Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm.

BACKGROUND: Children born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term. METHODS: Our study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups. RESULTS: Brain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ. CONCLUSIONS: These findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT. IMPACT: The article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy. Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes. While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes. We found no differences in volumetric asymmetry between children born EPT and at term.

The Stockholm-Gotland perinatal cohort-A population-based cohort including longitudinal data throughout pregnancy and the postpartum period.

BACKGROUND: Register-based reproductive and perinatal databases rarely contain detailed information from medical records or repeated measurements throughout pregnancy and delivery. This lack of enriched pregnancy and birth data led to the initiation of the Swedish Stockholm-Gotland Perinatal Cohort (SGPC). OBJECTIVES: To describe the strengths of the SGPC, as well as the unique research questions that can be addressed using this cohort. POPULATION: The SGPC is a prospectively collected, population-based cohort that includes all births (from 22 completed gestational weeks onwards) between 1 January 2008 and 15 June 2020 in the Stockholm and Gotland regions of Sweden (335,153 singleton and 11,025 multiple pregnancies). DESIGN: Descriptive study. METHODS: The SGPC is based on the electronic medical records of women and their infants. The medical record system is used for all antenatal clinic visits and admissions, delivery and neonatal admissions, as well as postpartum clinical visits. SGPC has been further enriched with data linkages to 10 Swedish National Health Care and Quality Registers. PRELIMINARY RESULTS: In contrast to other reproductive and perinatal databases available in Sweden, including the Medical Birth Register and the Pregnancy Register, SGPC contains highly detailed medical record data, including time-varying serial measurements for physiological parameters throughout pregnancy, delivery, and postpartum, for both mother and infant. These strengths have enabled studies that were previously inconceivable; the effects of serial measurements of pregnancy weight gain, changes in haemoglobin counts and blood pressure during pregnancy, fetal weight estimations by ultrasound, duration of stages and phases of labour, cervical dilatation and oxytocin use during delivery, and constructing reference curves for umbilical cord pH. CONCLUSIONS: The SGPC-with its rich content, repeated measurements and linkages to numerous health care and quality registers-is a unique cohort that enables high-quality perinatal studies that would otherwise not be possible.

Term-born infants with a perinatal stroke frequently had seizures and were prescribed anti-seizure medication at discharge.

AIM: We investigated the prevalence of seizures in term-born infants with a perinatal stroke in Swedish neonatal wards, assessed the anti-seizure medication prescribed and determined the accuracy of diagnostic codes. METHODS: This cross-sectional study used data from the Swedish Neonatal Quality Register. The cases were infants born at ≥37 weeks in 2009-2018 and admitted to a neonatal ward in Stockholm County with a stroke diagnosis, confirmed by their medical chart. The controls were all Swedish infants born during those years. RESULTS: There were 76 infants with a confirmed perinatal stroke: 51 ischaemic and 25 haemorrhagic. Seizures were documented in 66/76 (87%) of infants with a stroke and 0.2% of the controls. Anti-seizure medication was administered to 64/66 (97%) infants with a stroke and seizures. In 60 cases, the drugs administered were specified, with phenobarbital used in 59/60 cases (98%). More than one drug was administered to 25/60 (42%) infants and 31/60 (52%) were discharged with anti-seizure medication. The positive predictive value for the stroke diagnostic codes was 80.5% (95% CI 76.5-84.5). CONCLUSION: Seizures were common in infants with a perinatal stroke. More than one anti-seizure drug was often required and many infants were on anti-seizure medication at discharge, against Swedish recommendations.

Low Apgar score and need for resuscitation increased the probability of receiving therapeutic hypothermia more strongly than acidosis at birth.

AIM: The aim of this study was to investigate how individual markers for birth asphyxia, so-called A criteria, were associated with the probability of receiving therapeutic hypothermia. METHODS: This population-based cohort study included 1336 live-born singleton term infants with any A criterion in the Stockholm-Gotland Region, Sweden during 2008 to 2014. The Swedish Neonatal Quality Register and National Patient Register were used for data collection. Results were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: There were 89 infants, 44 boys and 45 girls with mean gestational age 40.5 weeks, who received therapeutic hypothermia. Low Apgar score, aOR 12.44 (95% CI 5.99-25.86), and resuscitation, aOR 9.18 (95% CI 3.77-22.34), were strongly associated with therapeutic hypothermia. A pH <7.0 was less associated with the outcome, aOR 2.02 (95% CI 1.02-4.0). No infant who received therapeutic hypothermia fulfilled the criteria of base deficit ≥16 mmol/L only. CONCLUSION: A low Apgar score of and/or a need for resuscitation is more relevant for identifying infants eligible for therapeutic hypothermia, compared to other A criteria. This knowledge could be used clinically to identify cases for review and avoid unnecessary monitoring of infants.

