classification by FMI and BMI percentiles shows a concordance for the < 75th and > 97th percentile, but a significant difference in percentile rank classifications between these two cut-off values (all p < 0.05). Based on FMI, 15.5% (221/1422) of the whole population and 29.4% (92/313) of those between the 75th and 97th percentiles are classified one category higher or lower than those assigned by BMI. CONCLUSION:  Classification of normal or pathologic body composition based on BMI and FMI shows good accordance in the clearly normal or pathologic range. In an intermediate range, FMI reclassifies categories based on BMI in more than a quarter of adolescents. Cut-off values to differentiate normal from pathologic FMI values on a biological basis are needed. TRIAL REGISTRATION: The study is registered at www. CLINICALTRIALS: gov  (Identifier: NCT04598685; Date of registration: October 22, 2020). WHAT IS KNOWN: • Chronic non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally, with major risk factors including unhealthy diets, harmful behaviors, and obesity. Obesity in children and adolescents is a key risk factor for later NCDs, which is commonly measured by Body Mass Index (BMI). • BMI can be misleading as it doesn't distinguish between fat mass (FM) and fat-free mass (FFM), leading to potential misclassification of obesity in children. Previous studies have already suggested the use of the Fat Mass Index (FMI) and Fat-Free Mass Index (FFMI) as a more accurate measures of body composition. WHAT IS NEW: • This study adds the first age- and sex-specific reference values for FMI and FFMI in Austrian adolescents using bioelectrical impedance analysis (BIA) as a safe and secure measurement method of a large representative cohort. • We found percentile misclassification between BMI and FMI when categorizing for obesity, especially in intermediate categories of body composition. Furthermore, when comparing the new reference values for FMI and FFMI to existing ones from the US, UK, and Germany we could show a good alignment within the European cohorts and major differences with American values, indicating and confirming the difference of FMI and FFMI for different populations of different ethnical background, living on different continents.

Relationship between Brain Function and Microstructural Brain Maturation in Preterm Infants.

INTRODUCTION: Preterm infants are at risk for impairment in brain maturation at term equivalent age (TEA). Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging (MRI) technique, quantitatively reflecting microstructural brain development of white matter regions with parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Amplitude-integrated electroencephalography (aEEG) assesses electrocortical activity and brain function. METHODS: Aim of this study was to investigate a possible correlation between functional and microstructural brain maturation using neonatal aEEG and DTI-MRI at TEA. The study was conducted as a retrospective single-center study in 446 infants born below 32 gestational weeks. Spearman rank's correlation coefficients were calculated between aEEG (total maturation score) and FA/ADC value. To compare aEEG and DTI-MRI to neurodevelopmental outcome at 24 months of corrected age, we performed a multivariate linear regression analysis. RESULTS: Analysis showed an all-time significant correlation between total maturation score and FA/ADC values of the corpus callosum at TEA with the strongest correlation at day 2, day 3, week 3, and week 4. After including perinatal variables in the model, this correlation remained highly significant at day 2 and 3. When comparing the association of aEEG and DTI-MRI to outcome, both the total maturation score at day 2, day 3, and FA/ADC of the splenium of the corpus callosum showed a significant correlation. CONCLUSION: This study indicates that early monitoring of functional brain maturation may predict later assessment of microstructural brain development of corpus callosum in preterm infants with a relation to neurodevelopmental outcome.

Association of aEEG and brain injury severity on MRI at term-equivalent age in preterm infants.

AIM: Measures to detect and monitor brain injury in preterm infants are amplitude-integrated electroencephalography (aEEG) and magnetic resonance imaging (MRI). To investigate the association between aEEG and MRI in a large cohort of preterm infants. Five hundred and twenty-three preterm infants were included in the study. METHODS: AEEG was interpreted for the total maturation score (TMS) according to Burdjalov. Cerebral MRI was evaluated using a validated scoring system by Kidokoro. RESULTS: One hundred and forty-six infants (27.9%) showed some form of brain injury, with 111 infants (21.2%) showing mild injury and 35 (6.7%) showing severe injury. TMS were significantly higher in infants without injury compared to severe injury. When comparing infants with isolated intraventricular haemorrhage  to infants without brain injury, TMS were significantly lower. CONCLUSION: Prediction of adverse outcome is an important aspect of neonatal care. The combination of diagnostic measures evaluating brain injury might enhance our abilities in neonatal care to provide accurate information about later outcome. Early aEEG is predictive for the severity of brain injury detected by MRI at term-equivalent age. Whether aEEG is also predictive for neurodevelopmental outcome needs to be further investigated in relation to the various patterns of preterm brain injury.

