Atypical brain structure mediates reduced IQ in young adults born preterm with very low birth weight.

Preterm birth with very low birth weight (VLBW) confers heightened risk for perinatal brain injury and long-term cognitive deficits, including a reduction in IQ of up to one standard deviation. Persisting gray and white matter aberrations have been documented well into adolescence and adulthood in preterm born individuals. What has not been documented so far is a plausible causal link between reductions in cortical surface area or subcortical brain structure volumes, and the observed reduction in IQ. The NTNU Low Birth Weight in a Lifetime Perspective study is a prospective longitudinal cohort study, including a preterm born VLBW group (birthweight ≤1500 g) and a term born control group. Structural magnetic resonance imaging data were obtained from 38 participants aged 19, born preterm with VLBW, and 59 term-born peers. The FreeSurfer software suite was used to obtain measures of cortical thickness, cortical surface area, and subcortical brain structure volumes. Cognitive ability was estimated using the Wechsler Adult Intelligence Scale, 3rd Edition, including four IQ-indices: Verbal comprehension, Working memory, Perceptual organization, and Processing speed. Statistical mediation analyses were employed to test for indirect effects of preterm birth with VLBW on IQ, mediated by atypical brain structure. The mediation analyses revealed negative effects of preterm birth with VLBW on IQ that were partially mediated by reduced surface area in multiple regions of frontal, temporal, parietal and insular cortex, and by reductions in several subcortical brain structure volumes. The analyses did not yield sufficient evidence of mediation effects of cortical thickness on IQ. This is, to our knowledge, the first time a plausible causal relationship has been established between regional cortical area reductions, as well as reductions in specific subcortical and cerebellar structures, and general cognitive ability in preterm born survivors with VLBW.

Multidisciplinary and neuroimaging findings in preterm born very low birthweight individuals from birth to 28 years of age: A systematic review of a Norwegian prospective cohort study.

BACKGROUND: Children born preterm with very low birthweight (VLBW) face long-lasting neurodevelopmental challenges, where multidisciplinary assessments are warranted. The International Classification of Functioning, Disability and Health (ICF) provides a framework for understanding and conceptualising these outcomes. OBJECTIVES: We aimed to review clinical and neuroimaging findings from birth to adulthood in a Norwegian cohort of individuals born preterm with VLBW (gestational age <37 weeks, birthweight ≤1500 g) within the framework of ICF. DATA SOURCES: We searched PubMed and Embase for articles reporting results of the Norwegian University of Science and Technology (NTNU) Low Birth Weight in a Lifetime Perspective study. STUDY SELECTION AND DATA EXTRACTION: We included original articles reporting proportions of adverse outcomes, mean group differences, risk factors or associations between outcomes. Data were extracted according to ICF's two-level classification. Body functions and structures comprised outcomes of brain structures, cognition, mental health, vision, pain and physical health. Activities and participation comprised motor skills, general and social functioning, education, employment, and health-related quality of life. SYNTHESIS: We performed a qualitative synthesis of included articles. Where mean (SD) was reported, we calculated group differences in SD units. RESULTS: Fifty-eight publications were included. Within body functions and structures, increased prevalence of brain structure pathology, lower cognitive performance, mental health problems, visual and physical health impairments through childhood, adolescence and young adulthood were reported among preterm VLBW participants compared with controls. Within activities and participation, motor problems, lower general and social functioning, and lower academic attainment were found. Perinatal factors were associated with several outcomes, and longitudinal findings suggested persistent consequences of being born preterm with VLBW. CONCLUSIONS: Being born preterm with VLBW has long-term influences on body functions and structures, activities and participation. The ICF is appropriate for assessing general domains of functioning and guiding the management of individuals born preterm with VLBW.

Increased interaction and procedural flexibility favoured participation: Study across European cohorts of preterm born individuals.