Perinatal risk factors for developmental coordination disorder in children born extremely preterm.

AIM: Children born extremely preterm frequently have developmental coordination disorder (DCD). We aimed to evaluate perinatal risk factors for DCD. METHODS: Swedish national cohort study including 226 children born before 27 gestational weeks without major neurodevelopmental disabilities at 6.5 years. Outcome was DCD, defined as ≤5th percentile on the Movement Assessment Battery for Children-Second Edition. Perinatal risk factors were evaluated using multivariable logistic regression. RESULTS: DCD was present in 84/226 (37.2%) children. Of the risk factors known at 40 weeks gestation, independent and significant risk factors for DCD were: mother's age at delivery (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80); pre-eclampsia (2.79, 1.14-6.80); mother born in a non-Nordic country (2.23, 1.00-4.99); gestational age per week increase (0.70, 0.50-0.99) and retinopathy of prematurity (2.48, 1.26-4.87). Of factors known at discharge, postnatal steroids exposure (2.24, 1.13-4.46) and mechanical ventilation (1.76, 1.06-2.09) were independent risk factors when added to the model in separate analyses. CONCLUSION: The risk of DCD in children born extremely preterm was multifactorial and associated with gestational age largely mediated by ROP, maternal factors, pre-eclampsia, administration of postnatal steroids and mechanical ventilation. These risk factors are common among children born extremely preterm, contributing to their high risk of DCD.

Stabilisation and resuscitation with intact cord circulation is feasible using a wide variety of approaches; a scoping review.

AIM: This scoping review identified studies on approaches to intact cord resuscitation and/or stabilisation (ICR/S) for neonates delivered by Caesarean section (C-section). METHODS: A systematic literature search was carried out using the PubMed, Web of Science, Scopus, Cochrane and CINAHL databases to identify papers published in English from inception to 14 November 2022. RESULTS: We assessed 2613 studies and included 18 from 10 countries, covering 1-125 C-sections: the United States, the United Kingdom, Australia, India, Italy, China, France, The Netherlands, New Zealand and Taiwan. The papers were published from 2014 to 2023, and the majority were randomised controlled trials and observational studies. Different platforms, equipment and staff positions in relation to the operating table were described. Options for resuscitation and stabilisation included different bedding and trolley approaches, and maintaining aseptic conditions was mainly addressed by the neonatal team scrubbing in. Hypothermia was prevented by using warm surfaces, polythene bags and radiant heaters. Equipment was kept easily accessible by mounting it on a trolley or a separate mobile pole. CONCLUSION: We could not reach definitive conclusions on the optimal method for performing ICR/S during a C-section, due to study variations. However, a number of equipment and management options appeared to be feasible approaches.

Adverse motor outcome after paediatric ischaemic stroke: A nationwide cohort study.

BACKGROUND: Various frequencies of adverse motor outcomes (cerebral palsy and hemiplegia) after paediatric ischaemic stroke have been reported. Few reports on the risks of adverse motor outcomes in nationwide cohorts and contributing risk factors are available. OBJECTIVES: To assess risk of adverse motor outcome and potential risk factors thereof after paediatric ischaemic stroke in a nationwide cohort. METHODS: This nationwide matched cohort study identified 877 children <18 years of age diagnosed with ischaemic stroke through the Swedish national health registers from 1997 to 2016. These children, exposed to ischaemic stroke, alive 1 week after stroke, were matched for age, sex and county of residence with 10 unexposed children. Using Cox regression, we estimated the risk of adverse motor outcomes in children with stroke compared to that in unexposed children. Logistic regression was applied to compare the characteristics of children with and without adverse motor outcomes after stroke. RESULTS: Out of the 877 children with ischaemic stroke, 280 (31.9%) suffered adverse motor outcomes compared with 21 (0.2%) of the 8770 unexposed: adjusted hazard ratio (aHR) 167.78 (95% confidence interval (CI) 107.58, 261.66). There were no differences between risk estimates of adverse motor outcome according to age at stroke: perinatal stroke (aHR 124.11, 95% CI 30.45, 505.84) and childhood stroke (aHR 182.37, 95% CI 113.65, 292.64). An association between adverse motor outcome and childhood stroke aOR 1.56 (95% CI 1.05, 2.31) was found when analysing only children with ischaemic stroke. No associations were found between adverse motor outcome and sex, gestational age or parental age at birth. CONCLUSIONS: The risk of adverse motor outcome is substantial after paediatric ischaemic stroke, especially childhood stroke, confirming results of previous smaller studies. This study found no associations between sex, gestational age or parental age and adverse motor outcome after paediatric ischaemic stroke.

