Preterm Subjects Research Articles

Increased white matter fibre dispersion and lower IQ scores in adults born preterm.

Preterm birth has been associated with altered microstructural properties of the white matter and lower cognitive ability in childhood and adulthood. Due to methodological limitations of the diffusion tensor model, it is not clear whether alterations in myelination or variation in fibre orientation are driving these differences. Novel models applied to multi-shell diffusion imaging have been used to disentangle these effects, but to date this has not been used to study the preterm brain in adulthood. This study investigated whether novel advanced diffusion MRI metrics such as microscopic anisotropy and orientation dispersion are altered in adults born preterm, and whether this was associated with cognitive performance. Seventy-two preterm born participants (<37 weeks gestational age) were recruited from a 1982-1984 cohort (33 males, mean age 33.5 ± 1.0 years). Seventy-two term born (>37 weeks gestational age) controls (34 males, mean age 30.9 ± 4.0 years) were recruited from the general population. Tensor FA was calculated with FSL, while microscopic FA and orientation dispersion entropy (ODE) were estimated using the Spherical Mean Technique (SMT). Estimated Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI) were obtained from the WASI-II (abbreviated) IQ test. Voxel-wise comparisons using FSL's tract-based spatial statistics were performed to test between-group differences in diffusion MRI metrics as well as within-group associations of diffusion MRI metrics and IQ outcomes. The preterm group had significantly lower FSIQ, VCI and PRI scores. Preterm subjects demonstrated widespread decreases in ODE reflecting increased fibre dispersion, but no differences in microscopic FA. Tensor FA was increased in a small area in the anterior corona radiata. Lower FA values in the preterm population were associated with lower FSIQ and PRI scores. An increase in fibre dispersion in white matter and lower IQ scores after preterm birth exist in adulthood. Advanced diffusion MRI metrics such as the orientation dispersion entropy can be used to monitor white matter alterations across the lifespan in preterm born individuals. Although not significantly different between preterm and term groups, tensor FA values in the preterm group were associated with cognitive outcome.

Myelination of preterm brain networks at adolescence

Prematurity and preterm stressors severely affect the development of infants born before 37 weeks of gestation, with increasing effects seen at earlier gestations. Although preterm mortality rates have declined due to the advances in neonatal care, disability rates, especially in middle-income settings, continue to grow. With the advances in MR imaging technology, there has been a focus on safely imaging the preterm brain to better understand its development and discover the brain regions and networks affected by prematurity. Such studies aim to support interventions and improve the neurodevelopment of preterm infants and deliver accurate prognoses. Few studies, however, have focused on the fully developed brain of preterm born infants, especially in extremely preterm subjects. To assess the long-term effect of prematurity on the adult brain, myelin related biomarkers such as myelin water fraction and g-ratio are measured for a cohort of 19-year-old extremely preterm born subjects. Using multi-modal imaging techniques that combine T2 relaxometry and neurite density information, the results show that specific brain regions associated with white matter injuries due to preterm birth, such as the posterior limb of the internal capsule and corpus callosum, are still less myelinated in adulthood. Furthermore, a weak positive relationship between myelin water fraction values and Full-Scale Intelligence Quotient (FSIQ) scores was found in multiple brain regions previously defined as less myelinated in the Extremely Preterm (EPT) cohort. These findings might suggest altered connectivity in the adult preterm brain and explain differences in cognitive outcomes.

The Development of Retinal Function and Refractive Error in Children With Retinopathy of Prematurity.

The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10degrees but not 30degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE). We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2degree diameter, 50ms, blue (λ < 510nm) flashes at 10degrees and 30degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13). We also tested Term-born (n = 28) controls. To determine the age at half-maximal sensitivity (Agehalf) for each group and eccentricity, we fit DATs to logistic growth curves. We obtained VA and SE for Preterm subjects and evaluated the course of threshold development at 10degrees and 30degrees for significant association with VA and SE predicted at age 10 years. DAT development at 10degrees was significantly delayed in ROP (Mild and Severe); ROP did not significantly alter DAT development at 30degrees. At age 10years, among Preterm subjects, both VA and SE were significantly associated with group (None,Mild, and Severe). SE was predicted by the course of DAT development at 30degrees. VA was not associated with the course of DAT development at 10degrees. At 10degrees, ROP-whether mild or severe-is associated with significant delays in DAT development, evidence that the late-maturing central retina is vulnerable to ROP. The association of 30degree threshold and myopia are evidence that more peripheral retina is important to refractive development.

