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Epidemiological data suggest that early life exposures are key determinants of immune-mediated disease later in life. Young children are also particularly susceptible to infections, warranting more analyses of immune system development early in life. Such analyses mostly have been performed in mouse models or human cord blood samples, but these cannot account for the complex environmental exposures influencing human newborns after birth. Here, we performed longitudinal analyses in 100 newborn children, sampled up to 4 times during their first 3 months of life. From 100 µL of blood, we analyze the development of 58 immune cell populations by mass cytometry and 267 plasma proteins by immunoassays, uncovering drastic changes not predictable from cord blood measurements but following a stereotypic pattern. Preterm and term children differ at birth but converge onto a shared trajectory, seemingly driven by microbial interactions and hampered by early gut bacterial dysbiosis.
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Sangre Fetal/inmunología , Sistema Inmunológico/fisiología , Recien Nacido Prematuro/inmunología , Inflamación , Linaje de la Célula , Disbiosis , Femenino , Microbioma Gastrointestinal , Humanos , Inmunoensayo , Recién Nacido , Leucocitos Mononucleares/metabolismo , Estudios Longitudinales , Masculino , Padres , Fenotipo , Nacimiento Prematuro/inmunología , TranscriptomaRESUMEN
Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.
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Neocórtex , Nacimiento Prematuro , Recién Nacido , Ratones , Animales , Humanos , Embarazo , Femenino , Neuronas/fisiología , Serotonina , Corteza Cerebral/fisiología , Recien Nacido Prematuro , Axones/fisiología , Tálamo/fisiologíaRESUMEN
Human parturition at term and preterm is an inflammatory process synchronously executed by both fetomaternal tissues to transition them from a quiescent state t an active state of labor to ensure delivery. The initiators of the inflammatory signaling mechanism can be both maternal and fetal. The placental (fetal)-maternal immune and endocrine mediated homeostatic imbalances and inflammation are well reported. However, the fetal inflammatory response (FIR) theories initiated by the fetal membranes (amniochorion) at the choriodecidual interface are not well established. Although immune cell migration, activation, and production of proparturition cytokines to the fetal membranes are reported, cellular level events that can generate a unique set of inflammation are not well discussed. This review discusses derangements to fetal membrane cells (physiologically and pathologically at term and preterm, respectively) in response to both endogenous and exogenous factors to generate inflammatory signals. In addition, the mechanisms of inflammatory signal propagation (fetal signaling of parturition) and how these signals cause immune imbalances at the choriodecidual interface are discussed. In addition to maternal inflammation, this review projects FIR as an additional mediator of inflammatory overload required to promote parturition.
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Trabajo de Parto , Placenta , Membranas Extraembrionarias/metabolismo , Femenino , Humanos , Recién Nacido , Inflamación/metabolismo , Trabajo de Parto/metabolismo , Parto/metabolismo , Placenta/metabolismo , EmbarazoRESUMEN
Preterm birth remains a worldwide health concern due to ongoing challenges in prediction and prevention. Current predictors are limited by poor performance, need for invasive sampling, and an inability to identify patients in a timely fashion to allow for effective intervention. The multiple etiologies of preterm birth often have an inflammatory component. Thus, a deeper understanding of the inflammatory mechanisms involved in preterm birth may provide opportunities to identify new predictors of preterm birth. This review will discuss the multiple etiologies of preterm birth, their links to inflammation, current predictors available, and new directions for the field.
