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1.
Artigo em Inglês | MEDLINE | ID: mdl-34948532

RESUMO

Children with below average cognitive ability represent a substantial yet under-researched population for whom cognitive and social demands, which increase in complexity year by year, may pose significant challenges. This observational study examines the longitudinal relationship between early cognitive ability and emotional-behavioral difficulties (EBDs) between the age of three and nine. Participants include 7134 children from the population-based cohort study growing up in Ireland. Cognitive ability was measured at age three using the Picture Similarities Scale. A t-score one to two standard deviations below the mean was defined as below average cognitive ability (n = 767). EBDs were measured using the Strengths and Difficulties Questionnaire (SDQ) at three, five, and nine years of age. Generalized linear mixed models and logistic regression were used to examine the relationship. Below average cognitive ability was an independent predictor of higher longitudinal SDQ scores. After adjustment, children with below average cognitive ability were 1.39 times more likely (AOR 1.39, 95% CI 1.17-1.66, p < 0.001) to experience a clinically significant EBD between the ages of three to nine years. This study demonstrates the increased risk of EBDs for children with below average cognitive ability. A scalable method of early identification of at-risk children should be a research priority for public health, enabling early intervention for cognitive and adaptive outcomes.


Assuntos
Cognição , Emoções , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Irlanda/epidemiologia , Fatores de Risco
2.
Sci Rep ; 11(1): 22315, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785716

RESUMO

Autism Spectrum disorder is one of the commonest and most important neurodevelopmental conditions affecting children today. With an increasing prevalence and an unclear aetiology, it is imperative we find early markers of autism, which may facilitate early identification and intervention. Alterations of gestational cytokine profiles have been reported in mothers of autistic children. Increasing evidence suggests that the intrauterine environment is an important determinant of autism risk. This study aims to examine the mid-gestational serum cytokine profiles of the mothers of autistic children from a well-characterised birth cohort. A nested sub-cohort within a large mother-child birth cohort were identified based on a confirmed multi-disciplinary diagnosis of autism before the age 10 years and neuro-typical matched controls in a 2:1 ratio. IFN-γ, IL-1ß, IL-4, IL-6, IL-8, IL-17A, GMCSF and TNFα were measured in archived maternal 20-week serum using MesoScale Diagnostics multiplex technology and validation of our IL-17A measurements was performed using an ultrasensitive assay. From a cohort of 2137 children, 25 had confirmed autism before 10 years and stored maternal serum from mid-gestation. We examined the sera of these 25 cases and 50 matched controls. The sex ratio was 4:1 males to females in each group, and the mean age at diagnosis was 5.09 years (SD 2.13). We found that concentrations of IL-4 were significantly altered between groups. The other analytes did not differ significantly using either multiplex or ultra-sensitive assays. In our well-characterised prospective cohort of autistic children, we confirmed mid-gestational alterations in maternal IL-4 concentrations in autism affected pregnancies versus matched controls. These findings add to promising evidence from animal models and retrospective screening programmes and adds to the knowledge in this field.

3.
Neonatology ; : 1-9, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34818237

RESUMO

INTRODUCTION: Hypoxic ischaemic encephalopathy (HIE) remains one of the top 10 contributors to the global burden of disease. Early objective biomarkers are required. Near-infrared spectroscopy (NIRS) may provide a valuable insight into cerebral perfusion and metabolism. We aimed to determine whether early NIRS monitoring (<6 h of age) can predict outcome as defined by grade of encephalopathy, brain MRI findings, and/or neurodevelopmental outcome at 1-2 years in infants with HIE. METHODS: We searched PubMed, Scopus, Web of Science, Embase, and The Cochrane Library databases (July 2019). Studies of infants born ≥36+0 weeks gestation with HIE who had NIRS recording commenced before 6 h of life were included. We planned to provide a narrative of all the studies included, and if similar clinically and methodologically, the results would be pooled in a meta-analysis to determine test accuracy. RESULTS: Seven studies were included with a combined total of 161 infants. Only 1 study included infants with mild HIE. A range of different oximeters and probes were utilized with varying outcome measures making comparison difficult. Although some studies showed a trend towards higher cSO2 values before 6 h in infants with adverse neurodevelopmental outcomes, in the majority, this was not significant until beyond 24 h of life. CONCLUSION: Very little data currently exists to assess the use of early NIRS to predict outcome in infants with HIE. Further studies using a standardized approach are required before NIRS can be evaluated as a potential objective assessment tool for early identification of at-risk infants.

