Neurodevelopmental Risk Factors Research Articles

Orbitofrontal sulcal patterns in catatonia.

Catatonia is a psychomotor syndrome frequently observed in disorders with neurodevelopmental impairments, including psychiatric disorders such as schizophrenia. The orbitofrontal cortex (OFC) has been repeatedly associated with catatonia. It presents with an important interindividual morphological variability, with three distinct H-shaped sulcal patterns, types I, II, and III, based on the continuity of the medial and lateral orbital sulci. Types II and III have been identified as neurodevelopmental risk factors for schizophrenia. The sulcal pattern of the OFC has never been investigated in catatonia despite the role of the OFC in the pathophysiology and the neurodevelopmental component of catatonia. In this context, we performed a retrospective analysis of the OFC sulcal pattern in carefully selected homogeneous and matched subgroups of schizophrenia patients with catatonia (N=58) or without catatonia (N=65), and healthy controls (N=82). Logistic regression analyses revealed a group effect on OFC sulcal pattern in the left (χ2=18.1; p<.001) and right (χ2=28.3; p<.001) hemispheres. Catatonia patients were found to have more type III and less type I in both hemispheres compared to healthy controls and more type III on the left hemisphere compared to schizophrenia patients without catatonia. Because the sulcal patterns are indirect markers of early brain development, our findings support a neurodevelopmental origin of catatonia and may shed light on the pathophysiology of this syndrome.

Creative music therapy for long-term neurodevelopment in extremely preterm infants: Results of a feasibility trial.

We tested the feasibility of a future randomised clinical trial (RCT) in which Creative Music Therapy (CMT), a family-integrating individualised approach in neonatal care, could improve neurodevelopment in extremely preterm infants (EPTs). In this feasibility trial, 12 EPTs received CMT, while the remaining 19 received standard neonatal care. Socio-demographic data and perinatal complications were compared between groups as risk factors. Bayley Scales of Infant and Toddler Development at 2-year follow-up (FU2) and KABC-II-Kaufman Assessment Battery for Children at 5-year follow-up (FU5) were analysed using the Mann-Whitney U-tests. Twenty-seven (87.1%) and 18 (58.1%) EPTs attended the FU2 and FU5 examination, respectively. The rate of neurodevelopmental risk factors at birth of the two groups was quite similar. While there was no difference in the FU2 outcomes between groups, there were higher values in the CMT group's Fluid-Crystallised Index of the KABC-II. Our results indicate neither a beneficial nor a detrimental effect of CMT on neurodevelopment at 2 years but a trend of improved cognitive outcomes at 5 years more similar to cognitive scores of term-born infants than of standard treatment EPTs. The findings favour an RCT but must be interpreted cautiously due to the reduced sample size and non-randomised design.

Associations Between Autism Spectrum Quotient and Integration of Visual Stimuli in 9-year-old Children: Preliminary Evidence of Sex Differences.

The dorsal stream vulnerability hypothesis posits that the dorsal stream, responsible for visual motion and visuo-motor processing, may be particularly vulnerable during neurodevelopment. Consistent with this, autism spectrum disorder (ASD) has been associated with deficits in global motion integration, though deficits in ventral stream tasks, such as form identification, have also been reported. In the current study, we examined whether a similar pattern of results is found in a cohort of 381 children born with neurodevelopmental risk factors and exhibiting a wide spectrum of caregiver-reported autistic traits. We examined the associations between global motion perception, global form perception, fine motor function, visual-motor integration, and autistic traits (autism spectrum quotient, AQ) using linear regression, accounting for possible interactions with sex and other factors relevant to neurodevelopment. All assessments of dorsal stream function were significantly associated with AQ such that worse performance predicted higher AQ scores. We also observed a significant sex interaction, with worse global form perception associated with higher AQ in boys (n = 202) but not girls (n = 179). We found widespread associations between dorsal stream functions and autistic traits. These associations were observed in a large group of children with a range of AQ scores, demonstrating a range of visual function across the full spectrum of autistic traits. In addition, ventral function was associated with AQ in boys but not girls. Sex differences in the associations between visual processing and neurodevelopment should be considered in the designs of future studies.

Early risk factors for conduct problem trajectories from childhood to adolescence: the 2004 Pelotas (BRAZIL) Birth Cohort

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.

