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.
Objective To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk–based preterm formula (BOV) or donor human ...milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. Study design Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). Results Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively ( P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. Conclusions In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit.
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.
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.
Premature birth entails an adverse cardiovascular risk profile, but the underlying mechanisms are insufficiently understood. Here, we employed an unbiased cardiovascular proteomics approach to ...profile former very preterm-born preschoolers.
This observational study investigated differences in plasma concentrations of 79 proteins, including putative cardiovascular biomarkers between very preterm- and term-born children on average 5.5 years old (53.1% male) using multiple-reaction monitoring mass spectrometry.
Very preterm-born (n = 38; median gestational age 29.6 weeks) compared to term-born (n = 26; 40.2 weeks) children featured lower plasma concentrations of platelet factor 4 (PLF4; -61.6%, P < 0.0001), platelet basic protein (CXCL7; -57.8%, P < 0.0001), and hemoglobin subunit beta (-48.3%, P < 0.0001). Results remained virtually unchanged when adjusting for complete blood count parameters, including platelet count. Conversely, whole blood hemoglobin was higher (+7.62%, P < 0.0001) in preterm-born children.
Very preterm birth was associated with decreased markers of platelet activation among preschoolers. These findings are consistent with reduced platelet reactivity persisting from very preterm birth to a preschool age.
Former very preterm-born preschoolers featured reduced levels of platelet activation markers. While lower platelet reactivity in very preterm-born compared to term-born infants in the first days of life was established, it was unknown when, if at all, reactivity normalizes. The current study suggests that platelet hyporeactivity due to very preterm birth persists at least up to a preschool age. "Immaturity of the hemostatic system" may be a persistent sequel of preterm birth, but larger studies are needed to investigate its potential clinical implications.
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 transcription factor FOXO3 has been associated in different tumor entities with hallmarks of cancer, including metastasis, tumor angiogenesis, maintenance of tumor-initiating stem cells, and drug ...resistance. In neuroblastoma (NB), we recently demonstrated that nuclear FOXO3 promotes tumor angiogenesis in vivo and chemoresistance in vitro. Hence, inhibiting the transcriptional activity of FOXO3 is a promising therapeutic strategy. However, as no FOXO3 inhibitor is clinically available to date, we used a medium-throughput fluorescence polarization assay (FPA) screening in a drug-repositioning approach to identify compounds that bind to the FOXO3-DNA-binding-domain (DBD). Carbenoxolone (CBX), a glycyrrhetinic acid derivative, was identified as a potential FOXO3-inhibitory compound that binds to the FOXO3-DBD with a binding affinity of 19 µM. Specific interaction of CBX with the FOXO3-DBD was validated by fluorescence-based electrophoretic mobility shift assay (FAM-EMSA). CBX inhibits the transcriptional activity of FOXO3 target genes, as determined by chromatin immunoprecipitation (ChIP), DEPP-, and BIM promoter reporter assays, and real-time RT-PCR analyses. In high-stage NB cells with functional TP53, FOXO3 triggers the expression of SESN3, which increases chemoprotection and cell survival. Importantly, FOXO3 inhibition by CBX treatment at pharmacologically relevant concentrations efficiently repressed FOXO3-mediated SESN3 expression and clonogenic survival and sensitized high-stage NB cells to chemotherapy in a 2D and 3D culture model. Thus, CBX might be a promising novel candidate for the treatment of therapy-resistant high-stage NB and other "FOXO-resistant" cancers.
Objective To evaluate the health benefits of an exclusively human milk–based diet compared with a diet of both human milk and bovine milk–based products in extremely premature infants. Study design ...Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk–based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk–based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. Results The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention ( P = .007). Conclusions For extremely premature infants, an exclusively human milk–based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk–based diet that also includes bovine milk–based products.
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