Impact of neonatal pain and opiate administration in animal models: A meta-analysis concerning pain threshold.

BACKGROUND AND AIM: Neonatal intensive care treatment, including frequently performed painful procedures and administration of analgesic drugs, can have different effects on the neurodevelopment. This systematic review and meta-analysis aimed to investigate the influence of pain, opiate administration, and pre-emptive opiate administration on pain threshold in animal studies in rodents, which had a brain development corresponding to preterm and term infants. METHODS: A systematic literature search of electronic data bases including CENTRAL (OVID), CINAHL (EBSCO), Embase.com, Medline (OVID), Web of Science, and PsycInfo (OVID) was conducted. A total of 42 studies examining the effect of pain (n = 38), opiate administration (n = 9), and opiate administration prior to a painful event (n = 5) in rodents were included in this analysis. RESULTS: The results revealed that pain (g = 0.42, 95%CI 0.16-0.67, p = 0.001) increased pain threshold leading to hypoalgesia. Pre-emptive opiate administration had the opposite effect, lowering pain threshold, when compared to pain without prior treatment (g = -1.79, 95%CI -2.71-0.86, p = 0.0001). Differences were found in the meta regression for type of stimulus (thermal: g = 0.66, 95%CI 0.26-1.07, p = 0.001; vs. mechanical: g = 0.13, 95%CI -0.98-1.25, p = 0.81) and gestational age (b = -1.85, SE = 0.82, p = 0.027). In addition, meta regression indicated an association between higher pain thresholds and the amount of cumulative pain events (b = 0.06, SE = 0.03, p = 0.05) as well as severity of pain events (b = 0.94, SE = 0.28, p = 0.001). CONCLUSION: Neonatal exposure to pain results in higher pain thresholds. However, caution is warranted in extrapolating these findings directly to premature infants. Further research is warranted to validate similar effects in clinical contexts and inform evidence-based practices in neonatal care.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

"Every breath you take": evaluating sound levels and acoustic characteristics of various neonatal respiratory support and ventilation modalities.

Background: Early sensory experiences have a significant impact on the later life of preterm infants. The NICU soundscape is profoundly influenced by various modalities of respiratory support or ventilation, which are often mandatory early in the care. The incubator, believed to shield from external noise, is less effective against noise originating inside. The objective of this study was to evaluate the sound levels and characteristics of frequently used respiratory support and ventilation modalities, taking into consideration the developing auditory system of premature infants. Methods: To evaluate sound dynamics inside and outside an incubator during respiratory support/ventilation, experimental recordings were conducted at the Center for Pediatric Simulation Training of the Medical University Vienna. The ventilator used was a FABIAN HFOI®. Results: Jet CPAP (Continuous positive airway pressure), whether administered via mask or prongs, generates significantly higher sound levels compared to High-flow nasal cannula (HFNC) and to High-frequency oscillatory ventilation (HFOV) delivered through an endotracheal tube. Upon evaluating the sound spectrum of jet CPAP support, a spectral peak is observed within the frequency range of 4 to 8 kHz. Notably, this frequency band aligns with the range where the hearing threshold of preterm infants is at its most sensitive. Conclusion: Non-invasive HFNC and invasive HFOV generate lower sound levels compared to those produced by jet CPAP systems delivered via masks or prongs. Moreover, HFNC and HFOV show a reduced acoustic presence within the frequency range where the preterm infant's hearing is highly sensitive. Therefore, it is reasonable to speculate that the potential for auditory impairment might be more pronounced in preterm infants who require prolonged use of jet CPAP therapy during their time in the incubator.

Quantitative Magnetic Resonance Imaging for Neurodevelopmental Outcome Prediction in Neonates Born Extremely Premature-An Exploratory Study.