4.
J Pediatr ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34626667

RESUMO

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden and describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks of gestation) requiring electroencephalographic (EEG) monitoring recruited to 2 multicenter European studies were included. Infants who received antiseizure medication exclusively after electrographic seizure onset were grouped based on the time to treatment of the first seizure: antiseizure medication within 1 hour, between 1 and 2 hours, and after 2 hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures, and antiseizure medication dose over the first 24 hours after seizure onset. RESULTS: Out of 472 newborns recruited, 154 (32.6%) had confirmed electrographic seizures. Sixty-nine infants received antiseizure medication exclusively after the onset of electrographic seizure, including 21 infants within 1 hour of seizure onset, 15 between 1 and 2 hours after seizure onset, and 33 at >2 hours after seizure onset. Significantly lower seizure burden and fewer seizures were noted in the infants treated with antiseizure medication within 1 hour of seizure onset (P = .029 and .035, respectively). Overall, 258 of 472 infants (54.7%) received antiseizure medication during the study period, of whom 40 without electrographic seizures received treatment exclusively during EEG monitoring and 11 with electrographic seizures received no treatment. CONCLUSIONS: Treatment of neonatal seizures may be time-critical, but more research is needed to confirm this. Improvements in neonatal seizure diagnosis and treatment are also needed.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34590504

RESUMO

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King's Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients.


Assuntos
Esclerose Amiotrófica Lateral , COVID-19 , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/diagnóstico , Teorema de Bayes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Capacidade Vital
6.
Proc Nutr Soc ; : 1-11, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34548120

RESUMO

Iron is essential for the functioning of all cells and organs, most critically for the developing brain in the fundamental neuronal processes of myelination, energy and neurotransmitter metabolism. Iron deficiency, especially in the first 1000 days of life, can result in long-lasting, irreversible deficits in cognition, motor function and behaviour. Pregnant women, infants and young children are most vulnerable to iron deficiency, due to their high requirements to support growth and development, coupled with a frequently inadequate dietary supply. An unrecognised problem is that even if iron intake is adequate, common pregnancy-related and lifestyle factors can affect maternal-fetal iron supply in utero, resulting in an increased risk of deficiency for the mother and her fetus. Although preterm birth, gestational diabetes mellitus and intrauterine growth restriction are known risk factors, more recent evidence suggests that maternal obesity and delivery by caesarean section further increase the risk of iron deficiency in the newborn infant, which can persist into early childhood. Despite the considerable threat that early-life iron deficiency poses to long-term neurological development, life chances and a country's overall social and economic progress, strategies to tackle the issue are non-existent, too limited or totally inappropriate. Prevention strategies, focused on improving the health and nutritional status of women of reproductive age are required. Delayed cord clamping should be considered a priority. Better screening strategies to enable the early detection of iron deficiency during pregnancy and early-life should be prioritised, with intervention strategies to protect maternal health and the developing brain.