OBJECTIVE: To understand participation and attrition phenomena variability in European cohorts of individuals born preterm through in-depth exploration of the interplay of situational elements involved. METHODS: Multi-situated qualitative design, using focus groups, semi-structured interviews and collaborative visual methodology with a purposive sample of adults born preterm, parents and professionals (n = 124) from eight cohorts in seven European countries. RESULTS: Most cohort participants were motivated by altruism/solidarity and gratitude/sense of duty to reciprocate (only absent in adults aged 19 - 21), followed by expectation of direct benefit to one's health and knowledge amongst participating adults. Common deterrents were perceived failure in reciprocity as in insufficient/inadequate interaction and information sharing, and postal questionnaires. Combining multipurpose, flexible strategies for contact and assessment, reminders, face-to-face and shorter periodicity and not simply adding retention strategies or financial incentives favoured participation. Professionals' main challenges entailed resources, funding and, European societal changes related to communication and geopolitical environment. CONCLUSION: Retention would benefit from tailoring inclusive strategies throughout the cohorts' life cycle and consistent promotion of reciprocal altruistic research goals. Investing in regular interaction, flexibility in procedures, participant involvement and return of results can help mitigate attrition as well as considering mothers as main facilitators to participating children and impaired adults.

Neurocognitive function and associations with mental health in adults born preterm with very low birthweight or small for gestational age at term.

Objectives: To assess neurocognitive function in adults born with low birthweight compared with controls and to explore associations between neurocognitive function and psychopathology in these groups. Methods: In this prospective cohort study, one group born preterm with very low birthweight (VLBW: birthweight <1,500 g, n = 53), one group born small for gestational age at term (SGA: birthweight <10th percentile, n = 63) and one term-born control group (birthweight ≥10th percentile, n = 81) were assessed with neurocognitive tests, diagnostic interviews, and self-report questionnaires at 26 years of age. Results: The VLBW group scored significantly below the control group on several neurocognitive measures, including IQ measures, psychomotor speed, verbal fluency, aspects of visual learning and memory, attention, social cognition, working memory and fine motor speed. The SGA group consistently scored at an intermediate level between the VLBW and the control group and had significantly lower scores than controls on Performance IQ and psychomotor speed, including switching. In the VLBW group, associations were found between lower spatial working memory and the presence of anxiety disorders, internalizing and attention problems, and autistic traits. Furthermore, lower Full scale IQ was associated with attention problems when adjusting for sex and parental socioeconomic status. Conclusion: Adults born preterm with VLBW or born term SGA displayed neurocognitive difficulties. Spatial working memory was associated with difficulties with attention, anxiety, and social function of VLBW adults. The finding and its clinical applicability should be further explored.

Is there an association between full IQ score and mental health problems in young adults? A study with a convenience sample.

BACKGROUND: Intelligence is the aggregate or global capacity of the individual to act purposefully, to think rationally and to deal effectively with the environment. Previous studies have shown that individuals with intellectual disability, IQ < 70, have increased risk of being diagnosed with one or more mental disorders. We wanted to investigate if this also applies to individuals with IQ between 70 and 85. METHODS: In this study, data was abstracted from a longitudinal follow-up study of individuals with low birth weight and a control group. In the present study, mental health of participants with borderline IQ, defined as a full IQ score 70-84, were compared with mental health of a reference group with full IQ scores ≥85. Mental health at age 19 was assessed using the Schedule for Affective Disorder and Schizophrenia for School-age Children Present and Lifetime (K-SADS P/L) whereby scores meeting the diagnostic criteria for a mental disorder were defined as having mental health problems. In addition the participants completed the ADHD-rating scale and the Autism Spectrum Quotient form (AQ). Logistic regression analyses were used to calculate odds ratio (OR) with 95% confidence intervals (CI) for high scores on the K-SADS. RESULTS: Thirty participants with borderline IQ and 146 controls were included. Sixteen (53%) of the participants with borderline IQ met the diagnostic criteria on the K-SADS for any diagnosis compared with 18 (12%) in the reference group (OR: 6.2; CI: 2.6-14.9). In particular the participants with borderline IQ had excess risk of ADHD and anxiety. These associations were slightly attenuated when adjusted for birth weight and parents' socioeconomic status. CONCLUSIONS: 53% of the participants with borderline IQ had increased risk for a research assessed psychiatric diagnosis compared to about one in ten in the reference group. The group with borderline IQ also had higher total scores and higher scores on some sub-scores included in the Autism Spectrum Quotient form. Our results points towards an increased vulnerability for mental illness in individuals with borderline low IQ. TRIAL REGISTRATION: The main study is recorded by the Regional Committee for Health Research Ethics in Mid-Norway (as project number 4.2005.2605).