Biochemical and Anthropometric Parameters for the Early Recognition of the Intrauterine Growth Restriction and Preterm Neonates at Risk of Impaired Neurodevelopment.

S100B and Tau are implicated with both brain growth and injury. Their urinary levels in 30-to-40-day-old full-term, preterm, IUGR, and preterm-IUGR subjects were measured to investigate their possible relationship with future delayed neurodevelopment. Values were related to the neuro-behavioral outcome at two years of age, as well as to brain volumes and urinary NGF assessed at the same postnatal time point. Using the Griffiths III test, cognitive and motor performances were determined to establish subgroups characterized by either normal or impaired neuro-behavior. The latter included preterm, IUGR, and preterm-IUGR individuals who exhibited significantly higher and lower S100B and Tau levels, respectively, along with markedly reduced cerebral volumes and urinary NGF, as previously demonstrated. Contrary to NGF, however, Tau and S100B displayed a weak correlation with brain volumes. Delayed cognitive and motor performances observed in two-year-old preterm and IUGR-born individuals were also found to be associated with anomalous urinary levels of S100B and Tau, assessed at 30-40 days of the postnatal period, and their changes did not correlate with brain growth. Thus, our data suggests that, in addition to cerebral volumes and NGF, urinary S100B and Tau can also be considered as valuable parameters for the early detection of future neurodevelopmental abnormalities.

Fetal growth rather than prematurity determines lung function in children with asthma.

Preterm birth or fetal growth has been associated with reduced lung function and asthma during childhood in the general population. We aimed to elucidate whether prematurity or fetal growth has a significant influence on lung function or symptoms in children with stable asthma. We included children with stable asthma who participated in the Korean childhood Asthma Study cohort. Asthma symptoms were determined by asthma control test (ACT). Percent predicted values of pre- and post-bronchodilator (BD) lung function including forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), and forced expiratory flow at 25%-75% of FVC (FEF25%-75% ) were measured. Lung function and symptoms were compared according to the history of preterm birth and birth weight (BW) for gestational age (GA). The study population consisted of 566 children (age range: 5-18 years). There were no significant differences in lung function and ACT between preterm and term subjects. We observed no significant difference in ACT but significant differences were observed in pre- and post-BD FEV1 , pre- and post-BD FVC, and post-BD FEF25%-75% according to BW for GA in total subjects. Two-way ANOVA revealed that BW for GA rather than prematurity was a significant determining factor for pre- and post-BD lung function. After regression analysis, BW for GA was still a significant determining factor of pre- and post-BD FEV1 and pre- and post-BD FEF25%-75% . Fetal growth rather than prematurity appears to have a significant effect on lung function in children with stable asthma.

How delayed full enteral feeding could affect extrauterine growth restriction in a neonatal intensive care unit: a retrospective, short-term, observational single-center study.

Achieving adequate growth in preterm newborns through enteral feeding is one of the most important aspects of providing medical assistance in neonatal intensive care units due to not only improved outcomes (the prevention of complications such as necrotizing enterocolitis) but also the evaluation of the well-known consequences of adequate weight gain beyond metabolism and cognitive abilities later in life. In our study, we evaluated how the impact of delayed full enteral feeding could influence the entity of extrauterine growth restriction. We retrospectively analyzed the data of preterm subjects from a neonatal intensive care unit anonymous database. We detected significant correlations between delayed full enteral feeding as well as prolonged parenteral nutrition and extrauterine growth restriction. The achievement of full enteral feeding in the shortest possible time may be reasonably considered an important aspect in preterm newborn care.

Underdevelopment of gut microbiota in failure to thrive infants of up to 12 months of age.

Laboratory and clinical studies have revealed the importance of gut microbiota in children with severe pediatric pathological conditions such as severe acute malnutrition (SAM); however, under relatively milder conditions such as, failure to thrive (FTT), the role of the gut microbiota remains poorly characterized. Here, we analyzed stool samples from 54 subjects with a clinical diagnosis of failure to thrive (FTT), 49 preterm subjects with corrected normal growth (NFTT-pre), and 49 healthy subjects (NFTT) between 3-12 months of age using 16S rRNA gene sequencing. We observed that the clinical condition of FTT, age, head circumference, intrauterine growth restriction (IUGR), and feeding methods significantly affected gut microbiota. The microbiota age of subjects was significantly correlated with their anthropomorphic features, and the FTT subjects exhibited underdeveloped gut microbiota characterized by a significantly decreased microbiota-for-age Z-score (MAZ). The FTT and NFTT-pre groups exhibited an obvious disrupted developmental trajectory of gut microbiota across age, and the development of their alpha diversities and the observed OTU and Shannon indices were inadequate, particularly in subjects with FTT. Moreover, sequential colonization and enrichment of bacteria such as Bacteroides, Bifidobacterium, Streptococcus and most age-discriminatory bacterial taxa and their microbial functions were disorganized in FTT compared to that in NFTT. Our results revealed an underdevelopment of the gut microbiota in infants with failure to thrive that possesses potential clinical and practical importance.

Assessing Lung Vasculature Development and Application to Early Preterm Gestation Patients

Individuals who were born prematurely undergo many difficulties from the time they are born to their adult lives. Obstructive lung diseases are a common occurrence in patients who were born prematurely. Unfortunately, the development of lungs in premature infants is an area in the science world that has not been fully studied. Therefore, this study’s objective is to determine trends in lung vessel growth as a patient advances in age, and discover quantitative measures that provide clinical insight regarding improving the quality of life of premature infants. This is a retrospective study where x-ray computed tomography (CT) scans were analyzed by using in-house software built upon the NIH ImageJ platform. For each scan, the lung volume was automatically identified and the pulmonary vessel trees extracted and characterized to quantify the total number of vessels in the left hemi-lung. The radius and length of each vessel tree were also recorded. CT scans of 16 pediatric patients were analyzed (7 prematurely born and 9 full-term). The vessel growth of full-term patients trended to increase as a patient aged, while vessel growth for premature patients decreased with age. The data also indicated a significantly larger difference in the number of vessel branches over time between female preterm and full term subjects. Limitations such as variations in image quality, children’s age, and changes in CT technology over time are being addressed to improve confidence in the results. Future works will include analysis on a larger data set and novel approaches to automatic vessel extraction from chest CTs.

Cerebellar development after preterm birth.

Preterm birth and its complications and the associated adverse factors, including brain hemorrhage, inflammation, and the side effects of medical treatments, are the leading causes of neurodevelopmental disability. Growing evidence suggests that preterm birth affects the cerebellum, which is the brain region involved in motor coordination, cognition, learning, memory, and social communication. The cerebellum is particularly vulnerable to the adverse effects of preterm birth because key cerebellar developmental processes, including the proliferation of neural progenitors, and differentiation and migration of neurons, occur in the third trimester of a human pregnancy. This review discusses the negative impacts of preterm birth and its associated factors on cerebellar development, focusing on the cellular and molecular mechanisms that mediate cerebellar pathology. A better understanding of the cerebellar developmental mechanisms affected by preterm birth is necessary for developing novel treatment and neuroprotective strategies to ameliorate the cognitive, behavioral, and motor deficits experienced by preterm subjects.

