Hand function after neonatal stroke: A graph model based on basal ganglia and thalami structure.

INTRODUCTION: Neonatal arterial ischemic stroke (NAIS) is a common model to study the impact of a unilateral early brain insult on developmental brain plasticity and the appearance of long-term outcomes. Motor difficulties that may arise are typically related to poor function of the affected (contra-lesioned) hand, but surprisingly also of the ipsilesional hand. Although many longitudinal studies after NAIS have shown that predicting the occurrence of gross motor difficulties is easier, accurately predicting hand motor function (for both hands) from morphometric MRI remains complicated. The hypothesis of an association between the structural organization of the basal ganglia (BG) and thalamus with hand motor function seems intuitive given their key role in sensorimotor function. Neuroimaging studies have frequently investigated these structures to evaluate the correlation between their volumes and motor function following early brain injury. However, the results have been controversial. We hypothesize the involvement of other structural parameters. METHOD: The study involves 35 children (mean age 7.3 years, SD 0.4) with middle cerebral artery NAIS who underwent a structural T1-weighted 3D MRI and clinical examination to assess manual dexterity using the Box and Blocks Test (BBT). Graphs are used to represent high-level structural information of the BG and thalami (volumes, elongations, distances) measured from the MRI. A graph neural network (GNN) is proposed to predict children's hand motor function through a graph regression. To reduce the impact of external factors on motor function (such as behavior and cognition), we calculate a BBT score ratio for each child and hand. RESULTS: The results indicate a significant correlation between the score ratios predicted by our method and the actual score ratios of both hands (p < 0.05), together with a relatively high accuracy of prediction (mean L1 distance < 0.03). The structural information seems to have a different influence on each hand's motor function. The affected hand's motor function is more correlated with the volume, while the 'unaffected' hand function is more correlated with the elongation of the structures. Experiments emphasize the importance of considering the whole macrostructural organization of the basal ganglia and thalami networks, rather than the volume alone, to predict hand motor function. CONCLUSION: There is a significant correlation between the structural characteristics of the basal ganglia/thalami and motor function in both hands. These results support the use of MRI macrostructural features of the basal ganglia and thalamus as an early biomarker for predicting motor function in both hands after early brain injury.

Early Intensive Bimanual Stimulation Program (BB-Bim) for Infants at Risk of Unilateral Cerebral Palsy: A Randomized, Multiple-Baseline, Single-Case Study.

IMPORTANCE: Clinical practice guidelines for infants at high risk of cerebral palsy (CP) emphasize the importance of very early and intensive intervention. OBJECTIVE: To determine the feasibility of a new, home-based, early intensive bimanual stimulation program (BB-Bim) and its impact on hand function in infants at risk of unilateral CP. DESIGN: Single case experimental design, multiple baseline across subjects, lasting from 12 to 15 wk, including a 4- to 7-wk randomized baseline, followed by 8 wk of BB-Bim. SETTING: Home. PARTICIPANTS: Infants (ages 3-12 mo) with suspected unilateral CP, whose parents agreed to participate in the stimulation program. INTERVENTION: Parent-provided bimanual stimulation 20 min/day, 6×/wk, with weekly occupational therapist coaching visits. MEASURES: Weekly repeated measures were the Hand Assessment in Infants (HAI) and Goal Attainment Scaling (GAS). Feasibility and relevance were assessed with a logbook and a parental report, including 10 continuous 0-10 scaled questions. RESULTS: Six infants were included (2 with left and 4 with right brain lesions). Parents provided a mean 3.4 to 6.2 stimulation sessions/wk. Feasibility and relevance were highly rated (Ms = 8.2-9.6, SDs = 0.2-1.3). Stimulation significantly improved HAI bimanual and total scores for all infants, with no impact on HAI unilateral scores. GAS scores improved with stimulation (significant for 3 infants). CONCLUSIONS AND RELEVANCE: BB-Bim was feasible and tended to improve bimanual function in infants at risk of unilateral CP. What This Article Adds: Parent-provided daily bimanual stimulation at home is feasible when parents are coached weekly by an occupational therapist. Bimanual stimulation seems to improve functional interactions between the hands among infants at high risk of unilateral CP.

Long-term developmental condition following neonatal arterial ischemic stroke: A systematic review.

