Abstract Background Prediction of long-term neurodevelopmental outcomes remains challenging after perinatal asphyxia. Here, we studied whether computational metrics of brain function derived from neonatal EEG are associated with long-term neurodevelopment in infants with perinatal asphyxia. Methods Total of 36 term-born infants with perinatal asphyxia with or without hypoxic-ischemic encephalopathy were studied with neonatal multichannel electroencephalography (EEG). We computed local EEG amplitudes and phase-amplitude coupling (PAC), as well as large-scale functional cortical networks estimated using amplitude-amplitude correlations (AAC) and phase-phase correlations (PPC). These EEG-derived markers were tested for associations with neurodevelopmental outcomes at two years, assessed using the Griffiths Scales of Child Development, 3rd edition (GMDS-III). Results EEG amplitudes showed positive associations with GMDS-III Foundations of Learning and General Development scores across most electrodes during quiet sleep, with the strongest effects observed at frontal and central regions (r = 0.44–0.66). PAC showed negative associations with the same scores mainly over parietal and temporal regions (r = −0.45 to −0.55). Cortical AAC networks demonstrated the most robust and widespread negative associations in all frequency bands during quiet sleep (r = −0.47 to −0.54), with 70–72% of connections significant in high delta frequency. In turn, PPC networks showed frequency-selective and more spatially constrained negative associations during quiet sleep (r = −0.48 to −0.53), involving 5–12% of the network. Conclusions Both local and network-based metrics in the newborn brain show significant association with neurodevelopmental outcome at 2 years after perinatal asphyxia.

AIM:To identify neuroimaging and neurophysiological markers predictive of infantile-onset and childhood-onset epilepsy after neonatal stroke. METHOD:This retrospective observational study included a population-based cohort of 55 consecutive newborn infants (born between 34 + 4 and 42 + 2 gestational weeks; 23 females) with neonatal stroke, who were followed up (median = 80 months, range = 33-139 months) for the epilepsy outcomes at ages 1 year (infantile-onset) and 4 years (childhood-onset). Outcome prediction was assessed in relation to neonatal magnetic resonance imaging, neonatal somatosensory evoked potentials, and electroencephalogram (EEG) findings from both the neonatal period and infancy. RESULTS:When compared to 1-year-olds without epilepsy, children with infantile-onset epilepsy (n = 6) had infarction of the proximal middle cerebral artery, asymmetry in neonatal EEG, and unilaterally or bilaterally absent somatosensory evoked potentials significantly more often. They also had higher total and maximal hourly seizure burden during the neonatal period and recurrent epileptiform activity already in their first follow-up EEG. In contrast, childhood-onset epilepsy (n = 3) was significantly linked only to asymmetry in neonatal EEG, compared with children without epilepsy at 4 years of age. INTERPRETATION:Neonatal neuroimaging and neurophysiology, combined with follow-up EEGs, enabled the identification of children at the highest risk for infantile-onset epilepsy after neonatal stroke.

The purpose of this study is to assess the cognitive and language skills of very preterm (VP) children using brief parental report instruments at age 2 years (corrected age), potential sex differences in children’s skills, and differences between four profile groups of typical/weak cognition/language. Cognitive and language skills of 110 VP children without major neurological impairment from Finnish-speaking families were assessed using brief validated parental report instruments (cognitive scale of PARCA-R, FinCDI-SF, sentence complexity subscale of PARCA-R, CSBS-DP-ITC). Based on norms, the prevalence of weak skills (< 10th percentile) varied across cognitive and language domains between 16 and 34

This study compared children born extremely preterm (EPT, before 28 weeks of gestation) with full-term children (FT) on social-cognitive abilities, sensorimotor function, socioemotional behavior, and sensory processing. Fifty-three EPT and 34 FT children aged 6 to 7 underwent standardized assessments of Affect Recognition, Theory of Mind, and Imitating Hand Positions, and parents completed validated questionnaires. EPT children showed weaker theory-of-mind abilities, greater difficulty with imitation, and more sensory processing problems than their FT peers. The findings highlight the need for research to understand the mechanisms behind these difficulties and to develop targeted interventions to improve long-term outcomes for EPT children.