Ophthalmic care of adults born preterm and full-term-results from the Gutenberg Prematurity Eye Study (GPES) : Premature birth and ophthalmological care

Prematurity and the presence of retinopathy of prematurity (ROP) increase the risk for the occurrence of amblyogenic risk factors in childhood and adolescence. The aim of the present study was to evaluate ocular morbidities and the ophthalmological care of former preterm and full-term persons in adulthood. The Gutenberg prematurity eye study (GPES) is aretrospective cohort study with aprospective ophthalmological examination of individuals formerly born preterm and full term between 1969 and 2002 (now aged 18-52years). All participants underwent adetailed ophthalmological examination and were asked about the frequency of ophthalmological care. Participants were grouped into those with normal gestational age (GA) ≥ 37 weeks (control group), preterm individuals without ROP and GA 33-36 weeks (group2), GA 29-32 weeks (group3), GA ≤ 28weeks (group4), and those with ROP without treatment (group5) and with ROP with treatment (group6). All participants were asked if they had an ophthalmological examination within the last 12months. In total, data from 140 term and 310 preterm adults were included in the present study. Strabismus was present in 2.1 % (3/140), 6.6 % (9/137), 17.4 % (16/92), 11.1 % (2/18), 27.1 % (13/48) and 60 % (9/15) in groups1-6, respectively. The proportion of subjects with an ophthalmological examination within the last 12months was highest in the groups of extremely preterm persons with and without ROP compared with the control group. Overall, 33.3 % (1/3) of the term and 57.1 % (28/49) of the preterm subjects with strabismus and 0 % (0/3) of the term and 46.9 % (15/32) of the preterm individuals with amblyopia had an ophthalmological examination within the past 12months. Extremely preterm adults with and without postnatal ROP showed the highest rate of eye diseases as well as the highest rate of ophthalmological check-ups within the last 12months. This suggests that extremely preterm adults particularly with the occurrence of postnatal ROP perceive more frequent ophthalmological check-ups throughout their lives.

Development of health-related quality of life and subjective health complaints in adults born extremely preterm: a longitudinal cohort study

PurposeTo study development trajectories to 34 years of age of health-related quality of life (HRQoL) and subjective health complaints in extremely preterm (EP) born subjects with and without disability, and to compare with term-born controls.MethodsA Norwegian longitudinal population-based cohort of subjects born in 1982–85 at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g and matched term-born controls completed the Norwegian version of the Short Form Health Survey-36 at ages 24 and 34 and the Health Behaviour in School-aged Children–Symptom Checklist at ages 17, 24 and 34 years. Data were analysed by unadjusted and adjusted mixed effects analyses with time by subject group as interaction term.ResultsA total of 35/49 (73%) surviving EP-born and 36/46 (78%) term-born controls participated at this third follow-up. EP-born subjects with severe disability reported clinical significant lower mean score in all domains compared to the term-born controls. Healthy EP-born subjects reported significantly lower mean scores for vitality, role emotional and mental health, and significantly higher mean score for total and psychological health complaints compared to term-born controls. There were no significant interactions with age regarding HRQoL and somatic health complaints, while there were significant differences in psychological health complaints; the EP-born scored higher at age 24 and lower at age 34.ConclusionsEP-born adults at age 34 reported inferior HRQoL versus term-born peers, especially in the mental health domains, indicating that the negative differences observed at 24 years remained unchanged.

Testing Epithelial Permeability in Fetal Tissue-Derived Enteroids

Human fetal tissue-derived enteroids are emerging as a promising in vitro model to study intestinal injuries in preterm infants. Enteroids exhibit polarity, consisting of a lumen with an apical border, tight junctions, and a basolateral outer layer exposed to growth media. The consequences of intestinal injuries include mucosal inflammation and increased permeability. Testing intestinal permeability in vulnerable preterm human subjects is often not feasible. Thus, an in vitro fetal tissue-derived intestinal model is needed to study intestinal injuries in preterm infants. Enteroids can be used to test changes in epithelial permeability regulated by tight junction proteins. In enteroids, intestinal stem cells differentiate into all epithelial cell types and form a three-dimensional structure on a basement membrane matrix secreted by mouse sarcoma cells. In this article, we describe the methods used for establishing enteroids from fetal intestinal tissue, characterizing the enteroid tight junction proteins with immunofluorescent imaging, and testing epithelial permeability. As gram-negative dominant bacterial dysbiosis is a known risk factor for intestinal injury, we used lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, to induce permeability in the enteroids. Fluorescein-labeled dextran was microinjected into the enteroid lumen, and serial dextran concentrations leaked into the culture media were measured to quantify the changes in paracellular permeability. The experiment showed that apical exposure to LPS induces epithelial permeability in a concentration-dependent manner. These findings support the hypothesis that gram-negative dominant dysbiosis contributes to the mechanism of intestinal injury in preterm infants.