7.
Front Mol Neurosci ; 14: 732199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566578

RESUMO

Background: Evidence suggests that earlier diagnosis and initiation of treatment immediately after birth is critical for improved neurodevelopmental outcomes following neonatal encephalopathy (NE). Current diagnostic tests are, however, mainly restricted to clinical diagnosis with no molecular tests available. Purines including adenosine are released during brain injury such as hypoxia and are also present in biofluids. Whether blood purine changes can be used to diagnose NE has not been investigated to date. Methods: Blood purines were measured in a mouse model of neonatal hypoxia and infants with NE using a novel point-of-care diagnostic technology (SMARTChip) based on the summated electrochemical detection of adenosine and adenosine metabolites in the blood. Results: Blood purine concentrations were ∼2-3-fold elevated following hypoxia in mice [2.77 ± 0.48 µM (Control) vs. 7.57 ± 1.41 µM (post-hypoxia), p = 0.029]. Data in infants with NE had a 2-3-fold elevation when compared to healthy controls [1.63 ± 0.47 µM (Control, N = 5) vs. 4.87 ± 0.92 µM (NE, N = 21), p = 0.0155]. ROC curve analysis demonstrates a high sensitivity (81%) and specificity (80%) for our approach to identify infants with NE. Moreover, blood purine concentrations were higher in infants with NE and seizures [8.13 ± 3.23 µM (with seizures, N = 5) vs. 3.86 ± 0.56 µM (without seizures, N = 16), p = 0.044]. Conclusion: Our data provides the proof-of-concept that measurement of blood purine concentrations via SMARTChip technology may offer a low-volume bedside test to support a rapid diagnosis of NE.

8.
J Med Internet Res ; 23(9): e28766, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550089

RESUMO

Despite recent and potent technological advances, the real-world implementation of remote digital health technology in the care and monitoring of patients with motor neuron disease has not yet been realized. Digital health technology may increase the accessibility to and personalization of care, whereas remote biosensors could optimize the collection of vital clinical parameters, irrespective of patients' ability to visit the clinic. To facilitate the wide-scale adoption of digital health care technology and to align current initiatives, we outline a road map that will identify clinically relevant digital parameters; mediate the development of benefit-to-burden criteria for innovative technology; and direct the validation, harmonization, and adoption of digital health care technology in real-world settings. We define two key end products of the road map: (1) a set of reliable digital parameters to capture data collected under free-living conditions that reflect patient-centric measures and facilitate clinical decision making and (2) an integrated, open-source system that provides personalized feedback to patients, health care providers, clinical researchers, and caregivers and is linked to a flexible and adaptable platform that integrates patient data in real time. Given the ever-changing care needs of patients and the relentless progression rate of motor neuron disease, the adoption of digital health care technology will significantly benefit the delivery of care and accelerate the development of effective treatments.


Assuntos
Doença dos Neurônios Motores , Tecnologia Biomédica , Cuidadores , Pessoal de Saúde , Humanos , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/terapia , Tecnologia
9.
Heliyon ; 7(7): e07411, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34278022

RESUMO

Hypoxic Ischemic Encephalopathy (HIE) remains a major cause of neurological disability. Early intervention with therapeutic hypothermia improves outcome, but prediction of HIE is difficult and no single clinical marker is reliable. Machine learning algorithms may allow identification of patterns in clinical data to improve prognostic power. Here we examine the use of a Random Forest machine learning algorithm and five-fold cross-validation to predict the occurrence of HIE in a prospective cohort of infants with perinatal asphyxia. Infants with perinatal asphyxia were recruited at birth and neonatal course was followed for the development of HIE. Clinical variables were recorded for each infant including maternal demographics, delivery details and infant's condition at birth. We found that the strongest predictors of HIE were the infant's condition at birth (as expressed by Apgar score), need for resuscitation, and the first postnatal measures of pH, lactate, and base deficit. Random Forest models combining features including Apgar score, most intensive resuscitation, maternal age and infant birth weight both with and without biochemical markers of pH, lactate, and base deficit resulted in a sensitivity of 56-100% and a specificity of 78-99%. This study presents a dynamic method of rapid classification that has the potential to be easily adapted and implemented in a clinical setting, with and without the availability of blood gas analysis. Our results demonstrate that applying machine learning algorithms to readily available clinical data may support clinicians in the early and accurate identification of infants who will develop HIE. We anticipate our models to be a starting point for the development of a more sophisticated clinical decision support system to help identify which infants will benefit from early therapeutic hypothermia.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34092157

