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Background Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO 2 ), arterial pO 2 levels, and supplemental oxygen (FiO 2 ) would associate with later neuroanatomic changes. Methods SpO 2 , arterial blood gases, and FiO 2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n  = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n  = 39), Hempel neurological examination ( n  = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n  = 58). Results The ELGANs with later WM abnormalities exhibited lower SpO 2 and pO 2 levels, and higher FiO 2 need during the first 3 days than those with normal WM. They also had higher pCO 2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO 2 and pO 2 levels and lower FiO 2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment. Conclusions Low oxygen levels and high FiO 2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets. Impact This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

•Extremely preterm birth has long-lasting effects on brain network functionality.•Functional connectivity of especially higher-order networks is compromised.•School-aged preterms show impaired connectivity modulation between brain-states.•Preterms and controls have opposite age-related changes in functional connectivity.•Functional connectivity associates with better n-back performance only in controls. Cognitive functions emerge from dynamic functional interplay of cortical and subcortical areas that form networks. Preterm birth poses a risk for the formation and functionality of brain networks which may lead to severe brain dysfunctions. Infants born extremely preterm have the highest risk of developing neurocognitive impairments. However, it is still poorly understood how functional brain networks are organized and linked with the cognitive impairments in extremely prematurely born children and adolescents. We applied network-based statistics to study functional network connectivity during two brain-states, resting-state (Rest) and visuospatial working memory n-back tasks (Task), in a unique cohort of extremely preterm-born school-aged children and adolescents (n = 24, mean age 10.3 y, range 7.4–16.4 y) with normal general cognitive abilities and in their term-born peers (n = 22, mean age 9.5 y, range 7.4–13.7 y). We found significant group differences in functional connectivity strength in networks that support complex cognitive performance. The preterm group, compared with controls, modulated functional connectivity between Rest and Task differently within the dorsal attention (DAN, p = 0.016), default mode (DMN, p = 0.026) and visual (VN, p = 0.022) networks, and between DMN – DAN (p = 0.024), DMN – ventral attention network (VAN) (p = 0.035), and DMN – frontoparietal network (FPN) (p = 0.015). The groups also showed opposite age-related changes in connectivity strength within the DAN (Task, p = 0.005; Rest, p = 0.012), DMN (Task, p = 0.015) and FPN (Task, p = 0.002), and between the DAN – VAN (p = 0.047) and DAN – FPN (p = 0.009) during Rest, and FPN – VAN (p =0.028), DAN – FPN (p = 0.006), DMN – DAN (p = 0.042), DMN – VAN (p = 0.023), and DMN – FPN (p = 0.007) during Task. In controls, stronger within-network connectivity associated with better n-back task performance, whereas in the preterm group, stronger between-network connectivity associated with poorer performance. These results suggest that adjustment of functional connectivity to the cognitive demands supports successful performance in school-aged children and adolescents and that extremely preterm birth compromises the dynamics and developmental trajectories of brain networks.

Introduction Cognitive development is characterized by the structural and functional maturation of the brain. Diffusion‐weighted magnetic resonance imaging (dMRI) provides methods of investigating the brain structure and connectivity and their correlations with the neurocognitive outcome. Our aim was to examine the relationship between early visual abilities, brain white matter structures, and the later neurocognitive outcome. Methods This study included 20 infants who were born before 28 gestational weeks and followed until the age of 6.5 years. At term age, visual alertness was evaluated and dMRI was used to investigate the brain white matter structure using fractional anisotropy (FA) in tract‐based spatial statistics analysis. The JHU DTI white matter atlas was used to locate the findings. The neuropsychological assessment was used to assess neurocognitive performance at 6.5 years. Results Optimal visual alertness at term age was significantly associated with better visuospatial processing (p < .05), sensorimotor functioning (p < .05), and social perception (p < .05) at 6.5 years of age. Optimal visual alertness related to higher FA values, and further, the FA values positively correlated with the neurocognitive outcome. The tract‐based spatial differences in FA values were detected between children with optimal and nonoptimal visual alertness according to performance at 6.5 years. Conclusion We provide neurobiological evidence for the global and tract‐based spatial differences in the white matter maturation between extremely preterm children with optimal and nonoptimal visual alertness at term age and a link between white matter maturation, visual alertness and the neurocognitive outcome at 6.5 years proposing that early visual function is a building block for the later neurocognitive development. The relationship between early visual abilities, brain white matter structures, and later neurocognitive outcome in extremely preterm born infants was examined. At term age, visual alertness was evaluated and dMRI was used to investigate the brain white matter structure and at 6.5 years neurocognitive performance was assessed. Optimal visual alertness related to widely increased mean fractional anisotropy (FA), and the mean FA values positively correlated with neurocognitive outcome proposing that early visual function is a building block for the later neurocognitive development.

Preterm birth(<37 gestational weeks) is associated with numerous adversities, however, data on positive developmental outcomes remain limited. We examined if preterm and term born(≥37 gestational weeks) adults differ in dispositional optimism/pessimism, a personality trait associated with health and wellbeing. We assessed if birth weight z-score, neurosensory impairments and parental education modified the outcome. We systematically searched PubMed and Web of Science for cohort or case-control studies(born ≥ 1970) with data on gestational age and optimism/pessimism reported using the Life-Orientation-Test-Revised in adulthood(≥18 years). The three identified studies(Helsinki Study of Very Low Birth Weight Adults; Arvo Ylppö Longitudinal Study; Avon Longitudinal Study of Parents and Children) provided data for the two-step random-effects linear regression Individual-Participant-Data meta-analysis. Preterm and term borns did not differ on optimism(p = 0.76). Preterms scored higher on pessimism than term borns(Mean difference = 0.35, 95%Confidence Interval 0.36, 0.60, p = 0.007), although not after full adjustment. Preterm born participants, but not term born participants, with higher birth weight z-score, had higher optimism scores (0.30 raw score units per standard deviation increase, 95% CI 0.10, 0.49, p = 0.003); preterm vs term x birth weight z-score interaction p = 0.004). Preterm and term born adults display similar optimism. In preterms, higher birth weight may foster developmental trajectories promoting more optimistic life orientations.

Low physical activity (PA) is a major risk factor for cardiovascular and metabolic disorders in all age groups. We measured intensity and volume of PA and examined the associations between PA and the metabolic syndrome (MS), its components and body composition among young Finnish adults. The study comprises 991 men and women born 1985-86, who participated in a clinical study during the years 2009-11 which included assessments of metabolism, body composition and PA. Objectively measured (SenseWear Armband) five-day PA data was available from 737 participants and was expressed in metabolic equivalents of task (MET). The prevalence of MS ranged between 8-10%. Higher total mean volume (MET-hours) or intensity (MET) were negatively associated with the risk of MS and separate components of MS, while the time spent at sedentary level of PA was positively associated with MS. MS was prevalent in approximately every tenth of the young adults at the age of 24 years. Higher total mean intensity and volume rates as well as longer duration spent at moderate and vigorous PA level had a beneficial impact on the risk of MS. Longer time spent at the sedentary level of PA increased the risk of MS.

Background It remains unclear whether it is more detrimental to be born too early or too small in relation to symptoms of attention deficit/hyperactivity disorder (ADHD). Thus, we tested whether preterm birth and small body size at birth adjusted for gestational age are independently associated with symptoms of ADHD in children. Methods A longitudinal regional birth cohort study comprising 1535 live-born infants between 03/15/1985 and 03/14/1986 admitted to the neonatal wards and 658 randomly recruited non-admitted infants, in Finland. The present study sample comprised 828 children followed up to 56 months. The association between birth status and parent-rated ADHD symptoms of the child was analysed with multiple linear and logistic regression analyses. Results Neither prematurity (birth < 37 weeks of gestation) nor lower gestational age was associated with ADHD symptoms. However, small for gestational age (SGA < -2 standard deviations [SD] below the mean for weight at birth) status and lower birth weight SD score were significantly, and independently of gestational age, associated with higher ADHD symptoms. Those born SGA, relative to those born AGA, were also 3.60-times more likely to have ADHD symptoms scores above the clinical cut-off. The associations were not confounded by factors implicated as risks for pregnancy and/or ADHD. Conclusions Intrauterine growth restriction, reflected in SGA status and lower birth weight, rather than prematurity or lower gestational age per se , may increase risk for symptoms of ADHD in young children.