Evaluation of neurodevelopmental impairments and risk factors in children following cardiac surgery: The first cohort from China

ObjectiveNeurodevelopmental impairment has been realized as the most common complication in children with congenital heart disease undergoing cardiac surgery during the past 30 years. But little attention has been paid to this problem in China. The potential risk factors for adverse outcomes include demographic, perioperative, and socioeconomic factors, which are vastly different in China compared with the developed countries in previous reports. MethodsFour hundred twenty-six patients (aged 35.9 ± 18.6 months) at about 1- to 3-year follow-up after cardiac surgery were prospectively enrolled from March 2019 to February 2022. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination, and performance skills. Demographic, perioperative, socioeconomic, and feeding type during the first year of life (breastfeeding, mixed, or never breastfeeding) were examined to identify the risk factors for adverse neurodevelopmental outcomes. ResultsMean scores were 90.0 ± 15.5 for development quotient, 92.3 ± 19.4 for locomotor, 89.6 ± 19.2 for personal-social, 85.5 ± 21.7 for language, 90.3 ± 17.2 for eye-hand coordination, and 92 ± 17.1 for performance subscales. For the entire cohort, the impairment in at least 1 subscale was found in 76.1% of the cohort (>1 SD below population mean) with 50.1% being severe (>2 SDs below the mean). The significant risk factors included prolonged hospital stay, peak level of postoperative C-reactive protein, socioeconomic status, and never breastfeeding or mixed feeding. ConclusionsNeurodevelopmental impairment is substantial in terms of incidence and severity in children with congenital heart disease undergoing cardiac surgery in China. Risk factors contributing to the adverse outcomes included prolonged hospital stay, early postoperative inflammatory response, socioeconomic status, and never breastfeeding or mixed feeding. There is an urgent need for standardized follow-up and neurodevelopmental assessment in this special group of children in China.

Associations of neurodevelopmental risk factors with psychosis proneness: Findings from a non-clinical sample of young adults

Psychotic disorders often develop as the continuum of subclinical symptoms that include hallucination-like and delusion-like experiences, and are commonly referred to as psychotic-like experiences (PLEs). To date, a number of neurodevelopmental risk factors of psychosis have been detected, yet their mutual interplay remains unknown. Therefore, we aimed to investigate the additive association of childhood trauma history, reading disabilities and symptoms of attention-deficit/hyperactivity disorder (ADHD) with psychosis proneness. A total of 3000 young adults (58.3% females, aged 18–35 years) with a negative history of psychiatric treatment were recruited to the cross-sectional study through computer-assisted web interview. Self-reports were administered to measure childhood trauma history, ADHD symptoms and reading disabilities. Linear regression analyses revealed significant main associations of childhood trauma history and reading disabilities with higher levels of PLEs. There were no significant main associations of ADHD with the level of PLEs. However, the associations of all possible interactions between neurodevelopmental risk factors with the level of PLEs were significant. Our findings suggest that childhood trauma history and reading disabilities may additively increase a risk of psychosis. The present findings bring new implications for early intervention strategies in psychosis and posit the rationale of recording the accumulation of neurodevelopmental vulnerabilities in clinical practice.

Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy.

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for autism have emerged. As a result, neurobehavioral abnormalities, neurobiological alterations in ASD, and the development of novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss the development of multiple animal models of ASD to contribute to the disease mechanisms of ASD, as well as new studies from multiple disciplines to assess the behavioral pathology of ASD. In addition, we summarize and highlight the mechanistic advances regarding gene transcription, RNA and non-coding RNA translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation and neural loop abnormalities in autism to provide a theoretical basis for the next step of precision therapy. Furthermore, we review existing autism therapy tactics and limits and present challenges and opportunities for translating multidisciplinary knowledge of ASD into clinical practice.

Neurodevelopmental Risk Factors in Premature Babies

Neurodevelopmental Risk Factors in Premature Babies

Predictors of enteral tube dependence in pediatric esophageal atresia.

Children with esophageal atresia (EA) may require enteral tube feedings in infancy and a subset experience ongoing feeding difficulties and enteral tube dependence. Predictors of enteral tube dependence have never been systematically explored in this population. We hypothesized that enteral tube dependence is multifactorial in nature, with likely important contributions from anastomotic stricture. Cross-sectional clinical, feeding, and endoscopic data were extracted from a prospectively collected database of endoscopies performed in EA patients between August 2019 and August 2021 at an international referral center for EA management. Clinical factors known or hypothesized to contribute to esophageal dysphagia, oropharyngeal dysphagia, or other difficulties in meeting caloric needs were incorporated into regression models for statistical analysis. Significant predictors of enteral tube dependence were statistically identified. Three-hundred thirty children with EA were eligible for analysis. Ninety-seven were dependent on enteral tube feeds. Younger age, lower weight Z scores, long gap atresia, neurodevelopmental risk factor(s), significant cardiac disease, vocal fold movement impairment, and smaller esophageal anastomotic diameter were significantly associated with enteral tube dependence in univariate analyses; only weight Z scores, vocal fold movement impairment, and anastomotic diameter retained significance in a multivariable logistic regression model. In the current study, anastomotic stricture is the only potentially modifiable significant predictor of enteral tube dependence that is identified.

Deficit of perineuronal net induced by maternal immune activation mediates the cognitive impairment in offspring during adolescence

Maternal immune activation (MIA) during pregnancy is considered a risk factor for neurodevelopment in the offspring, resulting in behavioral abnormalities. Furthermore, adolescence is a vulnerable period for developing different psycho-cognitive deficits. Here, we aimed to observe the cognitive consequences of prenatal MIA exposure in adolescents and explored the underlying mechanisms. We divided dams into CON and MIA groups after inducing a mouse model of MIA using lipopolysaccharide (120 μg/kg) on gestational day 15. Open field (OF), elevated plus maze (EPM), and novel object recognition (NOR) tests were performed on postnatal day (PD) 35–37. The expression of hippocampal Wisteria floribunda agglutinin (WFA)+ perineuronal net (PNN), parvalbumin (PV), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule-1(Iba-1) were evaluated using immunofluorescence, and the expression of matrix metalloprotein-9 (MMP-9) in the hippocampus was assessed using the western blot. Following the infusion of chondroitinase ABC (ChABC) into CA1 in the offspring from the CON group on PD 30, they were divided into ChABC and Sham groups. OF, EPM, and NOR were performed on PD 35–37. Compared to the CON group, decreased exploration time of the novel object and preference ratio were observed in the MIA group. Meanwhile, the MIA group presented significantly decreased WFA+ PNN in CA1, increased Iba-1+ microglia, and MMP-9 in the hippocampus. Additionally, the density of PV+ neurons and GFAP+ astrocytes was comparable between both groups. After digesting the PNN, the exploration time of novel object and preference ratio decreased in the ChABC group compared to the Sham group. Conclusively, the PNN deficit in CA1 caused by prenatal MIA might, at least partially, induce cognitive impairment in adolescents. Microglia and MMP-9 may also be potential candidates for PNN deficit after MIA.

A convergent mechanism of high risk factors ADNP and POGZ in neurodevelopmental disorders.

ADNP and POGZ are two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. Both ADNP and POGZ are chromatin regulators, which could profoundly affect gene transcription and cellular function in the brain. Using post-mortem tissue from patients with autism spectrum disorder, we found diminished expression of ADNP and POGZ in the prefrontal cortex, a region highly implicated in neurodevelopmental disorders. To understand the functional role of these neurodevelopmental disorder risk factors, we used viral-based gene transfer to investigate how Adnp or Pogz deficiency in mouse prefrontal cortex affects behavioural, transcriptomic and synaptic function. Mice with prefrontal cortex deficiency of Adnp or Pogz exhibited specific impairment of cognitive task performance. RNA-sequencing revealed that Adnp or Pogz deficiency induced prominent upregulation of overlapping genes enriched in neuroinflammation, similar to the elevation of pro-inflammatory genes in humans with neurodevelopmental disorders. Concomitantly, Adnp or Pogz deficiency led to the significant increase of pro-phagocytic microglial activation in prefrontal cortex, as well as the significant decrease of glutamatergic transmission and postsynaptic protein expression. These findings have uncovered the convergent functions of two top risk factors for autism spectrum disorder and intellectual disability in prefrontal cortex, providing a mechanism linking chromatin, transcriptional and synaptic dysregulation to cognitive deficits associated with neurodevelopmental disorders.

Altered brain structure in preschool-aged children with tetralogy of Fallot.

Neurodevelopmental abnormalities are prevalent in children with tetralogy of Fallot. Our aim was to investigate the structural brain alterations of preschool-aged children with tetralogy of Fallot and its correlation with neurodevelopmental outcome. T1-weighted structural images were obtained from 25 children with tetralogy of Fallot who had undergone cardiopulmonary bypass surgery and from 24 normal controls. Cortical morphological indices including gray matter volume, cortical thickness, sulcal depth, gyrification, and cortical surface complexity were compared between the two groups. Neurodevelopmental assessments of the children with tetralogy of Fallot were performed with the Wechsler Preschool and Primary Scale of Intelligence. Cortical morphological differences between groups were distributed throughout the right caudal middle frontal gyrus, right fusiform gyrus, right lateral occipital gyrus, right precuneus, and left inferior parietal lobule. Among children with tetralogy of Fallot, altered cortical structures were correlated with the visual spatial index, working memory index, and perioperative variables. Our results suggested that abnormal cortical structure in preschool-aged children with tetralogy of Fallot may be the persistent consequence of delayed cortical development in fetuses and cortical morphology can be used as an early potential biomarker to capture regional brain abnormalities that are relevant to neurodevelopmental outcomes. Altered cortical structures in preschool-aged children with ToF were correlated with both neurodevelopmental outcomes and clinical risk factors. Cortical morphology can be used as an effective tool to evaluate neuroanatomical changes and detect underlying neural mechanisms in ToF patients. Abnormal cortical structure may be the continuous consequence of delayed fetal brain development in children with ToF.

Assessment of Neurodevelopmental Status and Risk Factors for Adverse Neurodevelopmental Outcome in Late Preterm Infants at 6 Months Corrected Age : An Prospective Observational Study

Background: Late Preterm (LP) infants, previously considered low risk, have been identified to be at risk of developmental problems in infancy and early childhood. There is limited information on the outcome of these infants in low and middle income countries. This study was aimed to assess the neurodevelopmental status of LP born neonates and to determine factors associated with adverse neurodevelopmental outcome in a tertiary hospital of Chattogram, Bangladesh.&#x0D; Materials and methods: In this prospective observational study, 108 LP (34 to &lt;37 completed weeks gestation at birth) infants were enrolled from the Special Care Neonatal Unit (SCANU) Chittagong Medical College Hospital (CMCH) from June 2018 to May 2019. Neurodevelopmental assessment was done by Rapid Neurodevelopmental Assessment (RNDA) at 1, 3, and 6 months of Corrected Age (CA).&#x0D; Results: Of the 108 enrolled children, 30 (27.8%) attended all 3 follow-up, 69 (63.9%) had incomplete follow-up, and 9 (8.3%) died. At final follow-up, out of 30 infants, 25 (83.3%) had no abnormality in all 8 domains of RNDA. Three infants (10.0%) had abnormalities in one domain and 2 (6.7%) had abnormalities in 5 domains. Gross motor abnormality was most common abnormality (13.4%), followed by speech (10.0%), and cognition (6.7%). Small for gestational age was found to be the only independent predictive factor for Neurodevelopmental Abnormality (NDA) in LP infants.&#x0D; Conclusion: This study demonstrates that 16.7% of the LP infants had evidence of neurodevelopmental impairment at 6 months of corrected age. SGA was an important risk factor of adverse neurodevelopmental outcome. Thus, LP infants in Bangladesh require long-term follow-up to monitor developmental outcome.&#x0D; JCMCTA 2021 ; 32 (2) : 70-74

Coupling between prefrontal brain activity and respiratory sinus arrhythmia in infants and adults

Self-regulation is an essential aspect of healthy child development. Even though infants are dependent on their caregivers for co-regulation during the first years, they begin to gain early regulatory abilities through social interactions as well as their own cognitive development. These early regulatory abilities continue to increase with the maturation of both the prefrontal cortex and the vagal system. Importantly, theoretical accounts have suggested that the prefrontal cortex and the vagal system are linked through forward and backward feedback loops via the limbic system. Decreased coupling within this link is suggested to be associated with psychopathology.The primary goal of this study is to examine whether intrapersonal coupling of prefrontal brain activity and respiratory sinus arrythmia is evident in infancy. Using the simultaneous assessment of functional near-infrared spectroscopy and electrocardiography, we will use Cross-Recurrence Quantification Analysis to assess the coupling of prefrontal brain activity and respiratory sinus arrhythmia in 69 4–6-month-old infants and their mothers during rest.Understanding the developmental emergence of the neurobiological correlates of self- regulation will allow us to help identify neurodevelopmental risk factors.

Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain.

Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the Esr1 gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of Esr2, Gper1, Ahr, Arnt, Cyp19a1, Cyp1a1, and Atg7, and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes.