Psychiatric symptoms and risk factors in adults born preterm with very low birthweight or born small for gestational age at term.

BACKGROUND: We aimed to examine psychiatric symptoms in adults born preterm with very low birthweight or born at term small for gestational age compared with normal birthweight peers, and examine associations with perinatal factors and childhood motor and cognitive function. METHODS: In this longitudinal cohort study, one preterm born group with very low birthweight (VLBW: birthweight ≤1500 g), one term-born Small for Gestational Age (SGA: birthweight <10th percentile) group and one term-born non-SGA control group, were assessed at 26 years of age. Primary outcomes were scores on self-reported questionnaires: Achenbach System of Empirically Based Assessment - Adult Self-Report, The Autism-Spectrum Quotient and Peters et al. Delusions Inventory. Exposure variables were perinatal data, while childhood motor and cognitive function were examined as possible early markers. RESULTS: Both the preterm VLBW and the term SGA group reported higher levels of attention, internalizing and externalizing problems compared to the control group. In addition, the VLBW participants reported more critical items and a higher proportion had intermediate level autistic traits, while the SGA participants reported more intrusive behavior. Increasing length of respiratory support and hospital stay in the neonatal period, and motor problems in early adolescence, were associated with adult psychiatric symptoms in the VLBW group. CONCLUSIONS: Psychiatric symptoms were frequent in the preterm VLBW group and also in the term-born SGA group. Those who were sickest as babies were most at risk. Motor problems can possibly serve as an early marker of adult psychiatric symptoms in low birthweight individuals.

Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight.

Development of the cerebral cortex may be affected by aberrant white matter development. Preterm birth with very low birth weight (VLBW) has been associated with reduced fractional anisotropy of white matter and changes in cortical thickness and surface area. We use a new methodological approach to combine white and gray matter data and test the hypothesis that white matter injury is primary, and acts as a mediating factor for concomitant gray matter aberrations, in the developing VLBW brain. T1 and dMRI data were obtained from 47 young adults born preterm with VLBW and 73 term-born peers (mean age = 26). Cortical thickness was measured across the cortical mantle and compared between the groups, using the FreeSurfer software suite. White matter pathways were reconstructed with the TRACULA software and projected to their cortical end regions, where cortical thickness was averaged. In the VLBW group, cortical thickness was increased in anteromedial frontal, orbitofrontal, and occipital regions, and fractional anisotropy (FA) was reduced in frontal lobe pathways, indicating compromised white matter integrity. Statistical mediation analyses demonstrated that increased cortical thickness in the frontal regions was mediated by reduced FA in the corpus callosum forceps minor, consistent with the notion that white matter injury can disrupt frontal lobe cortical development. Combining statistical mediation analysis with pathway projection onto the cortical surface offers a powerful novel tool to investigate how cortical regions are differentially affected by white matter injury.

Preterm birth leads to hyper-reactive cognitive control processing and poor white matter organization in adulthood.

Individuals born preterm with very low birth weight (VLBW; birth weight ≤ 1500 g) are at high risk for perinatal brain injuries and deviant brain development, leading to increased chances of later cognitive, emotional, and behavioral problems. Here we investigated the neuronal underpinnings of both reactive and proactive cognitive control processes in adults with VLBW. We included 32 adults born preterm with VLBW (before 37th week of gestation) and 32 term-born controls (birth weight ≥10th percentile for gestational age) between 22 and 24 years of age that have been followed prospectively since birth. Participants performed a well-validated Not-X continuous performance test (CPT) adapted for use in a mixed block- and event-related fMRI protocol. BOLD fMRI and DTI data was acquired on a 3T scanner. Performance on the Not-X CPT was highly similar between groups. However, the VLBW group demonstrated hyper-reactive cognitive control processing and disrupted white matter organization. The hyper-reactive brain activation signature in VLBW adults was associated with lower gestational age, lower fluid intelligence score, and anxiety problems. Automated Multi-Atlas Tract Extraction (AutoMATE) analyses revealed that this disruption of normal brain function was accompanied by poorer white matter organization in the anterior thalamic radiation and the cingulum, as reflected in both reduced fractional anisotropy and increased mean diffusivity. These findings show that the preterm behavioral phenotype is associated with predominantly reactive-, rather than proactive cognitive control processing, as well as white matter abnormalities, that may underlie common difficulties that many preterm born individuals experience in everyday life.