PURPOSE: Neonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates. METHODS: T1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson's correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes. RESULTS: Cognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = -0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = -0.408; p = 0.018) and pontine tegmentum (r = -0.414; p = 0.017)); and FA (pontine tegmentum (r = -0.352; p = 0.045)). T2R/ADC (medulla oblongata) (cognitive outcomes (R2 = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R2 = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes. CONCLUSION: There are relationships between relaxometry­/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants.

Magnetic Resonance Imaging-Based Reference Values for Two-Dimensional Quantitative Brain Metrics in a Cohort of Extremely Preterm Infants.

INTRODUCTION: Cerebral magnetic resonance imaging (cMRI) is an important diagnostic tool in neonatology. In addition to qualitative analysis, quantitative measurements may help identify infants with impaired brain growth. This study aimed to create reference values for brain metrics of various brain areas in neonates without major brain injuries born before 28 weeks of gestation. METHODS: This retrospective study analyzes cMRI imaging data of high-risk patients without severe brain pathologies at term-equivalent age, collected over 4 years since November 2017. Nineteen brain areas were measured, reference values created, and compared to published values from fetal and postnatal MRI. Furthermore, correlations between brain metrics and gestational age at birth were evaluated. RESULTS: A total of 174 cMRI examinations were available for analysis. Reference values including cut-offs for impaired brain growth were established for different gestational age groups. There was a significant correlation between gestational age at birth and larger "tissue" parameters, as well as smaller "fluid" parameters, including intracerebral and extracerebral spaces. DISCUSSION: With quantitative brain metrics infants with impaired brain growth might be detected earlier. Compared to preexisting reference values, these are the first of a contemporary collective of extremely preterm neonates without severe brain injuries. Measurements can be easily performed by radiologists as well as neonatologists without specialized equipment or computational expertise. CONCLUSION: Two-dimensional cMRI brain measurements at term-equivalent age represent an easy and reliable approach for the evaluation of brain size and growth in infants at high risk for neurodevelopmental impairment.

Analysing heart rate variability in preterm infants: the effect of temporal adjustment of NN peaks and missing data.

The measurement of heart rate variability (HRV) in preterm infants provides important information on function to clinicians. Measuring the underlying electrocardiogram (ECG) in the neonatal intensive care unit is a challenge and there is a trade off between extracting accurate measurements of the HRV and the amount of ECG processed due to contamination. Knowledge on the effects of 1) quantization in the time domain and 2) missing data on the calculation of HRV features will inform clinical implementation. In this paper, we studied multiple 5 minute epochs from 148 ECG recordings on 56 extremely preterm infants. We found that temporal adjustment of NN peaks improves the estimate of the NN interval resulting in HRV features (m = 9) that are better correlated with age (median percentage increase in correlation of individual features: 0.2%, IQR: 0.0 to 5.6%; correlation with age predictor and age from 0.721 to 0.787). Improved (sub-sample) quantization of the NN intervals (via interpolation) reduced the overall value of HRV features (median percentage reduction in feature value: -1.3%, IQR: -18.8 to 0.0; m = 9), primarily through a reduction in the energy of high-frequency oscillations. HRV features were also robust to missing data, with measures such as mean NN, fractal dimension and the smoothed nonlinear energy operator (SNEO) less susceptible to missing data than features such as VLF, LF, and HF. Furthermore, age predictions derived from a combination of HRV measures were more robust to missing data than individual HRV measures.Clinical Relevance-Poor quantization in time when estimating the NN peak and the presence of missing data confound HRV measures, particularly spectral measures.

Perceived stress of mothers and fathers on two NICUs before and during the SARS-CoV-2 pandemic.