Background Anti-seizure medications (ASMs) are widely used in neonatal intensive care, but there is limited evidence for their safety and long-term outcomes. Phenobarbital is the only ASM generally recommended for use in neonates, but it has been linked with adverse effects in infants. Other anti-seizure medications, such as fosphenytoin, levetiracetam, and midazolam are used off-label in this population. Methods We performed a retrospective observational study of 18,548 infants in intensive care at an academic medical center, examining links between neonatal ASM exposure and neurological outcomes over the follow-up period of median 4.5 years (IQR 1.6-9.2 years). The real-world clinical data included comprehensive maternal, perinatal, and medication data. The outcomes of interest were cerebral palsy, epilepsy, intellectual disability, and visual impairment. Multivariable cause-specific Cox models were used to estimate hazard ratios (HRs) for phenobarbital, levetiracetam, midazolam, and fosphenytoin exposure. Models were adjusted for major perinatal confounders, including gestational age, birth weight, mode of delivery, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and stroke. Findings Exposure to the median cumulative dose of phenobarbital was associated with increased HR for epilepsy (HR 1.35; 95% CI, 1.11-1.62, p=0.002) visual impairment (HR 1.20; 95% CI, 0.99-1.45, p = 0.06), and intellectual disability (HR 1.18; 95% CI, 0.99-1.41, p = 0.06). In contrast, levetiracetam was associated with smaller risk increases for cerebral palsy (HR 1.13; 95% CI, 1.03-1.23, p=0.006, epilepsy (HR 1.14; 95% CI 1.05-1.24, p=0.002 and visual impairment (HR 1.18; 95% CI 1.11-1.26, p<0.0001). Midazolam exposure was associated with slightly increased risk of intellectual disability (HR 1.09, 95% CI, 1.02-1.16). Results for fosphenytoin were statistically not significant. We did not find evidence of a dose-dependent effect of phenobarbital, but increased maximum phenobarbital blood concentration were associated with elevated hazard ratios for cerebral palsy (HR 1.48; 95% CI, 1.07-2.06, p=0.02 for 50 µmol/l increase) and epilepsy (HR 1.64; 95% CI, 1.14-2.35, p=0.007 for 50 µmol/l increase). Interpretation The results align with previous findings linking phenobarbital to neurodevelopmental harm and emphasize the need for its cautious use in neonates. Levetiracetam had more favorable safety profile. These findings highlight the potential of real-world data to inform evidence-based neonatal pharmacotherapy when randomized trials are impractical. Funding The Foundation for Pediatric Research (Finland), the Association of Friends of the University Childrens' Hospitals (Lastenklinikoiden Kummit ry), and internal institutional funding. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by The Foundation for Pediatric Research (Finland), the Association of Friends of the University Childrens' Hospitals (Lastenklinikoiden Kummit ry), and internal institutional funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: HUS Helsinki University Hospital Institutional Review Board gave ethical approval for the study (HUS/617/2025). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

INTRODUCTION:Extremely preterm-born infants are at risk for neurodevelopmental impairments. Corticosteroids are used to reduce systemic inflammation. Early dexamethasone therapy is associated with poorer neurodevelopmental outcomes; thus, hydrocortisone is currently widely used. However, the long-term effects of hydrocortisone treatment on neurodevelopmental outcomes remain unclear, and thus, we conducted a pilot study of extremely preterm infants. METHODS:The study cohort included 66 extremely preterm-born infants, who were followed up for 6.5 years. Data on corticosteroid treatment were collected from medical records, and the cumulative doses of hydrocortisone and dexamethasone were calculated. Cognitive outcomes at 6.5 years were assessed using a standardized test of intelligence, and the associations with corticosteroid therapy were evaluated. RESULTS:Twenty-nine (44%) children were treated with corticosteroids, 18 with hydrocortisone, 3 with dexamethasone, and 8 with hydrocortisone and dexamethasone. The mean full-scale (FSIQ), performance (PIQ) and verbal (VIQ) intelligence quotients did not differ significantly between children treated with corticosteroids and those not treated at 6.5 years. The incidence of cognitive impairment (FSIQ, PIQ, and VIQ <85) was higher in children treated with corticosteroids than in those not treated. However, the difference was not statistically significant. CONCLUSION:This pilot study indicates that high-dose postnatal corticosteroid treatment may have long-term adverse effects on cognitive development. Longitudinal studies of the long-term effects of corticosteroid treatment are required to clarify their safety.