BACKGROUND: Neonatal arterial ischemic stroke (NAIS) is the most frequent subtype of perinatal stroke. Its elusive pathophysiology, its abrupt and unexpected occurrence, and the uncertainty of the post-NAIS developmental condition may lead to parental emotional distress and psychological difficulties. The aim of this study was to summarize the current data on long-term developmental conditions following NAIS to support parental information given within the neonatal unit. METHODS: This systematic review included clinical studies of term infants with NAIS, who had a developmental assessment at ≥5 years of age. Studies were identified from the Medline and Embase databases on June 1, 2022. The Joanna Briggs Institute (JBI) appraisal tool was used to assess the risk of bias. Results were synthesized using a narrative approach. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed to report this work. RESULTS: Three cohort studies enrolling 205 children assessed from 5 to 7 years after NAIS were included. Most of the children presented long-term developmental conditions allowing them to be integrated into a regular school program, to participate in physical activities, and to have a good quality of life. Global intellectual deficiency and moderate-to-severe cerebral palsy occurred in less than 10% of the children. CONCLUSION: Physicians should not overestimate the incidence of moderate-to-severe developmental outcome following NAIS when discussing the prognosis with parents. A parental information sheet about NAIS and its long-term developmental conditions is provided.

From early motor ability to global cognitive development seven years after neonatal arterial ischemic stroke.

The developmental condition of children after neonatal arterial ischemic stroke (NAIS) is characterized by cognitive and motor impairments. We hypothesized that independent walking age would be a predictor of later global cognitive functioning in this population. Sixty-one children with an available independent walking age and full-scale IQ score seven years after NAIS were included in this study. Full-scale IQ was assessed using the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV). Independent walking age was negatively correlated with full-scale IQ score at seven years of age (Pearson correlation coefficient of -0.27; 95% confidence interval from 0.48 to -0.01; p <0.05). Early motor function is correlated with later global cognitive functioning in children after NAIS. Assessing and promoting early motor ability is essential in this population.

Encephalitis and poor neuronal death-mediated control of herpes simplex virus in human inherited RIPK3 deficiency.

Inborn errors of TLR3-dependent type I IFN immunity in cortical neurons underlie forebrain herpes simplex virus-1 (HSV-1) encephalitis (HSE) due to uncontrolled viral growth and subsequent cell death. We report an otherwise healthy patient with HSE who was compound heterozygous for nonsense (R422*) and frameshift (P493fs9*) RIPK3 variants. Receptor-interacting protein kinase 3 (RIPK3) is a ubiquitous cytoplasmic kinase regulating cell death outcomes, including apoptosis and necroptosis. In vitro, the R422* and P493fs9* RIPK3 proteins impaired cellular apoptosis and necroptosis upon TLR3, TLR4, or TNFR1 stimulation and ZBP1/DAI-mediated necroptotic cell death after HSV-1 infection. The patient's fibroblasts displayed no detectable RIPK3 expression. After TNFR1 or TLR3 stimulation, the patient's cells did not undergo apoptosis or necroptosis. After HSV-1 infection, the cells supported excessive viral growth despite normal induction of antiviral IFN-ß and IFN-stimulated genes (ISGs). This phenotype was, nevertheless, rescued by application of exogenous type I IFN. The patient's human pluripotent stem cell (hPSC)-derived cortical neurons displayed impaired cell death and enhanced viral growth after HSV-1 infection, as did isogenic RIPK3-knockout hPSC-derived cortical neurons. Inherited RIPK3 deficiency therefore confers a predisposition to HSE by impairing the cell death-dependent control of HSV-1 in cortical neurons but not their production of or response to type I IFNs.

Classification Performance of the Ages and Stages Questionnaire: Influence of Maternal Education Level.

(1) Background: The Ages and Stages Questionnaire-Third Edition (ASQ-3) is a parental screening questionnaire increasingly being used to evaluate the development of preterm children. We aimed to assess the classification performance of the ASQ-3 in preterm infant follow-up. (2) Methods: In this cross-sectional study, we included 185 children from the SEVE longitudinal cohort born <33 weeks of gestational age between November 2011 and January 2018, who had both an ASQ-3 score at 24 months of corrected age (CA) and a revised Brunet-Lézine (RBL) scale score at 30 months of CA. The ASQ-3 overall score and sub-scores were compared to the RBL developmental quotient (DQ) scores domain by domain. The diagnostic performance of the ASQ-3 was evaluated with the RBL as the reference method by calculating sensitivity, specificity, and positive and negative likelihood ratios. A multivariate analysis assessed the association between low maternal education level and incorrect evaluation with the ASQ-3. (3) Results: The ASQ-3 overall score had a specificity of 91%, a sensitivity of 34%, a positive likelihood ratio of 3.82, and a negative likelihood ratio of 0.72. Low maternal education level was a major risk factor for incorrectly evaluating children with the ASQ-3 (odds ratio 4.16, 95% confidence interval 1.47-12.03; p < 0.01). (4) Conclusions: Regarding the low sensitivity and the impact of a low maternal education level on the classification performance of the ASQ-3, this parental questionnaire should not be used alone to follow the development of preterm children.

