From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth

Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain

Cranial ultrasound findings in late preterm infants and correlation with perinatal risk factors

Background: Late preterm infants are the most represented premature babies. They are exposed to a wide spectrum of brain lesions which are often clinically silent, supporting a possible role of cerebral ultrasound screening. Aim of the study is to describe the pattern of cranial ultrasound abnormalities in late preterm infants and to define the need for cranial ultrasound according to perinatal risk factors. Methods: A hospital-based cranial ultrasound screening was carried out by performing two scans (at 1 and 5 weeks). Unfavorable cranial ultrasound at 5 weeks was defined as either persistent periventricular hyperechogenicity or severe abnormalities. Results: One thousand one hundred seventy-two infants were included. Periventricular hyperechogenicity and severe abnormalities were observed in, respectively, 19.6 % and 1 % of late preterms at birth versus 1.8 % and 1.4 % at 5 weeks. Periventricular hyperechogenicity resolved in 91.3 %. At the univariate analysis gestational age (OR 0.5, 95 % CI 0.32-0.77), Apgar score <5 at 5' (OR 15.3, 1.35-173) and comorbidities (OR 4.62, 2.39-8.98) predicted unfavorable ultrasound at 5 weeks. At the multivariate analysis the accuracy in predicting unfavorable ultrasound, estimated by combined gestational age/Apgar/comorbidities ROC curve, was fair (AUC 74.6) and increased to excellent (AUC 89.4) when ultrasound at birth was included. Conclusion: Gestational age and comorbitidies are the most important risk factors for detecting brain lesions. The combination of being born at 34 weeks and developing RDS represents the strongest indication to perform a cranial ultrasound. Differently from other studies, twin pregnancy doesn't represent a risk factor

Consensus protocol for EEG and amplitude-integrated EEG assessment and monitoring in neonates

The aim of this work is to establish inclusive guidelines on electroencephalography (EEG) applicable to all neonatal intensive care units (NICUs). Guidelines on ideal EEG monitoring for neonates are available, but there are significant barriers to their implementation in many centres around the world. These include barriers due to limited resources regarding the availability of equipment and technical and interpretive round-the-clock personnel. On the other hand, despite its limitations, amplitude-integrated EEG (aEEG) (previously called Cerebral Function Monitor [CFM]) is a common alternative used in NICUs. The Italian Neonatal Seizure Collaborative Network (INNESCO), working with all national scientific societies interested in the field of neonatal clinical neurophysiology, performed a systematic literature review and promoted interdisciplinary discussions among experts (neonatologists, paediatric neurologists, neurophysiologists, technicians) between 2017 and 2020 with the aim of elaborating shared recommendations. A consensus statement on videoEEG (vEEG) and aEEG for the principal neonatal indications was established. The authors propose a flexible frame of recommendations based on the complementary use of vEEG and aEEG applicable to the various neonatal units with different levels of complexity according to local resources and specific patient features. Suggestions for promoting cooperation between neonatologists, paediatric neurologists, and neurophysiologists, organisational restructuring, and teleneurophysiology implementation are provided

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program

Near-Infrared Spectroscopy Measurement of Cerebro-Somatic Oxygenation Ratio (CSOR): May We Predict a Hemodynamically Significant Patent DuctusArteriosus (PDA)?

BACKGROUND: Definition of hemodynamically significant PDA (HS-PDA) is still controversial and its effects on cerebral and somatic tissue oxygenation (cSO2 and sSO2) as well as on fractional oxygen extraction (FOE) are not well known. OBJECTIVE: To use non invasive NIRS-technology in pretem infants 6433 wks GA to evaluate differences in cSO2, postductal sSO2 and FOE according to the presence of PDA. DESIGN/METHODS: cSO2 and thoraco-lumbar sSO2 were measured simultaneously using the INVOS oximeter (Somanetics) in clinically stable preterm babies and the mean values, over a 10-min period, were expressed as CSOR (=sSO2/cSO2). Cerebral and somatic FOE (cFOE and sFOE) were calculated according to the formula=(SaO2-regionalSO2)/SaO2. The presence and the flow pattern through PDA were assessed by echocardiography.Unpaired t-test was used. RESULTS: 21 measurements were performed in 14 preterm infants (mean GA 29.6\ub13.9wks, BW 1230\ub1460g, postnatal age 7.1\ub15.9 days). Mean CSOR was 1.101\ub10.127. No statistically significant differences were observed between babies with and without PDA for all parameters. Infants with pulsatile flow pattern at echocardiography (defined HS-PDA) showed an \u201cinverted\u201d CSOR<1 (mean value 0.874\ub10.076) mainly related to decrease in sSO2 while cSO2 was relatively spared. cFOE did not seem to be affected whereas a significant increase in sFOE was observed.[table1] CONCLUSIONS: Our results confirm previous studies\ub9 showing higher oxygenation of somatic compared with cerebral tissue in preterms and suggest that an \u201cinverted\u201d CSOR<1 might represent a sign of HS-PDA. NIRS technology could be routinely used as a trend monitor for cSO2 and sSO2 and might help in early detection of babies who would benefit from PDA closure. Due to the small sample size further studies are needed to confirm these data and adjust results for confounders. \ub9Petrova A PediatrCritCareMed 200