Testing Epithelial Permeability in Fetal Tissue-Derived Enteroids.

Human fetal tissue-derived enteroids are emerging as a promising in vitro model to study intestinal injuries in preterm infants. Enteroids exhibit polarity, consisting of a lumen with an apical border, tight junctions, and a basolateral outer layer exposed to growth media. The consequences of intestinal injuries include mucosal inflammation and increased permeability. Testing intestinal permeability in vulnerable preterm human subjects is often not feasible. Thus, an in vitro fetal tissue-derived intestinal model is needed to study intestinal injuries in preterm infants. Enteroids can be used to test changes in epithelial permeability regulated by tight junction proteins. In enteroids, intestinal stem cells differentiate into all epithelial cell types and form a three-dimensional structure on a basement membrane matrix secreted by mouse sarcoma cells. In this article, we describe the methods used for establishing enteroids from fetal intestinal tissue, characterizing the enteroid tight junction proteins with immunofluorescent imaging, and testing epithelial permeability. As gram-negative dominant bacterial dysbiosis is a known risk factor for intestinal injury, we used lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, to induce permeability in the enteroids. Fluorescein-labeled dextran was microinjected into the enteroid lumen, and serial dextran concentrations leaked into the culture media were measured to quantify the changes in paracellular permeability. The experiment showed that apical exposure to LPS induces epithelial permeability in a concentration-dependent manner. These findings support the hypothesis that gram-negative dominant dysbiosis contributes to the mechanism of intestinal injury in preterm infants.

Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.

Perinatal pharmacology is influenced by a myriad of physiological variables that are changing dynamically. The influence of these covariates has not been assessed systemically. The objective of this work was to use theophylline as a model drug and to predict its pharmacokinetics before, during (including prediction of the umbilical cord level), and after pregnancy as well as in milk (after single and multiple doses) and in neonates using a physiological-based pharmacokinetic (PBPK) model. Neonatal theophylline exposure from milk consumption was projected in both normal term and preterm subjects. Predicted infant daily doses were calculated using theophylline average and maximum concentration in the milk as well as an estimate of milk consumption. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted theophylline concentrations in non-pregnant and pregnant populations at different gestational weeks were within 2-fold of the observations and the observed concentrations fell within the 5th−95th prediction interval from the PBPK simulations. The PBPK model predicted an average cord-to-maternal plasma ratio of 1.0, which also agrees well with experimental observations. Predicted postpartum theophylline concentration profiles in milk were also in good agreement with observations with a predicted milk-to-plasma ratio of 0.68. For an infant of 2 kg consuming 150 ml of milk per day, the lactation model predicted a relative infant dose (RID) of 12 and 17% using predicted average (Cavg,ss) and maximum (Cmax,ss) concentration in milk at steady state. The maximum RID of 17% corresponds to an absolute infant daily dose of 1.4 ± 0.5 mg/kg/day. This dose, when administered as 0.233 mg/kg every 4 h, to resemble breastfeeding frequency, resulted in plasma concentrations as high as 3.9 (1.9–6.8) mg/L and 2.8 (1.3–5.3) (5th−95th percentiles) on day 7 in preterm (32 GW) and full-term neonatal populations.

Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity.

Inhaled nitric oxide (INO) is used to treat hypoxic respiratory failure without clear evidence of benefit. Future trials to evaluate its use will be designed based on an understanding of the populations in which this therapy is provided and with outcomes based on patient characteristics, for example, a history of premature birth. This was a multi-center prospective observational study that evaluated subjects in the pediatric ICU who were treated with INO for a respiratory indication, excluding those treated in the neonatal ICU or treated for birth-related disease. We used logistic regression to evaluate characteristics associated with mortality and duration of mechanical ventilation. Specifically, we compared subjects born early preterm (<32 weeks post-conceptual age), late preterm (32-37 weeks post-conceptual age), and full term. A total of 163 children (median age [interquartile range], 1.8 [0.7-6.0] y) were included, 41 (25.2%) had a history of preterm birth (18 born early preterm and 23 born late preterm). INO was initiated for less-severe lung disease in the early preterm versus late preterm versus full-term subjects (median mean airway pressures, 16 vs 19 vs 19 cm H2O; P = .03), although the oxygenation index and oxygenation saturation index did not differ. The early preterm subjects had more ventilator-free days (median, 18.0, 7.0, 4.5 d; P = .02) and lower 28-d mortality (0, 26.1, 32.0%; P = .007). Lower respiratory tract disease, but not a history of prematurity, was independently associated with lower mortality. INO was used differently in early preterm subjects. Clinical trials that evaluate INO use should have standardized oxygenation deficit thresholds for initiation of therapy and should consider stratifying by early preterm status.

Health perception by young adults born very preterm.

This study assessed the self-reported health perception and use of health care by adults born very preterm before 30weeks of gestation. The participants were part of a cross-sectional observational study that assessed the global health of young adults aged 18-29years born very preterm in Quebec, Canada. Health perception was explored from 2011 to 2016 using the second Short-Form 36 Health Survey (SF-36v2), and objective health measures were obtained. Further in-depth open-ended questions were asked in 2018. The 101 preterm subjects had similar perceptions of their health to 105 term-born controls, according to the SF-36v2, despite significantly more adverse health conditions. Their healthcare use was similar. However, the later in-depth questionnaire showed that 23% of 45 preterm subjects and 3% of 34 term-born subjects perceived their health as poorer than the general population. Major factors that could improve their respective health were lifestyle habits (74% vs. 81%) and eliminating specific adverse symptoms (52% vs. 27%). Only 10% of preterm individuals had been asked about their perinatal history by physicians. Adults born very preterm said their health was poorer than the general population and identified specific factors that should be addressed during routine health monitoring.

FERTILITY AND ABORTION RATES FOLLOWINGHYSTEROSCOPIC RESECTION OF UTERINE SEPTA

Objectives: the presented work studied the effect of uterine septum resection in patients with short and long septa on obstetric outcomes specially the abortion rates and preterm deliveries Subjects and methods: 100 hundred patients known to have uterine septum had been recruited to a private clinic in Benha city –Egypt and classified into two groups according to the length of septum, group A with short septum&lt;2.5cmand groupB with long septum &gt;2.5 cm, all patients subjected to hysterosopic resection of septa after counseling and signed informed consent. Results: The infertility rate was significantly lower in group b after surgery (39.47% vs 10.53%, P = .006). However, no significant difference was observed in the infertility rate between groups A and B. There were no significant differences in pregnancy rate, and preterm live births rate among the 2 groups (P &gt;.05 for all). In Group A the change is only in the rate of term and preterm which was significant but abortion rate didnt differ, this was the group of the smalls septum &lt;2.5cm.Significant change occurred in the rate of abortion in group b (25 before resection dropped to 10 after with p value of 0.001 a high significant difference also there were a significant change in all other items including the pregnancy rate and term pregnancy (pregnancy rate elevated from 35 cases to 40 cases with p value 0.01 also the rate of term pregnancy highly increased from25 cases before septum resection to 38 cases after resection with p value 0.007 Conclusion: large uterine septum &gt;2.5cm resection associated with increase in fertility and decreased rates of abortions.