White matter alterations and their associations with motor function in young adults born preterm with very low birth weight.

Very low birth weight (VLBW: ≤ 1500 g) individuals have an increased risk of white matter alterations and neurodevelopmental problems, including fine and gross motor problems. In this hospital-based follow-up study, the main aim was to examine white matter microstructure and its relationship to fine and gross motor function in 31 VLBW young adults without cerebral palsy compared with 31 term-born controls, at mean age 22.6 ± 0.7 years. The participants were examined with tests of fine and gross motor function (Trail Making Test-5: TMT-5, Grooved Pegboard, Triangle from Movement Assessment Battery for Children-2: MABC-2 and High-level Mobility Assessment Tool: HiMAT) and diffusion tensor imaging (DTI). Probabilistic tractography of motor pathways of the corticospinal tract (CST) and corpus callosum (CC) was performed. Fractional anisotropy (FA) was calculated in non-crossing (capsula interna in CST, body of CC) and crossing (centrum semiovale) fibre regions along the tracts and examined for group differences. Associations between motor test scores and FA in the CST and CC were investigated with linear regression. Tract-based spatial statistics (TBSS) was used to examine group differences in DTI metrics in all major white matter tracts. The VLBW group had lower scores on all motor tests compared with controls, however, only statistically significant for TMT-5. Based on tractography, FA in the VLBW group was lower in non-crossing fibre regions and higher in crossing fibre regions of the CST compared with controls. Within the VLBW group, poorer fine motor function was associated with higher FA in crossing fibre regions of the CST, and poorer bimanual coordination was additionally associated with lower FA in crossing fibre regions of the CC. Poorer gross motor function was associated with lower FA in crossing fibre regions of the CST and CC. There were no associations between motor function and FA in non-crossing fibre regions of the CST and CC within the VLBW group. In the TBSS analysis, the VLBW group had lower FA and higher mean diffusivity compared with controls in all major white matter tracts. The findings in this study may indicate that the associations between motor function and FA are caused by other tracts crossing the CST and CC, and/or by alterations in the periventricular white matter in the centrum semiovale. Some of the associations were in the opposite direction than hypothesized, thus higher FA does not always indicate better function. Furthermore, widespread white matter alterations in VLBW individuals persist into young adulthood.

Early metabolite changes after melatonin treatment in neonatal rats with hypoxic-ischemic brain injury studied by in-vivo1H MR spectroscopy.

Melatonin is a promising neuroprotective agent after perinatal hypoxic-ischemic (HI) brain injury. We used in-vivo 1H magnetic resonance spectroscopy to investigate effects of melatonin treatment on brain metabolism after HI. Postnatal day 7 Sprague-Dawley rats with unilateral HI brain injury were treated with either melatonin 10 mg/kg dissolved in phosphate-buffered saline (PBS) with 5% dimethyl sulfoxide (DMSO) or vehicle (5% DMSO and/or PBS) directly and at 6 hours after HI. 1H MR spectra from the thalamus in the ipsilateral and contralateral hemisphere were acquired 1 day after HI. Our results showed that injured animals had a distinct metabolic profile in the ipsilateral thalamus compared to sham with low concentrations of total creatine, choline, N-acetyl aspartate (NAA), and high concentrations of lipids. A majority of the melatonin-treated animals had a metabolic profile characterized by higher total creatine, choline, NAA and lower lipid levels than other HI animals. When comparing absolute concentrations, melatonin treatment resulted in higher glutamine levels and lower lipid concentrations compared to DMSO treatment as well as higher macromolecule levels compared to PBS treatment day 1 after HI. DMSO treated animals had lower concentrations of glucose, creatine, phosphocholine and macromolecules compared to sham animals. In conclusion, the neuroprotective effects of melatonin were reflected in a more favorable metabolic profile including reduced lipid levels that likely represents reduced cell injury. Neuroprotective effects may also be related to the influence of melatonin on glutamate/glutamine metabolism. The modulatory effects of the solvent DMSO on cerebral energy metabolism might have masked additional beneficial effects of melatonin.

Peak Bone Mass and Bone Microarchitecture in Adults Born With Low Birth Weight Preterm or at Term: A Cohort Study.