Background and aims Children with extremely low‐birth weight (ELBW) have a high risk for cognitive, motor, and attention impairments and learning disabilities. Longitudinal follow‐up studies to a later age are needed in order to increase understanding of the changes in neurodevelopmental trajectories in targeting timely intervention. The aims of this study were to investigate cognitive and motor outcomes, attention‐deficit hyperactivity (ADHD) behaviour, school performance, and overall outcomes in a national cohort of ELBW children at preadolescence, and minor neuromotor impairments in a subpopulation of these children and to compare the results with those of full‐term controls. The additional aim was to report the overall outcome in all ELBW infants born at 22 to 26 gestational weeks. Methods This longitudinal prospective national cohort study included all surviving ELBW (birth weight <1000 g) children born in Finland in 1996 to 1997. No children were excluded from the study. Perinatal, neonatal, and follow‐up data up to the age of 5 years of these children were registered in the national birth register. According to birth register, the study population included all infants born at the age under 27 gestational weeks. At 11 years of age general cognitive ability was tested with the Wechsler Intelligence Scale for Children, ADHD behavior evaluated with a report from each child's own teacher (ADHD Rating Scale IV), and school performance with a parental questionnaire. An ELBW subpopulation consisting of a cohort representative children from the two university hospitals from two regions (n = 63) and the age‐matched full‐term born controls born in Helsinki university hospital (n = 30) underwent Movement Assessment Battery for Children and Touwen neurological examination comprising developmental coordination disorder (DCD) and minor neurological dysfunction (MND), respectively. Results Of 206 ELBW survivors 122 (73% of eligible) children and 30 (100%) full‐term control children participated in assessments. ELBW children had lower full‐scale intellectual quotient than controls (t‐test, 90 vs 112, P < .001), elevated teacher‐ reported inattention scores (median = 4.0 vs 1.0, P = .021, r = .20) and needed more educational support (47% vs 17%, OR 4.5, 95% CI 1.6‐12.4, P = .02). In the subpopulation, the incidences of DCD were 30% in ELBW and 7% in control children (P = .012, OR 6.0 CI 1.3‐27.9), and complex MND 12.5% and 0%, (P = .052; RR 1.1 95% CI 1.04‐1.25), respectively. Of survivors born in 24 to 26 gestational weeks, 29% had normal outcome. Conclusion As the majority of the extremely preterm born children had some problems, long‐term follow‐up is warranted to identify those with special needs and to design individual multidisciplinary support programs.

BackgroundRecent longitudinal studies suggest stable cognitive development in preterm children, although with great individual variation. This prospective neurocognitive follow-up study of extremely low birthweight (ELBW, <1000 g) children aimed to characterise groups with different developmental trajectories from preschool to preteen age.MethodsELBW children (n=115) born in Finland in 1996–1997 participated in cognitive assessments at a median age of 5.0 years and 11.3 years. A standardised test of intelligence (Wechsler Preschool and Primary Scale of Intelligence–Revised or Wechsler Intelligence Scale for Children–third edition) was administered at both ages.ResultsThree ELBW groups with different developmental trajectories over time were identified with latent class growth analysis. Children with average (Full-Scale IQ (FSIQ): 85–115) and below average (FSIQ: <85) intelligence at 5 years of age had significant decreases in intelligence scores by 11 years of age (–11.7 points and –14.9 points, respectively, both p<0.001), while those with above average intelligence (FSIQ: >115) showed stable development (–3.2 points, p=0.250). Multiple linear regression showed that neonatal complications (intraventricular haemorrhage grade 3–4 and blood culture positive sepsis) and maternal education significantly predicted lower intelligence at the second assessment (F(3,106)=7.27, p<0.001, adjusted R2=0.147).ConclusionsELBW children represent a heterogeneous patient population in which groups with different cognitive trajectories can be detected. Deterioration may occur particularly in children with initial average or below average cognitive performance at 5 years of age, with neonatal complications and lower maternal education presenting as risk factors. Catch-up in cognitive functions seems more uncommon in the ELBW population, which should be noted in clinical work.

Background/ObjectivesMaternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m2) or GDM are associated with dietary quality or intake in adult offspring.Subjects/MethodsParticipants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537).ResultsAmong men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [−587.2 kJ/day (−1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (−0.38, 1.18); women 0.25 (−0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (−0.62, 0.80); women −0.17 (−0.93, 0.59)].ConclusionsOur study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.

Background Empirical evidence suggests that prenatal growth is associated with attention deficit/hyperactivity disorder (ADHD) and its symptoms. Data on the importance of postnatal growth is, however scanty. We studied whether pre- and postnatal growth up to 56 months is associated with symptoms of ADHD in children. Method A longitudinal regional birth cohort study comprising 893 children followed up to 56 months. The associations between pre- and postnatal growth and parent-rated ADHD symptoms of the child were analyzed with multiple linear regression analyses and repeated-measures analyzes of covariance. Results Children born lighter, thinner, shorter, and with a smaller head circumference, adjusted for length of gestation, received higher parent-rated ADHD symptoms scores at 56 months. Further, smaller head circumference throughout the period of growth from birth up to 56 months was related to higher ADHD symptoms scores. The associations changed only little after adjusting for several pre- and neonatal factors. The associations were not modified by sex and there were no evidence of non-linear associations. Conclusions Slower prenatal growth in weight, body-mass index, length, and head circumference may pose a risk for higher ADHD symptoms in childhood. The consistently smaller head circumference from birth up to 56 months characterizing children with higher ADHD symptoms may point to a lack of catch-up growth in head circumference in childhood as a predisposing factor.