Term-born Controls Research Articles

Imprint of preterm birth with very low birth weight on optic disc OCT in adulthood-A two-country birth cohort study.

To determine the pattern, degree and prevalence of optic disc optical coherence tomography (OCT) alterations in adults born preterm with very low birth weight (VLBW; birth weight < 1500 g). Optic disc OCT was assessed in 98 VLBW participants and 139 term-born controls from birth cohorts in Finland and Norway at the mean age of 36 years. The participants had not been treated for retinopathy of prematurity and had no diagnosed brain abnormality. OCT assessment included parameters for optic disc size, neural rim and peripapillary retinal nerve fibre layer thickness (pRNFLT), and for the foveal developmental stage. Background data, visual acuity, refractive error and intraocular pressure were recorded. In the VLBW group, optic disc neural rim and pRNFLT were significantly decreased, most frequently in the nasal and inferior sectors. In 40% (95% CI: 33-47) of the VLBW eyes, nerve fibre thickness of at least one optic disc sector was below the fifth percentile of the control group, including 9% (95% CI: 6-14) subgroup falling below the first percentile, that is, clinically below normal limits. VLBW participants with nerve fibre thickness below the fifth percentile did not differ by perinatal data or foveal developmental stage from the other VLBW participants. All participants had normal visual acuity. A moderate decrease of the optic disc neural rim and pRNFLT is frequently seen in clinically healthy adults born preterm with VLBW. Awareness of the VLBW-related optic disc nerve fibre shallowness especially in the inferior and nasal sectors is important while evaluating acquired optic disc pathology in adulthood.

Romantic and sexual relationships of young adults born very preterm: An individual participant data meta-analysis.

To compare romantic and sexual relationships between adults born very preterm (VP; <32 weeks of gestation) or with very low birth weight (VLBW; <1500 g) and at term, and to evaluate potential biological and environmental explanatory factors among VP/VLBW participants. This individual participant data (IPD) meta-analysis included longitudinal studies assessing romantic and sexual relationships in adults (mean sample age ≥ 18 years) born VP/VLBW compared with term-born controls. Following PRISMA-IPD guidelines, 11 of the 13 identified cohorts provided IPD from 1606 VP/VLBW adults and 1659 term-born controls. IPD meta-analyses were performed using one-stage approach. Individuals born VP/VLBW were less likely to be in a romantic relationship (OR 0.49; 95% CI 0.31-0.76), to be married/cohabiting (OR 0.70, 95% CI 0.53-0.92), or to have had sexual intercourse (OR 0.21, 95% CI 0.09-0.36) than term-born adults. If sexually active, VP/VLBW participants were more likely to experience their first sexual intercourse after the age of 18 years (OR 1.93, 95% CI 1.24-3.01) than term-born adults. Among VP/VLBW adults, males, and those with neurosensory impairment were least likely to experience romantic relationships. These findings reflect less optimal social functioning and may have implications for socioeconomic and health outcomes of adults born VP/VLBW.

Predictors of language and reading outcomes in 12-year-old children born very preterm.

To investigate predictors of language and reading outcomes in 12-year-old Swedish children born very preterm (<32 gestational weeks) in 2004-2007. Children born very preterm (n = 78, 43 girls), and term-born controls (n = 50, 32 girls), were examined on verbal IQ, semantic and phonemic fluency, sentence recall, reading fluency, word and phonological decoding at 12 years of age. The results were related to neonatal characteristics, language development, measured with Bayley-III, at 2.5 years corrected age, and concurrent non-verbal IQ. Preterm children showed language and reading difficulties that were not completely accounted for by level of concurrent non-verbal IQ. Extremely preterm born children (<28 gestational weeks) demonstrated specific linguistic weaknesses. Administration of antenatal steroids, retinopathy of prematurity and persistent ductus arteriosus explained unique variance in language and reading outcomes. Language assessments at 2.5 years had low predictive value for language and reading outcomes at age 12. Language and reading difficulties in 12-year-old children born preterm were not fully explained by concurrent non-verbal IQ, and were not reliably predicted by language assessments at 2.5 years. Renewed language assessments at school age are warranted for identifying children with persisting linguistic difficulties.

Brain volumes and cortical thickness and associations with cognition in children born extremely preterm.

Children born extremely preterm (EPT) have altered brain volumes and cortical thickness and lower cognition than children born at term. Associations between these have remained largely unexplored, due to the lack of studies focusing on children born EPT. Children underwent brain magnetic resonance imaging (MRI) at term and/or 10 years and cognitive assessments at 12 years. The study comprised of 42 children born EPT and 29 term-born controls with cognitive data and MRI data at 10 years, 25 children born EPT had MRI data at term age and 20 had longitudinal MRI data. Cognition was positively associated with brain volumes at 10 years, but negatively associated with cortical thickness at 10 years. Most associations between term age brain volumes and cognitive outcomes were non-significant for children born EPT. Growth from term to 10 years in children born EPT was not associated with cognition. Insular volume was positively associated with cognition in children born EPT. Imaging assessments at 10 years had similar associations to cognition in children born EPT and term-born controls. Insular volume could be a biomarker for cognitive outcome. Associations between brain volumetric growth and cognition require further investigation. This study investigated brain volumes, volumetric growth, and cortical thickness in children born extremely preterm, who have rarely been studied exclusively, and compared the data with term-born controls. In both groups, brain volumes at 10 years were positively associated with cognitive outcome at 12 years, but cortical thickness at 10 years was negatively associated with cognitive outcome at 12 years. Volumetric growth from term age to 10 years was not associated with cognitive outcome in the subset of children born extremely preterm with longitudinal data. Insular volume may be a potential biomarker for cognitive outcome in children born extremely preterm.

Neurosensory, cognitive and academic outcomes at 8 years in children born 22–23 weeks’ gestation compared with more mature births

Despite providing intensive care to more infants born <24 weeks’ gestation, data on school-age outcomes, critical for counselling and decision-making, are sparse.ObjectiveTo compare major neurosensory, cognitive and academic impairment among...

Brain 3T magnetic resonance imaging in neonates: features and incidental findings from a research cohort enriched for preterm birth

Background and objectivesThe survival rate and patterns of brain injury after very preterm birth are evolving with changes in clinical practices. Additionally, incidental findings can present legal, ethical and practical...

Sensitivity and specificity of the Neonatal Visual Assessment to predict motor and cognitive outcomes in infants born very preterm

BackgroundVery preterm infants are at increased risk of neurodevelopmental impairments. The Neonatal Visual Assessment (NVA) assesses visual function and outcomes and has been used to assess early neurodevelopmental outcomes. This study aimed to compare NVA results of very preterm and term-born infants and to calculate the sensitivity and specificity of the NVA at term equivalent age (TEA) and three months corrected age (CA) to predict motor and cognitive outcomes at 12 months CA in very preterm infants. MethodsThis prospective observational cohort study recruited infants born before 31 weeks gestation and a healthy term-born control group. The NVA was assessed at TEA and three months CA, and neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, Third Edition; Neurosensory Motor Developmental Assessment; Alberta Infant Motor Scale) were performed at 12 months CA. The sensitivity and specificity of the NVA to predict outcomes were calculated based on a previously published optimality score. Results248 preterm (54 % male) and 46 term-born infants (48 % male) were analysed. The mean NVA scores of preterm and term-born infants were significantly different at TEA (preterm 3.1±2.1; term-born 1.2±1.7, p < 0.001). The NVA had moderate sensitivity (59–78 %) and low specificity (25–27 %) at TEA, and low sensitivity (21–28 %) and high specificity (86–87 %) at three months CA for the prediction of preterm infants' outcomes at 12 months CA. ConclusionThe NVA at TEA and three months CA was not a strong predictor of motor and cognitive impairments in this contemporary cohort of very preterm infants.

Foveal thickness and its association with visual acuity in adults born preterm with very low birth weight: A two-country birth cohort study.

To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best-corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term-born controls were examined with spectral-domain optical coherence tomography and BCVA at age 31-43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 μm (28.2) and 272.4 μm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 μm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function.

Impact of a mindfulness-based intervention on neurobehavioral functioning and its association with large-scale brain networks in preterm young adolescents.

Adolescents born very preterm (VPT; <32 weeks of gestation) face an elevated risk of executive, behavioral, and socioemotional difficulties. Evidence suggests beneficial effects of mindfulness-based intervention (MBI) on these abilities. This study seeks to investigate the association between the effects of MBI on executive, behavioral, and socioemotional functioning and reliable changes in large-scale brain networks dynamics during rest in VPT young adolescents who completed an 8-week MBI program. Neurobehavioral assessments and resting-state functional magnetic resonance imaging were performed before and after MBI in 32 VPT young adolescents. Neurobehavioral abilities in VPT participants were compared with full-term controls. In the VPT group, dynamic functional connectivity was extracted by using the innovation-driven coactivation patterns framework. The reliable change index was used to quantify change after MBI. A multivariate data-driven approach was used to explore associations between MBI-related changes on neurobehavioral measures and temporal brain dynamics. Compared with term-born controls, VPT adolescents showed reduced executive and socioemotional functioning before MBI. After MBI, a significant improvement was observed for all measures that were previously reduced in the VPT group. The increase in executive functioning, only, was associated with reliable changes in the duration of activation of large-scale brain networks, including frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks. The improvement in executive functioning after an MBI was associated with reliable changes in large-scale brain network dynamics during rest. These changes encompassed frontolimbic, amygdala-hippocampus, dorsolateral prefrontal, and visual networks that are related to different executive processes including self-regulation, attentional control, and attentional awareness of relevant sensory stimuli.

Feature similarity gradients detect alterations in the neonatal cortex associated with preterm birth.

The early life environment programmes cortical architecture and cognition across the life course. A measure of cortical organisation that integrates information from multimodal MRI and is unbound by arbitrary parcellations has proven elusive, which hampers efforts to uncover the perinatal origins of cortical health. Here, we use the Vogt-Bailey index to provide a fine-grained description of regional homogeneities and sharp variations in cortical microstructure based on feature gradients, and we investigate the impact of being born preterm on cortical development at term-equivalent age. Compared with term-born controls, preterm infants have a homogeneous microstructure in temporal and occipital lobes, and the medial parietal, cingulate, and frontal cortices, compared with term infants. These observations replicated across two independent datasets and were robust to differences that remain in the data after matching samples and alignment of processing and quality control strategies. We conclude that cortical microstructural architecture is altered in preterm infants in a spatially distributed rather than localised fashion.

Bullying victimisation in childhood and mental health in early adulthood: comparison of prospective and retrospective reports

The association between childhood bullying victimisation and mental health problems in adulthood has been consistently reported in the literature. Previous studies used both retrospective and prospective reports to measure bullying victimisation. However, there could be biases in both reports. We aimed to assess agreement between prospective and retrospective reports of childhood bullying victimisation, to compare their associations with mental health in early adulthood, and to examine the associations of consistent prospectively and retrospectively reported bullying victimisation with adult mental health. Data were from the prospective Bavarian Longitudinal Study of neonatal at-risk children and term-born controls recruited at birth. 489 participants were followed from birth to age 26 (mean [SD]: 26.4 [0.8] years). Adult mental health was assessed using both the Achenbach Young Adult Self-Report (YSR) and standardised diagnostic interviews. Childhood bullying victimisation was prospectively reported by participants and parents at age 13 and retrospectively self-reported at age 26. We showed that the agreement between retrospective and prospective self-reports of bullying victimisation was fair (Kappa 0.30) with only slight agreement (Kappa 0.18) when compared with prospective parent-reports. Both prospectively and retrospectively self-reported bullying victimisation was associated with poor mental health. Retrospective reports tended to produce stronger associations. Participants who reported being bullied both retrospectively and prospectively had a particularly elevated risk for mental health problems. In conclusion, prospective and retrospective reports capture partly different individuals with exposure to bullying victimisation. Exposure to bullying victimisation, whether it was retrospectively or prospectively self-reported, was associated with an increased risk for mental health problems.

Physical activity and cognitive function in adults born very preterm or with very low birth weight-an individual participant data meta-analysis.

Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association. Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase. Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments. Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Cardiopulmonary Exercise Performance of Children Born Non-Extremely Preterm.

Data on exercise tolerance of children born non-extremely preterm are sparse. We aimed to explore the cardiopulmonary exercise testing (CPET) characteristics in this population. We studied 63 children (age 7-12 years) born at 290/7-366/7 weeks of gestation (34 were late preterm, 29 were preterm) and 63 age-matched, term-born controls. All performed spirometry and CPET (cycle ergometry). There were no differences in activity levels and spirometric parameters between the group of preterm-born children and controls. A peak oxygen uptake (VO2peak) of <80% was noted in 25.4% of the term-born and 49.2% of preterm-born children (p = 0.001). Term-born participants presented similar VO2peak to late-preterm children but higher than those born at <340/7 weeks of gestation (p = 0.002). Ventilatory limitation was noted in 4.8% of term and 7.9% of preterm participants, while only one preterm child presented cardiovascular limitation. Children born before 34 weeks of gestation had higher respiratory rates and smaller tidal volumes at maximum exercise, as well as lower oxygen uptake for the level of generated work. We conclude that school-age children born at 29-34 weeks of gestation may present decreased exercise performance attributed to an altered ventilatory response to exercise and impaired O2 utilization by their skeletal muscles rather than other cardiopulmonary limiting factors.

Visual outcomes and their association with grey and white matter microstructure in adults born preterm with very low birth weight

Individuals born with very low birth weight (VLBW; < 1500 g) have a higher risk of reduced visual function and brain alterations. In a longitudinal cohort study, we assessed differences in visual outcomes and diffusion metrics from diffusion tensor imaging (DTI) at 3 tesla in the visual white matter pathway and primary visual cortex at age 26 in VLBW adults versus controls and explored whether DTI metrics at 26 years was associated with visual outcomes at 32 years. Thirty-three VLBW adults and 50 term-born controls was included in the study. Visual outcomes included best corrected visual acuity, contrast sensitivity, P100 latency, and retinal nerve fibre layer thickness. Mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy was extracted from seven regions of interest in the visual pathway: splenium, genu, and body of corpus callosum, optic radiations, lateral geniculate nucleus, inferior-fronto occipital fasciculus, and primary visual cortex. On average the VLBW group had lower contrast sensitivity, a thicker retinal nerve fibre layer and higher axial diffusivity and radial diffusivity in genu of corpus callosum and higher radial diffusivity in optic radiations than the control group. Higher fractional anisotropy in corpus callosum areas were associated with better visual function in the VLBW group but not the control group.

Monitoring persistent pulmonary hypertension of the newborn using the arterial to end tidal carbon dioxide gradient

Persistent pulmonary hypertension of the newborn (PPHN) can be monitored theoretically by the difference of the partial pressure of arterial (PaCO2) to end-tidal CO2 (EtCO2). We aimed to test the hypothesis that the PaCO2–EtCO2 gradient in infants with PPHN would be higher compared to infants without PPHN. Prospective, observational study of term-born ventilated infants with echocardiographically-confirmed PPHN with right-to-left shunting and term-born control infants without respiratory disease. The PaCO2–EtCO2 gradient was calculated as the difference between the PaCO2 measured from indwelling arterial sample lines and EtCO2 measured by continuous Microstream sidestream capnography. Twenty infants (9 with PPHN and 11 controls) were studied with a median (IQR) gestational age of 39.5 (38.7–40.4) weeks, a birthweight of 3.56 (3.15–3.93) kg and a birthweight z-score of 0.03 (− 0.91 to 1.08). The PaCO2–EtCO2 gradient was larger in the infants with PPHN compared to those without PPHN after adjusting for differences in the mean airway pressure and fraction of inspired oxygen (adjusted p = 0.037). In the infants with PPHN the median PaCO2–EtCO2 gradient decreased from 10.7 mmHg during the acute illness to 3.3 mmHg pre-extubation. The median difference in the gradient was significantly higher in infants with PPHN (6.2 mmHg) compared to infants without PPHN (-3.2 mmHg, p = 0.022). The PaCO2–EtCO2 gradient was higher in infants with PPHN compared to term born infants without PPHN and decreased over the first week of life in infants with PPHN. The gradient might be utilised to monitor the evolution and resolution of PPHN.