Post traumatic cerebral sinovenous thrombosis in children: A retrospective and multicenter study.

CONTEXT: Cerebral sinovenous thrombosis (CSVT) is a rare but life-threatening condition in the pediatric population and there is no pediatric guidelines regarding anticoagulation for post traumatic CSVT. OBJECTIVE: This study aims to describe a cohort of children with post traumatic CSVT and the use of anticoagulant therapy in this population. METHODS: A multicenter retrospective study. Patients admitted with post traumatic CSVT in the six participating Pediatric Intensive Care Unit were included. RESULTS: Overall, 29 patients (median age 8.2 years [IQR 4.8-14.6], n = 22 (76%) males) were included in the study (Table 1). CSVT was observed within the first 24 h after admission for a half of the patients (n = 14, 50%). Anticoagulation was initiated in 18 patients (62%). No patient received thrombolytic therapy or endovascular treatment. The presence of epidural hematoma was associated with the absence of anticoagulation (n = 0 versus n = 10, p = 0.003). One patient (3%) died of extracranial injury (not related with adverse event of anticoagulation) and in survivors, median Pediatric Overall Performance Category Outcome (POPC) score at discharge from PICU was 2 [IQR 2-4] (i.e., mild disability). Regarding the outcomes of patients, we found no association according to the anticoagulation status (p = 1). Overall, 23 patients (79%) had a follow-up cerebral imaging with a median delay of 42 days [IQR 6-63] after admission. CSVT was still seen in 9 patients (31%). We found no difference regarding the persistence of CSVT between patients according to the anticoagulation status (p = 0.36). The median duration of anticoagulant treatment was 58 days [IQR 44-91] and one patient (3%) experienced adverse event related to anticoagulation. CONCLUSION: There were minimal adverse events in patients with post traumatic CSVT treated with therapeutic anticoagulation. However, the effect of anticoagulation on outcomes needs to be confirmed in further studies.

Perinatal inflammation exposure and developmental outcomes 7 years after neonatal arterial ischaemic stroke.

AIM: To test the association between perinatal inflammation exposure and Full-Scale IQ (FSIQ) score 7 years after neonatal arterial ischaemic stroke (NAIS). METHOD: We conducted a cross-sectional ancillary study nested in a multicentric longitudinal French cohort of infants born at term with NAIS between November 2003 and October 2006. Seventy-three children were included (45 males, 28 females). The a priori defined primary outcome measure was the FSIQ score assessed with the Wechsler Intelligence Scale for Children, Fourth Edition at 7 years of age. RESULTS: Seventeen (23%) of the included children were exposed to perinatal inflammation. Exposure to perinatal inflammation was independently associated with an increase of FSIQ score (coefficient 13.4, 95% confidence interval 1.3-25.4; p = 0.03). Children exposed to perinatal inflammation had a higher median cerebral volume, a lower median lesion volume, and less extensive lesion distributions compared to non-exposed children. INTERPRETATION: We propose the existence of two NAIS categories: arteritis-associated NAIS in children exposed to perinatal inflammation and embolism-associated NAIS in children non-exposed to perinatal inflammation. Identifying these two NAIS categories would open the possibility for specific curative strategies: anti-inflammatory strategy in arteritis-associated NAIS and recanalization strategy in embolism-associated NAIS.

Necroptosis Blockade Potentiates the Neuroprotective Effect of Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal encephalopathy (NE) caused by hypoxia-ischemia (HI) affects around 1 per 1000 term newborns and is the leading cause of acquired brain injury and neurodisability. Despite the use of hypothermia (HT) as a standard of care, the incidence of NE and its devastating outcomes remains a major issue. Ongoing research surrounding add-on neuroprotective strategies against NE is important as HT effects are limited, leaving 50% of treated patients with neurological sequelae. Little is known about the interaction between necroptotic blockade and HT in neonatal HI. Using a preclinical Lewis rat model of term human NE induced by HI, we showed a neuroprotective effect of Necrostatin-1 (Nec-1: a compound blocking necroptosis) in combination with HT. The beneficial effect of Nec-1 added to HT against NE injuries was observed at the mechanistic level on both pMLKL and TNF-α, and at the anatomical level on brain volume loss visualized by magnetic resonance imaging (MRI). HT alone showed no effect on activated necroptotic effectors and did not preserve the brain MRI volume. This study opens new avenues of research to understand better the specific cell death mechanisms of brain injuries as well as the potential use of new therapeutics targeting the necroptosis pathway.

Structural brain connectivity in children after neonatal stroke: A whole-brain fixel-based analysis.

INTRODUCTION: Neonatal arterial ischemic stroke (NAIS) has been shown to affect white matter (WM) microstructure beyond the lesion. Here, we employed fixel-based analysis, a technique which allows to model and interpret WM alterations in complex arrangements such as crossing fibers, to further characterize the long-term effects of NAIS on the entire WM outside the primary infarct area. MATERIALS AND METHODS: 32 children (mean age 7.3 years (SD 0.4), 19 male) with middle cerebral artery NAIS (18 left hemisphere, 14 right hemisphere) and 31 healthy controls (mean age 7.7 years (SD 0.6), 16 male) underwent diffusion MRI scans and clinical examination for manual dexterity. Microstructural and macrostructural properties of the WM were investigated in a fixel-based whole-brain analysis, which allows to detect fiber-specific effects. Additionally, tract-averaged fixel metrics in interhemispheric tracts, and their correlation with manual dexterity, were examined. RESULTS: Significantly reduced microstructural properties were identified, located within the parietal and temporal WM of the affected hemisphere, as well as within their interhemispheric connecting tracts. Tract-averaged fixel metrics showed moderate, significant correlation with manual dexterity of the affected hand. No increased fixel metrics or contralesional alterations were observed. DISCUSSION: Our results show that NAIS leads to long-term alterations in WM microstructure distant from the lesion site, both within the parietal and temporal lobes as well as in their interhemispheric connections. The functional significance of these findings is demonstrated by the correlations with manual dexterity. The localization of alterations in structures highly connected to the lesioned areas shift our perception of NAIS from a focal towards a developmental network injury.

[Arterial ischemic stroke in children]. / Accident vasculaire ischémique cérébral chez l'enfant.

Arterial ischemic stroke in children Stroke in children is an event of sudden occurrence with severe impact on the child's life. Most children will have consequences, lasting all lifelong. Early recognition of first symptoms, most often unilateral sudden motor deficit, is crucial to launch a pediatric stroke alert. MRI is the first and only imaging modality in this setting. Written protocols of early management improve early management for all patients. Rapid management permits the opportunity to consider recanalization treatments (intravenous thrombolysis, endovascular thrombectomy) in selected patients. Follow-up must be prolonged, adjusted to the age of stroke occurrence and to the personal developmental trajectory. Not only motor and cognitive deficits are considered, but also social participation and the preparation of the child's adult life.

Accident vasculaire ischémique cérébral chez l'enfant L'accident vasculaire ischémique cérébral chez l'enfant est un événement soudain aux conséquences graves, puisque la majorité d'entre eux en gardent des séquelles. La reconnaissance précoce des signes aigus, le plus souvent un déficit moteur unilatéral, doit mener à une prise en charge en urgence adaptée, au sein d'une filière identifiée. L'imagerie par résonance magnétique est à réaliser en première intention. La prise en charge urgente permet d'envisager des traitements de recanalisation (trombolyse, thrombectomie) chez certains patients et d'améliorer l'ensemble de la prise en charge pour tous. Le suivi est prolongé, ajusté à l'âge de survenue, au parcours développemental, et s'attache aux plans moteur, cognitif ainsi qu'à la participation sociale et la préparation de sa future vie d'adulte.

A computational approach for detecting physiological homogeneity in the midst of genetic heterogeneity.

The human genetic dissection of clinical phenotypes is complicated by genetic heterogeneity. Gene burden approaches that detect genetic signals in case-control studies are underpowered in genetically heterogeneous cohorts. We therefore developed a genome-wide computational method, network-based heterogeneity clustering (NHC), to detect physiological homogeneity in the midst of genetic heterogeneity. Simulation studies showed our method to be capable of systematically converging genes in biological proximity on the background biological interaction network, and capturing gene clusters harboring presumably deleterious variants, in an efficient and unbiased manner. We applied NHC to whole-exome sequencing data from a cohort of 122 individuals with herpes simplex encephalitis (HSE), including 13 individuals with previously published monogenic inborn errors of TLR3-dependent IFN-α/ß immunity. The top gene cluster identified by our approach successfully detected and prioritized all causal variants of five TLR3 pathway genes in the 13 previously reported individuals. This approach also suggested candidate variants of three reported genes and four candidate genes from the same pathway in another ten previously unstudied individuals. TLR3 responsiveness was impaired in dermal fibroblasts from four of the five individuals tested, suggesting that the variants detected were causal for HSE. NHC is, therefore, an effective and unbiased approach for unraveling genetic heterogeneity by detecting physiological homogeneity.