Context and Objectives: Peak bone mass (PBM) is regarded as the most important determinant of osteoporosis. Growing evidence suggests a role of intrauterine programming in skeletal development. We examined PBM and trabecular bone score (TBS) in adults born preterm with very low birth weight (VLBW) or small for gestational age (SGA) at term compared with term-born controls. Design, Setting, Participants, and Outcomes: This follow-up cohort study included 186 men and women (25 to 28 years); 52 preterm VLBW (≤1500 g), 59 term-born SGA (<10th percentile), and 75 controls (>10th percentile). Main outcome was bone mineral density (BMD) by dual x-ray absorptiometry. Secondary outcomes were bone mineral content (BMC), TBS, and serum bone markers. Results: VLBW adults had lower BMC and BMD vs controls, also when adjusted for height, weight, and potential confounders, with the following BMD Z-score differences: femoral neck, 0.6 standard deviation (SD) (P = 0.003); total hip, 0.4 SD (P = 0.01); whole body, 0.5 SD (P = 0.007); and lumbar spine, 0.3 SD (P = 0.213). The SGA group displayed lower spine BMC and whole-body BMD Z-scores, but not after adjustment. Adjusted odds ratios for osteopenia/osteoporosis were 2.4 and 2.0 in VLBW and SGA adults, respectively. TBS did not differ between groups, but it was lower in men than in women. Serum Dickkopf-1 was higher in VLBW subjects vs controls; however, it was not significant after adjustment for multiple comparisons. Conclusions: Both low-birth-weight groups displayed lower PBM and higher frequency of osteopenia/osteoporosis, implying increased future fracture risk. The most pronounced bone deficit was seen in VLBW adults.

Self-Reported Mental Health Problems Among Adults Born Preterm: A Meta-analysis.

CONTEXT: Preterm birth increases the risk for mental disorders in adulthood, yet findings on self-reported or subclinical mental health problems are mixed. OBJECTIVE: To study self-reported mental health problems among adults born preterm at very low birth weight (VLBW; ≤1500 g) compared with term controls in an individual participant data meta-analysis. DATA SOURCES: Adults Born Preterm International Collaboration. STUDY SELECTION: Studies that compared self-reported mental health problems using the Achenbach Young Adult Self Report or Adult Self Report between adults born preterm at VLBW (n = 747) and at term (n = 1512). DATA EXTRACTION: We obtained individual participant data from 6 study cohorts and compared preterm and control groups by mixed random coefficient linear and Tobit regression. RESULTS: Adults born preterm reported more internalizing (pooled ß = .06; 95% confidence interval .01 to .11) and avoidant personality problems (.11; .05 to .17), and less externalizing (-.10; -.15 to -.06), rule breaking (-.10; -.15 to -.05), intrusive behavior (-.14; -.19 to -.09), and antisocial personality problems (-.09; -.14 to -.04) than controls. Group differences did not systematically vary by sex, intrauterine growth pattern, neurosensory impairments, or study cohort. LIMITATIONS: Exclusively self-reported data are not confirmed by alternative data sources. CONCLUSIONS: Self-reports of adults born preterm at VLBW reveal a heightened risk for internalizing problems and socially avoidant personality traits together with a lowered risk for externalizing problem types. Our findings support the view that preterm birth constitutes an early vulnerability factor with long-term consequences on the individual into adulthood.

A longitudinal study of associations between psychiatric symptoms and disorders and cerebral gray matter volumes in adolescents born very preterm.