Obstetric risk factors for poor neonatal adaptation at birth

Purpose: To identify obstetric risk factors of delivering a neonate with poor neonatal adaptation at birth. Material and methods: Nested case\u2013control study. Poor neonatal adaptation was defined for presence of at least: umbilical cord artery pH <7.10, base deficit 6512\u2009mmol/L, Apgar score at 1\u2032 645. Controls were selected from the same population and matched with cases. The association between clinical parameters and poor neonatal adaptation was analyzed by logistic regression. Results: One hundred and thirty three women (2.1% of all live births) with a neonate presenting a poor neonatal adaptation were matched with 133 subsequent controls. Significant contributions for the prediction of poor neonatal adaptation were provided by maternal age 6535 years (p\u2009 64\u2009.001, odds ratio (OR) 3.9 [95%CI: 2.3\u20136.8]), nulliparity (p\u2009 64\u2009.001, OR 3.3 [95%CI: 1.8\u20136]), complications during pregnancy (p\u2009=\u2009.032, OR 2.2 [95%CI: 1.1\u20134.4]), gestational age at delivery <37 weeks (p\u2009=\u2009.008, OR 5.2 [95%CI: 1.5\u201317.8]) and cardiotocography category II or III (p\u2009 64\u2009.001, OR 36.3 [95%CI: 16.5\u201380.1]). The receiver operative characteristic curve was 0.91 [95%CI: 0.87\u20130.95], and detection rates 82.7% and 89.5% at 10% and 20% of false positive rates, respectively. Conclusions: Several obstetric risk factors before and during labor can identify a subgroup of newborns at higher risk of a poor neonatal adaptation at birt

Effects of Early Intervention on Visual Function in Preterm Infants : A Randomized Controlled Trial

Objectives: To determine the effectiveness of an early intervention program in enhancing visual function in very preterm infants. Methods: We conducted a RCT. We included preterm infants born between 25+0 and 29+6 weeks of gestational age (GA), without severe morbidities, and their families. Infants were randomized to either receive Standard Care (SC) or Early Intervention (EI). SC, according to NICU protocols, included Kangaroo Mother Care and minimal handling. EI included, in addition to routine care, parental training according to the PremieStart program, and multisensory stimulation (infant massage and visual interaction) performed by parents. Visual function was assessed at term equivalent age (TEA) using a prevalidated battery evaluating ocular spontaneous motility, ability to fix and follow a target, reaction to color, stripes discrimination and visual attention at distance. Results: Seventy preterm (EI n = 34, SC n = 36) infants were enrolled. Thirteen were excluded according to protocol. Fifty-seven infants (EI = 27, SC = 30) were assessed at TEA. The two groups were comparable for parental and infant characteristics. In total, 59% of infants in the EI group achieved the highest score in all the nine assessed items compared to 17% in the SC group (p = 0.001): all infants in both groups showed complete maturation in four items, but EI infants showed more mature findings in the other five items (ocular motility both spontaneous and with target, tracking arc, stripes discrimination and attention at distance). Conclusions: Our results suggest that EI has a positive effect on visual function maturation in preterm infants at TEA. Trial Registration: clinicalTrial.gov (NCT02983513)

Neonatal stroke

The perinatal ischemic stroke is defined as "a group of heterogenous conditions with a focal disruption of cerebral flow secondary to an arterial or a venous thrombosis or embolization between the 20 week of foetal life through the 28 post-natal day". Three subgroups are identified: arterial ischemic stroke (AIS), cerebral sinovenous thrombosis (CSVT) and haemorragic infarct. Many strokes are detected in the neonatal period due to early onset seizures, although symptoms can be more subtle leading to a significant delay in the diagnosis. MRI-DWI remains the best tool for a correct diagnosis, extension of the lesion and suggestion of timing. Lesions detected in utero or at early neonatal imaging with signs of tissue loss are considered "foetal stroke". The "neonatal stroke", with the symptoms in the first 4 days, shows the typical abnormalities of the acute phase evolving later in a white matter loss. The AIS shows the ischemic area of restriction at the early DWI in a arterial territory, mainly the middle cerebral artery. The MR-Venogram is useful in the CVST to detect the thrombus in a sinovenous vessel and the potentially associated lesion, such as intraventricular haemorrage and parenchymal oedema. The extension of the lesion and the involvement of the basal ganglia and thalami have a negative prognostic value for the development of hemiplegia especially in the presence of abnormal PLIC. An early diagnosis