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B cell participation in early embryo/fetal development and the underlying molecular pathways have not been explored. To understand whether maternal B cell absence or impaired signaling interferes with placental and fetal growth, we paired CD19-deficient (CD19-/-) mice, females with B cell-specific MyD88 (BMyD88-/-) or IL10 (BIL10-/-) deficiency as well as wild-type and MyD88-/- controls on C57Bl/6 background with BALB/c males. Pregnancies were followed by ultrasound and Doppler measurements. Implantation number was reduced in BMyD88-/- and MyD88-/- mice. Loss of MyD88 or B cell-specific deletion of MyD88 or IL10 resulted in decreased implantation areas at gestational day (gd) 5, gd8 and gd10, accompanied by reduced placental thickness, diameter and areas at gd10. Uterine artery resistance was enhanced in BIL10-/- dams at gd10. Challenge with 0.4â mg lipopolysaccharide/kg bodyweight at gd16 revealed that BMyD88-/-, BIL10-/- and CD19-/- mothers delivered preterm, whereas controls maintained their pregnancy. B cell-specific MyD88 and IL10 expression is essential for appropriate in utero development. IL10+B cells are involved in uterine blood flow regulation during pregnancy. Finally, B cell-specific CD19, MyD88 and IL10 expression influences susceptibility towards preterm birth.
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Linfocitos B/metabolismo , Desarrollo Fetal , Feto/embriología , Transducción de Señal , Arteria Uterina/metabolismo , Útero , Resistencia Vascular , Animales , Antígenos CD19/genética , Antígenos CD19/metabolismo , Femenino , Interleucina-10/deficiencia , Interleucina-10/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/deficiencia , Factor 88 de Diferenciación Mieloide/metabolismo , Embarazo , Útero/irrigación sanguínea , Útero/metabolismoRESUMEN
Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal-fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4+ T cells being more observable within the umbilical cord blood, whereas CD8+ T cells became relatively more abundant in fetal membranes. CD4+ and CD8+ T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8+ T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T-cell-activation-induced preterm birth could be alleviated by the depletion of CD8+ T but not CD4+ T cells in vivo. Collectively, we showed that CD8+ T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.
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Trabajo de Parto Prematuro , Nacimiento Prematuro , Embarazo , Animales , Ratones , Humanos , Femenino , Recién Nacido , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/prevención & control , Linfocitos T CD8-positivos , Membranas Extraembrionarias , FenotipoRESUMEN
Early life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks. Our aims were to: chart typical longitudinal cortical development and sex differences in cortical development from birth to adolescence in healthy term-born children; estimate differences in cortical development between children born at term and very preterm; and estimate differences in cortical development between children with normal and impaired cognition in adolescence. This longitudinal cohort study included children born at term (≥37 weeks' gestation) and very preterm (<30 weeks' gestation) with MRI scans at ages 0, 7 and 13 years (n = 66 term-born participants comprising 34 with one scan, 18 with two scans and 14 with three scans; n = 201 very preterm participants comprising 56 with one scan, 88 with two scans and 57 with three scans). Cognitive assessments were performed at age 13 years. Cortical surface reconstruction and parcellation were performed with state-of-the-art, equivalent MRI analysis pipelines for all time points, resulting in longitudinal cortical volume, surface area and thickness measurements for 62 cortical regions. Developmental trajectories for each region were modelled in term-born children, contrasted between children born at term and very preterm, and contrasted between all children with normal and impaired cognition. In typically developing term-born children, we documented anticipated patterns of rapidly increasing cortical volume, area and thickness in early childhood, followed by more subtle changes in later childhood, with smaller cortical size in females than males. In contrast, children born very preterm exhibited increasingly reduced cortical volumes, relative to term-born children, particularly during ages 0-7 years in temporal cortical regions. This reduction in cortical volume in children born very preterm was largely driven by increasingly reduced cortical thickness rather than area. This resulted in amplified cortical volume and thickness reductions by age 13 years in individuals born very preterm. Alterations in cortical thickness development were found in children with impaired language and memory. This study shows that the neurobiological impact of very preterm birth on cortical growth is amplified from infancy to adolescence. These data further inform the long-lasting impact on cortical development from very preterm birth, providing broader insights into neurodevelopmental consequences of early life experiences.
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Nacimiento Prematuro , Lactante , Niño , Recién Nacido , Humanos , Masculino , Preescolar , Femenino , Adolescente , Estudios Longitudinales , Cognición , Edad Gestacional , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagenRESUMEN
In the perinatal period, reward and cognitive systems begin trajectories, influencing later psychiatric risk. The basal ganglia is important for reward and cognitive processing but early development has not been fully characterized. To assess age-related development, we used a measure of basal ganglia physiology, specifically brain tissue iron, obtained from nT2* signal in resting-state functional magnetic resonance imaging (rsfMRI), associated with dopaminergic processing. We used data from the Developing Human Connectome Project (n = 464) to assess how moving from the prenatal to the postnatal environment affects rsfMRI nT2*, modeling gestational and postnatal age separately for basal ganglia subregions in linear models. We did not find associations with tissue iron and gestational age [range: 24.29-42.29] but found positive associations with postnatal age [range:0-17.14] in the pallidum and putamen, but not the caudate. We tested if there was an interaction between preterm birth and postnatal age, finding early preterm infants (GA < 35 wk) had higher iron levels and changed less over time. To assess multivariate change, we used support vector regression to predict age from voxel-wise-nT2* maps. We could predict postnatal but not gestational age when maps were residualized for the other age term. This provides evidence subregions differentially change with postnatal experience and preterm birth may disrupt trajectories.
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Recien Nacido Prematuro , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Imagen por Resonancia Magnética , Nacimiento Prematuro/patología , Hierro , Ganglios Basales/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.
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Diabetes Mellitus Tipo 1 , Edad Gestacional , Sistema de Registros , Humanos , Diabetes Mellitus Tipo 1/epidemiología , Finlandia/epidemiología , Noruega/epidemiología , Suecia/epidemiología , Femenino , Masculino , Recién Nacido , Niño , Adolescente , Adulto Joven , Nacimiento Prematuro/epidemiología , Factores de Riesgo , Adulto , EmbarazoRESUMEN
Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses. Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing. These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth.
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Imagen por Resonancia Magnética , Núcleos Talámicos , Humanos , Adulto , Femenino , Masculino , Núcleos Talámicos/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Recién Nacido , Recien Nacido Extremadamente Prematuro , Recién Nacido de muy Bajo PesoRESUMEN
Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties. The objective of the study was to evaluate the efficacy of direct fetal creatine supplementation to reduce inflammation and oxidative stress in fetal lungs arising from an in utero proinflammatory stimulus. Fetal lambs (n = 51) were instrumented at 90 days gestation to receive a continuous infusion of creatine monohydrate (6 mg·kg-1·h-1) or saline for 17 days. Maternal chorioamnionitis was induced with intra-amniotic lipopolysaccharide (LPS; 1 mg, O55:H6) or saline 7 days before delivery at 110 days gestation. Tissue creatine content was assessed with capillary electrophoresis, and inflammatory markers were analyzed with Luminex Magpix and immunohistochemistry. Oxidative stress was measured as the level of protein thiol oxidation. The effects of LPS and creatine were analyzed using a two-way ANOVA. Fetal creatine supplementation increased lung creatine content by 149% (PCr < 0.0001) and had no adverse effects on lung morphology. LPS-exposed groups showed increased levels of interleukin-8 in the bronchoalveolar lavage (PLPS < 0.0001) and increased levels of CD45+ leukocytes (PLPS < 0.0001) and MPO+ (PLPS < 0.0001) cells in the lung parenchyma. Creatine supplementation significantly reduced the levels of CD45+ (PCr = 0.045) and MPO+ cells (PCr = 0.012) in the lungs and reduced thiol oxidation in plasma (PCr < 0.01) and lung tissue (PCr = 0.02). In conclusion, fetal creatine supplementation reduced markers of inflammation and oxidative stress in the fetal lungs arising from chorioamnionitis.NEW & NOTEWORTHY We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine.
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Corioamnionitis , Creatina , Suplementos Dietéticos , Lipopolisacáridos , Pulmón , Estrés Oxidativo , Animales , Corioamnionitis/tratamiento farmacológico , Corioamnionitis/metabolismo , Corioamnionitis/patología , Creatina/farmacología , Femenino , Estrés Oxidativo/efectos de los fármacos , Embarazo , Ovinos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Neumonía/metabolismo , Neumonía/prevención & control , Neumonía/tratamiento farmacológico , Neumonía/patología , Modelos Animales de Enfermedad , Feto/metabolismo , Feto/efectos de los fármacosRESUMEN
Extremely preterm infants are often exposed to long durations of mechanical ventilation to facilitate gas exchange, resulting in ventilation-induced lung injury (VILI). New lung protective strategies utilizing noninvasive ventilation or low tidal volumes are now common but have not reduced rates of bronchopulmonary dysplasia. We aimed to determine the effect of 24 h of low tidal volume ventilation on the immature lung by ventilating preterm fetal sheep in utero. Preterm fetal sheep at 110 ± 1(SD) days' gestation underwent sterile surgery for instrumentation with a tracheal loop to enable in utero mechanical ventilation (IUV). At 112 ± 1 days' gestation, fetuses received either in utero mechanical ventilation (IUV, n = 10) targeting 3-5 mL/kg for 24 h, or no ventilation (CONT, n = 9). At necropsy, fetal lungs were collected to assess molecular and histological markers of lung inflammation and injury. IUV significantly increased lung mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) compared with CONT, and increased surfactant protein (SP)-A1, SP-B, and SP-C mRNA expression compared with CONT. IUV produced modest structural changes to the airways, including reduced parenchymal collagen and myofibroblast density. IUV increased pulmonary arteriole thickness compared with CONT but did not alter overall elastin or collagen content within the vasculature. In utero ventilation of an extremely preterm lung, even at low tidal volumes, induces lung inflammation and injury to the airways and vasculature. In utero ventilation may be an important model to isolate the confounding mechanisms of VILI to develop effective therapies for preterm infants requiring prolonged respiratory support.NEW & NOTEWORTHY Preterm infants often require prolonged respiratory support, but the relative contribution of ventilation to the development of lung injury is difficult to isolate. In utero mechanical ventilation allows for mechanistic investigations into ventilation-induced lung injury without confounding factors associated with sustaining extremely preterm lambs ex utero. Twenty-four hours of in utero ventilation, even at low tidal volumes, increased lung inflammation and surfactant protein expression and produced structural changes to the lung parenchyma and vasculature.
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Neumonía , Lesión Pulmonar Inducida por Ventilación Mecánica , Humanos , Recién Nacido , Ovinos , Animales , Recien Nacido Extremadamente Prematuro , Pulmón/metabolismo , Feto/metabolismo , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Colágeno/metabolismo , Neumonía/patología , Tensoactivos/metabolismo , ARN Mensajero/metabolismoRESUMEN
Infants born preterm face an increased risk of deleterious effects on lung and brain health that can significantly alter long-term function and quality of life and even lead to death. Moreover, preterm birth is also associated with a heightened risk of diabetes and obesity later in life, leading to an increased risk of all-cause mortality in young adults born prematurely. While these preterm-birth-related conditions have been well characterized, less is known about the long-term effects of preterm birth on skeletal muscle health and, specifically, an individual's skeletal muscle hypertrophic potential later in life. In this review, we discuss how a confluence of potentially interrelated and self-perpetuating elements associated with preterm birth might converge on anabolic and catabolic pathways to ultimately blunt skeletal muscle hypertrophy, identifying critical areas for future research.