Parents of very low birth weight (VLBW) infants in a neonatal intensive care unit experienced additional stress during the SARS-CoV-2 pandemic due to the related restrictions in hospital visiting policies. Our study aimed to compare parents' burdens before and during the pandemic. This survey included 121 parents of 76 VLBW infants in two European Level IV perinatal centers before and during the pandemic. We performed standardized parent questionnaires with mothers and fathers separately to evaluate their emotional stress and well-being. The pandemic worsened the emotional well-being of parents of VLBW infants, particularly of mothers. During the pandemic, mothers reported significantly higher state anxiety levels (48.9 vs. 42.9, p = 0.026) and hampered bonding with the child (6.3 vs. 5.2, 0 = 0.003) than before. In addition, mothers felt more personally restricted than fathers (6.1 vs. 5.2, p = 0.003). Fathers experienced lower levels of stress than mothers; they were equally burdened before and during the pandemic. Restrictions in visiting policies for families of VLBW infants during the SARS-CoV-2 pandemic have a significant negative impact on parental stress and should therefore be applied cautiously.

Inter-site generalizability of EEG based age prediction algorithms in the preterm infant.

Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants.Approach. We used a 'bag of features' with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2.Main results. The age predictor based on all features and trained on site 1 was not validated on site 2 (p< 0.001; MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 2.1 weeks,n= 36). The MAE was improved by training on a restricted features set (MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 1.1 weeks,n= 36), resulting in a validated age predictor when applied to site 2 (p= 0.68). The features selected from the restricted feature set when training on site 1 closely aligned with features selected when trained on a combination of data from site 1 and site 2.Significance. The ability of EEG classifiers, such as brain age prediction, to maintain accuracy on data collected at other sites may be challenged by unexpected, site-dependent differences in EEG signals. Permitting a small amount of data leakage between sites improves generalization, leading towards universal methods of EEG interpretation in preterm infants.

NeoCheck: A New Checklist to Assess Performance during Newborn Life Support-A Validation Study.

BACKGROUND: The aim of this study was to design and validate a new checklist and standardized scenario for assessing providers' performance during Newborn Life Support (NLS). METHODS: We invited twelve experts in Neonatology to take part in a three-step Delphi process. They rated the importance of each item of a newly designed assessment tool to evaluate participants' performance during Newborn Life Support independently on a numeric rating scale from 1 to 5 (1 = lowest; 5 = highest) and were able to give additional comments. All items achieving a mean rating below four after the third round were deleted. For the reliability of the checklist, we calculated interrater reliability. RESULTS: Using a standardized Delphi process, we revised the initial checklist according to the experts' ratings and comments. The final assessment tool includes 38 items covering all relevant steps during NLS. The mean expert rating of all items was 4.40. Interrater reliability showed substantial agreement between the two raters in the first draft (κ = 0.80) as well as in the final draft of the checklist (κ = 0.73). CONCLUSION: We designed a feasible assessment tool for evaluating performance during NLS. We proved the checklist to be valid and reasonable using a Delphi validation process and calculating interrater reliability.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Living in a box: Understanding acoustic parameters in the NICU environment.

Background: In the last years, a significant body of scientific literature was dedicated to the noisy environment preterm-born infants experience during their admission to Neonatal Intensive Care Units (NICUs). Nonetheless, specific data on sound characteristics within and outside the incubator are missing. Therefore, this study aimed to shed light on noise level and sound characteristics within the incubator, considering the following domain: environmental noise, incubator handling, and respiratory support. Methods: The study was performed at the Pediatric Simulation Center at the Medical University of Vienna. Evaluation of noise levels inside and outside the incubator was performed using current signal analysis libraries and toolboxes, and differences between dBA and dBSPL values for the same acoustic noises were investigated. Noise level results were furthermore classed within previously reported sound levels derived from a literature survey. In addition, sound characteristics were evaluated by means of more than 70 temporal, spectral, and modulatory timbre features. Results: Our results show high noise levels related to various real-life situations within the NICU environment. Differences have been observed between A weighted (dBA) and unweighted (dBSPL) values for the same acoustic stimulus. Sonically, the incubator showed a dampening effect on sounds (less high frequency components, less brightness/sharpness, less roughness, and noisiness). However, a strong tonal booming component was noticeable, caused by the resonance inside the incubator cavity. Measurements and a numerical model identified a resonance of the incubator at 97 Hz and a reinforcement of the sound components in this range of up to 28 dB. Conclusion: Sound characteristics, the strong low-frequency incubator resonance, and levels in dBSPL should be at the forefront of both the development and promotion of incubators when helping to preserve the hearing of premature infants.