OBJECTIVE:To characterize 2-year neurodevelopment of infants with perinatal asphyxia without hypoxic-ischemic encephalopathy (HIE) or with mild HIE (HIE1) and analyse possible correlations with sex, brain MRI findings or early neurological examination. METHODS:Term infants with perinatal asphyxia and a control group were prospectively recruited from the neonatal units of Helsinki University Hospital in 2016-2020. The study cohort included infants with no or minor neurological symptoms during first 6 h after birth. Neurodevelopment was assessed using Hammersmith Infant Neurological Examination (HINE) at three months and at two years, Griffiths Scales of Child Development, 3rd edition (GMDS-III) and Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) at two years. RESULTS:Study included 89 infants: 32 study cohort infants and 57 healthy controls. In the study cohort 1/32 and in the control group 0/57 of the infants showed significantly below normative mean cognitive score in BSID-III. Respective frequency of significantly below normative mean receptive language score were 2/32 and 0/57 and expressive language score 4/32 and 8/57. Females with perinatal asphyxia performed better in the language scores of GMDS-III and BSID-III. Children with asphyxia-related findings in brain MRI had statistically significantly lower total score, language and communication and foundations of learning subscore of GMDS-III. CONCLUSIONS:Most infants with perinatal asphyxia without HIE or with HIE1 performed typically at two years. However, infants with asphyxia-related MRI findings showed lower cognitive and language scores. Our results suggest that female sex may be associated with a lower risk of any subtle effects.

The aims of this prospective study were to describe feeding difficulties in term infants with perinatal asphyxia and to determine whether the time it takes to achieve full oral feeding correlates with early neurological outcome in a high-income setting. Recruitment included 52 term infants with perinatal asphyxia: 32 without hypoxic-ischaemic encephalopathy (HIE), 9 with mild HIE, and 11 with moderate HIE. The time in days it takes to achieve full oral independent feeding was used as a marker of feeding difficulty. Early neurological outcome was evaluated using neonatal brain magnetic resonance imaging (MRI) and Hammersmith Infant Neurological Examination (HINE) at 3 months. In this cohort, 85% of infants (44/52) needed short-term assisted feeding after birth. The time it takes to achieve full oral feeding correlated with neonatal brain MRI findings and structured neurological examination results at three months. The time it takes to achieve full oral feeding could be a useful clinical measure to assess neurologic recovery after perinatal asphyxia, especially in low-resource settings.

Perinatal asphyxia can lead to clinical hypoxic-ischemic encephalopathy (HIE) associated with high morbidity and mortality, but less is known about long-lasting effects of perinatal asphyxia alone (PA). Here, we investigate how PA with versus without clinical HIE affects cortical activity networks at two years of age. Electroencephalographic (EEG) recordings were acquired during sleep from three cohorts of children (PA only (n = 10), PA with mild to moderate HIE (n = 8), and healthy controls (n = 37)), and we assessed the group differences in local cortical function and cortico-cortical networks. Compared with the healthy controls, both PA and HIE were linked to reduced frequency-specific amplitudes. In two-year-old children with PA, the amplitude-related networks were stronger at low frequencies and weaker at higher frequencies, however, two-year-olds with HIE showed decreased connectivity at all frequencies. Likewise, phase-related networks in children with PA were stronger at lower frequencies and weaker at higher frequencies. Local phase-amplitude coupling was affected by PA or HIE in only a few cortical regions. Our findings suggest that PA, even without clinical HIE, may be associated with long-lasting changes to both local cortical activity and the large-scale cortical networks, which could potentially affect normal brain functions.

Cognitive functions emerge from dynamic functional interplay of cortical and subcortical areas that form networks. Preterm birth poses a risk for the formation and functionality of brain networks which may lead to severe brain dysfunctions. Infants born extremely preterm have the highest risk of developing neurocognitive impairments. However, it is still poorly understood how functional brain networks are organized and linked with the cognitive impairments in extremely prematurely born children and adolescents. We applied network-based statistics to study functional network connectivity during two brain-states, resting-state (Rest) and visuospatial working memory n-back tasks (Task), in a unique cohort of extremely preterm-born school-aged children and adolescents (n = 24, mean age 10.3 y, range 7.4-16.4 y) with normal general cognitive abilities and in their term-born peers (n = 22, mean age 9.5 y, range 7.4-13.7 y). We found significant group differences in functional connectivity strength in networks that support complex cognitive performance. The preterm group, compared with controls, modulated functional connectivity between Rest and Task differently within the dorsal attention (DAN, p = 0.016), default mode (DMN, p = 0.026) and visual (VN, p = 0.022) networks, and between DMN - DAN (p = 0.024), DMN - ventral attention network (VAN) (p = 0.035), and DMN - frontoparietal network (FPN) (p = 0.015). The groups also showed opposite age-related changes in connectivity strength within the DAN (Task, p = 0.005; Rest, p = 0.012), DMN (Task, p = 0.015) and FPN (Task, p = 0.002), and between the DAN - VAN (p = 0.047) and DAN - FPN (p = 0.009) during Rest, and FPN - VAN (p =0.028), DAN - FPN (p = 0.006), DMN - DAN (p = 0.042), DMN - VAN (p = 0.023), and DMN - FPN (p = 0.007) during Task. In controls, stronger within-network connectivity associated with better n-back task performance, whereas in the preterm group, stronger between-network connectivity associated with poorer performance. These results suggest that adjustment of functional connectivity to the cognitive demands supports successful performance in school-aged children and adolescents and that extremely preterm birth compromises the dynamics and developmental trajectories of brain networks.

