Secular trends in physical growth, biological maturation, and intelligence in children and adolescents born between 1978 and 1993.

Introduction: Human physical growth, biological maturation, and intelligence have been documented as increasing for over 100 years. Comparing the timing of secular trends in these characteristics could provide insight into what underlies them. However, they have not been examined in parallel in the same cohort during different developmental phases. Thus, the aim of this study was to examine secular trends in body height, weight, and head circumference, biological maturation, and intelligence by assessing these traits concurrently at four points during development: the ages of 4, 9, 14, and 18 years. Methods: Data derived from growth measures, bone age as an indicator of biological maturation, and full-scale intelligence tests were drawn from 236 participants of the Zurich Longitudinal Studies born between 1978 and 1993. In addition, birth weight was analyzed as an indicator of prenatal conditions. Results: Secular trends for height and weight at 4 years were positive (0.35 SD increase per decade for height and an insignificant 0.27 SD increase per decade for weight) and remained similar at 9 and 14 years (height: 0.46 SD and 0.38 SD increase per decade; weight: 0.51 SD and 0.51 SD increase per decade, respectively) as well as for weight at age 18 years (0.36 SD increase per decade). In contrast, the secular trend in height was no longer evident at age 18 years (0.09 SD increase per decade). Secular trends for biological maturation at 14 years were similar to those of height and weight (0.54 SD increase per decade). At 18 years, the trend was non-significant (0.38 SD increase per decade). For intelligence, a positive secular trend was found at 4 years (0.54 SD increase per decade). In contrast, negative secular trends were observed at 9 years (0.54 SD decrease per decade) and 14 years (0.60 SD decrease per decade). No secular trend was observed at any of the four ages for head circumference (0.01, 0.24, 0.17, and - 0.04 SD increase per decade, respectively) and birth weight (0.01 SD decrease per decade). Discussion: The different patterns of changes in physical growth, biological maturation, and intelligence between 1978 and 1993 indicate that distinct mechanisms underlie these secular trends.

Processing Speed Partially Mediates Executive Function Impairments in Adolescents with Congenital Heart Disease: Results from a Prospective Cohort Study.

OBJECTIVE: To assess processing speed, fine motor function, attention, and executive function (EF) impairments in adolescents with complex congenital heart disease (CHD) who underwent open-heart surgery during infancy. STUDY DESIGN: We administered a comprehensive neuropsychological test battery evaluating 5 EF domains: working memory, inhibition, cognitive flexibility, fluency, and planning and primary neurodevelopmental processes (PNPs): processing speed, fine motor function, and attention. The sample included 100 adolescents with complex CHD from a previous University Children's Hospital Zurich study, with 104 healthy controls for comparison. We generated scores for each EF domain and computed an EF summary score. Group comparisons and associations were analyzed with multiple regressions accounting for parental education. Mediation analysis explored how PNPs mediate the effect between a CHD diagnosis and EF. RESULTS: In adolescents with complex CHD, all EF domains and the EF summary score were impaired (ß = 0.20 to 0.37, all P < .05). Furthermore, they exhibited slower processing speed (ß = 0.27, P < .01) than healthy controls, with no differences in attention (ß = -0.07, P = .34) and fine motor function (ß = 0.08, P = .34). Processing speed showed a strong association with the EF summary score (ß = 0.60, P < .001) and partially mediated the relationship between CHD diagnosis and the EF summary score (ß = 0.37, 95% CI [0.24, 0.50], P < .001). CONCLUSION: Adolescents with complex CHD show difficulties in EFs and processing speed. Notably, processing speed is strongly associated with EFs and partly accounts for EFs disparities between patients and healthy controls. Early detection and interventions for processing speed difficulties may improve EF outcomes in these patients.

Cerebral perfusion differences are linked to executive function performance in very preterm-born children and adolescents.

