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.

Associations between the aetiology of preterm birth and mortality and neurodevelopment up to 11 years.

AIM: To investigate how the aetiology of very preterm birth/very low birth weight is associated with mortality and later neurodevelopmental outcomes. METHODS: Very preterm/very low-birth weight singletons were categorised based on the aetiology of preterm birth: spontaneous preterm birth (n = 47, 28.1%), preterm premature rupture of membranes (n = 56, 33.5%) or placental vascular pathology (n = 64, 38.3%). Mortality, cerebral palsy, severe cognitive impairment by 11 years of age (<2SD) and mean full-scale intelligence quotient at 11 years were studied in association with birth aetiology. RESULTS: There was no difference in mortality or rate of cerebral palsy according to birth aetiologies. The rate of severe cognitive impairment was lower (4.9% vs. 15.3%) in the preterm premature rupture of the membrane group in comparison to the placental vascular pathology group (OR 0.2, 95% CI 0.03-0.9, adjusted for gestational age). At 11 years, there was no statistically significant difference in the mean full-scale intelligence quotient. CONCLUSION: Placental vascular pathology, as the aetiology of very preterm birth/very low birth weight, is associated with a higher rate of severe cognitive impairments in comparison to preterm premature rupture of membranes, although there was no difference in the mean full-scale intelligence quotient at 11 years. The aetiology of very preterm birth/very low birth weight was not associated with mortality or the rate of cerebral palsy.

Brain MRI findings and their association with visual impairment in young adolescents born very preterm.

PURPOSE: Very preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes. METHODS: We included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up. RESULTS: Evans index (0.27 vs 0.25, p<0.001) and a proposed "posterior ventricle index" (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (ß=10.7, 95%CI 0.59-20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×1011, 95%CI=7.78-1.48×1021) and contrast sensitivity <0.5 (OR=2.6×1027, 95%CI=1.9×108-3.5×1046). Decreased peritrigonal white matter thickness associated with impaired visual acuity (ß=0.04, 95%CI 0.002-0.07). CONCLUSION: More white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.

Web-based follow-up tool (ePIPARI) of preterm infants-study protocol for feasibility and performance.

BACKGROUND: Preterm infants have a risk of health and developmental problems emerging after discharge. This indicates the need for a comprehensive follow-up to enable early identification of these problems. In this paper, we introduce a follow-up tool "ePIPARI - web-based follow-up for preterm infants". Our future aim is to investigate whether ePIPARI is a feasible tool in the follow-up of preterm infants and whether it can identify children and parents in need of clinical interventions. METHODS: ePIPARI includes eight assessment points (at term age and at 1, 2, 4, 8, 12, 18, and 24 months of corrected age) when the child´s health and growth, eating and feeding, neurodevelopment, and parental well-being are evaluated. ePIPARI consists of several widely used, standardized questionnaires, in addition to questions typically presented to parents in clinical follow-up visits. It also provides video guidance and written information about age-appropriate neurodevelopment for the parents. Parents of children born before 34 weeks of gestation during years 2019-2022 are being invited to participate in the ePIPARI study, in which web-based follow-up with ePIPARI is compared to clinical follow-up. In addition, the parents of children born before 32 weeks of gestation, who reached the corrected age of two years during 2019-2021 were invited to participate for the assessment point of 24 months of ePIPARI. The parents are asked to fill in the online questionnaires two weeks prior to each clinical follow-up visit. DISCUSSION: The web-based tool, ePIPARI, was developed to acquire a sensitive and specific tool to detect infants and parents in need of further support and clinical interventions. This tool could allow individualized adjustments of the frequency and content of the clinical visits. TRIAL REGISTRATION: ClinicalTrials.cov, NCT05238168 . Registered 11 April 2022 - Retrospectively registered.

Pre-notifications increase retention in a 17-year follow-up of adolescents born very preterm.

OBJECTIVE: Retention is essential in follow-up studies to reduce missing data, which can cause bias and limit the generalizability of the results. We investigated whether pre-notification letters would increase the response rates of approval forms and questionnaires and reduce the need for post-notifications in a prospective follow-up study of 17-year-old adolescents. STUDY DESIGN: and settings This long-term follow-up study included 269 adolescents were randomized (1:1) into a pre-notification group (n = 132) and a no pre-notification group (n = 137). The pre-notification letter was sent prior to the approval form and questionnaires. The outcome measures were the response rates to the approval forms and questionnaires and the rate of post-notifications required. RESULTS: The adolescents who received the pre-notifications were more likely to return approval forms (n = 88/132, 67%) than the adolescents who did not receive the pre-notifications (n = 79/137, 58%) (OR 1.5, 95% CI 0.9-2.4). The rates of returned questionnaires were higher in the pre-notification group (n = 82/88, 93%) than in the no pre-notification group (n = 68/79, 86%) (OR 2.2, 95% CI 0.8-6.3). The adolescents who did not receive the pre-notifications were more likely to need the post-notifications than the adolescents who received the pre-notifications (OR 3.0, 95% CI 1.4 to 6.5). CONCLUSIONS: Pre-notifications decreased the need for post-notifications and may increase retention in 17-year-old adolescents. Based on our findings, pre-notification letters are recommended in future follow-up studies in adolescents. TRIAL REGISTRATION: The Ethics Review Committee of the Hospital District of South-West Finland approved the 17-year PIPARI Study protocol in January 2018 (23.1.2018; 2/180/2012). The study has been registered to the SWAT repository as SWAT 179. Filetoupload,1457904,en.pdf (qub.ac.uk).

Five-to-Fifteen-Parental Perception of Developmental Profile from Age 5 to 8 Years in Children Born Very Preterm.

Children born very preterm have increased risk of developmental difficulties. We examined the parental perception of developmental profile of children born very preterm at 5 and 8 years by using the parental questionnaire Five-to-Fifteen (FTF) compared to full-term controls. We also studied the correlation between these age points. The study included 168 and 164 children born very preterm (gestational age < 32 weeks and/or birth weight ≤ 1500 g) and 151 and 131 full-term controls. The rate ratios (RR) were adjusted for sex and the father's educational level. At 5 and 8 years, children born very preterm were more likely to have higher scores (more difficulties) compared to controls in motor skills (RR = 2.3, CI 95% = 1.8-3.0 at 5 years and RR = 2.2, CI 95% = 1.7-2.9 at 8 years), executive function (1.7, 1.3-2.2 and 1.5, 1.2-2.0), perception (1.9, 1.4-2.5 and 1.9, 1.5-2.5), language (1.5, 1.1-1.9 and 2.2, 1.7-2.9), and social skills (1.4, 1.1-1.8 and 2.1, 1.6-2.7), and at 8 years in learning (1.9, 1.4-2.6) and memory (1.5, 1.2-2.0). There were moderate-to-strong correlations (r = 0.56-0.76, p < 0.001) in all domains between 5 and 8 years in children born very preterm. Our findings suggest that FTF might help to earlier identify children at the greatest risk of incurring developmental difficulties persisting to school-age.

Predictive value of Bayley-III Motor Index for later motor difficulties in children born extremely preterm.

AIM: To investigate the predictive ability of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) Motor Index, in children born extremely preterm (<27 gestational weeks) without cerebral palsy. METHODS: Children from the EXPRESS study (all extremely preterm births in Sweden, 2004-2007) without neurosensory impairments assessed with Bayley-III at 2.5 years corrected age and Movement Assessment Battery for Children, Second Edition (MABC-2), at 6.5 years comprised the eligible study population (n = 282). Motor difficulty was defined as MABC-2 ≤5th percentile. RESULTS: Motor difficulties were found in 57 of 282 children (20.2%) at 6.5 years. The Bayley-III explained 18.0% of the variance in the MABC-2 (p < 0.001). The area under the receiver operating curve was 0.71 (95% confidence interval 0.64-0.79, p < 0.001). At a Bayley-III cut-off value of 85, sensitivity, specificity and positive and negative predictive values for motor difficulties were 26.3% (15.5-39.7), 92.9% (88.1-95.9), 48.4% (33.0-64.0) and 83.3% (80.9-85.4). Likelihood ratios were inconclusive. CONCLUSION: The Bayley-III at 2.5 years corrected age was a modest predictor of motor outcome in children born extremely preterm at 6.5 years, and underestimated the rate of motor difficulties. Children require follow-up beyond preschool age.

Altered temporal connectivity and reduced meta-state dynamism in adolescents born very preterm.

Adolescents born very preterm have an increased risk for anxiety, social difficulties and inattentiveness, i.e. the 'preterm behavioural phenotype'. The extreme end of these traits comprises the core diagnostic features of attention and hyperactivity disorders and autism spectrum disorder, which have been reported to show aberrant dynamic resting-state functional network connectivity. This study aimed to compare this dynamism between adolescents born very preterm and controls. A resting-state functional magnetic resonance imaging was performed on 24 adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) and 32 controls born full term (≥37 weeks of gestation) at 13 years of age. Group-wise comparisons of dynamic connectivity between the resting-state networks were performed using both hard clustering and meta-state analysis of functional network connectivity. The very preterm group yielded a higher fraction of time spent in the least active connectivity state in hard clustering state functional network connectivity, even though no group differences in pairwise connectivity patterns were discovered. The meta-state analysis showed a decreased fluidity and dynamic range in the very preterm group compared with controls. Our results suggest that the 13-year-old adolescents born very preterm differ from controls in the temporal characteristics of functional connectivity. The findings may reflect the long-lasting effects of prematurity and the clinically acknowledged 'preterm behavioural phenotype'.

Maternal obesity, gestational diabetes mellitus, and diet in association with neurodevelopment of 2-year-old children.

BACKGROUND: Maternal metabolic disturbances and diet may influence long-term infantile neurodevelopment. We investigated whether maternal gestational diabetes mellitus (GDM), obesity, and diet could affect the neurodevelopment of 2-year-old children. METHODS: Neurodevelopment of children (n = 243) born to mothers with overweight or obesity was assessed with the Bayley Scales of Infant and Toddler Development-Third Edition, and the Hammersmith Infant Neurological Examination. Maternal adiposity was determined by air displacement plethysmography, and GDM with an oral glucose tolerance test. Dietary assessment included diet quality and fish consumption questionnaires, and three-day food diaries, from which dietary inflammatory index (DII®) scores were computed. RESULTS: GDM was associated with weaker expressive language skills (adj.ß = -1.12, 95% CI = -2.10;-0.15), and higher maternal adiposity with weaker cognitive, language, and motor skills in children (adj.p < 0.05). Maternal good dietary quality (adj.ß = 0.87, 95% CI = 0.004;1.73) and higher fish consumption (adj.p = 0.02) were related to better expressive language skills. DII scores were not associated with children's neurodevelopment. CONCLUSIONS: Findings suggest that GDM and higher maternal adiposity may lead to weaker neurodevelopmental skills, although still within the mean normative range in this population of children. Good dietary quality and higher fish consumption during pregnancy could benefit a child's language development. IMPACT: Gestational diabetes mellitus and maternal higher adiposity may have unfavorable effects on a 2-year-old child's neurodevelopment. An overall good quality of diet and higher fish consumption during pregnancy may result in more favorable cognitive and language skills when the child is 2-year-old. Our findings reveal that women with overweight or obesity, a risk group for pregnancy complications, could benefit from dietary counseling to support their children's neurodevelopment.

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.

Motor Performance in Association with Perceived Loneliness and Social Competence in 11-Year-Old Children Born Very Preterm.

Background: Very preterm birth may affect motor performance and social competence up to adulthood. Our objective was to describe perceived loneliness and social competence in children born very preterm in relation to motor impairment. Methods: 165 children born very preterm (birth weight ≤ 1500 g and/or gestational age < 32 weeks) were assessed at 11 years of age. Cerebral palsy (CP) was diagnosed by 2 years of age. At 11 years of age, motor outcome was assessed using the Movement Assessment Battery for Children­Second edition (Movement ABC-2). Loneliness was evaluated by using the Peer Network and Dyadic Loneliness scale and social competence by using the Multisource Assessment of Children's Social Competence Scale. Results: In total, 6 (4%) children had CP, 18 (11%) had Developmental Coordination Disorder (DCD) (Movement ABC-2 ≤ 5th percentiles), and 141 (85%) had typical motor development. There was no correlation between percentiles for total scores of the Movement ABC-2 and perceived loneliness or social competence when the children with motor impairment (CP or DCD) were excluded. Children with DCD reported less perceived loneliness, but more problems with social competence compared to children with CP. Conclusions: It is important to recognize children born very preterm with DCD to provide interventions and support services to prevent social exclusion.