Recognition, identification, and diagnosis announcement of neonatal arterial ischemic stroke: A combined exploratory quantitative and qualitative study on parents' lived experiences.

OBJECTIVES: To examine the epidemiology of neonatal arterial ischemic stroke (NAIS) and the chronology of care from early reported manifestations to formal diagnosis obtained by imaging. To explore how parents experienced the sequence of events, their own perception of potential diagnostic delay, diagnosis announcement, and prognosis discussion, and their current view of their child's quality of life. METHODS: We retrospectively analyzed data of all NAIS cases that have been treated in our institution. Quantitative data came from both newborns' and mothers' medical records. Qualitative data were collected from parents in semi-structured interviews based on a standardized questionnaire composed of open-ended questions. RESULTS: A total of 14 neonates were treated for NAIS in our institution between January 2008 and December 2017. The incidence of NAIS during this period was one out of 4258 births. The majority of neonates presented within 48 hours with a mean of 27h after birth, most often in the form of repetitive focal clonus (13/14). The mean time before diagnosis consideration and confirmation was 5 and 33h, respectively. Late consideration of early reported symptoms was identified as the main source of delay. Despite good reported health outcome, NAIS was associated with significant acute and long-standing parental emotional stress. CONCLUSION: Maternity hospital caregivers' awareness of NAIS is crucial to reach early diagnosis. Improving this aspect would not only allow better early management, but also make it possible to set up acute neuroprotective strategies. Clinicians should be attentive to the modalities of diagnosis and prognosis announcements, which are associated with considerable stress and misconceptions.

A connectome-based approach to assess motor outcome after neonatal arterial ischemic stroke.

OBJECTIVE: Studies of motor outcome after Neonatal Arterial Ischemic Stroke (NAIS) often rely on lesion mapping using MRI. However, clinical measurements indicate that motor deficit can be different than what would solely be anticipated by the lesion extent and location. Because this may be explained by the cortical disconnections between motor areas due to necrosis following the stroke, the investigation of the motor network can help in the understanding of visual inspection and outcome discrepancy. In this study, we propose to examine the structural connectivity between motor areas in NAIS patients compared to healthy controls in order to define the cortical and subcortical connections that can reflect the motor outcome. METHODS: Thirty healthy controls and 32 NAIS patients with and without Cerebral Palsy (CP) underwent MRI acquisition and manual assessment. The connectome of all participants was obtained from T1-weighted and diffusion-weighted imaging. RESULTS: Significant disconnections in the lesioned and contra-lesioned hemispheres of patients were found. Furthermore, significant correlations were detected between the structural connectivity metric of specific motor areas and manuality assessed by the Box and Block Test (BBT) scores in patients. INTERPRETATION: Using the connectivity measures of these links, the BBT score can be estimated using a multiple linear regression model. In addition, the presence or not of CP can also be predicted using the KNN classification algorithm. According to our results, the structural connectome can be an asset in the estimation of gross manual dexterity and can help uncover structural changes between brain regions related to NAIS.

Additional validation study and French cross-cultural adaptation of the Pediatric Stroke Outcome Measure-Summary of Impressions (PSOM-SOI).

BACKGROUND: The Pediatric Stroke Outcome Measure-Summary of Impressions (PSOM-SOI) measures neurological function across right and left sensorimotor domains (Item A), language production (Item B), language comprehension (Item C), and cognition/behaviour (Item D). OBJECTIVE: This study was a cross-cultural adaptation into French of the PSOM-SOI and an assessment of its reliability and limitations of use. MATERIAL AND METHODS: The translation and adaptation of the PSOM-SOI was followed by the assessment of its reliability in a cohort of 69 children with diagnosed acute neonatal arterial ischemic stroke. Three independent raters retrospectively scored the PSOM-SOI based on data from in-person neurological examination and results of standardized tests performed at age 7 in the cohort database. Comparison 1 (C1) involved a less experienced rater and an experienced rater and comparison 2 (C2) involved 2 experienced raters. Inter-rater reliability (IRR) was measured with Kappa coefficients. RESULTS: The cross-cultural adaptation was easily performed, and no rater had difficulties using the French PSOM-SOI. The IRR was better in C1 than C2. For Item A, the agreement in C1 (κ=0.47) and C2 (κ=0.44) was moderate. The C1 agreement was substantial for Items B (κ=0.71) and C (κ=0.70); the C2 agreement was fair for Item B (κ=0.23) and slight for Item C (κ=0.16). For Item D, the agreement was moderate in C1 (κ=0.52) and fair in C2 (κ=0.35). In all but one comparison, agreement or minor disagreement (≤0.5 points) was obtained for more than 90% of the item scores. Regarding the total score, agreement for normal function (≤0.5) versus abnormal function (>0.5) was achieved for 90% in C1 and 67% in C2. CONCLUSION: The IRR of the French PSOM-SOI gave variable results depending on the item and rater's experience, but the extent of disagreements was minor for individual items and total score. Additional prospective validation studies using the French PSOM-Short Neurological Exam to score the PSOM-SOI are needed. A dichotomised total score (cut-off≤0.5) could be used to define normal function versus poor outcome.

Hyperacute Recanalization Strategies and Childhood Stroke in the Evidence Age.

No controlled pharmacological studies are available in the field of pediatric stroke, except for sickle cell disease. Therefore, while pharmacological and mechanical recanalization treatments have repeatedly shown clinical benefit in adults with arterial ischemic stroke, pediatric strokologists still cannot base their therapeutic management (including hyperacute strategies) on high-level evidence. Once again, pediatricians face the same dichotomic choice: adapting adult procedures now versus waiting-for a long time-for the corresponding pediatric trials. One way out is building a compromise based on observational studies with large, longitudinal, comprehensive, real-life, and multisource dataset. Two recent high-quality observational studies have delivered promising conclusions on recanalization treatments in pediatric arterial ischemic stroke. TIPSTER (Thrombolysis in Pediatric Stroke Extended Results) showed that the risk of severe intracranial hemorrhage after intravenous thrombolysis is low; the Save Childs Study reported encouraging data about pediatric thrombectomy. Beyond the conclusion of a satisfactory global safety profile, a thorough analysis of the methods, populations, results, and therapeutic complications of these studies helps us to refine indications/contraindications and highlights the safeguards we need to rely on when discussing thrombolysis and thrombectomy in children. In conclusion, pediatric strokologists should not refrain from using clot lysis/retrieval tools in selected children with arterial ischemic stroke. But the implementation of hyperacute care is only feasible if the right candidate is identified through the sharing of common adult/pediatric protocols and ward collaboration, formalized well before the child's arrival. These anticipated protocols should never undervalue contraindications from adult guidelines and must involve the necessary pediatric expertise when facing specific causes of stroke, such as focal cerebral arteriopathy of childhood.

Perinatal inflammation is associated with social and motor impairments in preterm children without severe neonatal brain injury.

OBJECTIVE: To test the association between exposure to perinatal inflammation - i.e. clinical chorioamnionitis or early-onset neonatal infection - in preterm children without severe neonatal brain injury and neurodevelopmental outcome at 30 months of corrected age (CA). DESIGN: Cross-sectional study from a French regional cohort of clinical follow-up (SEVE Network). PATIENTS: One hundred sixty-four surviving neonates without severe brain injury - namely, grade III and IV cerebral hemorrhage and cystic periventricular leukomalacia - and without late-onset neonatal inflammation exposure - namely, late-onset neonatal infection and necrotizing enterocolitis -, born at less than 33 weeks of gestational age from November 2011 to June 2015 and enrolled in the SEVE Network. MAIN OUTCOME MEASURE: Global developmental quotient (DQ) score of the revised Brunet-Lézine scale and its four indices measured by the same neuropsychologist at 30 months of CA. RESULTS: After multivariate analysis, exposure to perinatal inflammation was not found significantly associated with a modification of the global DQ score (coefficient -1.7, 95% CI -4.8 to 1.3; p = 0.26). Exposure to perinatal inflammation was associated with a decrease of the gross motor function DQ score (coefficient -6.0, 95% CI -9.9 to -2.1; p < 0.01) and a decrease of the sociability DQ score (coefficient -5.1, 95% CI -9.2 to -0.9; p = 0.02). Language and visuospatial coordination DQ scores were not affected by exposure to perinatal inflammation. CONCLUSION: Exposure to perinatal inflammation in preterm children without severe neonatal brain injury is independently associated with decreased motor and social abilities at 30 months of CA.