RESUMO

Forced vital capacity (FVC) is an essential respiratory measurement for assessment and monitoring of patients with Amyotrophic Lateral Sclerosis (ALS). Our clinic rapidly implemented remote assessment of FVC after COVID-19 related restrictions on respiratory testing were imposed, using mini-spirometers and video consultation. We sought to evaluate the patient's experiences of performing remote respiratory assessments to guide future development and optimisation of the service. Twenty-five patients completed surveys. The mean age was 65.2 years and average time from diagnosis was 17.04 (2-99) months. Seventy-two percent (n = 18) required help from a caregiver to perform the tests. Ninety-two percent (n = 23) of patients reported that overall, they were satisfied and were happy to continue with remote respiratory assessment. Reducing the number of clinic visits for review and assessment was valued by 92% (n = 23) and reducing the risk associated with COVID-19 was valued by 96% (n = 24). The highest frequency reported as acceptable for performing the remote breathing assessments was monthly (60%, n = 15), followed by every second month (28%, n = 7). Remote respiratory testing is viewed positively by patients. These technologies used in combination with video-consultations and other novel forms of remote monitoring implemented in response to the COVID-19 crisis will continue to be valuable tools for clinical care in future. However, further evaluation of the validity of remote respiratory assessment is required.

12.
J Am Heart Assoc ; 10(11): e020051, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34039012

RESUMO

Background Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking, and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and Results Seven European birth cohorts, including 232 390 offspring (2469 CHD cases [1.1%]), were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking, and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression, adjusting for confounders and the other parent's exposure and combined estimates using a fixed-effects meta-analysis. In adjusted analyses, maternal overweight (odds ratio [OR], 1.15 [95% CI, 1.01-1.31]) and obesity (OR, 1.12 [95% CI, 0.93-1.36]), compared with normal weight, were associated with higher odds of CHD, but there was no clear evidence of a linear increase in odds across the whole BMI distribution. Associations of paternal overweight, obesity, and mean BMI were similar to the maternal associations. Maternal pregnancy smoking was associated with higher odds of CHD (OR, 1.11 [95% CI, 0.97-1.25]) but paternal smoking was not (OR, 0.96 [95% CI, 0.85-1.07]). The positive association with maternal smoking appeared to be driven by nonsevere CHD cases (OR, 1.22 [95% CI, 1.04-1.44]). Associations with maternal moderate/heavy pregnancy alcohol consumption were imprecisely estimated (OR, 1.16 [95% CI, 0.52-2.58]) and similar to those for paternal consumption. Conclusions We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for the importance of smoking cessation during pregnancy.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Índice de Massa Corporal , Pai/estatística & dados numéricos , Cardiopatias Congênitas/etiologia , Mães/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Adulto , Europa (Continente)/epidemiologia , Feminino , Cardiopatias Congênitas/epidemiologia , Humanos , Incidência , Masculino , Gravidez , Fatores de Risco
13.
Ir J Med Sci ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792855

RESUMO

BACKGROUND: Schools in Ireland closed in March 2020 as part of a national strategy to contain the spread of severe acute respiratory syndrome (SARS-CoV-2). The extent to which schools contribute to the overall propagation of SARS-CoV-2 was continuing to evolve internationally. AIMS: To examine regional data on SARS-CoV-2 transmission in primary, post-primary and special schools in Cork and Kerry, two counties in southwest Ireland, during the first 6 weeks of the 2020-2021 academic year and determine the rate of in-school transmission. METHODS: Data were obtained from the Computerised Infectious Disease Reporting (CIDR) system and supplemented with digital records from the regional Department of Public Health (Dept PH) and from the Health Service Executive (HSE) Covid Care Tracker application. The positivity rate among school close contacts was calculated to determine the rate of in-school SARS-CoV-2 transmission. RESULTS: The overall rate of in-school transmission of SARS-CoV-2 was low at 4.1%. Positivity rates among students and staff who were close contacts were similarly low (3.1% vs. 6.9%, p = 0.07). One secondary case of coronavirus disease 2019 (COVID-19) emerged, on average, for every 7.6 infectious days spent by an index case in school. Schools accounted for 2.2% of all notified cases of COVID-19 in the region during the observation period. CONCLUSIONS: During the first 6 weeks of the academic year, the rate of in-school SARS-CoV-2 transmission in the region was low, and schools did not contribute substantially to the overall burden of COVID-19.