Implementation of neurally adjusted ventilatory assist and high flow nasal cannula in very preterm infants in a tertiary level NICU.

Preterm infants treated with invasive ventilation are often affected by bronchopulmonary dysplasia, brain structure alterations, and later neurodevelopmental impairment. We studied the implementation of neurally adjusted ventilatory assist (NAVA) and high flow nasal cannula (HFNC) in a level III neonatal unit, and its effects on pulmonary and central nervous system outcomes. This retrospective cohort study included 193 surviving infants born below 32 weeks of gestation in preimplementation (2007-2008) and postimplementation (2016-2017) periods in a single study center in Finland. The proportion of infants requiring invasive ventilation decreased from 67% in the pre- to 48% in the postimplementation period (p = 0.009). Among infants treated with invasive ventilation, 68% were treated with NAVA after its implementation. At the same time, the duration of invasive ventilation of infants born at or below 28 weeks increased threefold compared with the preimplementation period (p = 0.042). The postimplementation period was characterized by a gradual replacement of nasal continuous positive airway pressure (nCPAP) with HFNC, earlier discontinuation of nCPAP, but a longer duration of positive pressure support. The proportion of normal magnetic resonance imaging (MRI) findings at term corrected age increased from 62% to 84% (p = 0.018). Cognitive outcome improved by one standard score between the study periods (p = 0.019). NAVA was used as the primary mode of ventilation in the postimplementation period. During this period, invasive ventilation time was significantly prolonged. HFNC led to a decrease in the use of nCPAP. The change in the respiratory support might have contributed to the improvement in brain MRI findings and cognitive outcomes.

Fewer maternal depression symptoms after the Close Collaboration with Parents intervention: Two-year follow-up.

AIM: To test whether the implementation of the Close Collaboration with Parents intervention at a neonatal intensive care unit (NICU) decreases depression symptoms of mothers up to two years after the delivery of preterm infants. METHODS: We used a non-equivalent two-group design, comparing mothers of very low birthweight infants in the same NICU before (2001-2006) and after (2011-215) the intervention. The unit carried out the educational intervention (2009-2012) that was targeted at its healthcare team and aimed to improve their skills to collaborate with parents. Maternal depression symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) six months and two years after the expected birth date of the infant. RESULTS: We found a median difference of 2.56 (95% CI from 1.64 to 3.48) in EPDS at the two-year follow-up between the pre-intervention and post-intervention groups, p < 0.001. Furthermore, we found no interaction between measurement time-points and group, implying that the intervention effect on maternal depression symptoms was similar at the six-month and two-year time-points. CONCLUSION: The intervention seems to have long-term preventive effects on maternal depressive symptoms. This effect is of clinical significance as prolonged maternal depression associates with adverse child outcomes.

Maternal smoking during pregnancy negatively affects brain volumes proportional to intracranial volume in adolescents born very preterm.

Background: Maternal smoking during pregnancy has been shown to associate with smaller frontal lobe and cerebellar volumes in brain magnetic resonance imaging (MRI) at term age in very preterm infants. The aim of this study was to examine the effect of maternal smoking during pregnancy on volumetric brain MRI findings at 13 years. We hypothesized that adverse effects of smoking during pregnancy on brain volumes are still seen during adolescence. Methods: Included adolescents were born very preterm (gestational age < 32 weeks and/or birth weight ≤ 1,500 g) between April 2004 and December 2006 at the Turku University Hospital, Finland. Information on maternal smoking status (yes or no) during pregnancy was collected from medical records and maternal questionnaires before discharge. Adolescents underwent volumetric brain MRI at 13 years of age. Image post-processing was performed with FreeSurfer. Regional volumes, cortical thickness, surface area, and curvature were computed from 33 cortical regions of interest (ROIs). Additionally, volumes were calculated for 18 subcortical regions, as well as for white matter, gray matter, and intracranial volume. We normalized quantified absolute volumes for head size by dividing volumes with corresponding intracranial volumes. false discovery rate (FDR) correction for multiple comparisons across regions was used. Results: A total of 9/44 (21%) adolescents had been exposed to maternal smoking during pregnancy. No statistically significant differences in absolute volumes were observed between the groups (p > 0.05). Regarding volumes proportional to intracranial volume, the adolescents in the exposed group exhibited smaller gray matter volumes in the inferotemporal (FDR corrected p = 0.022) and parahippocampal (p = 0.018) regions compared to the unexposed group. The surface area in the exposed group was also smaller in the parahippocampal (p = 0.046) and postcentral (p = 0.046) regions compared to the unexposed group. No statistically significant differences after correction for multiple comparisons were found for either curvature or cortical thickness between the groups. Conclusion: Maternal smoking exposure during pregnancy may have long-term effects on brain volumes up to 13 years in adolescents born very preterm. Our findings emphasize the importance of smoking-free pregnancy.

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.

Associations between Language at 2 Years and Literacy Skills at 7 Years in Preterm Children Born at Very Early Gestational Age and/or with Very Low Birth Weight.

Preterm children (born <37 gestational weeks) who are born at very early gestational age (<32 weeks, very preterm, VP) and/or with very low birth weight (≤1500 g, VLBW) are at increased risk for language and literacy deficits. The continuum between very early language development and literacy skills among these children is not clear. Our objective was to investigate the associations between language development at 2 years (corrected age) and literacy skills at 7 years in VP/VLBW children. Participants were 136 VP/VLBW children and 137 term controls (a 6-year regional population cohort, children living in Finnish-speaking families). At 2 years of corrected age, language (lexical development, utterance length) was assessed using the Finnish version of the MacArthur-Bates Communicative Development Inventory and the Expressive Language Scale from Bayley scales of Infant Development, second edition. At 7 years, children's literacy skills (pre-reading skills, reading, and writing) were evaluated. Statistically significant correlations were found in both groups between language development at 2 years and literacy skills at 7 years (r-values varied between 0.29 and 0.43, p < 0.01). In the VP/VLBW group, 33% to 74% of the children with early weak language development had weak literacy skills at 7 years relative to those with more advanced early language skills (11% to 44%, p < 0.001 to 0.047). Language development at 2 years explained 14% to 28% of the variance in literacy skills 5 years later. Language development at 2 years had fair predictive value for literacy skills at 7 years in the VP/VLBW group (area under the receiver operating characteristic (ROC) curve (AUC) values varied between 0.70 and 0.77, p < 0.001). Findings provide support for the continuum between very early language development and later language ability, in the domain of literacy skills in preterm children.

Neurological and Cognitive Performance After Childhood Encephalitis.

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood. Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995-2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire. Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ < 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008). Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.

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.

Using different definitions affected the reported prevalence of neurodevelopmental impairment in children born very preterm.

AIM: We investigated the impact of varying definitions on the prevalence of neurodevelopmental impairment (NDI) in children born very preterm at 6.5 years of age. METHODS: Cognitive development and neurosensory impairments were assessed in 91 children (40/51 girls/boys) born <32 gestational weeks, in 2004-2007 in Uppsala county, Sweden. The results were compared with data from a reference group of 67 children born full term. The prevalence of NDI in the present cohort was reported according to definitions used by seven contemporary studies of children born very or extremely preterm. RESULTS: The prevalence of severe NDI varied from 2% to 23% depending on the definition used. The prevalence of cognitive impairment varied from 2% (-3 SD according to test norms) to 16% (-2 SD according to control group), the prevalence of cerebral palsy from 0% (severe) to 9% (any) and the prevalence of severe visual impairment from 0% (blindness) to 1% (visual acuity < 0.3). There were no children with severe hearing impairment. CONCLUSION: A high variability in definitions affects the reporting of the prevalence of NDI in long-term follow-up studies of very or extremely preterm born children. There is a need for a better consensus to enable comparisons across studies.