Literature Review: Neurodevelopmental and psychosocial risk factors in serial killers and mass murderers

In the research article “Neurodevelopmental and psychosocial risk factors in serialkillers and mass murderers” by Allely et. al. (2014), the researchers explored the prevalenceof autistic spectrum disorder (ASD), head injuries, and psychosocial stressors in serial killersand mass murderers. They studied a sample size of 239 killers and organized the informationin data tables and statistics. Mass and serial killings are rare, which makes it hard to analysecases and earlier studies as they were not precise and lacked rigor (Allely et al, 2014). Thisarticle had limitations such as only having data from places in the United States and havingthe article available only in English. The strengths of the journal article were includingmultiple statistics and data tables to support their claims. The information provided in thisarticle can lead to further research on more neurodevelopmental and psychosocial disordersand childhood factors that can influence violent behaviour.

Effects of neurodevelopmental risk factors on brainstem maturation in premature infants.

Interpeak latencies (IPL), as measured by the auditory brainstem-evoked responses (ABR) test, represent the conduction time, and therefore the maturation of the brainstem auditory pathway. We aimed to study the effect of various risk factors for the neurodevelopmental delay on the conduction time in the auditory pathway among normal hearing premature infants, at term postmenstrual age (PMA). Retrospective analysis of 239 premature infants (gestational age 32.5 ± 2.1 weeks, birth weight 1827 ± 483 g). Interpeak latencies, demographic data, and risk factors were recorded. Sex, PMA at ABR test, being small for gestational age (SGA), intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), and days of invasive ventilation were found to significantly affect the IPL's in the auditory pathway in a univariate analysis. Multivariable regression analysis revealed that male sex and less advanced PMA at the examination were independent factors associated with prolonged IPL's, while bronchopulmonary dysplasia, IVH or PVL and being SGA shortened the IPL's. Non-invasive mechanical ventilation, did not affect the caudal part of the auditory pathway, despite its high noise level. Among various risk factors for the neurodevelopmental delay, male sex was associated with delayed, while IVH or PVL, BPD and SGA could be associated with accelerated auditory brainstem maturation. Auditory brainstem-evoked response (ABR) test, among normal hearing infants, can serve as a clinical tool to assess brainstem auditory maturation. Different neurodevelopmental risk factors could have different effects on the maturity of the auditory pathway. Male sex is significantly associated with prolonged interpeak latencies (IPL) among preterm and term infants, while intraventricular hemorrhage or periventricular leukomalacia, bronchopulmonary dysplasia, and being small for gestation age may be associated with shortened IPL The corrected age at ABR testing is of significance, among preterm and term infants.

A transdiagnostic data-driven study of children’s behaviour and the functional connectome

Behavioural difficulties are seen as hallmarks of many neurodevelopmental conditions. Differences in functional brain organisation have been observed in these conditions, but little is known about how they are related to a child’s profile of behavioural difficulties. We investigated whether behavioural difficulties are associated with how the brain is functionally organised in an intentionally heterogeneous and transdiagnostic sample of 957 children aged 5–15. We used consensus community detection to derive data-driven profiles of behavioural difficulties and constructed functional connectomes from a subset of 238 children with resting-state functional Magnetic Resonance Imaging (fMRI) data. We identified three distinct profiles of behaviour that were characterised by principal difficulties with hot executive function, cool executive function, and learning. Global organisation of the functional connectome did not differ between the groups, but multivariate patterns of connectivity at the level of Intrinsic Connectivity Networks (ICNs), nodes, and hubs significantly predicted group membership in held-out data. Fronto-parietal connector hubs were under-connected in all groups relative to a comparison sample and children with hot vs cool executive function difficulties were distinguished by connectivity in ICNs associated with cognitive control, emotion processing, and social cognition. This demonstrates both general and specific neurodevelopmental risk factors in the functional connectome.

Phase-Based Cortical Synchrony Is Affected by Prematurity

Inter-areal synchronization by phase–phase correlations (PPCs) of cortical oscillations mediates many higher neurocognitive functions, which are often affected by prematurity, a globally prominent neurodevelopmental risk factor. Here, we used electroencephalography to examine brain-wide cortical PPC networks at term-equivalent age, comparing human infants after early prematurity to a cohort of healthy controls. We found that prematurity affected these networks in a sleep state-specific manner, and the differences between groups were also frequency-selective, involving brain-wide connections. The strength of synchronization in these networks was predictive of clinical outcomes in the preterm infants. These findings show that prematurity affects PPC networks in a clinically significant manner, suggesting early functional biomarkers of later neurodevelopmental compromise that may be used in clinical or translational studies after early neonatal adversity.

Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants.

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions.Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age.Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis.Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67–0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19–5.26; p = 0.015) were significantly associated with severe functional disability.Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.