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.

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.

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.

Prophylactic low-dose paracetamol for ductal closure and neurodevelopmental outcome in very preterm infants.

AIM: To investigate the direct effect of prophylactic low-dose paracetamol administration for ductal closure on neurodevelopmental outcome in very preterm infants who did not receive ibuprofen or surgical ligation for treatment of a patent ductus arteriosus. METHODS: Infants < 32 gestational weeks born 10/2014-12/2018 received prophylactic paracetamol (paracetamol group, n = 216); infants born 02/2011-09/2014 did not receive prophylactic paracetamol (control group, n = 129). Psychomotor (PDI) and mental (MDI) outcome were assessed using Bayley Scales of Infant Development at 12 and 24 months corrected age. RESULTS: Our analyses showed significant differences in PDI and MDI at age 12 months (B = 7.8 (95% CI 3.90-11.63), p < 0.001 and B = 4.2 (95% CI 0.81-7.63), p = 0.016). At age 12 months, the rate of psychomotor delay was lower in the paracetamol group (OR 2.22, 95% CI 1.28-3.94, p = 0.004). There was no significant difference between the rates of mental delay at any time-point. All group differences remained significant after adjustment for potential confounders (PDI 12 months B = 7.8 (95% CI 3.77-11.34), p < 0.001, MDI 12 months B = 4.3 (95% CI 0.79-7.45), p = 0.013, PDI < 85 12 months OR 2.65 (95% CI 1.44-4.87), p = 0.002). CONCLUSION: We found no impairment of psychomotor and mental outcome at age 12 and 24 months in very preterm infants after prophylactic low-dose paracetamol administration.

Amplitude-integrated electroencephalography shows alterations in children born preterm displaying poor literacy precursor skills.

AIM: To assess whether amplitude-integrated electroencephalography (aEEG) alterations in the newborn period are associated with poor precursor skills of literacy at five years of age in children born preterm. METHODS: Between October 2007 and September 2011 248 preterm infants were eligible for the study at Innsbruck Medical University Hospital. aEEG was analysed for dominating background activity, calculation of the percentage of continuous activity, the Burdjalov scoring system, the minimum, mean and maximum amplitude. At the age of five years, we evaluated preterm born children by the Bielefelder screening (BISC) to assess for early diagnosis of reading problems and weak spelling and classified them as normal performers (n = 64) or poor performers (n = 20). Completion of testing was not possible for one infant. RESULTS: The minimum amplitude was significantly lower in the poor BISC performance group as compared to the normal BISC performance group at postnatal week two. The percentage of continuous background activity was significantly higher in infants with normal BISC performance than in infants with poor BISC performance at postnatal week three. CONCLUSION: Children with poor developed precursor skills of literacy showed alterations in aEEG signals. The aEEG could be useful in further diagnosing preterm infants at risk for developmental complications.

The Impact of Being Born Preterm or Small for Gestational Age on Early Vascular Aging in Adolescents.

OBJECTIVE: To assess the impact of being born preterm or small for gestational age (SGA) on early vascular aging (EVA) in a cohort of healthy Tyrolean adolescents. STUDY DESIGN: This study is part of an ongoing clinical trial, EVA Tyrol, a regional cohort study being conducted in western Austria. EVA was assessed in adolescents (mean age, 16 years) by means of carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), and blood pressure measurements. Adolescents were grouped as either term or preterm. Subsequently, being born SGA was taken into consideration in subgroup analysis. Complete data on gestational age and birth weight were available for 930 adolescents. RESULTS: Systolic blood pressure and diastolic blood pressure were significantly higher in the preterm (mean gestational age, 34.8 ± 2.3 weeks) and appropriate for gestational age (AGA) group than in the term and AGA group (P < .05). This finding remained significant in linear regression analysis after adjustment for covariables in all models. PWV was significantly higher in the term-SGA group than in the term-AGA group (6.67 ± 1.73 m/s vs 6.07 ± 1.09 m/s; P < .05). In the linear regression analysis, this finding remained significant in all models. There were no differences in cIMT between study groups. CONCLUSION: Being born preterm or SGA might render persons susceptible to EVA. Long-term follow-up of preterm and SGA individuals is warranted to confirm these results.

Former very preterm infants show alterations in plasma amino acid profiles at a preschool age.

