Ultrasonographic evaluation of the early brain growth pattern in very low birth weight infants

BACKGROUND: Preterm infants develop smaller brain volumes compared to term newborns. Our aim is to study early brain growth related to perinatal factors in very low birth weight infants (VLBWI). METHODS: Manual segmentation of total brain volume (TBV) was performed in weekly 3D-ultrasonographies in our cohort of VLBWI. We studied the brain growth pattern related to term magnetic resonance image (term-MRI). RESULTS: We found different brain growth trajectories, with smaller brain volumes and a decrease in brain growth rate in those VLBWI who would later have an abnormal term-MRI (mean TBV 190.68 vs. 213.9 cm3; P = 0.0001 and mean TBV growth rate 14.35 (±1.27) vs. 16.94 (±2.29) cm3/week; P = 0.0001). TBV in those with normal term-MRI was related to gestational age (GA), being small for gestational age (SGA), sex, and duration of parenteral nutrition (TPN) while in those with abnormal term-MRI findings it was related to GA, SGA, TPN, and comorbidities. We found a deceleration in brain growth rate in those with ≥3 comorbidities. CONCLUSIONS: An altered brain growth pattern in VLBWI who subsequently present worst scores on term-MRI is related to GA, being SGA and comorbidities. Early ultrasonographic monitoring of TBV could be useful to detect deviated patterns of brain growth

Descrição dos achados linguísticos e neurológicos de gemelares nascidos pré-termo aos dois anos de idade

Introduction: Prematurity, low birth weight and multiple births are risk factors for structural changes in the brain, as well as deviations in motor, cognitive, social and language development. Objective: To describe language findings and investigate the presence of neurological changes in preterm twins born at two years of age. Method: This is a cross-sectional study based on data analysis of the medical records of six pairs of low birth weight preterm twins, of both sexes, at two years of age, attended to at the State Center for the Prevention and Rehabilitation of Persons withDisabilities - CEPRED, in Salvador-Bahia-Brazil. To this end, information regarding birth was collected; the clinical history; the imaging exams; and the speech, neurological and interdisciplinary assessments. Results: preterm twins had atypical language development and neurological changes that may compromise oral language development. From the neurological point of view, abnormalities common to the premature newborn, such as peri-intraventricular hemorrhage, were observed. Conclusion: Multiple births associated with prematurity and low birth weight may pose risks to the childs language acquisition.Introdução: A prematuridade, o baixo peso ao nascer e os nascimentos múltiplos são fatores de risco para alterações estruturais no cérebro, assim como para desvios no desenvolvimento motor, cognitivo, social e de linguagem. Objetivo: Descrever os achados linguísticos e investigar a presença de alterações neurológicas em gemelares nascidos pré-termo, aos dois anos de idade. Método: Trata-se de um estudo do tipo corte transversal, realizado por meio da análise de dados dos prontuários de seis pares de gêmeos nascidos pré-termo, com baixo peso ao nascer, de ambos os sexos, aos dois anos de idade, atendidos no Centro Estadual de Prevenção e Reabilitação da Pessoa com Deficiência – CEPRED, em Salvador-Bahia-Brasil. Para tanto, foram coletadas as informações referentes ao nascimento; a história clínica; os exames de imagem; e as avaliações fonoaudiológica, neurológica e interdisciplinar. Resultados: Os gemelares nascidos pré-termo apresentaram desenvolvimento linguístico atípico e alterações neurológicas que podem comprometer o desenvolvimento da linguagem oral. Do ponto de vista neurológico, foram observadas anormalidades comuns ao recém-nascido prematuro, como a hemorragia peri-intraventricular. Conclusão: Os nascimentos múltiplos associados à prematuridade e ao baixo peso ao nascer podem oferecer riscos à aquisição da linguagem da criança