14.
BMC Pediatr ; 21(1): 180, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865345

RESUMO

BACKGROUND: Diet, physical activity, sedentary behaviours, and sleep time are considered major contributory factors of the increased prevalence of childhood overweight and obesity. The aims of this study were to (1) identify behavioural clusters of 5 year old children based on lifestyle behaviours, (2) explore potential determinants of class membership, and (3) to determine if class membership was associated with body measure outcomes at 5 years of age. METHODS: Data on eating behaviour, engagement in active play, TV watching, and sleep duration in 1229 5 year old children from the Cork BASELINE birth cohort study was obtained through in-person interviews with parent. Latent class analysis was used to identify behavioural clusters. Potential determinants of cluster membership were investigated using multinomial logistic regression. Associations between the identified classes and cardio metabolic body measures were examined using multivariate logistic and linear regression, with cluster membership used as the independent variable. RESULTS: 51% of children belonged to a normative class, while 28% of children were in a class characterised by high scores on food avoidance scales in combination with low enjoyment of food, and 20% experienced high scores on the food approach scales. Children in both these classes had lower conditional probabilities of engaging in active play for at least 1 hour per day and sleeping for a minimum of 10 h, and higher probability of watching TV for 2 hours or more, compared to the normative class. Low socioeconomic index (SEI) and no breastfeeding at 2 months were found to be associated with membership of the class associated with high scores on the food avoidance scale, while lower maternal education was associated with the class defined by high food approach scores. Children in the class with high scores on the food approach scales had higher fat mass index (FMI), lean mass index (LMI), and waist-to-height ratio (WtHR) compared to the normative class, and were at greater risk of overweight and obesity. CONCLUSION: Findings suggest that eating behaviour appeared to influence overweight and obesity risk to a greater degree than activity levels at 5 years old. Further research of how potentially obesogenic behaviours in early life track over time and influence adiposity and other cardio metabolic outcomes is crucial to inform the timing of interventions.


Assuntos
Exercício Físico , Comportamento Alimentar , Índice de Massa Corporal , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Humanos , Análise de Classes Latentes , Sono
15.
Pediatr Res ; 90(1): 117-124, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33879847

RESUMO

BACKGROUND: Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants. METHODS: Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003-2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups. RESULTS: Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups. CONCLUSIONS: Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE. IMPACT: Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.

16.
Front Pediatr ; 9: 622381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681100

RESUMO

Background: The increasing prevalence of childhood obesity is an important public health issue and the development of obesity in early life and associated risk factors need to be better understood. The aim of this study was to identify distinct body mass index trajectories in the first 5 years of life and to examine their associations with factors identified in pregnancy, including metabolic parameters. Methods: BMI measurements from 2,172 children in Ireland enrolled in the BASELINE cohort study with BMI assessments at birth, 2, 6, and 12 months, and 2 and 5 years were analyzed. Growth mixture modeling was used to identify distinct BMI trajectories, and multivariate multinomial logistic regression was used to assess the association between these trajectories and antenatal factors. Results: Three distinct BMI trajectories were identified: normal (89.6%); rapid gain in the first 6 months (7.8%); and rapid BMI after 12 months (2.6%). Male sex and higher maternal age increased the likelihood of belonging to the rapid gain in the first 6 months trajectory. Raised maternal BMI at 15 weeks of pregnancy and lower cord blood IGF-2 were associated with rapid gain after 1 year. Conclusion: Sex, maternal age and BMI, and IGF-2 levels were found to be associated with BMI trajectories in early childhood departing from normal growth. Further research and extended follow-up to examine the effects of childhood growth patterns are required to understand their relationship with health outcomes.

17.
Neuropediatrics ; 52(4): 261-267, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33706404

RESUMO

BACKGROUND: Activin A protein and its receptor ACVR2B have been considered viable biomarkers for the diagnosis of hypoxic-ischemic encephalopathy (HIE). This study aimed to assess umbilical cord blood (UCB) levels of Activin A and Acvr2b messenger RNA (mRNA) as early biomarkers of mild and moderate HIE and long-term neurodevelopmental outcome. METHODS: One-hundred and twenty-six infants were included in the analyses from the BiHiVE2 cohort, a multi-center study, recruited in Ireland and Sweden (2013 to 2015). UCB serum Activin A and whole blood Acvr2b mRNA were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. RESULTS: Activin A analysis included 101 infants (controls, n = 50, perinatal asphyxia, n = 28, HIE, n = 23). No differences were detected across groups (p = 0.69). No differences were detected across HIE grades (p = 0.12). Acvr2b mRNA analysis included 67 infants (controls, n = 22, perinatal asphyxia, n = 23, and HIE, n = 22), and no differences were observed across groups (p = 0.75). No differences were detected across HIE grades (p = 0.58). No differences were detected in neurodevelopmental outcome in infants followed up to 18 to 36 months in serum Activin A or in whole blood Acvr2b mRNA (p = 0.55 and p = 0.90, respectively). CONCLUSION: UCB Activin A and Acvr2b mRNA are not valid biomarkers of infants with mild or moderate HIE; they are unable to distinguish infants with HIE or infants with poor neurodevelopmental outcomes.

18.
Am J Clin Nutr ; 113(4): 1032-1041, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33515035

RESUMO

BACKGROUND: Iron is critical to the developing brain, but fetal iron accretion is compromised by several maternal and pregnancy-related factors. Little consideration has been given to the long-term neurologic consequences of neonatal iron deficiency, especially in generally healthy, low-risk populations. OBJECTIVE: We aimed to investigate the association between neonatal iron deficiency and neurologic development at 2 and 5 y of age. DESIGN: We measured umbilical cord serum ferritin concentrations in the prospective maternal-infant Cork BASELINE (Babies after SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints) Birth Cohort. Lifestyle and clinical data were collected from 15 weeks of gestation to 5 y of age. Standardized neurologic assessments were performed at 2 y [Bayley Scales of Infant Development/Child Behavior Checklist (CBCL)] and 5 y (Kaufman Brief Intelligence Test/CBCL). RESULTS: Among 697 maternal-infant pairs, median (IQR) cord ferritin concentrations were 200.9 (139.0, 265.8) µg/L; 8% had neonatal iron deficiency (ferritin <76 µg/L). Using fully adjusted models, there was no association between neonatal iron deficiency and cognitive or behavioral outcomes at 2 or 5 y. We conducted an a priori sensitivity analysis in 306 high-risk children, selected using known risk factors for neonatal iron deficiency (smoking/obesity/cesarean section delivery/small-for-gestational age birth). In this high-risk subgroup, children with iron deficiency at birth (12%) had similar cognitive outcomes, but the behavioral assessments showed higher internalizing [9.0 (5.3, 12.0) compared with 5.0 (3.0, 10.0), P = 0.006; adjusted estimate (95% CI): 2.8 (0.5, 5.1), P = 0.015] and total [24.5 (15.3, 40.8) compared with 16.0 (10.0, 30.0), P = 0.009; adjusted estimate (95% CI): 6.6 (0.1, 13.1), P = 0.047] problem behavior scores at 5 y compared with those born iron sufficient. CONCLUSIONS: We have demonstrated lasting behavioral consequences of neonatal iron deficiency in high-risk children from our generally healthy, low-risk maternal-infant cohort. Although larger investigations are warranted, this study provides strong association data to suggest that interventions and strategies targeting the fetal and neonatal period should be prioritized for the prevention of iron deficiency and associated neurologic consequences.


Assuntos
Anemia Ferropriva/complicações , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Ferritinas/sangue , Pré-Escolar , Estudos de Coortes , Humanos , Recém-Nascido , Fatores de Risco
19.
J Pediatr ; 228: 74-81.e2, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32828883

RESUMO

OBJECTIVE: To evaluate umbilical cord messenger RNA (mRNA) expression as biomarkers for the grade of hypoxic-ischemic encephalopathy (HIE) and long-term neurodevelopment outcome. STUDY DESIGN: Infants were recruited from the BiHiVE1 study, Ireland (2009-2011), and the BiHiVE2 study, Ireland, and Sweden (2013-2015). Infants with HIE were assigned modified Sarnat scores at 24 hours and followed at 18-36 months. mRNA expression from cord blood was measured using quantitative real-time polymerase chain reaction. RESULTS: We studied 124 infants (controls, n = 37; perinatal asphyxia, n = 43; and HIE, n = 44). Fzd4 mRNA increased in severe HIE (median relative quantification, 2.98; IQR, 2.23-3.68) vs mild HIE (0.88; IQR, 0.46-1.37; P = .004), and in severe HIE vs moderate HIE (1.06; IQR, 0.81-1.20; P = .003). Fzd4 mRNA also increased in infants eligible for therapeutic hypothermia (1.20; IQR, 0.92-2.37) vs those who were ineligible for therapeutic hypothermia group (0.81; IQR, 0.46-1.53; P = .017). Neurodevelopmental outcome was analyzed for 56 infants. Nfat5 mRNA increased in infants with severely abnormal (1.26; IQR, 1.17-1.39) vs normal outcomes (0.97; IQR, 0.83-1.24; P = .036), and also in infants with severely abnormal vs mildly abnormal outcomes (0.96; IQR, 0.80-1.06; P = .013). Fzd4 mRNA increased in infants with severely abnormal (2.51; IQR, 1.60-3.56) vs normal outcomes (0.74; IQR, 0.48-1.49; P = .004) and in infants with severely abnormal vs mildly abnormal outcomes (0.97; IQR, 0.75-1.34; P = .026). CONCLUSIONS: Increased Fzd4 mRNA expression was observed in cord blood of infants with severe HIE; Nfat5 mRNA and Fzd4 mRNA expression were increased in infants with severely abnormal long-term outcomes. These mRNA may augment current measures as early objective markers of HIE severity at delivery.


Assuntos
Asfixia Neonatal/genética , Receptores Frizzled/genética , Hipóxia-Isquemia Encefálica/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Regulação para Cima , Asfixia Neonatal/sangue , Asfixia Neonatal/diagnóstico , Biomarcadores/sangue , Eletroencefalografia , Feminino , Seguimentos , Receptores Frizzled/metabolismo , Humanos , Hipóxia-Isquemia Encefálica/sangue , Recém-Nascido , Masculino , Prognóstico , RNA Mensageiro/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Transcrição/sangue
20.
J Pediatr ; 229: 175-181.e1, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33039387

RESUMO

OBJECTIVE: To validate our previously identified candidate metabolites, and to assess the ability of these metabolites to predict hypoxic-ischemic encephalopathy (HIE) both individually and combined with clinical data. STUDY DESIGN: Term neonates with signs of perinatal asphyxia, with and without HIE, and matched controls were recruited prospectively at birth from 2 large maternity units. Umbilical cord blood was collected for later batch metabolomic analysis by mass spectroscopy along with clinical details. The optimum selection of clinical and metabolites features with the ability to predict the development of HIE was determined using logistic regression modelling and machine learning techniques. Outcome of HIE was determined by clinical Sarnat grading and confirmed by electroencephalogram grade at 24 hours. RESULTS: Fifteen of 27 candidate metabolites showed significant alteration in infants with perinatal asphyxia or HIE when compared with matched controls. Metabolomic data predicted the development of HIE with an area under the curve of 0.67 (95% CI, 0.62-0.71). Lactic acid and alanine were the primary metabolite predictors for the development of HIE, and when combined with clinical data, gave an area under the curve of 0.96 (95% CI, 0.92-0.95). CONCLUSIONS: By combining clinical and metabolic data, accurate identification of infants who will develop HIE is possible shortly after birth, allowing early initiation of therapeutic hypothermia.


Assuntos
Sangue Fetal/metabolismo , Hipóxia-Isquemia Encefálica/diagnóstico , Alanina/sangue , Índice de Apgar , Asfixia Neonatal/complicações , Biomarcadores/sangue , Estudos de Casos e Controles , Eletroencefalografia , Humanos , Recém-Nascido , Ácido Láctico/sangue , Modelos Logísticos , Aprendizado de Máquina , Metabolômica , Valor Preditivo dos Testes , Estudos Prospectivos , Ressuscitação , Sensibilidade e Especificidade
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