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Preterm birth (PTB) remains a key public health issue that disproportionately affects Black individuals. Since spontaneous PTB (sPTB) and medically indicated PTB (mPTB) may have different causes and interventions, we quantified racial disparities for sPTB and mPTB, and we characterized the geographic patterning of these phenotypes, overall and according to race/ethnicity. We examined a pregnancy cohort of 83,952 singleton births at 2 Philadelphia hospitals from 2008-2020, and classified each PTB as sPTB or mPTB. We used binomial regression to quantify the magnitude of racial disparities between non-Hispanic Black and non-Hispanic White individuals, then generated small area estimates by applying a Bayesian model that accounts for small numbers and smooths estimates of PTB risk by borrowing information from neighboring areas. Racial disparities in both sPTB and mPTB were significant (relative risk of sPTB = 1.83, 95% confidence interval: 1.70, 1.98; relative risk of mPTB = 2.20, 95% confidence interval: 2.00, 2.42). The disparity was 20% greater in mPTB than sPTB. There was substantial geographic variation in PTB, sPTB, and mPTB risks and racial disparity. Our findings underscore the importance of distinguishing PTB phenotypes within the context of public health and preventive medicine. Future work should consider social and environmental exposures that may explain geographic differences in PTB risk and disparities.
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Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/epidemiología , Teorema de Bayes , Philadelphia/epidemiología , Factores de Riesgo , EtnicidadRESUMEN
Epidemiologists have long argued that side effects of the stress response include preterm birth. Research reports that fear of lethal infection stressed pregnant persons at the outset of the COVID-19 pandemic and that "shutdowns" and "social distancing" impeded access to social support and prenatal care. The decline in preterm births in high-income countries, including the United States (US), during the early months of the pandemic therefore poses a paradox for science. Explanations of this "pandemic preterm paradox" remain untested. We apply time-series modeling to data describing 80 monthly conception cohorts begun in the US from July 2013 through February 2020 to determine which of 3 explanations most parsimoniously explains the paradox. We infer that "prior loss," or the argument that an increase in spontaneous abortions and stillbirths depleted the population of fetuses at risk of preterm birth, best explains data currently available. We describe the implications of these results for public health practice.
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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.
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Nacimiento Prematuro , Sustancia Blanca , Masculino , Adulto , Femenino , Humanos , Recién Nacido , Sustancia Blanca/diagnóstico por imagen , Nacimiento Prematuro/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia MagnéticaRESUMEN
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.
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Recien Nacido Prematuro , Nacimiento Prematuro , Lactante , Embarazo , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/diagnóstico por imagen , Encéfalo , Imagen por Resonancia Magnética , CogniciónRESUMEN
The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the underlying mechanisms are not known. In a translational hyperoxia model, exposing mice pups at P5 to 80% oxygen for 48â h to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin-expressing interneurons until adulthood. Developmental delay of cortical myelin was observed, together with decreased expression of oligodendroglial glial cell-derived neurotrophic factor (GDNF), a factor involved in interneuronal development. Electrophysiological and morphological properties of remaining interneurons were unaffected. Behavioral deficits were observed for social interaction, learning and attention. These results demonstrate that neonatal oxidative stress can lead to decreased interneuron density and to psychiatric symptoms. The obtained cortical myelin deficit and decreased oligodendroglial GDNF expression indicate that an impaired oligodendroglial-interneuronal interplay contributes to interneuronal damage.
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Lesiones Encefálicas/metabolismo , Neuronas GABAérgicas/metabolismo , Hiperoxia/metabolismo , Interneuronas/metabolismo , Parvalbúminas/metabolismo , Nacimiento Prematuro/metabolismo , Roedores/metabolismo , Animales , Línea Celular , Cognición/fisiología , Modelos Animales de Enfermedad , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Oligodendroglía/metabolismo , Conducta SocialRESUMEN
Despite advances in perinatal medicine, racial disparity in birth outcomes remains a public health problem in the USA. The underlying mechanisms for this long-standing racial disparity are incompletely understood. This review presents transgenerational risk factors for racial disparities in preterm birth, exploring the impact of interpersonal and structural racism, theoretical models of stress, and biological markers of racial disparities.
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Inequidades en Salud , Nacimiento Prematuro , Racismo , Femenino , Humanos , Recién Nacido , Embarazo , Negro o Afroamericano , Atención PrenatalRESUMEN
BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.