Neonatal Morbidities in Infants Born Late Preterm at 35-36 Weeks of Gestation: A Swedish Nationwide Population-based Study.

OBJECTIVE: To assess risk for neonatal morbidities among infants born late preterm at 35-36 gestational weeks, early term (37-38 weeks), and late-term (41 weeks) infants, compared with full-term (39-40 weeks) infants. STUDY DESIGN: This nationwide population-based cohort study included 1 650 450 non-malformed liveborn singleton infants born at 35-41 weeks between 1998 and 2016 in Sweden. The relative risks for low Apgar score (0-3) at 5 minutes; respiratory, metabolic, infectious, and neurologic morbidities; and severe neonatal morbidity (composite outcome) were adjusted for maternal, pregnancy, delivery, and infant characteristics. RESULTS: Compared with infants born at 39-40 weeks, the adjusted relative risks and proportions of infants born at 35-36 weeks were higher for metabolic morbidity 7.79 (95%, 7.61 to 7.97; 33.75% vs 3.11%), respiratory morbidity 5.54 (95% CI, 5.24 to 5.85; 5.49% vs 0.75%), severe neonatal morbidity 2.42 (95% CI, 2.27 to 2.59; 3.40% versus 1.03%), infectious morbidity 1.98 (95% CI, 1.83 to 2.14; 2.53% vs 0.95%), neurologic morbidity 1.74 (95% CI, 1.48 to 2.03; 0.54% vs 0.23%), and low Apgar score 2.07 (95% CI, 1.72 to 2.51; 0.42% vs 0.12%). The risks for respiratory, severe neonatal morbidity, infectious, neurologic morbidities, and low Apgar score were highest at 35 weeks, gradually decreased until 39 weeks, and increased during 39-41 weeks. CONCLUSIONS: Infants born late preterm at 35-36 weeks of gestation are at increased risk of neonatal morbidities, although the absolute risks for severe neonatal morbidities are low. Our findings reinforce the need of preventing late preterm delivery to decrease the burden of neonatal morbidity and help professionals and families with a better risk assessment.

Minor neurological dysfunction and associations with motor function, general cognitive abilities, and behaviour in children born extremely preterm.

AIM: To study the prevalence of minor neurological dysfunction (MND) at 6 years of age in a cohort of children born extremely preterm without cerebral palsy (CP) and to investigate associations with motor function, cognitive abilities, and behaviour. METHOD: This study assessed 80 children born at less than 27 weeks of gestation and 90 children born at term age between 2004 and 2007 at a mean age of 6 years 6 months. The assessments included a simplified version of the Touwen Infant Neurological Examination, the Movement Assessment Battery for Children, Second Edition (MABC-2), Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV), the Strengths and Difficulties Questionnaire (SDQ), and the parent version of the Five to Fifteen questionnaire. RESULTS: Fifty-one of the children born preterm had normal neurology, 23 had simple MND, and six had complex MND compared with 88 who had normal neurology and two simple MND in the term-born group (p<0.001). There were significant differences between the children with normal neurology and MND in the preterm group in MABC-2-assessed motor function (p<0.001), general cognitive abilities with WISC-IV (p=0.005), and SDQ overall behavioural problems and peer problems reported by the parents (p=0.021 and p=0.003 respectively). SDQ teacher-reported overall behavioural and hyperactivity problems were significantly different between children with normal and simple MND (p=0.036 and p=0.019). INTERPRETATION: Children born extremely preterm, in the absence of CP, are at risk of MND and this is associated with motor function, cognitive ability, and behaviour. WHAT THIS PAPER ADDS: Extremely preterm birth carries a risk of minor neurological dysfunction (MND). MND in children born extremely preterm is associated with impaired motor function and cognitive abilities, and behavioural problems. Male sex is associated with MND in children born extremely preterm.

National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years.

AIM: This study aimed to explain the relationship between visual-motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes. METHODS: This was part of the population-based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term-born controls. At six-and-a-half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <-1 standard deviation (SD). RESULTS: The mean (SD) VMI score was 87 (±12) in preterm children compared to 98 (±11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22-23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual-motor performance, whereas low manual dexterity and cognitive function showed a stronger association. CONCLUSION: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.