Preterm Birth Is Associated With Depression From Childhood to Early Adulthood

Objective:  There have been inconsistent findings on the associations between prematurity, poor fetal growth and depression. We examined the associations between gestational age, poor fetal growth and depression in individuals aged 5 to 25 years.Method:  We identified 37,682 cases based on ICD-9 code 2961 and ICD-10 codes F32.0-F32.9 and F33.0-F33.9 from the Care Register for Health Care, and 148,795 matched controls from the Finnish Central Population Register. Conditional logistic regression examined the associations between gestational age by each gestational week, poor fetal growth and depression. The associations were adjusted for parental age and psychopathology, paternal immigrant status, maternal substance abuse, depression, number of previous births, marital status, socio-economic status, smoking during pregnancy and the infant's birthplace.Results:  In the adjusted models, increased risk of depression was found in children born ≤ 25 weeks (1.89, 1.08-3.31), at 26 weeks (2.62, 1.49-4.61), at 27 weeks (1.93, 1.05-3.53) and ≥ 42 weeks (1.11, 1.05-1.19). In girls, extremely preterm birth was associated with depression diagnosed at 5 to 12 years (2.70, 1.83-3.98) and 13 to 18 years (2.97, 1.84-4.78). In boys, post-term birth (≥42 weeks) was associated with depression diagnosed at 19 to 25 years (1.28, 1.07-1.54). Poor fetal growth was associated with an increased risk of depression in full-term infants (1.06, 1.03-1.10) and post-term infants (1.24, 1.08-1.43).Conclusion:  Preterm birth before 28 weeks of gestation appeared to play a role in the development of childhood depression. Smaller effects were also seen in post-term births, especially in boys.</div

Longitudinal study of neonatal brain tissue volumes in preterm infants and their ability to predict neurodevelopmental outcome

Premature birth has been associated with poor neurodevelopmental outcomes. However, the relation between such outcomes and brain growth in the neonatal period has not yet been fully elucidated. This study investigates longitudinal brain development between birth and term-equivalent age (TEA) by quantitative imaging in a cohort of premature infants born between 26 and 36 weeks gestational age (GA), to provide insight into the relation of brain growth with later neurodevelopmental outcomes.Longitudinal T2-weighted magnetic resonance images (MRI) of 84 prematurely born infants acquired shortly after birth and TEA were automatically segmented into cortical gray matter (CGM), unmyelinated white matter (UWM), subcortical gray matter (SGM), cerebellum (CB) and cerebrospinal fluid (CSF). General linear models and correlation analysis were used to study the relation between brain volumes and their growth, and perinatal variables. To investigate the ability of the brain volumes to predict children's neurodevelopmental outcome at 18-24 months and at 5 years of age, a linear discriminant analysis classifier was tested and several general linear models were fitted and compared by statistical tests.From birth to TEA, relative volumes of CGM, CB and CSF with respect to total intracranial volume increased, while relative volumes of UWM and SGM decreased. The fastest growing tissues between birth and TEA were found to be the CB and the CGM. Lower GA at birth was associated with lower growth rates of CGM, CB and total tissue. Among perinatal factors, persistent ductus arteriosus was associated with lower SGM, CB and IC growth rates, while sepsis was associated with lower CSF and intracranial volume growth rates.Model comparisons showed that brain tissue volumes at birth and at TEA contributed to the prediction of motor outcomes at 18-24 months, while volumes at TEA and volume growth rates contributed to the prediction of cognitive scores at 5 years of age. The family socio-economic status (SES) was not correlated with brain volumes at birth or at TEA, but was strongly associated with the cognitive outcomes at 18-24 months and 5 years of age.This study provides information about brain growth between birth and TEA in premature children with no focal brain lesions, and investigates their association with subsequent neurodevelopmental outcome. Parental SES was found to be a major determinant of neurodevelopmental outcome, unrelated to brain growth. However, further research is necessary in order to fully explain the variability of neurodevelopmental outcomes in this population

Role of perinatal inflammation in preterm brain injury

Perinatal inflammation is associated with an increased risk of brain injury and neurodevelopmental impairment in preterm infants but the immune mediators driving this association are not well understood. This PhD thesis seeks to further characterise the inflammatory response associated with preterm birth, describe the relationship between perinatal inflammation and white matter development and explore the effect of specific inflammation-associated proteins on the development of human cortical neurons derived from induced pluripotent stem cells (iPSCs). In the first study, I investigated the inflammatory profile at birth in 55 very preterm infants, compared to 59 term-born controls and then used this profile to predict exposure to intrauterine inflammation in the preterm group. Preterm infants had a distinct pro-inflammatory profile in umbilical cord blood at delivery when compared to term-born controls and IL-8 was found to be the strongest predictor of intrauterine inflammation. In the second study, I investigated the association between specific inflammation-associated proteins and white matter microstructure in 71 very preterm infants using structural MRI and diffusion-weighted imaging of the brain. Elevated IL-8 in the first week of life was associated with white matter dysmaturation at term-equivalent age. Following this discovery, I investigated the effect of IL-8 on the maturation and morphology of iPSC-derived cortical neurons and found that exposure was associated with impaired neurite outgrowth. This thesis provides further evidence to support the role of inflammation in the aetiology of preterm brain injury and suggests that IL-8 dysregulation may link systemic inflammation with atypical cortical development and white matter disease in preterm infants