BACKGROUND: Amino acid analysis is a valuable tool for cardiovascular risk assessment. Preterm infants display plasma amino acid changes in the newborn period. Whether these changes persist is unknown to date. The aim of this study was to assess whether former very preterm infants (VPI) show alterations in amino acid patterns indicative of an unfavorable cardiovascular risk profile at a preschool age. METHODS: From 5-7 y-old children born at term or <32 wk gestation (VPI) were included in the study. Plasma amino acid concentrations were determined after an overnight fast. RESULTS: 29 former term infants and 79 former VPI were included in the study. Former VPI showed changes in various plasma amino acids including glutamine, arginine, citrulline, tryptophan, glutamate, ornithine, and taurine. Branched-chain amino acids were lower, alanine/lysine ratios significantly higher in the preterm population. CONCLUSION: Former VPI show altered plasma amino acid profiles indicative of a dualistic cardiovascular risk profile (e.g., potentially beneficial elevations in citrulline, arginine, glutamine, and tryptophan, but also raised alanine/lysine ratios, low ornithine and taurine levels) at a preschool age. Whether this is associated with an adverse cardiovascular outcome has to be addressed by future studies. Long-term cardiometabolic follow-up of VPI might be warranted.

Amplitude-integrated electroencephalography can predict neurodevelopmental outcome at 12 months of corrected age in very preterm infants.

AIM: It is difficult to find diagnostic tools than can reliably predict neurodevelopmental outcomes in very preterm infants in clinical practice. This study evaluated whether amplitude-integrated electroencephalography predicted neurodevelopmental outcome in preterm infants when they reached 12 months of corrected age. METHODS: Between October 2007 and December 2013, we studied 232 preterm infants (51% male) at Innsbruck Medical University Hospital, Austria. Their mean birthweight was 1264 g, and their mean gestational age was 29.5 weeks. Amplitude-integrated electroencephalography was evaluated using the Burdjalov score, and outcomes were assessed using the Bayley Scales of Infant Development - Second Edition. RESULTS: The cohort was divided into three subgroups: 154 infants with normal outcomes, 53 infants with moderate delays and 25 infants with severe delays. The amplitude-integrated electroencephalography Burdjalov scores were lower in infants with moderate delays than in infants with normal outcomes and even lower in infants with severe delays. The highest area under the curve (0.776) for the Burdjalov score was at 18-24 hours of life. CONCLUSION: Our study confirmed the predictive value of amplitude-integrated electroencephalography and showed that this needed to be carried out early in life to provide reliable information on neurodevelopmental outcomes in very preterm infants.

An unusual cause of inspiratory stridor in the newborn: congenital pharyngeal teratoma--a case report.

BACKGROUND: Neonatal inspiratory stridor is an important examination finding that requires immediate and adequate evaluation of the underlying etiology. Depending on the severity of the airway obstruction and the presence or absence of associated symptoms such as respiratory distress and feeding problems, early initiation of a complete diagnostic workup can be crucial. The most common cause of neonatal inspiratory stridor is laryngomalacia, however, several differential diagnoses need to be investigated. More rare causes include oral or laryngeal masses. Teratomas of the head and neck region are one of the most unusual causes of respiratory distress during the neonatal period. We present a case of a mature teratoma in the oropharynx presenting with airway obstruction in a newborn infant. CASE PRESENTATION: A four-day-old female Caucasian infant was admitted to the neonatal intensive care unit of our hospital because of inspiratory stridor and profound desaturations while feeding. Diagnostic workup by ultrasound, magnetic resonance imaging and flexible endoscopy revealed a pediculated lesion in the pharyngeal region causing intermittent complete airway obstruction. The mass was surgically removed by transoral laser resection on the seventh day of life. Histological evaluation was consistent with a mature teratoma without any signs of malignancy. The further hospital course was uneventful, routine follow-up examinations at 3, 6 and 9 months of age showed no evidence of tumor recurrence. CONCLUSION: Neonatal stridor is a frequent symptom in the neonatal period and is mostly caused by non-life-threatening pathologies. On rare occasions, however, the underlying conditions are more critical. A careful stepwise diagnostic investigation to rule out these conditions, to identify rare causes and to initiate early treatment is therefore warranted.

Comparing growth charts demonstrated significant deviations between the interpretation of postnatal growth patterns in very preterm infants.

AIM: This study compared postnatal growth patterns calculated using different reference data in a large cohort of very preterm infants. METHODS: The weight, length and head circumference of 551 very preterm infants born in the Tyrol, Austria, between 2003 and 2011, were obtained at birth, discharge and the corrected ages of three, 12 and 24 months. Growth data are presented as Z-scores in relation to four reference populations: LMS growth by Pan et al., Fenton preterm growth charts, the Euro-Growth Study Group and the World Health Organization (WHO) Anthro programme. RESULTS: We observed significant differences in mean weight Z-scores using the four reference populations, with the WHO data being the highest. The mean head circumference Z-scores also differed significantly at all time points. We observed a pronounced gap in the microcephaly rate, which was 10 times higher at the age of 24 months if the Pan data were used instead of the WHO data. CONCLUSION: Our findings revealed significant deviations between the interpretation of postnatal growth depending on the reference data used, with the most striking differences seen in head circumference. The choice of reference data, and particularly the conclusions drawn from the data, must be interpreted with utmost care.

Poor postdischarge head growth is related to a 10% lower intelligence quotient in very preterm infants at the chronological age of five years.

AIM: This study examined the relationship between head growth and cognitive outcome at the age of five years in preterm infants born at less than 32 weeks of gestation from 2003 to 2009, as previous research has mostly focused on outcomes in toddlers. METHODS: The head circumference of 273 very preterm infants born in Tyrol, Austria, was measured at birth, discharge, the corrected ages of three, 12 and 24 months and the chronological age of five years. Suboptimal head size was defined as a head circumference of more than one standard deviation below the mean. Full-scale intelligence quotient (IQ) at five years was determined using Wechsler Preschool and Primary Scales of Intelligence, third edition. RESULTS: Infants with a suboptimal head size at the age of three months had a significantly lower median IQ than those with a normal head size (90 [20-122] versus 98 [20-138], p = 0.001) and from three months onwards they were more likely to exhibit cognitive delay. CONCLUSION: A suboptimal head size from the age of three months was consistently related to a 10% lower IQ, and this study adds further evidence that head growth failure, especially during the early postdischarge period, is related to impaired cognitive abilities.

Very preterm children are at increased risk of reduced processing speed at 5 years of age, predicted by typical complications of prematurity and prenatal smoking.

AIM: Very little is known about risk predictors for the development of reduced processing speed, which can cause intellectual problems in later life. This study identified risk predictors at 5 years of age in a population-based cohort of very preterm infants. METHODS: Between January 2003 and August 2006, all preterm infants born before 32 weeks of gestation in Tyrol were prospectively enrolled (n = 223), and 161 underwent a detailed examination at 5 years of age, including a cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence, third edition. The processing speed quotient is calculated on the basis of two subtests that assess symbol search and coding. The association between prenatal and postnatal factors and reduced processing speed was analysed by means of logistic regression analysis. RESULTS: Of 161 children tested, 55 (34.2%) showed reduced processing speed. In 55.6% (n = 30) of these children, reduced processing speed was related to full-scale intelligence quotient scores of <85. Smoking in pregnancy, steroids for chronic lung disease and intracerebral haemorrhage predicted reduced processing speed at 5 years of age. CONCLUSION: More than a third of the very preterm children we tested showed reduced processing speed at 5 years of age, and predictors were typical complications of prematurity and smoking in pregnancy.

Trends in Amplitude-Integrated Electroencephalography in the Smallest Preterm Neonates.

BACKGROUND: Amplitude-integrated electroencephalography is increasingly used for the neuromonitoring of premature infants. However, it is still not clear how bioelectrical activity changes in the smallest gestational age newborns. The aim of our study was to evaluate the bioelectrical activity of amplitude-integrated electroencephalograms in premature newborns of different gestational age to assess how gestational age and postnatal age influence patterns of amplitude-integrated electroencephalograms and to test the hypothesis of whether the bioelectrical activity of the brain matures faster after the birth of premature newborns than in utero. METHODS: We prospectively included infants born before 32 weeks of gestational age between June 2020 and July 2022. Serial recordings of amplitude-integrated electroencephalograms were performed at three time points of age (days 1-3, 13-15, and 27-29). Recordings were analyzed for background patterns, the onset and appearance of cyclicity, and lower amplitude border and bandwidth, which were used to derive a composite Burdjalov score. RESULTS: In total, 140 premature neonates were included in the study, and 112 of them completed the study. The median gestational age of the newborns enrolled in the study was 29 (27-30) weeks, and the mean weight was 1206 (350) g. Burdjalov scores increased with increasing gestational age. Higher scores were observed in every dimension of the amplitude-integrated electroencephalograms for newborns of lower gestational age when compared to newborns of higher gestational age of the same postmenstrual age. There was a significant correlation between gestational age and parameters of amplitude-integrated electroencephalograms at all time points. CONCLUSIONS: A higher gestational age has a positive effect on the bioelectrical activity of amplitude-integrated electroencephalograms. Increasing postnatal age affected amplitude-integrated electroencephalograms more than gestational age. Our hypothesis that the bioelectrical activity of the brain matures faster for premature newborns after birth than in the womb was confirmed.

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.

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.

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.

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.