BACKGROUND:Infants born extremely preterm (EPT) face a variety of neurodevelopmental challenges. Those most at risk of adverse outcomes should be detected early. AIMS:To assess General Movements (GMs) at fidgety age in EPT infants and to investigate whether fidgety movements (FMs) and Motor Optimality Scores - Revised (MOS-R) are associated with neurodevelopmental outcome at six years. STUDY DESIGN:Longitudinal cohort study. SUBJECTS:Thirty-eight EPT children (< 28 weeks of gestation, 11 girls). OUTCOME MEASURES:GMs were assessed from video recordings at three months corrected age using the Prechtl General Movements Assessment and The Motor Optimality Score for 3- to 5-Month-Old Infants - Revised. Neurological (Touwen), cognitive (WPPSI-III) and neuropsychological (NEPSY-II, visuospatial and attention) outcomes were evaluated at six years. RESULTS:Nine (24 %) of the infants had aberrant (abnormal/sporadic/absent) FMs and all but one had abnormal movement character. Median MOS-R was 21. Infants with aberrant FMs had significantly higher odds ratio (OR) for full-scale intelligence quotient ≤ 85 (FSIQ, OR 7.7, p = 0.03) and auditory attention ≤ -1SD (OR 12.8, p = 0.04). MOS-R scores correlated positively with FSIQ (Spearman r = 0.39, p = 0.02), performance IQ (r = 0.47, p = 0.004), visuospatial processing (Geometric Puzzles, r = 0.53, p = 0.006) and visual attention (r = 0.29, p = 0.01). Overall outcome or neurological outcome did not reach statistical significance in associations with aberrant FMs or MOS-R. CONCLUSION:Aberrant FMs and lower MOS-R are associated with worse neurodevelopmental outcomes when compared to normal FMs and/or higher MOS-R.

Objective: To evaluate the utility of a fully automated deep learning -based quantitative measure of EEG background, Brain State of the Newborn (BSN), for early prediction of clinical outcome at four years of age. Methods: The EEG monitoring data from eighty consecutive newborns was analyzed using the automatically computed BSN trend. BSN levels during the first days of life (a of total 5427 hours) were compared to four clinical outcome categories: favorable, cerebral palsy (CP), CP with epilepsy, and death. The time dependent changes in BSN-based prediction for different outcomes were assessed by positive/negative predictive value (PPV/NPV) and by estimating the area under the receiver operating characteristic curve (AUC). Results: The BSN values were closely aligned with four visually determined EEG categories (p < 0.001), as well as with respect to clinical milestones of EEG recovery in perinatal Hypoxic Ischemic Encephalopathy (HIE; p < 0.003). Favorable outcome was related to a rapid recovery of the BSN trend, while worse outcomes related to a slow BSN recovery. Outcome predictions with BSN were accurate from 6 to 48 hours of age: For the favorable outcome, the AUC ranged from 95 to 99% (peak at 12 hours), and for the poor outcome the AUC ranged from 96 to 99% (peak at 12 hours). The optimal BSN levels for each PPV/NPV estimate changed substantially during the first 48 hours, ranging from 20 to 80. Conclusions: We show that the BSN provides an automated, objective, and continuous measure of brain activity in newborns. Significance: The BSN trend discloses the dynamic nature that exists in both cerebral recovery and outcome prediction, supports individualized patient care, rapid stratification and early prognosis. (c) 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and .”will be stratified for the two treatment groups. Discussion The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

To assess whether computational electroencephalogram (EEG) measures during the first day of life correlate to clinical outcomes in infants with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE). We analyzed four-channel EEG monitoring data from 91 newborn infants after perinatal asphyxia. Altogether 42 automatically computed amplitude- and synchrony-related EEG features were extracted as 2-hourly average at very early (6 h) and early (24 h) postnatal age; they were correlated to the severity of HIE in all infants, and to four clinical outcomes available in a subcohort of 40 newborns: time to full oral feeding (nasogastric tube NGT), neonatal brain MRI, Hammersmith Infant Neurological Examination (HINE) at three months, and Griffiths Scales at two years. At 6 h, altogether 14 (33

We aimed to describe clinical practices and criteria for discharge of very preterm infants in Nordic neonatal units. Medical directors of all 89 level-2 and level-3 units in Denmark, Finland, Iceland, Norway and Sweden were invited by e-mail to complete a web-based multiple-choice survey with the option to make additional free-text comments. We received responses from 83/89 units (93%). In all responding units, discharge readiness was based mainly on clinical assessment with varying criteria. In addition, 36% used formal tests of cardiorespiratory stability and 59% used criteria related to infant weight or growth. For discharge with feeding tube, parental ability to speak the national language or English was mandatory in 45% of units, with large variation among countries. Post-discharge home visits and video-consultations were provided by 59% and 51%, respectively. In 54% of units, parental preparation for discharge were not initiated until the last two weeks of hospital stay. Discharge readiness was based mainly on clinical assessment, with criteria varying among units despite similar population characteristics and care structures. This variation indicates a lack of evidence base and may unnecessarily delay discharge; further studies of this matter are needed. Earlier parental preparation and use of interpreters might facilitate earlier discharge.

Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% ( p  < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. Management of very preterm infants exhibited significant regional variations in the Nordic countries.

Background: Data on the cerebral effects of analgesic and sedative drugs are needed for the development of safe and effective treatments during neonatal intensive care. Electroencephalography (EEG) is an objective, but interpreter-dependent method for monitoring cortical activity. Quantitative computerized analyses might reveal EEG changes otherwise not detectable. Methods: EEG registrations were retrospectively collected from 21 infants (mean 38.7 gestational weeks; range 27–42) who received dexmedetomidine during neonatal care. The registrations were transformed into computational features and analyzed visually, and with two computational measures quantifying relative and absolute changes in power (range EEG; rEEG) and cortico-cortical synchrony (activation synchrony index; ASI), respectively. Results: The visual assessment did not reveal any drug effects. In rEEG analyses, a negative correlation was found between the baseline and the referential frontal (rho = 0.612, p = 0.006) and parietal (rho = −0.489, p = 0.035) derivations. The change in ASI was negatively correlated to baseline values in the interhemispheric (rho = −0.753; p = 0.001) and frontal comparisons (rho = −0.496; p = 0.038). Conclusion: Cerebral effects of dexmedetomidine as determined by EEG in newborn infants are related to cortical activity prior to DEX administration, indicating that higher brain activity levels (higher rEEG) during baseline links to a more pronounced reduction by DEX. The computational measurements indicate drug effects on both overall cortical activity and cortico-cortical communication. These effects were not evident in visual analysis.

Abstract Introduction Cognitive development is characterized by the structural and functional maturation of the brain. Diffusion‐weighted magnetic resonance imaging (dMRI) provides methods of investigating the brain structure and connectivity and their correlations with the neurocognitive outcome. Our aim was to examine the relationship between early visual abilities, brain white matter structures, and the later neurocognitive outcome. Methods This study included 20 infants who were born before 28 gestational weeks and followed until the age of 6.5 years. At term age, visual alertness was evaluated and dMRI was used to investigate the brain white matter structure using fractional anisotropy (FA) in tract‐based spatial statistics analysis. The JHU DTI white matter atlas was used to locate the findings. The neuropsychological assessment was used to assess neurocognitive performance at 6.5 years. Results Optimal visual alertness at term age was significantly associated with better visuospatial processing (p < .05), sensorimotor functioning (p < .05), and social perception (p < .05) at 6.5 years of age. Optimal visual alertness related to higher FA values, and further, the FA values positively correlated with the neurocognitive outcome. The tract‐based spatial differences in FA values were detected between children with optimal and nonoptimal visual alertness according to performance at 6.5 years. Conclusion We provide neurobiological evidence for the global and tract‐based spatial differences in the white matter maturation between extremely preterm children with optimal and nonoptimal visual alertness at term age and a link between white matter maturation, visual alertness and the neurocognitive outcome at 6.5 years proposing that early visual function is a building block for the later neurocognitive development.