Decreased ventricular size and mass mediate the reduced exercise capacity in adolescents and adults born premature

BackgroundPremature birth is associated with lower levels of cardiorespiratory fitness (CRF) but the underlying mechanisms responsible remain unclear. This study assessed whether differences in cardiac morphology or function mediate differences in CRF among adolescents and young adults born preterm. MethodsAdolescents and young adults born moderately to extremely premature (gestational age ≤ 32 weeks or birth weight < 1500 g) and age-matched term born participants underwent resting cardiac MRI and maximal exercise testing. Mediation analysis assessed whether individual cardiovascular variables accounted for a significant proportion of the difference in maximal aerobic capacity between groups. ResultsIndividuals born preterm had lower VO2max than those born term (41.7 ± 8.6 v 47.5 ± 8.7, p < 0.01). Several variables differed between term and preterm born subjects, including systolic and diastolic blood pressure, mean pulmonary artery pressure, indexed left ventricular end-diastolic volume (LVEDVi), right ventricular end-diastolic volume (RVEDVi), LV mass (LVMi), LV stroke volume index (LVSVi), and LV strain (p < 0.05 for all). Of these variables, LVEDVi, RVEDVi, LVSVi, LVMi, and LV longitudinal strain were significantly related to VO2max (p < 0.05 for all). Significant portions of the difference in VO2max between term and preterm born subjects were mediated by LVEDVi (74.3%, p = 0.010), RVEDVi (50.6%, p = 0.016), and LVMi (43.0%, p = 0.036). ConclusionsLower levels of CRF in adolescents and young adults born preterm are mediated by differences in LVEDVi, RVEDVi, and LVMi. This may represent greater risk for long-term cardiac morbidity and mortality in preterm born individuals.

Multi-Channel 4D Parametrized Atlas of Macro- and Microstructural Neonatal Brain Development.

Structural (also known as anatomical) and diffusion MRI provide complimentary anatomical and microstructural characterization of early brain maturation. However, the existing models of the developing brain in time include only either structural or diffusion MRI channels. Furthermore, there is a lack of tools for combined analysis of structural and diffusion MRI in the same reference space. In this work, we propose a methodology to generate a multi-channel (MC) continuous spatio-temporal parametrized atlas of the brain development that combines multiple MRI-derived parameters in the same anatomical space during 37–44 weeks of postmenstrual age range. We co-align structural and diffusion MRI of 170 normal term subjects from the developing Human Connectomme Project using MC registration driven by both T2-weighted and orientation distribution functions channels and fit the Gompertz model to the signals and spatial transformations in time. The resulting atlas consists of 14 spatio-temporal microstructural indices and two parcellation maps delineating white matter tracts and neonatal transient structures. In order to demonstrate applicability of the atlas for quantitative region-specific studies, a comparison analysis of 140 term and 40 preterm subjects scanned at the term-equivalent age is performed using different MRI-derived microstructural indices in the atlas reference space for multiple white matter regions, including the transient compartments. The atlas and software will be available after publication of the article1.

White matter analysis of the extremely preterm born adult brain

The preterm brain has been analysed after birth by a large body of neuroimaging studies; however, few studies have focused on white matter alterations in preterm subjects beyond infancy, especially in individuals born at extremely low gestation age - before 28 completed weeks. Neuroimaging data of extremely preterm young adults are now available to investigate the long-term structural alterations of disrupted neurodevelopment. We examined white matter hierarchical organisation and microstructure in extremely preterm young adults. Specifically, we first identified the putative hubs and peripheral regions in 85 extremely preterm young adults and compared them with 53 socio-economically matched and full-term born peers. Moreover, we analysed Fractional Anisotropy (FA), Mean Diffusivity (MD), Neurite Density Index (NDI), and Orientation Dispersion Index (ODI) of white matter in hubs, peripheral regions, and over the whole brain. Our results suggest that the hierarchical organisation of the extremely preterm adult brain remains intact. However, there is evidence of significant alteration of white matter connectivity at both the macro- and microstructural level, with overall diminished connectivity, reduced FA and NDI, increased MD, and comparable ODI; suggesting that, although the spatial configuration of WM fibres is comparable, there are less WM fibres per voxel. These alterations are found throughout the brain and are more prevalent along the pathways between deep grey matter regions, frontal regions and cerebellum. This work provides evidence that white matter abnormalities associated with the premature exposure to the extrauterine environment not only are present at term equivalent age but persist into early adulthood.