Determinants of Diet Quality in Adolescents: Results from the Prospective Population-Based EVA-Tyrol and EVA4YOU Cohorts.

(1) Background: Unhealthy dietary behaviors are estimated to be one of the leading causes of death globally and are often shaped at a young age. Here, we investigated adolescent diet quality and its predictors, including nutrition knowledge, in two large Central European cohorts. (2) Methods: In 3056 participants of the EVA-Tyrol and EVA4YOU prospective population-based cohort studies aged 14 to 19 years, diet quality was assessed using the AHEI-2010 and DASH scores, and nutrition knowledge was assessed using the questionnaire from Turconi et al. Associations were examined utilizing multivariable linear regression. (3) Results: The mean overall AHEI-2010 score was 42%, and the DASH score was 45%. Female participants (60.6%) had a significantly higher diet quality according to the AHEI-2010 and DASH score. AHEI-2010 and DASH scores were significantly associated (p < 0.001) with sex, school type, smoking, and total daily energy intake. The DASH score was additionally significantly associated (p < 0.001) with age, socioeconomic status, and physical activity. Participants with better nutrition knowledge were more likely to be older, to attend a general high school, to live in a high-income household, to be non-smokers, and to have a higher diet quality according to the AHEI-2010 and DASH score. (4) Conclusions: Predictors of better diet quality included female sex, physical activity, educational level, and nutrition knowledge. These results may aid focused interventions to improve diet quality in adolescents.

Striatal Lacunar Infarction in a Late Preterm Infant Born to a Mother with Active Peripartum SARS-CoV-2 Infection.

Background: The current literature suggests that neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections generally have a mild course. Data on how in utero exposure to maternal infection affects neonatal health outcomes are limited, but there is evidence that neurological damage to the fetus and thromboembolic events may occur. Case Presentation. We describe the case of a late preterm infant, who presented with striatal lacunar infarction in the neonatal period, born to a mother with active peripartum SARS-CoV-2 infection. Diagnostic workup did not identify risk factors apart from the maternal SARS-CoV-2 infection. Repeated reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 using oropharyngeal swab specimens of the patient were negative. IgG, but not IgM antibodies against spike protein S1 receptor-binding domain (S1RBD) epitope were detectable in umbilical cord blood and neonatal serum collected at 48 hours of life. Anti-SARS-CoV-2 total antibody titers against nucleocapsid protein in umbilical cord blood were negative. Conclusions: Bearing in mind a possible association of in utero exposure to SARS-CoV-2 and neonatal thromboembolic events, neonatologists should be aware of these complications even in well-appearing preterm infants.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age.

INTRODUCTION: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. METHODS: Infants <32 gestational weeks (02/2011-11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. RESULTS: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. CONCLUSION: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Microstructural Brain Development and Neurodevelopmental Outcome of Very Preterm Infants of Mothers with Gestational Diabetes Mellitus.

INTRODUCTION: There are data linking gestational diabetes mellitus (GDM) with adverse neurodevelopmental outcome in the offspring. We investigated the effect of GDM on microstructural brain development and neurodevelopmental outcome of very preterm infants. MATERIALS AND METHODS: Preterm infants <32 gestational weeks of mothers with GDM obtained cerebral magnetic resonance imaging (MRI) including diffusion-tensor imaging at term-equivalent age. For every infant, two gestational age-, sex-, and MRI scanner type-matched controls were included. Brain injury was assessed and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured in 14 defined cerebral regions. Neurodevelopmental outcome was quantified at the corrected age of 24 months using the Bayley Scales of Infant Development. RESULTS: We included 47 infants of mothers with GDM and 94 controls. There were no differences in neonatal morbidity between the groups, nor in any type of brain injury. The GDM group showed significantly higher FA values in the centrum semiovale, the posterior limb of the internal capsule and the pons bilaterally, in the corpus callosum and the right occipital white matter, as well as lower ADC values in the right centrum semiovale, the right occipital white matter and the corpus callosum. Neurodevelopmental outcome did not differ between the groups. CONCLUSION: We found no impairment of brain development in GDM-exposed infants compared to matched controls, but differences in white matter microstructure in specific regions indicating an enhanced maturation. However, neurodevelopmental outcome was equal in both groups. Further studies are needed to better understand brain maturation in preterm infants exposed to GDM.

Early Vascular Ageing in adolescents with migraine with aura: a community-based study.

BACKGROUND: Migraine with aura is associated with an increased risk of cardiovascular disease, yet the pathophysiology is unknown. Suggested underlying mechanisms of aura formation point into the direction of an abnormal vasoreactivity that also extends to the extracranial vasculature. METHODS: In the Early Vascular Ageing Tyrol study, a community-based non-randomized controlled trial conducted in 45 schools and companies in Tyrol (Austria) and South-Tyrol (Italy) between May 2015 and September 2018 aiming to increase cardiovascular health in adolescents, headache syndromes were classified according to the International Classification of Headache Disorders in a face-to-face interview. Carotid-femoral pulse-wave-velocity was measured by applanation tonometry and carotid intima-media-thickness by high-resolution ultrasound of the distal common carotid arteries. Differences in pulse-wave-velocity and carotid intima-media-thickness in youngsters with migraine with aura were compared respectively to those without headache and with other headaches by multivariable linear regression analysis. RESULTS: Of the 2102 study participants 1589 were aged 14 to 19 (mean 16.8) years and had complete data. 43 (2.7%) reported migraine with aura and 737 (46.4%) other headaches. Mean pulse-wave-velocity was 6.17 m/s (± 0.85) for migraine with aura, 6.06 m/s (± 0.82) for all other headaches and 6.15 (0.95) m/s for participants without headaches. Carotid intima-media-thickness was 411.3 µm (± 43.5) for migraine with aura, 410.9 µm (± 46.0) for all other headaches and 421.6 µm (± 48.4) for participants without headaches. In multivariable linear regression analysis, we found no differences in carotid-femoral pulse-wave-velocity or carotid intima-media-thickness in young subjects with migraine with aura, all other headaches, or no headaches. CONCLUSIONS: In line with previous large-scale studies in adults, we could not demonstrate relevant associations of migraine with aura with markers of arterial stiffness or subclinical atherosclerosis making early vascular ageing an unlikely pathophysiological link between migraine with aura and cardiovascular diseases. TRIAL REGISTRATION: First registered on ClinicalTrials.gov 29/04/2019 (NCT03929692).

Plasma homocysteine levels and associated factors in community-dwelling adolescents: the EVA-TYROL study.

Background: Homocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease. Methods: Hcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis. Results: Mean plasma Hcy was 11.3 ± 4.5 µmol/L. Distribution of Hcy was characterized by extreme right skew. Males exhibited higher Hcy and sex differences increased with increasing age. Univariate associations with Hcy emerged for age, sex, body mass index, high-density lipoprotein cholesterol, and for factors pertaining to blood pressure, glucose metabolism, renal function, and diet quality, whereas the most important multivariate predictors of Hcy were sex and creatinine. Discussion: Clinical and laboratory factors associated with Hcy in adolescents were manifold, with sex and high creatinine identified as strongest independent determinants. These results may aid when interpreting future studies investigating the vascular risk of homocysteine.

Cardiovascular health profiles in adolescents being born term or preterm-results from the EVA-Tyrol study.

BACKGROUND AND AIMS: Preterm birth has been linked with an increased risk of cardiovascular (CV) disease from childhood into adolescence and early adulthood. In this study, we aimed to investigate differences in CV health profiles between former term- and preterm-born infants in a cohort of Tyrolean adolescents. METHODS: The Early Vascular Aging (EVA)-Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Metrics of CV health (body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), smoking, physical activity, dietary patterns, total cholesterol and fasting blood glucose) were assessed and compared between former term- and preterm-born girls and boys. RESULTS: In total, 1,491 study participants (59.5% female, mean age 16.5 years) were included in the present analysis. SBP and DBP were significantly higher in former preterm-born adolescents (mean gestational age 34.6 ± 2.4 weeks) compared to term-born controls (p < 0.01). In the multivariate regression analysis these findings remained significant after adjustment for potential confounders in all models. No differences were found in all other CV health metrics. The number of participants meeting criteria for all seven health metrics to be in an ideal range was generally very low with 1.5% in former term born vs. 0.9% in former preterm born adolescents (p = 0.583). CONCLUSIONS: Preterm birth is associated with elevated SBP and DBP in adolescence, which was even confirmed for former late preterm-born adolescents in our cohort. Our findings underscore the importance of promoting healthy lifestyles in former term- as well as preterm-born adolescents. In addition, we advise early screening for hypertension and long-term follow-up in the group of preterm-born individuals.