BACKGROUND: Being born preterm with very low birthweight (VLBW ≤ 1500 g) poses a risk for cortical and subcortical gray matter (GM) abnormalities, as well as for having more psychiatric problems during childhood and adolescence than term-born individuals. The aim of this study was to investigate the relationship between cortical and subcortical GM volumes and the course of psychiatric disorders during adolescence in VLBW individuals. METHODS: We followed VLBW individuals and term-born controls (birth weight ≥10th percentile) from 15 (VLBW;controls n = 40;56) to 19 (n = 44;60) years of age. Of these, 30;37 individuals were examined longitudinally. Cortical and subcortical GM volumes were extracted from MRPRAGE images obtained with the same 1.5 T MRI scanner at both time points and analyzed at each time point with the longitudinal stream of the FreeSurfer software package 5.3.0. All participants underwent clinical interviews and were assessed for psychiatric symptoms and diagnosis (Schedule for Affective Disorders and Schizophrenia for School-age Children, Children's Global Assessment Scale, Attention-Deficit/Hyperactivity Disorder Rating Scale-IV). VLBW adolescents were divided into two groups according to diagnostic status from 15 to 19 years of age: persisting/developing psychiatric diagnosis or healthy/becoming healthy. RESULTS: Reduction in subcortical GM volume at 15 and 19 years, not including the thalamus, was limited to VLBW adolescents with persisting/developing diagnosis during adolescence, whereas VLBW adolescents in the healthy/becoming healthy group had similar subcortical GM volumes to controls. Moreover, across the entire VLBW group, poorer psychosocial functioning was predicted by smaller subcortical GM volumes at both time points and with reduced GM volume in the thalamus and the parietal and occipital cortex at 15 years. Inattention problems were predicted by smaller GM volumes in the parietal and occipital cortex. CONCLUSIONS: GM volume reductions in the parietal and occipital cortex as well as smaller thalamic and subcortical GM volumes were associated with the higher rates of psychiatric symptoms found across the entire VLBW group. Significantly smaller subcortical GM volumes in VLBW individuals compared with term-born peers might pose a risk for developing and maintaining psychiatric diagnoses during adolescence. Future research should explore the possible role of reduced cortical and subcortical GM volumes in the pathogenesis of psychiatric illness in VLBW adolescents.

Psychiatric Disorders and General Functioning in Low Birth Weight Adults: A Longitudinal Study.

OBJECTIVE: To examine psychiatric morbidity and overall functioning in adults born with low birth weight compared with normal birth weight controls at age 26 years and to study longitudinal trajectories of psychiatric morbidity from early adolescence to adulthood. METHODS: Prospective cohort study wherein 44 preterm very low birth weight (≤1500 g), 64 term small for gestational age (SGA; <10th percentile), and 81 control adults were examined using the MINI-International Neuropsychiatric Interview: M.I.N.I. Plus, Norwegian version, the Global Assessment of Functioning, and questions on daily occupation and level of education. Prevalence of psychiatric disorders from previous follow-ups at age 14 and 19 years were included for longitudinal analysis. RESULTS: From adolescence to adulthood, the term SGA group had a marked increase in the estimated probability of psychiatric disorders from 9% (95% confidence interval, 4-19) to 39% (95% confidence interval, 28-51). At 26 years, psychiatric diagnoses were significantly more prevalent in the preterm very low birth weight group (n = 16, 36%; P = .003) and the term SGA group (n = 24, 38%; P = .019) compared with the control group (n = 11, 14%). Both low birth weight groups had lower educational level and functioning scores than controls and a higher frequency of unemployment and disability benefit. CONCLUSIONS: Low birth weight was a substantial risk factor for adult psychiatric morbidity and lowered overall functioning. The results underscore the need for long-term follow-up of low birth weight survivors through adolescence and adulthood, focusing on mental health. The longitudinal increase in psychiatric morbidity in the term SGA group calls for additional investigation.

Blood Pressure in Young Adults Born at Very Low Birth Weight: Adults Born Preterm International Collaboration.

Adults born preterm at very low birth weight (VLBW; <1500 g) have higher blood pressure than those born at term. It is not known whether all VLBW adults are at risk or whether higher blood pressure could be attributed to some of the specific conditions underlying or accompanying preterm birth. To identify possible risk or protective factors, we combined individual-level data from 9 cohorts that measured blood pressure in young adults born at VLBW or with a more stringent birth weight criterion. In the absence of major heterogeneity, we performed linear regression analysis in our pooled sample of 1571 adults born at VLBW and 777 controls. Adults born at VLBW had 3.4 mm Hg (95% confidence interval, 2.2-4.6) higher systolic and 2.1 mm Hg (95% confidence interval, 1.3-3.0) higher diastolic pressure, with adjustment for age, sex, and cohort. The difference in systolic pressure was present in men (1.8 mm Hg; 95% confidence interval, 0.1-3.5) but was stronger in women (4.7 mm Hg; 95% confidence interval, 3.2-6.3). Among the VLBW group, blood pressure was unrelated to gestational age, maternal smoking, multiple pregnancy, retinopathy of prematurity, or bronchopulmonary dysplasia. Blood pressure was higher than that of controls among VLBW adults unexposed to maternal preeclampsia. Among those exposed, it was even higher, especially if born appropriate for gestational age. In conclusion, although female sex and maternal preeclampsia are additional risk factors, the risk of higher blood pressure is not limited to any etiologic subgroup of VLBW adults, arguing for vigilance in early detection of high blood pressure in all these individuals.