Impact of Retinopathy of Prematurity on Visual Motor Integration.

BACKGROUND: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age. METHODS: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years. RESULTS: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01). CONCLUSION: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.

The impact of pandemic restrictive visiting policies on infant wellbeing in a NICU.

BACKGROUND: Given the countrywide lockdown in the first pandemic period and the respective Hospital restrictive policies, we aimed to investigate if the SARS-COV-2 pandemic was associated to a reduced parental presence in the NICU and in which form this had an impact on infant wellbeing. METHODS: Retrospective cohort study about altered NICUs parental presence (measured by number of visits and kangaroo care time) due to pandemic restrictive policies and its impact on infant wellbeing (measured through The Neonatal Pain Agitation and Sedation scale and nurses' descriptive documentation). RESULTS: Presence of both parents at the same time was significantly lower during pandemic. Contrary, maternal presence only and total kangaroo-care time were higher within the pandemic (163.36 ± 94.07 vs 122.71 ± 64.03; p = 0.000). Lower NPASS values were documented during the lookdown (1.28 ± 1.7 vs 1.78 ± 2.2; p = 0.000). CONCLUSION: Data collected through the pandemic confirm the importance of parental presence for infants' wellbeing in a NICU setting. IMPACT: Parental support is an extremely important aspect for infants hospitalized in an intensive care unit. Their presence was limited in many NICUs worldwide during the SARS-COV-2 pandemic. This study confirm the importance of parental presence for infants' wellbeing also in a pandemic situation. Our results support a family-centered newborn individualized developmental care approach in the NICU.

Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production.

OBJECTIVE: Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production. METHODS: Monocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes. RESULTS: GCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production. CONCLUSIONS: Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.

Pain and neurodevelopmental outcomes of infants born very preterm.

AIM: To investigate the impact of the level of pain experienced by infants born preterm on neurodevelopmental outcomes during their stay in a neonatal intensive care unit. METHOD: In this retrospective data analysis we included all surviving infants born preterm with a gestational age between 23 and 32 weeks from 2011 to 2015, who were assessed using the Neonatal Pain, Agitation, and Sedation Scale and examined at 1 year of age using the Bayley Scales of Infant Development. We excluded all infants who had suffered severe neurological morbidities and undergone surgical interventions. RESULTS: A total of 196 infants born preterm were included in the analyses: 105 in the 'no pain group' and 91 in the 'pain group'. Significant differences between the groups were detected for both mental and motor development (p = 0.003, 95% confidence interval [CI] 2.23-10.92; p = 0.025, 95% CI 0.64-9.78). The results remained significant after controlling for other important medical conditions (p = 0.001, 95% CI -19.65 to -5.40; p = 0.010, 95% CI -16.18 to -2.29). INTERPRETATION: Neonatal pain exposure was associated with altered neurodevelopmental outcomes of infants born very preterm at a corrected age of 12 months. This observation highlights the importance of adequate pain management to reduce the risk of poor neurodevelopmental outcomes in these vulnerable patients.

Bedside tracking of functional autonomic age in preterm infants.