Children and adolescents born very preterm are at risk of cognitive impairment, particularly affecting executive functions. To date, the neural correlates of these cognitive differences are not yet fully understood, although converging evidence points to a pattern of structural and functional brain alterations, including reduced brain volumes, altered connectivity, and altered brain activation patterns. In very preterm neonates, alterations in brain perfusion have also been reported, but the extent to which these perfusion alterations persist into later childhood is not yet known. This study evaluated global and regional brain perfusion, measured with arterial spin labelling (ASL) MRI, in 26 very preterm children and adolescents and 34 term-born peers. Perfusion was compared between groups and relative to executive function (EF) scores, derived from an extensive EF battery assessing working memory, cognitive flexibility, and planning. Very preterm children and adolescents showed regions of altered perfusion, some of which were also related to EF scores. Most of these regions were located in the right hemisphere and included regions like the thalamus and hippocampus, which are known to play a role in executive functioning and can be affected by prematurity. In addition, perfusion decreased with age during adolescence and showed a significant interaction between birth status and sex, such that very preterm girls showed lower perfusion than term-born girls, but this trend was not seen in boys. Taken together, our results indicate a regionally altered perfusion in very preterm children and adolescents, with age and sex related changes during adolescence.

Comparing neuromotor functions in 45- and 65-year-old adults with 18-year-old adolescents.

Aim: This cross-sectional analysis investigates how neuromotor functions of two independent cohorts of approximately 45- and 65-year-old individuals are different from 18-year-old adolescents using the Zurich Neuromotor Assessment-2 (ZNA-2). Methods: A total of 186 individuals of the Zurich Longitudinal Studies (ZLS) born in the 1950s (mean age 65.1 years, SD = 1.2 year, range of ages 59.0-67.5 years, n = 151, 82 males) and 1970s (mean age 43.6 years, SD = 1.3 year, range of ages 40.8-46.6 years, n = 35, 16 males) were tested with the ZNA-2 on 14 motor tasks combined in 5 motor components: fine motor, pure motor, balance, gross motor, and associated movements. Motor performance measures were converted into standard deviation scores (SDSs) using the normative data for 18-year-old individuals as reference. Results: The motor performance of the 45-year-old individuals was remarkably similar to that of the 18-year-olds (SDS from -0.22 to 0.25) apart from associated movements (-0.49 SDS). The 65-year-olds showed lower performance than the 18-year-olds in all components of the ZNA-2, with the smallest difference observed for associated movements (-0.67 SDS) and the largest for gross motor skills (-2.29 SDS). Higher body mass index (BMI) was associated with better performance on gross motor skills for 45-year-olds but with worse performance for 65-year-olds. More educational years had positive effects on gross motor skills for both ages. Interpretation: With the exception of associated movements, neuromotor functions as measured with the ZNA-2 are very similar in 45- and 18-year-olds. In contrast, at age 65 years, all neuromotor components show significantly lower function than the norm population at 18 years. Some evidence was found for the last-in-first-out hypothesis: the functions that developed later during adolescence, associated movements and gross motor skills, were the most vulnerable to age-related decline.

Secular trends in motor performance in Swiss children and adolescents from 1983 to 2018.

Introduction: Environmental changes, including globalization, urbanization, social and cultural changes in society, and exposure to modern digital technology undoubtedly have an impact on children's activity and lifestyle behavior. In fact, marked reductions in children's physical activity levels have been reported over the years and sedentary behavior has increased around the world. The question arises whether these environmental changes had an impact on general motor performance in children and adolescents. The study aimed to investigate secular trends of motor performance in Swiss children and adolescents, aged between 7 and 18 years, over a period of 35 years from 1983 to 2018. Methods: Longitudinal data on the five motor components of the Zurich Neuromotor Assessment (ZNA) - pure motor (PM), fine motor (FM), dynamic balance (DB), static balance (SB), and contralateral associated movements (CAM) - were pooled with cross-sectional data on PM and FM from eight ZNA studies between 1983 and 2018. Regression models were used to estimate the effect of the year of birth on motor performance and body mass index (BMI) measurements. Models were adjusted for age, sex, and socioeconomic status. Results: The secular trend estimates in standard deviation scores (SDS) per 10 years were - 0.06 [-0.33; 0.22, 95% Confidence Interval] for PM, -0.11 [-0.41; 0.20] for FM, -0.38 [-0.66; -0.09] for DB (-0.42 when controlled for BMI), -0.21 [-0.47; 0.06] for SB, and - 0.01 [-0.32; 0.31] for CAM. The mean change in BMI data was positive with 0.30 SDS [0.07; 0.53] over 10 years. Discussion: Despite substantial societal changes since the 1980s, motor performance has remained relatively stable across generations. No secular trend was found in FM, PM, SB, and CAM over a period of 35 years. A secular trend in DB was present independent of the secular trend in body mass index.

Congenital heart disease in school-aged children: Cognition, education, and participation in leisure activities.

BACKGROUND: Children with congenital heart disease (CHD) are at risk for neurodevelopmental deficits. This study aimed to investigate the impact of cognitive deficits on educational outcome and participation in leisure activities. METHODS: A prospective cohort of 134 children with CHD who underwent cardiopulmonary bypass surgery (CPB) was examined at 10 years of age. IQ was assessed with the WISC-IV and executive functions with the BRIEF (parent- and teacher-report). Parents reported on type and level of education and educational support, and leisure activity participation. Ordinal regression analyses assessed the association between cognitive deficits and educational outcome and participation. RESULTS: Total IQ (P = 0.023), working memory (P < 0.001), processing speed (P = 0.008), and teacher-reported metacognition (P = 0.022) were lower than norms. Regular school was attended by 82.4% of children with CHD compared to 97% of the general Swiss population (P < 0.001). Seventy-five percent of children participated in leisure activities. Lower total IQ and teacher-rated global executive functions were associated with more educational support and lower IQ was associated with less participation. CONCLUSION: As school-aged children with CHD experience cognitive deficits, follow-up is required to provide optimal support with regard to educational outcome and participation in leisure activities. IMPACT: Contemporary cohorts of children with congenital heart disease undergoing cardiopulmonary bypass surgery remain at increased risk for cognitive deficits. Cognitive deficits affect educational outcome and leisure activities. These findings underline the importance of early detection of cognitive deficits and recommend support with respect to cognitive functioning.

Functional networks of working memory abilities in children with complex congenital heart disease: a sleep EEG study.

Working memory is frequently impaired in children with complex congenital heart disease (CHD), but little is known about the functional neuronal correlates. Sleep slow wave activity (SWA; 1-4.5 Hz EEG power) has previously been shown to reliably map neurofunctional networks of cognitive abilities in children with and without neurodevelopmental impairments. This study investigated whether functional networks of working memory abilities are altered in children with complex CHD using EEG recordings during sleep. Twenty-one children with complex CHD (aged 10.9 [SD: 0.3] years) and 17 typically-developing peers (10.5 [0.7] years) completed different working memory tasks and an overnight high-density sleep EEG recording (128 electrodes). The combined working memory score tended to be lower in children with complex CHD (CHD group: -0.44 [1.12], typically-developing group: 0.55 [1.24], d = 0.59, p = .06). The working memory score and sleep SWA of the first hour of deep sleep were correlated over similar brain regions in both groups: Strong positive associations were found over prefrontal and fronto-parietal brain regions - known to be part of the working memory network - and strong negative associations were found over central brain regions. Within these working memory networks, the associations between working memory abilities and sleep SWA (r between -.36 and .58, all p < .03) were not different between the two groups (no interactions, all p > .05). The current findings suggest that sleep SWA reliably maps working memory networks in children with complex CHD and that these functional networks are generally preserved in these patients.

White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: A pooled case-control study.

Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population.

Mental sequelae of the COVID-19 pandemic in children with and without complex medical histories and their parents: well-being prior to the outbreak and at four time-points throughout 2020 and 2021.

The objective of this study is to understand the long-term mental sequelae for families over the course of the COVID-19 pandemic by longitudinally investigating the well-being of children with and without complex medical histories and their parents. Well-being of 200 children (between 7 and 18 years of age; 73 typically developing, 46 born very preterm, 73 with complex congenital heart disease) and 175 of their parents was assessed prior to and during the first (April-May 2020), second (October-November 2020), third (April-May 2021), and fourth wave (October-November 2021) of the pandemic with standardized questionnaires. Linear mixed models were used to investigate longitudinal changes in child and parent well-being compared to before the pandemic. Social and COVID-19-specific determinants were investigated as predictors of impaired well-being. To illustrate clinical relevance, the proportion of children and parents scoring > 1 SD below normative mean/median was reported. Compared to before the pandemic, child proxy-reported well-being was lower during the first but not the second, third, and fourth waves. Child self-reported well-being was not lower during the pandemic compared to before. Parent well-being dropped during the first wave and remained low throughout the subsequent waves. Proxy-reported child and self-reported parent well-being was lower in families with sparse social support and poor family functioning. Parents of typically developing children reported lower well-being than parents of children born very preterm or with a complex congenital heart disease. In November 2021, 20% of children (both self- and proxy-report) and 24% of parents scored below the normal range compared to 11% (child self-report), 10% (child proxy-report), and 16% (parent self-report), respectively, before the pandemic. The pandemic continues to impact the well-being of parents of school-aged children with and without complex medical histories more than 1 year after its outbreak. Children's well-being was specifically affected during the first wave of the pandemic and has recovered thereafter. Families with sparse social support and poor family functioning are particularly at risk for compromised well-being and support should be provided to them.

Similarities and Differences in the Neurodevelopmental Outcome of Children with Congenital Heart Disease and Children Born Very Preterm at School Entry.

OBJECTIVE: To describe the similarities and differences in the neurodevelopmental outcome of children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery compared with children born very preterm (VPT) at school entry. STUDY DESIGN: IQ, motor abilities, behavior, and therapy use were assessed in 155 children with CHD as part of a prospective, single-center, longitudinal study, and in 251 children born VPT as part of a national follow-up register at the same center. Group differences were tested using independent t-tests and χ2-tests. Equivalence testing was used to investigate similarities between the groups. RESULTS: Mild (ie, 70 ≤ IQ < 85) and severe intellectual impairments (ie, IQ < 70) occurred in 17.4% and 4.5% of children with CHD compared with 22.1% and 5.5% in children VPT, respectively. Motor and behavioral functions were impaired in 57.0% and 15.3% of children with CHD compared with 37.8% and 11.5% of children born VPT, respectively. Children with CHD had poorer global motor abilities (d = -0.26) and poorer dynamic balance (d = -0.62) than children born VPT, and children born VPT had poorer fine motor abilities than children with CHD (d = 0.34; all P < .023). Peer problems were statistically similar between the groups (P = .020). Therapies were less frequent in children with CHD compared with children born VPT (23.4% vs 40.3%; P < .001). CONCLUSIONS: Children with CHD undergoing cardiopulmonary bypass surgery and children born VPT share an overall risk for neurodevelopmental impairments that manifest in different domains. Despite this, children with CHD receive fewer therapies, indicating a lack of awareness of the neurodevelopmental burden these children face.

Effects of Correcting for Prematurity on Executive Function Scores of Children Born Very Preterm at School Age.

OBJECTIVE: To investigate whether correction for prematurity affects executive function scores in school-aged children born very preterm. STUDY DESIGN: Executive functions were assessed with standardized neuropsychological tests in 142 children born very preterm (born at ≤32 weeks of gestational age or with a birth weight of ≤1500 g) and 391 control children, aged 7-13 years. Four-month age bands were established from the data of control children. Differences between uncorrected and corrected scores were compared against zero difference and between very preterm children born before and after 28 weeks of gestation. Regression models were used to compare the uncorrected and corrected scores of children born very preterm with control children. RESULTS: For all executive functions, significant, larger-than-zero differences between uncorrected and corrected scores were apparent in children born very preterm. Mean differences ranged from 0.04 to 0.18 SDs. Weak evidence was found that the effect of age correction is more pronounced in very preterm children born before 28 weeks of gestation than in those born after 28 weeks. Differences in executive function scores between children born very preterm and control children were attenuated if scores were corrected for prematurity. CONCLUSIONS: Test scores based on corrected rather than uncorrected age may more accurately determine the developmental stage of very preterm children's executive functions at school age. Potential consequences for clinical and research practice need to be discussed in the future.

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis.

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-Methyl-d-Aspartate Receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity. We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of Non-Rapid Eye Movement (NREM) sleep (factor 'hour') for patients and controls (factor 'group'). There was a significant interaction between 'hour' and 'group' (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs. These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.

Impact of the COVID-19 pandemic on children with and without risk for neurodevelopmental impairments.

AIM: To examine how the ongoing COVID-19 pandemic impacts child well-being and family functioning, particularly among children at risk for neurodevelopmental impairments. METHODS: Families of 73 typically developing children, 54 children born very preterm (VPT) and 73 children with congenital heart disease (CHD) from two prospective cohort studies were assessed prior to (mean age: 10.4 [SD: 1.2] years) and during (mean age: 12.8 [SD: 2.0] years) the pandemic, more specifically, in April/May 2020. Child well-being and family functioning were assessed with validated, parent-reported questionnaires and tested with linear mixed models. Group comparison of child distress and parental concerns related to medical implications of COVID-19 and homeschooling, assessed with 5-point Likert scales, was done with Mann-Whitney U tests. RESULTS: Children's psychological well-being and family functioning (both, p < 0.001) decreased significantly during the pandemic, irrespective of group. Children with CHD were reported to be more concerned about becoming infected with SARS-CoV-2 than were others. Child distress due to homeschooling and parents' concerns about children's academic achievements were significantly higher in VPT and CHD children than in typically developing peers (all p < 0.001). CONCLUSION: The COVID-19 pandemic substantially impacts the whole family and leads to additional distress in families with children at risk for neurodevelopmental impairments. These families should receive individualised counselling and assistance from healthcare providers and schools during the pandemic.

Social and Behavioral Difficulties in 10-Year-Old Children With Congenital Heart Disease: Prevalence and Risk Factors.

Children with congenital heart disease (CHD) may be at increased risk for neurodevelopmental impairments. Long-term behavioral profiles and respective risk factors are less frequently described. The aim of this study was to evaluate multidimensional behavioral outcomes and associated medical, psychological, and social risk factors in children with complex CHD. At 10-years of age, 125 children with CHD were assessed for general behavioral difficulties, attention deficit hyperactivity disorder (ADHD)-related behavior, and social interaction problems and were compared to normative data. Medical and cardiac factors, IQ, maternal mental health at 4 years of age and parental socioeconomic status were tested as predictors for all behavioral outcomes. Children with CHD showed no significant differences in general behavioral difficulties. However, increased ADHD-related symptoms (p < 0.05) and difficulties in social interaction (p < 0.05) were observed. In 23% of the children, a combination of ADHD-related symptoms and social interaction problems was reported by parents. In multivariate analyses, IQ (p < 0.01) and maternal mental health (p < 0.03) at 4 years of age were found to be predictive for all behavioral outcomes at 10 years while medical and cardiac risk factors were not. Our findings reveal significant difficulties in ADHD-related symptoms and social interaction problems with a significant comorbidity. Behavioral difficulties were not detected with a screening tool but with disorder-specific questionnaires. Furthermore, we demonstrate the importance of maternal mental health during early childhood on later behavioral outcomes of children with CHD. This underlines the importance of identifying and supporting parents with mental health issues at an early stage in order to support the family and improve the child's neurodevelopment.

Executive function deficits mediate the association between very preterm birth and behavioral problems at school-age.

BACKGROUND & AIMS: Children and adolescents born very preterm are at increased risk to develop executive function deficits and to suffer from social, emotional and attentional problems. This study investigated whether executive function deficits contribute to behavioral problems in children and adolescents born very preterm at school-age. STUDY DESIGN: Thirty-eight children and adolescents born very preterm and 41 age-matched term-born peers were assessed at a mean age of 12.9 (±1.8) years with a comprehensive battery of executive function tests, including working memory, planning, cognitive flexibility, and verbal fluency. A composite score was calculated to reflect overall executive function abilities. To assess behavioral problems, parents completed the Strengths and Difficulties Questionnaire (SDQ). Mediation analysis was applied to quantify the effect of preterm birth on behavioral problems with executive function abilities as a mediating variable. RESULTS: Executive function abilities were poorer in the very preterm compared to the term-born group (d = 0.62, p = .005) and the parents of very preterm children reported more behavioral problems on the SDQ Total Difficulties Score (d = 0.54, p = .01). The effect of birth status on behavioral problems was significantly mediated by executive function abilities while adjusting for age at assessment, sex, and socioeconomic status (F(2, 76) = 6.42, p = .002, R2 = 0.14). CONCLUSION: Results from this study suggest that the increase in behavioral symptoms in very preterm children at school-age compared to term-born peers may partly be explained by their executive function deficits. These findings highlight the importance of continuously monitoring the development of children born very preterm to provide optimal care as they grow up.

Inhibition is associated with whole-brain structural brain connectivity on network level in school-aged children born very preterm and at term.

Inhibition abilities are often impaired in children born very preterm. In typically-developing individuals, inhibition has been associated with structural brain connectivity (SC). As SC is frequently altered following preterm birth, this study investigated whether aberrant SC underlies inhibition deficits in school-aged children born very preterm. In a group of 67 very preterm participants aged 8-13 years and 69 term-born peers, inhibition abilities were assessed with two tasks. In a subgroup of 50 very preterm and 62 term-born participants, diffusion tensor imaging (DTI) data were collected. Using network-based statistics (NBS), mean fractional anisotropy (FAmean) was compared between groups. Associations of FAmean and inhibition abilities were explored through linear regression. The composite score of inhibition abilities was lower in the very preterm group (M â€‹= â€‹-0.4, SD â€‹= â€‹0.8) than in the term-born group (M â€‹= â€‹0.0, SD â€‹= â€‹0.8) but group differences were not significant when adjusting for age, sex and socio-economic status (ߠ​= â€‹-0.13, 95%-CI [-0.30, 0.04], p â€‹= â€‹0.13). In the very preterm group, FAmean was significantly lower in a network comprising thalamo-frontal, thalamo-temporal, frontal, cerebellar and intra-hemispheric connections than in the term-born group (t â€‹= â€‹5.21, lowest p-value â€‹= â€‹0.001). Irrespective of birth status, a network comprising parietal, cerebellar and subcortical connections was positively associated with inhibition abilities (t â€‹= â€‹4.23, lowest p-value â€‹= â€‹0.02). Very preterm birth results in long-term alterations of SC at network-level. As networks underlying inhibition abilities do not overlap with those differing between the groups, FAmean may not be adequate to explain inhibition problems in very preterm children. Future studies should combine complementary measures of brain connectivity to address neural correlates of inhibition abilities.

Multimodal assessment shows misalignment of structural and functional thalamocortical connectivity in children and adolescents born very preterm.

Thalamocortical connections are altered following very preterm birth but it is unknown whether structural and functional alterations are linked and how they contribute to neurodevelopmental deficits. We used a multimodal approach in 27 very preterm and 35 term-born children and adolescents aged 10-16 years: Structural thalamocortical connectivity was quantified with two measures derived from probabilistic tractography of diffusion tensor data, namely the volume of thalamic segments with cortical connections and mean fractional anisotropy (FA) within the respective segments. High-density sleep EEG was recorded and sleep spindles were identified at each electrode. Sleep spindle density and integrated spindle activity (ISA) were calculated to quantify functional thalamocortical connectivity. In term-born participants, the volume of the global thalamic segment with cortical connections was strongly related to sleep spindles across the entire head (mean r â€‹= â€‹.53 â€‹± .10; range â€‹= â€‹0.35 to 0.78). Regionally, the volume of the thalamic segment connecting to frontal brain regions correlated with sleep spindle density in two clusters of electrodes over fronto-temporal brain regions (.42 â€‹± .06; 0.35 to 0.51 and 0.43 â€‹± .08; 0.35 to 0.62) and the volume of the thalamic segment connecting to parietal brain regions correlated with sleep spindle density over parietal brain regions (mean r â€‹= â€‹.43 â€‹± .07; 0.35 to 0.61). In very preterm participants, the volume of the thalamic segments was not associated with sleep spindles. In the very preterm group, mean FA within the global thalamic segment was negatively correlated with ISA over a cluster of frontal and temporo-occipital brain regions (mean r â€‹= â€‹-.53 â€‹± .07; -.41 to -.72). No association between mean FA and ISA was found in the term-born group. With this multimodal study protocol, we identified a potential misalignment between structural and functional thalamocortical connectivity in children and adolescents born very preterm. Eventually, this may shed further light on the neuronal mechanisms underlying neurodevelopmental sequelae of preterm birth.

The Importance of Childhood for Adult Health and Development-Study Protocol of the Zurich Longitudinal Studies.

Evidence is accumulating that individual and environmental factors in childhood and adolescence should be considered when investigating adult health and aging-related processes. The data required for this is gathered by comprehensive long-term longitudinal studies. This article describes the protocol of the Zurich Longitudinal Studies (ZLS), a set of three comprehensive cohort studies on child growth, health, and development that are currently expanding into adulthood. Between 1954 and 1961, 445 healthy infants were enrolled in the first ZLS cohort. Their physical, motor, cognitive, and social development and their environment were assessed comprehensively across childhood, adolescence, and into young adulthood. In the 1970s, two further cohorts were added to the ZLS and assessed with largely matched study protocols: Between 1974 and 1979, the second ZLS cohort included 265 infants (103 term-born and 162 preterm infants), and between 1970 and 2002, the third ZLS cohort included 327 children of participants of the first ZLS cohort. Since 2019, the participants of the three ZLS cohorts have been traced and invited to participate in a first wave of assessments in adulthood to investigate their current health and development. This article describes the ZLS study protocol and discusses opportunities, methodological and conceptual challenges, and limitations arising from a long-term longitudinal cohort recruited from a study about development in early life. In the future, the ZLS will provide data to investigate childhood antecedents of adult health outcomes and, ultimately, will help respond to the frequent call of scientists to shift the focus of aging research into the first decades of life and, thus, to take a lifespan perspective on aging.

Development and Health of Adults Formerly Placed in Infant Care Institutions - Study Protocol of the LifeStories Project.

A growing volume of research from global data demonstrates that institutional care under conditions of deprivation is profoundly damaging to children, particularly during the critical early years of development. However, how these individuals develop over a life course remains unclear. This study uses data from a survey on the health and development of 420 children mostly under the age of three, placed in 12 infant care institutions between 1958 and 1961 in Zurich, Switzerland. The children exhibited significant delays in cognitive, social, and motor development in the first years of life. Moreover, a follow-up of a subsample of 143 children about 10 years later revealed persistent difficulties, including depression, school related-problems, and stereotypies. Between 2019 and 2021, these formerly institutionalized study participants were located through the Swiss population registry and invited to participate once again in the research project. Now in their early sixties, they are studied for their health, further development, and life-course trajectories. A mixed-methods approach using questionnaires, neuropsychological assessments, and narrative biographical interviews was implemented by a multidisciplinary team. Combining prospective and retrospective data with standardized quantitative and biographical qualitative data allows a rich reconstruction of life histories. The availability of a community sample from the same geographic location, the 1954-1961 cohort of the Zurich Longitudinal Studies, described in detail in a paper in this issue (Wehrle et al., 2020), enables comparison with an unaffected cohort. This article describes the study design and study participants in detail and discusses the potential and limitations of a comparison with a community sample. It outlines a set of challenges and solutions encountered in the process of a lifespan longitudinal study from early childhood into the cusp of old age with a potentially vulnerable sample and summarizes the lessons learned along the way.