Neurological development in children born moderately or late preterm: national cohort study.

OBJECTIVE: To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term). DESIGN: Nationwide cohort study. SETTING: Sweden. PARTICIPANTS: 1 281 690 liveborn singleton children without congenital malformations born at 32+0 to 41+6 weeks between 1998 and 2012. MAIN OUTCOME MEASURES: The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment. RESULTS: During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term. CONCLUSIONS: The findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.

Changes in prevalence of non-optimal neurological condition between 6.5 and 12 years in children born extremely preterm.

AIM: To assess prevalence of non-optimal neurological condition and associations with motor function in children born extremely preterm (EPT) up to early adolescence, and to examine potential changes in neurological condition between 6.5 and 12 years. METHOD: A prospective cohort of one hundred six children (EPT n = 62, term n = 44) was assessed at 6.5 and 12 years. Four domains derived from the Touwen Neurological Examination (coordination and balance, posture and muscle tone, reflexes, and nerve function of the eyes and face) were used to assess the presence of a non-optimal neurological condition (defined as the presence of any abnormal domain). The Movement Assessment Battery for Children 2nd ed. was used to evaluate motor function. RESULTS: Twenty-seven children born EPT (44%) were assessed as having a non-optimal neurological condition compared with 4 (9%) in the control group (p=<0.001) at 12 years. Between age 6.5 and 12 years the number of children born EPT with a non-optimal neurological condition decreased from 37 to 27 (p = 0.007). At 12 years these children also had significantly lower MABC-2 total test scores, compared to those with normal neurology: median (range) 57 (32-79) versus 75 (43-99), respectively (p=<0.001). The same was shown for subscale scores; manual dexterity (p=<0.001), aiming/catching (p = 0.004), and balance (p = 0.004). CONCLUSION: The prevalence of a non-optimal neurological condition reduced with increasing age. However, still, at 12 years, these neurological impairments remained significantly more common in the EPT group than in their term-born peers and was shown to be related to a reduced motor function.

Extreme prematurity and perinatal risk factors related to extremely preterm birth are associated with complex patterns of regional brain volume alterations at 10 years of age: a voxel-based morphometry study.

Objective: Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group. Methods: At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term. Results: We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05). Conclusions: Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.

First stage of labour duration and associated risk of adverse neonatal outcomes.

Prior evidence evaluating the benefits and harms of expectant labour duration during active first stage is inconclusive regarding potential consequences for the neonate. Population-based cohort study in Stockholm-Gotland region, Sweden, including 46,040 women (Robson 1), between October 1st, 2008 and June 15th, 2020. Modified Poisson regression was used for the association between active first stage of labour duration and adverse neonatal outcomes. 94.2% experienced a delivery with normal neonatal outcomes. Absolute risk for severe outcomes increased from 1.9 to 3.0%, moderate outcomes increased from 2.8 to 6.2% (> 10.1 h). Compared to the reference, (< 5.1 h; median), the adjusted relative risk (aRR) of severe neonatal outcome significantly increased beyond 10.1 h (> 90th percentile) (aRR 1.53, 95% CI 1.26, 1.87), for moderate neonatal outcome the aRR began to slowly increase beyond 5.1 h (≥ 50 percentile; aRR 1.40, 95% CI 1.24, 1.58). Mediation analysis indicate that most of the association was due to a longer active first stage of labour, 13% (severe neonatal outcomes) and 20% (moderate neonatal outcomes) of the risk was mediated (indirect effect) by longer second stage of labour duration. We report an association between increasing active first stage duration and increased risk of adverse neonatal outcomes. We did not observe a clear labour duration risk threshold.

Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: Ischemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. Our aim was to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke and in their first-degree relatives. METHODS: In this cohort study, individuals with ischemic stroke from 1969 to 2016, <18 years of age, alive 1 week after stroke, and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyze sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke. RESULTS: Of the 1,322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls (adjusted hazard ratio [aHR] 3.02, 95% CI 2.15-4.25). There was no significant difference in risk of autism according to age at stroke: perinatal (aHR 2.69, 95% CI 1.44-5.03) and childhood stroke (aHR 3.18, 95% CI 2.12-4.78). The increased risk remained after exclusion of children born preterm or small for gestational age (aHR 3.78, 95% CI 2.55-5.60) and when children with stroke diagnosed from 1997 to 2014 were analyzed (aHR 2.91, 95% CI = 1.95-4.35). Compared to controls, the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR 7.05, 95% CI 3.74-13.30), as well as adverse motor outcome (aHR 4.28, 95% CI 2.44-7.51). When individuals with adverse motor outcome and epilepsy were censored, the risk of autism was still increased (aHR 2.37, 95% CI 1.45-3.85). Sex, gestational age, and having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke. DISCUSSION: An increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome, implying that all children with ischemic stroke should be readily screened for autism if the disorder is suspected.

Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder.

Importance: Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. Objective: To assess the risk of ADHD in children after pediatric ischemic stroke. Design, Setting, and Participants: Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. Exposures: Pediatric ischemic stroke. Main Outcomes and Measures: Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. Results: Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI ,1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). Conclusions and Relevance: This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD, particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

Exploring the distribution of grey and white matter brain volumes in extremely preterm children, using magnetic resonance imaging at term age and at 10 years of age.

OBJECTIVES: To investigate differences in brain volumes between children born extremely preterm and term born controls at term age and at 10 years of age. STUDY DESIGN: Children born extremely preterm (EPT), up to 26 weeks and 6 days gestational age, in Stockholm between January 1 2004 to March 31 2007 were included in this population-based cohort study. A total of 45 EPT infants were included at term age and 51 EPT children were included at 10 years of age. There were 27 EPT children included at both time points. Two different control groups were recruited; 15 control infants were included at term age and 38 control children at 10 years of age. The primary outcomes were the grey and white matter volumes. Linear regression, adjusted for intracranial volume and sex, was used. RESULTS: At term age, the extremely preterm infants had significantly smaller grey matter volume compared to the control infants with an adjusted mean difference of 5.0 cm3 and a 95% confidence interval of -8.4 to -1.5 (p = 0.004). At 10 years of age the extremely preterm children had significantly smaller white matter volume compared to the control children with an adjusted mean difference of 6.0 cm3 and a 95% confidence interval of -10.9 to -1.0 (p = 0.010). CONCLUSION: Extremely preterm birth was associated with reduced grey matter volume at term age and reduced white matter volume at 10 years of age compared to term born controls.

Cerebral visual impairment captured with a structured history inventory in extremely preterm born children aged 6.5 years.

PURPOSE: To investigate whether a questionnaire can identify cerebral visual impairment (CVI) in a group of 6.5-year-old children born extremely preterm (EPT) as accurately as direct assessments. METHODS: This prospective population-based study included 120 children born before 27 weeks' gestational age (66 males; mean, 25.4 ± 1.0 weeks) and 97 full-term controls (56 males; mean, 39.9 ± 1.1 weeks) at the age of 6.5 years, as part of the Extremely Preterm Infants in Sweden Study (EXPRESS). A questionnaire for detection of CVI was evaluated and compared with visual, perceptual, and cognitive assessments. RESULTS: Parents of children born EPT reported more CVI features than the parents of control children, with median sum scores of 25 (95% CI, 18.1-31.9) and 11 (95% CI, 8.8-13.2), respectively (P < 0.001), and a median difference of 14 (95% CI, 6.6-21.4). Low rates of reported CVI features were significantly associated with better results from direct assessments within the EPT group and with less pronounced differences compared to controls. CONCLUSIONS: The questionnaire discriminated well between children born EPT and controls, and the scores were congruent with other evidence of visual, perceptual, and cognitive deficits. The easily used questionnaire compared favorably with direct assessment in identifying CVI in children born EPT and also provides valuable information to clinicians, and parents about the daily life problems associated with CVI.

Visual-motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study.

OBJECTIVES: This exploratory study aimed to investigate associations between neonatal brain volumes and visual-motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years of age. SETTING: Prospective population-based cohort study in Stockholm, Sweden, during 3 years. PARTICIPANTS: All children born before gestational age, 27 weeks, during 2004-2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age. MAIN OUTCOME MEASURES: Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual-Motor Integration-sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children-second edition, at 6½ years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex. RESULTS: Out of 107 children born at gestational age <27 weeks, 83 were assessed at 6½ years and 66/83 were without major brain lesions or cerebral palsy and included in the analyses. A representative subsample underwent morphometric analyses: automatic segmentation (n=34) and atlas-based segmentation (n=26). The precentral gyrus was associated with both VMI (r=0.54, P=0.007) and fine motor skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=-0.38, P=0.04). CONCLUSIONS: Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 6½ years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible.