Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age

Background Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (PPeer reviewe

Microstructural alterations in association tracts and language abilities in schoolchildren born very preterm and with poor fetal growth

Background Prematurity and perinatal risk factors may influence white matter microstructure. In turn, these maturational changes may influence language development in this high-risk population of children.Objective To evaluate differences in the microstructure of association tracts between preterm and term children and between preterm children with appropriate growth and those with fetal growth restriction and to study whether the diffusion tensor metrics of these tracts correlate with language abilities in schoolchildren with no severe neurological impairment.Materials and methods This study prospectively followed 56 very preterm children (mean gestational age: 28.7 weeks) and 21 age- and gender-matched term children who underwent diffusion tensor imaging at a mean age of 9 years. We used automated probabilistic tractography and measured fractional anisotropy in seven bilateral association tracts known to belong to the white matter language network. Both groups participated in language assessment using five standardised tests at the same age.Results Preterm children had lower fractional anisotropy in the right superior longitudinal fasciculus 1 compared to term children (P P (P Conclusion There were some microstructural differences in language-related tracts between preterm and term children and between preterm children with appropriate and those with restricted fetal growth. Children with better language abilities had a higher fractional anisotropy in distinct white matter tracts.</p

Antenatal and neonatal risk factors in very preterm children were associated with language difficulties at 9 years of age

Aim: This Finnish study compared language and reading abilities between schoolchildren born at a very low gestational age (VLGA) of <32 weeks and at term and analysed any associations between antenatal and neonatal risk factors and language skills in the VLGA group. Methods: We prospectively followed 76 children born at a VLGA and 50 children born at term when they reached a mean age of 9.0 (8.1–10.0) years. They attended mainstream schools and had no severe neurosensory disabilities. Receptive language ability, rapid naming and word reading were evaluated using standardised tests. Results: Children in the VLGA group had lower scores for receptive language abilities (median 55.0 vs. 57.0, p = 0.01) and word reading (mean 4.4 vs. 5.1, p = 0.03) than the children in the term group. In the VLGA group, foetal growth restriction was associated with lower scores for rapid naming, early intraventricular haemorrhage was associated with poor word reading and respiratory distress syndrome was associated with poor rapid naming (p < 0.05). Conclusion: Schoolchildren born at a VLGA had more difficulties with receptive language abilities and word reading than children born at term. Foetal growth restriction and early neonatal morbidities were associated with language difficulties.publishedVersionPeer reviewe

Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age

Background Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (PConclusion Prematurity has a long-term effect on frontostriatal white matter microstructure that might contribute to difficulties in executive functioning.</div

HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H-TM protein

HIDEA syndrome is caused by biallelic pathogenic variants in P4HTM. The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic P4HTM variants, including three novel variants. We describe two Finnish enriched pathogenic P4HTM variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported P4HTM pathogenic variants associated with HIDEA in silico. All known pathogenic variants in P4HTM result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H-TM protein. In all cases, normal P4H-TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease.publishedVersio

Perinatal factors as predictors of brain damage and neurodevelopmental outcome:study of children born very preterm

Abstract Children born preterm are prone to acute brain insults related to subsequent neurodevelopmental impairments. However, the role of specific biomarkers and perinatal clinical factors in the pathogenesis of brain injury and neurodevelopmental sequelae has remained poorly understood. The present study evaluated whether specific immunoproteins at birth predict the risk of intraventricular hemorrhage (IVH) and whether their receptors are localized at the bleeding site. We further investigated whether children who went on to develop cerebral palsy (CP) could be identified on the basis of blood immunoproteins collected during the perinatal period. The association between single nucleotide polymorphisms in the chemokine CCL18 gene and susceptibility to CP was also studied. Finally, we investigated the association of pre- and postnatal factors with cognitive outcomes in very preterm-born schoolchildren without impairments. The present study revealed that a low concentration of CCL18 in cord blood was an independent risk factor of IVH in very preterm infants. The CCL18 receptor, CCR3, was detectable in the periventricular area and in the neurons of the hippocampus in preterm infants already at 23 weeks of gestation. We also identified a cluster of cord blood cytokines that was associated with the risk of CP. In addition, inflammatory cytokine levels were associated with CP risk on days 1 and 7 after birth. The genetic study showed that both IVH and the CCL18 polymorphism independently and additively had an influence on CP susceptibility. Our study further demonstrated that schoolchildren born very preterm without CP or cognitive impairment had poorer performance in visuospatial–sensorimotor skills and in attention–executive functions than term-born children. Fetal growth restriction was an independent risk factor of compromised neurocognitive outcome in very preterm children predicting difficulties in language, memory and learning. In conclusion, specific cytokines and cytokine clusters serve as biomarkers of different pathways involved in damage to the brain structures and in the pathogenesis of CP. In addition, genetic factors can affect these processes. Further, fetal growth restriction and prematurity play important roles in neurocognitive development later in life.Tiivistelmä Hyvin ennenaikaisina syntyneet lapset ovat alttiita akuuteille aivovaurioille sekä myöhemmin ilmeneville kehityshäiriöille. Eri välittäjäaineiden sekä raskaudenaikaisten ja syntymänjälkeisten kliinisten tekijöiden vaikutusta aivojen vaurioherkkyyteen sekä neurologiseen ja neurokognitiiviseen kehitykseen ei kuitenkaan ole tutkittu riittävästi. Tässä tutkimuksessa tarkasteltiin, ennustaako jokin napaverestä tutkituista sytokiineista aivoverenvuotoa hyvin ennenaikaisesti syntyneillä vastasyntyneillä. Lisäksi selvitettiin, onko sytokiinin spesifinen reseptori osoitettavissa vuotoherkällä alueella aivoissa. Tutkimme myös, ennustaako jokin napaveren immunoproteiini-profiilin komponentti CP-vamman syntyä joko itsenäisesti tai yhdessä muiden perinataalisten riskitekijöiden kanssa sekä lisääkö tietyn sytokiinin (CCL18) geneettinen vaihtelu CP-vamman riskiä hyvin ennenaikaisesti syntyneillä lapsilla. Lisäksi selvitimme, vaikuttavatko raskaudenaikaiset tekijät ja vastasyntyneisyyskauden sairaudet neurokognitiiviseen kehitykseen kouluiässä. Tämän tutkimuksen mukaan napaveren matala CCL18-kemokiinipitoisuus oli itsenäinen aivoverenvuodon riskitekijä. CCR3-reseptori, johon CCL18 sitoutuu, oli osoitettavissa sekä vuotoherkällä alueella että hermosoluissa 23. raskausviikon iästä lähtien. Havaitsimme myös, että tietyt napaveren sytokiiniryppäät ja yksittäisten tulehdusvastevälittäjäaineiden pitoisuudet 1. ja 7. elinpäivänä olivat yhteydessä CP-riskiin. Lisäksi havaitsimme yhteyden CCL18-kemokiinin geneettisen vaihtelun ja aivoverenvuodon sekä CP-vamman kehittymisen välillä. Tutkimuksemme mukaan hyvin ennenaikaisesti syntyneet koululaiset, joilla ei ollut CP- tai kehitysvammaa, suoriutuivat täysiaikaisina syntyneitä verrokkeja heikommin visuaalista hahmotusta ja sensomotoriikkaa sekä tarkkaavuutta ja toiminnanohjausta mittaavissa testeissä. Lisäksi havaitsimme sikiöaikaisen kasvuhäiriön ennustavan itsenäisesti heikkoa suoritusta kieltä, muistia ja oppimista testaavissa tehtävissä ennenaikaisesti syntyneillä lapsilla. Tietyt sytokiinit ja sytokiiniryppäät ovat yhteydessä aivovauriomekanismeihin. Nämä mekanismit saattavat yhdessä perinnöllisen alttiuden kanssa vaikuttaa myös CP-vamman syntyyn. Sikiöaikainen kasvuhäiriö ja ennenaikaisuus vaikuttavat lapsen myöhempään neurokognitiiviseen kehitykseen

Microstructural alterations in association tracts and language abilities in schoolchildren born very preterm and with poor fetal growth

Abstract Background: Prematurity and perinatal risk factors may influence white matter microstructure. In turn, these maturational changes may influence language development in this high-risk population of children. Objective: To evaluate differences in the microstructure of association tracts between preterm and term children and between preterm children with appropriate growth and those with fetal growth restriction and to study whether the diffusion tensor metrics of these tracts correlate with language abilities in schoolchildren with no severe neurological impairment. Materials and methods: This study prospectively followed 56 very preterm children (mean gestational age: 28.7 weeks) and 21 age- and gender-matched term children who underwent diffusion tensor imaging at a mean age of 9 years. We used automated probabilistic tractography and measured fractional anisotropy in seven bilateral association tracts known to belong to the white matter language network. Both groups participated in language assessment using five standardised tests at the same age. Results: Preterm children had lower fractional anisotropy in the right superior longitudinal fasciculus 1 compared to term children (P &lt; 0.05). Preterm children with fetal growth restriction had lower fractional anisotropy in the left inferior longitudinal fasciculus compared to preterm children with appropriate fetal growth (P &lt; 0.05). Fractional anisotropy in three dorsal tracts and in two dorsal and one ventral tract had a positive correlation with language assessments among preterm children and preterm children with fetal growth restriction, respectively (P &lt; 0.05). Conclusions: There were some microstructural differences in language-related tracts between preterm and term children and between preterm children with appropriate and those with restricted fetal growth. Children with better language abilities had a higher fractional anisotropy in distinct white matter tracts

Children born before 32 weeks of gestation displayed impaired reading fluency, comprehension and spelling skills at 9 years of age

Abstract Aim: Our aim was to study whether prematurity, associated with prenatal and neonatal risk factors, affects specific literacy skills among school children born at a very low gestational age (VLGA) of &lt;32 weeks. Methods: The study group comprised 76 prospectively followed VLGA children born between November 1998 and November 2002 at Oulu University Hospital, Finland, and 51 term controls. The median gestational age of the VLGA children was 29.0 (24.1‐31.9) weeks. All children were examined at a median age of 8.9 (8.0‐9.9) years in Oulu between November 2007 and November 2011. Reading fluency, comprehension and spelling skills were evaluated using standardised tests for Finnish‐speaking children. Results: Very low gestational age children had significantly poorer test results in reading comprehension (median 6.9 vs 8.3, P = .014) and spelling (median 35.7 vs 38.0, P = .013) than term children. Furthermore, VLGA children more often performed below the 10th percentile normal values in spelling (P = .012) compared with term controls. Foetal growth restriction was associated with lower scoring in reading fluency (P = .023) and spelling (P = .004) among VLGA children. Conclusion: Very low gestational age school children performed poorer in reading comprehension and spelling than term children. In addition, poor foetal growth in VLGA children was associated with literacy problems

Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age

Abstract Background: Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective: The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods: The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results: Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (P&lt;0.05, corrected for multiple comparison) in dorsolateral prefrontal caudate and ventrolateral prefrontal caudate tracts as compared to term-born children. We found negative correlations between the diffusion tensor imaging metrics of frontostriatal tracts and inhibition functions (P&lt;0.05, corrected for multiple comparison) in very preterm children. Conclusion: Prematurity has a long-term effect on frontostriatal white matter microstructure that might contribute to difficulties in executive functioning