BACKGROUND: Preterm birth predisposes infants to adverse outcomes that, without early intervention, impacts their long-term health. To assist bedside monitoring, we developed a tool to track the autonomic maturation of the preterm by assessing heart rate variability (HRV) changes during intensive care. METHODS: Electrocardiogram (ECG) recordings were longitudinally recorded in 67 infants (26-38 weeks postmenstrual age (PMA)). Supervised machine learning was used to generate a functional autonomic age (FAA), by combining 50 computed HRV features from successive 5-minute ECG epochs (median of 23 epochs per infant). Performance of the FAA was assessed by correlation to PMA, clinical outcomes and the infant's functional brain age (FBA), an index of maturation derived from the electroencephalogram. RESULTS: The FAA was strongly correlated to PMA (r = 0.86, 95% CI: 0.83-0.93) with a mean absolute error (MAE) of 1.66 weeks and also accurately estimated FBA (MAE = 1.58 weeks, n = 54 infants). The relationship between PMA and FAA was not confounded by neurodevelopmental outcome (p = 0.18, n = 45), sex (p = 0.88, n = 56), patent ductus arteriosus (p = 0.08, n = 56), IVH (p = 0.63, n = 56) or body weight at birth (p = 0.95, n = 56). CONCLUSIONS: The FAA, an index derived from the ubiquitous ECG signal, offers direct avenues towards estimating autonomic maturation at the bedside during intensive care monitoring. IMPACT: The development of a tool to track functional autonomic age in preterm infants based on heart rate variability features in the electrocardiogram provides a rapid and specialized view of autonomic maturation at the bedside. Functional autonomic age is linked closely to postmenstrual age and central nervous system function response, as determined by its relationship to functional brain age from the electroencephalogram. Tracking functional autonomic age during neonatal intensive care unit monitoring offers a unique insight into cardiovascular health in infants born extremely preterm and their maturational trajectories to term age.

Sex differences in neural processing of speech in neonates.

The large majority of studies shows that girls develop their language skills faster than boys in the first few years of life. Are girls born with this advantage in language development? The present study used fNIRS in neonates to investigate sex differences in neural processing of speech within the first days of life. We found that speech stimuli elicited significantly more brain activity than non-speech stimuli in both groups of male and female neonates. However, whereas girls showed significant HbO changes to speech stimuli only within the left hemisphere, boys exhibited simultaneous neural activations in both hemispheres, with a larger and more significant fronto-temporal cluster in the right hemisphere. Furthermore, in boys, the variation in time-to-peak latencies was considerably greater than in girls. These findings suggest an earlier maturation of language-related brain areas in girls and highlight the importance of sex-specific investigations of neural language networks in infants.

Audio Feature Analysis for Acoustic Pain Detection in Term Newborns.

INTRODUCTION: Crying newborns signal a need or discomfort as part of the innate communication system. Exposure to pain is related to infants' unfavorable neurodevelopmental outcomes. There is a tremendous need for more objective methods to assess neonatal pain. An audio analysis of acoustic utterances could provide specific information on the patient's pain level. METHODS: We analyzed 67 videos of 33 term-born newborns recorded during a planned capillary blood sample, including the stimuli, non-noxious thermal stimulus, short noxious stimulus, and prolonged unpleasant stimulus, between December 2020 and March 2021. Two expert raters evaluated the infants' pain responses using the Neonatal Facial Coding System (NFCS). The mean values of 123 timbre features of the recorded audio data were analyzed by using specific toolboxes and libraries from the following programming environments: MIRtoolbox (MATLAB), MiningSuite (MATLAB), Essentia (Python), AudioCommons timbral models (Python), and Librosa (Python). RESULTS: The NFCS values were significantly higher during the short noxious stimulus (p < 0.001) and prolonged unpleasant stimulus (p < 0.001) than during the non-noxious thermal stimulus, whereas NFCS values during the short noxious stimulus and prolonged unpleasant stimulus were similar (p = 0.79). Brightness, roughness, percussive energy, and attack times were identified as the features having the highest impact on the NFCS. CONCLUSION: This hypothesis-generating study identified several salient acoustic features highly associated with pain responses in term newborns. Our analysis is an encouraging starting point for the targeted analysis of pain-specific acoustic features of neonatal cries and vocalizations from the perspective of real-time acoustic processing.