The relevance of the irrelevant: Attention and task-set adaptation in prematurely born adults.

OBJECTIVE: To investigate attention and task-set adaptation in a preterm born very low birth weight (PT/VLBW) population by means of event-related potential components from an adapted cued go/no-go task. METHODS: P3 components after target and non-target cues, as well as target, no-go and non-target imperative stimuli were compared in 30 PT/VLBW young adults and 33 term-born controls. Changes in P3 amplitudes as a function of time-on-task were also investigated. RESULTS: The PT/VLBW group had larger P3 amplitudes to non-target cues and non-targets compared with controls. There were no significant group differences in the P3s to target or no-go stimuli. Moreover, the amplitude of the P3 to non-target cues and non-targets decreased significantly over time in the control group but not in the PT/VLBW group. CONCLUSIONS: PT/VLBW young adults allocate more attention to behaviorally irrelevant information than term-born controls, and persist in attending to this information over time. SIGNIFICANCE: This is the first study to investigate ERP components in an adult population born preterm with very low birth weight.

Long-term follow-up of mental health, health-related quality of life and associations with motor skills in young adults born preterm with very low birth weight.

BACKGROUND: Being born with very low birth weight (VLBW: ≤ 1,500 g) is related to long-term disability and neurodevelopmental problems, possibly affecting mental health and health-related quality of life (HRQoL). However, studies in young adulthood yield mixed findings. The aim of this study was to examine mental health and HRQoL at 23 years, including changes from 20 to 23 years and associations with motor skills in VLBW young adults compared with controls. METHODS: In a geographically based follow-up study, 35 VLBW and 37 term-born young adults were assessed at 23 years by using Achenbach Adult Self-Report (ASR), Short Form 36 Health Survey (SF-36), Beck Depression Inventory (BDI) and various motor tests. The ASR and SF-36 were also used at 20 years. Longitudinal changes in ASR and SF-36 from 20 to 23 years were analysed by linear mixed models and associations with motor skills at 23 years by linear regression. RESULTS: At 23 years, total ASR score was 38.6 (SD: 21.7) in the VLBW group compared with 29.0 (SD: 18.6) in the control group (p = 0.048). VLBW participants had higher scores for attention problems, internalizing problems and critical items, and they reported to drink less alcohol than controls. BDI total score did not differ between groups. On SF-36, VLBW participants reported significantly poorer physical and social functioning, more role-limitations due to physical and emotional problems, more bodily pain and lower physical and mental component summaries than controls. In the VLBW group, total ASR score increased by 9.0 (95 % CI: 3.3 to 14.7) points from 20 to 23 years (p = 0.009 vs controls), physical and mental component summaries of SF-36 decreased by 2.9 (95 % CI: -4.8 to -1.1) and 4.4 (95 % CI: -7.1 to -1.7) points, respectively (p = 0.012 and p = 0.022 vs controls). Among VLBW participants, more mental health problems and lower physical and mental HRQoL were associated with poorer motor skills at 23 years. CONCLUSIONS: VLBW young adults reported poorer and declining mental health and HRQoL in the transitional phase into adulthood. They seemed to have a cautious lifestyle with more internalizing problems and less alcohol use. The associations of mental health problems and HRQoL with motor skills are likely to reflect a shared aetiology.

Mental health and cerebellar volume during adolescence in very-low-birth-weight infants: a longitudinal study.