Transition to Adulthood for Extremely Preterm Survivors.

To compare transition into adulthood of survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) in the postsurfactant era with term-born controls. Prospective longitudinal cohort study of all EP/ELBW survivors born in the State of Victoria, Australia between January 1, 1991 and December 31, 1992 and matched term-born controls. Outcomes include educational attainment, employment, financial status, romantic partnering, living arrangements, parenthood, physical health and mental health, risk-taking behaviors, life satisfaction, and interpersonal relationships at 25 years. Data were available from 165 EP/ELBW and 127 control participants. Overall, there was little evidence for differences between the EP/ELBW and control groups on most comparisons after adjustment for social risk and multiple births. However, compared with controls, the EP/ELBW group was more likely to have their main source of income from government (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.21-5.13; P = .01) and to have never moved out of the parental home (aOR 2.13, 95% CI 1.27-3.58; P = .01), and fewer had ever engaged in smoking (aOR 0.52, 95% CI 0.28-0.98; P = .04), binge drinking (aOR 0.41, 95% CI 0.18-0.93; P = .03), or street drugs (aOR 0.56, 95% CI 0.32-0.98; P = .04). Aside from clinically important differences in main income source, leaving the parental home, and reduced risk-taking behavior, survivors born EP/ELBW in the era since surfactant was introduced are transitioning into adulthood similarly to term-born controls in some areas assessed but not all.

Body composition in adults born preterm with very low birth weight

BackgroundStudies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults.MethodsWe studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years.ResultsIn mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, –1.5% to 3.5%, men 0.8%; –2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3).ConclusionCompared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age.ImpactIn mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height.First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults.Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

Association of early and current life factors with telomere length in preterm-born children

Background Telomeres shorten after each cell division. Since preterm-born babies are delivered early and often suffer from inflammatory conditions such as bronchopulmonary dysplasia (BPD), their telomere length may be altered. Objectives We assessed associations of early and current life factors with telomere length in saliva samples obtained from 7–12-year-old children born at ≤34 weeks’ gestation and term-born controls. Study design Relative telomere length was measured by qPCR on extracted DNA. Groups were compared using independent t-tests or ANOVA with post-hoc correction. Linear regression analysis was also used. Results 534 children had satisfactory telomere data including 383 who were preterm-born (mean (SD) birthweight 1732g (558g), gestation 31.1 (2.6) weeks) and 151 term-born (3464g (510g); 39.8 (1.3) weeks). Telomere length was longer in children who had intrauterine growth restriction (IUGR) at birth: mean (SD): 464.6 (166.3) vs. 418.6 (110.7) in the no-IUGR group; in females: 440.2 (130.1) vs. 405.7 (101.5) in males; and in the least deprived group (397.8 (95.0) vs. 437.6 (121.9) most vs least deprivation quintile). Differences were most notable in females with IUGR. However, telomere length was not different between the preterm and term groups; the BPD and no BPD groups nor was it related to lung function or cardiovascular measurements. In multivariable regression analyses, telomere length was associated with sex, IUGR and deprivation with the greatest difference observed in females with IUGR. Conclusions Telomere length was associated with sex, IUGR and deprivation, especially in females with IUGR, but not with prematurity, BPD, lung function or cardiovascular measurements.

Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm

BackgroundChildren born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term.MethodsOur study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups.ResultsBrain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ.ConclusionsThese findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT.ImpactThe article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy.Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes.While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes.We found no differences in volumetric asymmetry between children born EPT and at term.

Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect.