Major brain injuries at term continue to influence DTI parameters in adolescents born very preterm: a 13-year follow-up study.

BACKGROUND: Major brain injuries in structural brain magnetic resonance imaging (MRI) at term affect concurrent diffusion tensor imaging (DTI) parameters in very preterm infants. White matter is known to gradually maturate along with increasing gestational age, which is characterized by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). PURPOSE: To study the difference between DTI parameters at term and 13 years in adolescents born very preterm with and without major pathologies in structural brain MRI at term. MATERIAL AND METHODS: Adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) in 2004-2006 at Turku University Hospital, Finland were included. We evaluated FA and MD at term and 13 years in 18 regions of interest using the JHU-neonate-SS atlas to compare the differences in these parameters between adolescents with and without major injuries identified on MRI at term. RESULTS: A total of 24 adolescents underwent brain MRI including DTI both at term and 13 years. Adolescents with major brain injury pathologies (n = 6) in structural MRI at term had decreased FA in the left corpus callosum and right cingulate gyrus part, and increased MD in the left corpus callosum, right anterior limb of internal capsule, and right posterior limb of the internal capsule at 13 years, in comparison with adolescents without major brain injuries (n = 18) in structural MRI at term. CONCLUSION: Our findings suggest that major brain injuries identified on structural MRI at term affect brain maturation, with adverse effects in FA and MD still during adolescence.

Functional Magnetic Resonance Imaging during Visual Perception Tasks in Adolescents Born Prematurely.

OBJECTIVES: Impairments in visual perception are among the most common developmental difficulties related to being born prematurely, and they are often accompanied by problems in other developmental domains. Neural activation in participants born prematurely and full-term during tasks that assess several areas of visual perception has not been studied. To better understand the neural substrates of the visual perceptual impairments, we compared behavioral performance and brain activations during visual perception tasks in adolescents born very preterm (birth weight ≤1500 g or gestational age <32 weeks) and full-term. METHODS: Tasks assessing visual closure, discrimination of a deviating figure, and discrimination of figure and ground from the Motor-Free Visual Perception Test, Third Edition were performed by participants born very preterm (n = 37) and full-term (n = 34) at 12 years of age during functional magnetic resonance imaging. RESULTS: Behavioral performance in the visual perception tasks did not differ between the groups. However, during the visual closure task, brain activation was significantly stronger in the group born very preterm in a number of areas including the frontal, anterior cingulate, temporal, and posterior medial parietal/cingulate cortices, as well as in parts of the cerebellum, thalamus, and caudate nucleus. CONCLUSIONS: Differing activations during the visual closure task potentially reflect a compensatory neural process related to premature birth or lesser neural efficiency or may be a result of the use of compensatory behavioral strategies in the study group born very preterm.

Hammersmith Infant Neurological Examination and long-term cognitive outcome in children born very preterm.

AIM: To study the association between the Hammersmith Infant Neurological Examination (HINE) at age 2 years and neurocognition at age 11 years in children born very preterm. We hypothesized that the HINE at 2 years would be associated with neurocognition, that is, neurological, motor, and cognitive outcomes at 11 years. METHOD: A total of 174 children (mean gestational age 29.0wks, SD 2.7; minimum 23.0, maximum 35.9; 95 [55%] males, 79 [45%] females) born very preterm (birthweight ≤1500g/gestational age <32wks), were included in a prospective cohort recruited from 2001 to 2006 in Turku, Finland. The HINE was performed at 2 years' corrected age. Neurocognition at 11 years was assessed with the Touwen neurological examination, Movement Assessment Battery for Children, Second Edition (MABC-2), and full-scale IQ (Wechsler Intelligence Scale for Children, Fourth Edition). RESULTS: The HINE global score was associated with the results of the Touwen neurological examination (odds ratio [OR]=0.9, 95% confidence interval [CI] 0.8-0.9, p=0.001), MABC-2 (ß=1.4, 95% CI 0.7-2.2, p<0.001), and full-scale IQ (ß=1.2, 95% CI 0.8-1.7, p<0.001), even when adjusted. When children with cerebral palsy (CP) were excluded, the HINE was still associated with full-scale IQ (unadjusted ß=1.2, 95% CI 0.3-2.1, p=0.01). INTERPRETATION: A higher HINE global score at 2 years was associated with better general intelligence at 11 years even in children without CP. The HINE may be a useful tool to detect children at risk for later cognitive impairment. What this paper adds A Hammersmith Infant Neurological Examination (HINE) global score at 2 years was associated with long-term neurocognitive function. Severe cognitive impairment was significantly more common in 11-year-old children with complex minor neurological dysfunction compared to typically developing children. The HINE performed at 2 years detects risks of cognitive impairment at 11 years in children born very preterm. A higher HINE score at 2 years was associated with better general intelligence at 11 years.

Diffusion tensor imaging is associated with motor outcomes of very preterm born children at 11 years of age.

AIM: Very preterm children born <32 weeks of gestation are at risk for motor difficulties such as cerebral palsy and developmental coordination disorder. This study explores the association between diffusion tensor imaging metrics at term and motor outcomes at 11 years of age. METHODS: A cohort of 37 very preterm infants (mean gestational age 29 4/7, SD 2 0/7) born in 2004-2006 in Turku University Hospital underwent diffusion tensor imaging at term. A region of interest analysis of fractional anisotropy and mean diffusivity was performed. Motor outcomes at 11 years of age were measured with the Movement Assessment Battery for Children - Second Edition. RESULTS: The diffusion metrics of the corpus callosum (genu P = .005, splenium P = .049), the left corona radiata (P = .035) and the right optic radiation (P = .017) were related to later motor performance. Mean diffusivity decreased and fractional anisotropy increased in proportion to the improving performance. CONCLUSION: The diffusion metrics of the genu and splenium of the corpus callosum, the left corona radiata and the right optic radiation at term were associated with motor skills at 11 years of age. Diffusion tensor imaging should be further studied as a potential tool in recognising children at risk for motor impairment.

Peripapillary retinal nerve fibre layer thickness and macular ganglion cell layer volume in association with motor and cognitive outcomes in 11-year-old children born very preterm.

PURPOSE: The purpose of the study was to study the association between retinal parameters and motor and cognitive outcomes in children born very preterm. METHODS: This study is part of a prospective cohort study of very preterm infants (birth weight ≤ 1500 grams/gestational age < 32 weeks). At 11 years of age, the ophthalmological assessment included a retinal optical coherence tomography (OCT) examination of the peripapillary retinal nerve fibre layer (PRNFL) and the macular ganglion cell layer (GCL). The motor performance was assessed with the Movement Assessment Battery for Children-Second Edition (Movement ABC-2), and the cognitive outcome with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). RESULTS: A total of 141 children were included. The mean (SD) average PRNFL was 95 µm (10.2 µm). The mean (SD) macular GCL volume was 0.34 mm3 (0.03 mm3 ). Higher PRNFL thickness associated with higher percentiles for total scores in the motor assessment (b = 0.5, 95% CI 0.1-0.8, p = 0.01) and higher macular GCL volume with higher scores in the cognitive assessment (b = 1.4, 95% CI 0.5-2.3, p = 0.002), also when adjusted for gender, birth weight z-score (birth weight in relation to gestational age) and major brain pathology at term. CONCLUSION: The associations between higher average PRNFL thickness and better motor performance as well as higher macular GCL volume and better cognitive performance refer to more generalized changes in the brain of 11-year-old children born very preterm. Retinal OCT examinations might provide a deeper insight than mere eyesight in long-term neurodevelopmental follow-up of children born very preterm.

HBM4EU feasibility studies: Lessons learned in combining health and human biomonitoring studies.

BACKGROUND: The European Human Biomonitoring Initiative (HBM4EU) is a joint program evaluating humans' exposure to several environmental substances and their potential health effects. One of the main objectives of HBM4EU is to make use of human biomonitoring (HBM) to assess human exposure to chemicals in Europe to better understand the associated health impacts and to improve chemical risk assessment. In parallel to HBM studies, health examination surveys (HESs), nutrition/dietary surveys, and disease specific health surveys are conducted in many European countries. In HESs, information collected by questionnaire(s) is supplemented with physical examinations and analysis of clinical and biological biomarkers in biological samples. HBM and health examination survey (HES) use similar data collection methods and infrastructures hence the feasibility of combining these two is explored in this paper. METHODS: Within HBM4EU, three feasibility studies (in Finland, Germany, and UK/England) were conducted to evaluate opportunities and obstacles of combining HBM and health studies. In this paper we report lessons learned from these feasibility studies. RESULTS: The Finnish feasibility study called KouBio-KUOPIO study was a new initiative without links to existing studies. The German feasibility study added a HBM module to the first follow-up examination of the LIFE-Adult-Study, a population-based cohort study. The UK feasibility integrates a sustainable HBM module into the Health Survey for England (HSfE), an annual health examination survey. Benefits of combining HBM and HESs include the use of shared infrastructures. Furthermore, participants can receive additional health information from HES, and participation rates tend to be higher due to the potential to obtain personal health information. Preparatory phases including obtaining ethical approval can be time-consuming and complicated. Recruitment of participants and low participation rates are common concerns in survey research and therefore designing user-friendly questionnaires with low participant burden is important. Unexpected events such as the COVID-19 pandemic can cause substantial challenges and delays for such studies. Furthermore, experiences from several countries demonstrated that long-term funding for combined studies can be difficult to obtain. CONCLUSIONS: In the future, incorporating HBM modules into existing HESs can provide a feasible and cost-effective method to conduct HBM studies and obtain a wide range of relevant data to support public health policies and research.

Performance in Hand Coordination Tasks and Concurrent Functional MRI Findings in 13-Year-Olds Born Very Preterm.

BACKGROUND: Fine motor and coordination problems are frequently reported among adolescents born preterm. We aimed to assess performance in hand coordination tasks and to compare concurrent brain activation between adolescents born very preterm and at term at 13 years. METHODS: A total of 34 right-handed adolescents born very preterm (gestational age less than 32 weeks/birth weight ≤1500 grams) and 37 controls born at term during 2003 to 2006 in Turku University Hospital, Finland, were recruited. At 13 years, finger opposition and diadochokinesis were assessed, and brain functional magnetic resonance imaging data were acquired while the adolescents performed unimanual hand coordination tasks in response to visual cue. RESULTS: Adolescents born very preterm performed similar to controls in hand coordination tasks. The very preterm group evoked greater brain activation than the controls in the right precentral gyrus and in the right postcentral gyrus during left-hand finger opposition and in the right postcentral gyrus during left-hand diadochokinesis. Within the very preterm group, lower gestational age was associated with reduced activation in the left superior parietal lobule during right-hand diadochokinesis. Regarding left-hand tasks, lower gestational age was associated with stronger activation in the right cerebellar lobule V and left cerebellar lobule VI during finger opposition and stronger activation in the right superior parietal lobule during diadochokinesis. CONCLUSIONS: Very preterm birth affected hand coordination-related brain activation. Most of the effects were found for nondominant hand. Clinical performance during the hand coordination tasks was similar in adolescents born very preterm and controls.

Preterm children's developmental coordination disorder, cognition and quality of life: a prospective cohort study.

OBJECTIVE: To evaluate the rate of developmental coordination disorder (DCD) and its correlation to cognition and self-experienced health-related quality of life (HRQoL) in children born very preterm. DESIGN: Prospective follow-up study. SETTING: Regional population of children born very preterm in Turku University Hospital, Finland, in 2001-2006. PATIENTS: A total of 170 children born very preterm were followed up until 11 years of age. MAIN OUTCOME MEASURES: Motor and cognitive outcomes were evaluated using the Movement Assessment Battery for Children - Second Edition (Movement ABC-2) and the Wechsler Intelligence Scale for Children - Fourth Edition, respectively, and HRQoL using the 17-Dimensional Illustrated Questionnaire (17D). The Touwen neurological examination was performed to exclude other neurological conditions affecting the motor outcome. RESULTS: Eighteen children born very preterm (17 boys) (11.3%) had DCD, defined as Movement ABC-2 total test score ≤5th percentile. A positive correlation between motor and cognitive outcome (r=0.22, p=0.006) was found. Children born very preterm with DCD had lower cognitive scores than those without DCD (Full-Scale IQ mean 76.8 vs 91.6, p=0.001). Moreover, children born very preterm with DCD reported lower HRQoL than children born very preterm without motor impairment (17D mean 0.93 vs 0.96, p=0.03). However, HRQoL was higher in this group of children born very preterm compared with population-based normative test results (p<0.001). CONCLUSIONS: DCD was still common at 11 years of age in children born very preterm in 2000s. DCD associated with adverse cognitive development and lower self-experienced HRQoL. However, this group of children born very preterm reported better HRQoL in comparison with Finnish norms.