BACKGROUND: Preterm birth at very low birth weight (VLBW) poses a risk for cerebellar abnormalities and increased psychiatric morbidity compared with reference populations. We aimed to study cerebellar volumes (grey and white matter; GM, WM) and mental health in VLBW individuals and controls at 15 and 19 years of age, as well as changes between the two time points. METHODS: Forty VLBW (≤1500 g) and 56 control adolescents were included in the study at 15 years of age, and 44 VLBW and 60 control adolescents at 19 years of age. We had longitudinal data for 30 VLBW participants and for 37 controls. Clinical diagnoses were assessed following the schedule for affective disorders and schizophrenia for school-age children (KSADS). Psychiatric symptoms and function were further investigated with the Achenbach System of Empirically Based Assessment (ASEBA), ADHD Rating Scale-IV and the children's global assessment scale (CGAS). An automatic segmentation of cerebellar GM and WM volumes was performed in FreeSurfer. The MRI scans were obtained on the same 1.5T scanner at both ages. RESULTS: The VLBW group had higher rates of psychiatric disorders at both ages. Cerebellar growth trajectories did not differ between VLBW adolescents and controls, regardless of psychiatric status. However, VLBW adolescents who had a psychiatric diagnosis at both ages or developed a psychiatric disorder from 15 to 19 years had maintained smaller cerebellar WM and GM volumes than controls and also smaller volumes than VLWB adolescents who were or became healthy in this period. Moreover, there were no differences in cerebellar WM and GM volumes between controls and those VLBW who were healthy or became healthy. In the VLBW group, cerebellar WM and GM volumes correlated positively with psycho-social function at both 15 and 19 years of age, and smaller GM volumes were associated with inattention at 15 years. CONCLUSIONS: Smaller cerebellar volume in adolescents born very preterm and with VLBW may be a biomarker of increased risk of psychiatric problems in young adulthood.

Executive function relates to surface area of frontal and temporal cortex in very-low-birth-weight late teenagers.

BACKGROUND: Being born with very low birth weight (VLBW; birth weight (BW) ≤1500 g) is associated with increased risk of maldevelopment of the immature brain which may affect neurological functioning. Deficits in attention and executive function problems have been reported in VLBW survivors compared with healthy subjects. AIMS: The aim of this study was to evaluate attention and executive functions and to relate the clinical test results to cortical morphometry findings in VLBW young adults compared with term-born controls. STUDY DESIGN: Prospective follow-up study of three year cohorts of VLBW and control children from birth to adulthood. OUTCOME MEASURES: A comprehensive neuropsychological test battery was administered to 55 VLBW subjects born preterm (mean BW: 1217 g) and 81 term-born controls (mean BW: 3707 g) at age 19-20. Cerebral MRI was successfully obtained in 46 VLBW subjects and 61 controls. The FreeSurfer software package was applied for the cortical analyses based on T1-weighted MRI images. RESULTS: The VLBW group obtained inferior scores on 15 of the 29 neuropsychological measures assessing attention and executive function and on both the attention and executive function domain scores. We found positive correlations between the executive function domain score and cortical surface area, especially in the antero-medial frontal and the temporal lobes of the brain in the VLBW group. CONCLUSION: Young adults born with VLBW show deficits in attention and executive function compared with controls. The executive problems were related to smaller cortical surface area in brain regions known to be involved in higher order cognitive functioning.

Cortical trajectories during adolescence in preterm born teenagers with very low birthweight.

While cross-sectional neuroimaging studies on cortical development predict reductions in cortical volume (surface area and thickness) during adolescence, this is the first study to undertake a longitudinal assessment of cortical surface area changes across the continuous cortical surface during this period. We studied the developmental dynamics of cortical surface area and thickness in adolescents and young adults (aged 15-20) born with very low birth weight (VLBW; <1500 g) as well as in term-born controls. Previous studies have demonstrated brain structural abnormalities in cortical morphology, as well as long-term motor, cognitive and behavioral impairments, in adolescents and young adults with VLBW, but the developmental dynamics throughout adolescence have not been fully explored. T1-weighted MRI scans from 51 VLBW (27 scanned twice) and 79 term-born adolescents (37 scanned twice) were used to reconstruct the cortical surface and produce longitudinal estimates of cortical surface area and cortical thickness. Linear mixed model analyses were performed, and the main effects of time and group, as well as time × group interaction effects, were investigated. In both groups, cortical surface area decreased up to 5% in some regions, and cortical thickness up to 8%, over the five-year period. The most affected regions were located on the lateral aspect of the hemispheres, in posterior temporal, parietal and to some extent frontal regions. There was no significant interaction between time and group for either morphometry variable. In conclusion, cortical thickness decreases from 15 to 20 years of age, in a similar fashion in the clinical and control groups. Moreover, we show for the first time that developmental trajectories of cortical surface area in preterm and term-born adolescents do not diverge during adolescence.