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1.
Cochlear Implants Int ; : 1-7, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31530102

RESUMO

Objective: Cochlear implantation is associated with vestibular impairment due to the close proximity of the structures. The aim of the study was to quantify dizziness/vertigo, gaze instability, balance and gait problems in a sample of adult cochlear implant (CI) users. Methods: An observational, cross sectional study evaluated subjective dizziness (Vestibular Rehabilitation Benefit Questionnaire (VRBQ)), balance confidence (Activities Specific Balance Questionnaire (ABC)), gait (Functional Gait Assessment (FGA) and 10m walk test), balance (Equitest Sensory Organisation Test (SOT)), and computerised dynamic visual acuity (DVA). The Dix Hallpike test was performed to test for benign paroxysmal positional vertigo (BPPV). Results: Twenty participants (n=10F), 2.8(±2.7) years post implantation, with mean age 59.3(±15.8) years were assessed. Subjective dizziness (VRBQ) was low (15.0% (±15.5)) and balance confidence was high (ABC: 82.1%±14.9). FGA scores (25.1 ± 4.4) and gait speed (1.8 (±0.3) m/sec) were below normal. Dx Hallpike was positive in 3. Gaze instability was found in 50% (DVA loss, 0.29 (± 0.16) LogMAR), while 79% demonstrated balance impairment (mean SOT score, 57.8%±14.5), with 42% falling on SOT condition 5. Discussion: Evidence of vestibular dysfunction was identified in these adult CI users. Conclusion: Access to vestibular function assessment and rehabilitation is required in adult CI users.

2.
Acta Paediatr ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520432

RESUMO

AIM: Breastfeeding is associated with IQ, school attendance and income. Despite the known benefits of breastfeeding, the rate of exclusive breastfeeding up to 6-months is low globally. We examined the effect of short-term breastfeeding on long-term IQ. METHODS: In this secondary analysis of the prospective Cork BASELINE Birth Cohort Study, children were categorised as predominantly breastfed (n = 288) versus exclusively formula-fed (n = 254) at 2-months of age. Infants (n = 404) receiving mixed-feeding were excluded. Outcome was assessed using the KBIT II at 5-years. Multivariable linear regression was used to adjust for confounding variables. RESULTS: Following adjustment for confounding variables, children, predominately breastfed at 2-months of age, demonstrated increased overall IQ (2.00 points (95% CI: 0.35 to 3.65) ; p = 0.018) and non-verbal IQ at 5-years of age (1.88 points (95% CI: 0.22 to 3.54); p = 0.027) compared to those never breastfed. No significant relationship was found with verbal IQ (p = 0.154). CONCLUSION: A significant increase in composite and non-verbal IQ at 5-years of age was associated with short-term breastfeeding. This study adds to a growing body of evidence that short-term breastfeeding promotes healthy cognitive development. This article is protected by copyright. All rights reserved.

3.
Dev Med Child Neurol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518001

RESUMO

AIM: To establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy (HIE). METHOD: Children born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome. RESULTS: Forty-two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1-40.0wks]). The aetiology for infantile spasms was identified in almost two-thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138). INTERPRETATION: This study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31313597

RESUMO

Objective: Sniff nasal inspiratory pressure (SNIP) is a commonly used clinical measure of respiratory impairment in amyotrophic lateral sclerosis (ALS), which is used to guide the initiation of noninvasive ventilation (NIV). SNIP can be completed with either an occluded or an un-occluded contralateral nostril. The aim of this study was to compare occluded and un-occluded SNIP measurements and to examine the decline in occluded SNIP over time compared to the ALSFRS-R respiratory subscore. Methods: This was a prospective longitudinal study examining occluded and un-occluded SNIP scores in ALS and PLS patients recorded between 2001 and 2018. Bland and Altman graphs were plotted for occluded vs. un-occluded SNIP measurements taking account of the repeated measures nature of the data. Longitudinal models were constructed as linear mixed effects multi-level models with follow-up in ALS limited to 6 years. Results: SNIP measured with an occluded contralateral nostril was systematically higher than with an un-occluded nostril. SNIP measured using both methods declined non-linearly, particularly after 2-3 years. The best fit model for decline in occluded SNIP included a main effect and interaction between site of onset and time, with age and diagnostic delay as independent variables. This showed a linear decline in spinal onset with a floor effect in bulbar-onset ALS. Conclusion: SNIP measured with an occluded and un-occluded contralateral nostril is not interchangeable, which is relevant in interpreting thresholds for initiation of NIV. SNIP declines non-linearly, which is explained in spinal onset ALS by age and diagnostic delay, but an apparent floor effect remains in bulbar onset.

5.
Handb Clin Neurol ; 162: 281-293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31324315

RESUMO

The widespread introduction of therapeutic hypothermia as a standard of care in hypoxic-ischemic encephalopathy (HIE) has brought increasing pressure on clinicians to make an early and accurate assessment of the degree of hypoxic injury (HI) that has occurred and the severity of the encephalopathy that will ensue. No single blood-based marker is currently robust enough to detect significant HI or predict outcome. However, research in the field has been active in the last 10 years and we know that HIE is associated with predictable alterations in the expression of a number of inflammatory proteins, neuron-specific proteins, metabolite pathways, and microRNA. These alterations evolve quickly over the first hours and days of life. Predictive power varies depending on the timing of measurement of the biomarker, the sample type, and the case mix of the cohort examined. Combining clinical data with biochemical measurements is currently the most likely path toward improved detection and prediction of outcome in neonatal HIE.

6.
Am J Clin Nutr ; 109(5): 1353-1360, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051509

RESUMO

BACKGROUND: Air-displacement plethysmography (ADP) is a good candidate for monitoring body composition in newborns and young infants, but reference centile curves are lacking that allow for assessment at birth and across the first 6 mo of life. OBJECTIVE: Using pooled data from 4 studies, we aimed to produce new charts for assessment according to gestational age at birth (30 + 1 to 41 + 6 wk) and postnatal age at measurement (1-27 wk). METHODS: The sample comprised 222 preterm infants born in the United States who were measured at birth; 1029 term infants born in Ireland who were measured at birth; and 149 term infants born in the United States and 57 term infants born in Italy who were measured at birth, 1 and 2 wk, and 1, 2, 3, 4, 5, and 6 mo of age. Infants whose birth weights were <3rd or >97th centile of the INTERGROWTH-21st standard were excluded, thereby ensuring that the charts depict body composition of infants whose birth weights did not indicate suboptimal fetal growth. Sex-specific centiles for fat mass (kg), fat-free mass (kg), and percentage body fat were estimated using the lambda-mu-sigma (LMS) method. RESULTS: For each sex and measure (e.g., fat mass), the new charts comprised 2 panels. The first showed centiles according to gestational age, allowing term infants to be assessed at birth and preterm infants to be monitored until they reached term. The second showed centiles according to postnatal age, allowing all infants to be monitored to age 27 wk. The LMS values underlying the charts were presented, enabling researchers and clinicians to convert measurements to centiles and z scores. CONCLUSIONS: The new charts provide a single tool for the assessment of body composition, according to ADP, in infants across the first 6 mo of life and will help enhance early-life nutritional management.

7.
J Dev Orig Health Dis ; : 1-5, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31134881

RESUMO

Breastfeeding may reduce obesity risk, but this association could be confounded by breastfeeding families' characteristics. We investigated if body composition differs at birth among infants who were either exclusively breast- or formula-fed. We hypothesized the two groups would differ in body composition, even at birth, prior to their post-natal feeding experience. Healthy primiparous carrying singleton pregnancy were recruited at 15 weeks' gestation. PEA POD® measured body composition within 72 hours of delivery and infant feeding was prospectively captured. Out of the 1,152 infants recruited, 117 (10.2%) and 239 (20.7%) went on to be either exclusively breast- or formula-fed, respectively. Breastfed infants were heavier at birth, but their percentage fat mass (FM) was lower than that of exclusively formula-fed infants (covariate adjusted ß = -1.91 percentage points of FM; 95% CI -2.82 to -1.01). Differences in intra-uterine exposures, irrespective of early diet, may partly explain an infant's obesity risk.

8.
Obes Rev ; 20(7): 998-1015, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30942535

RESUMO

Childhood obesity is an important public health issue. We aimed to systematically review studies that used group-based trajectory modelling approaches to investigate body mass index (BMI) trajectories in early childhood, explore associated determinants, and the association with body composition outcomes. Five databases were searched systematically for studies using group-based trajectory modelling approaches to track BMI trajectories from birth. Fourteen studies using latent class growth analysis or growth mixture modelling to track BMI trajectories were identified. Three or four trajectories were identified in most studies. High maternal pre-pregnancy BMI was the most frequently identified risk factor for membership of a rapid gain trajectory. Significant associations between rapid weight gain and stable high trajectories and body measures at follow-up were identified by several studies. Relatively similar trajectories were identified across studies. Trajectories characterized by rapid weight gain were associated with several predictors, as well as body measures at follow-up, however not with great consistency. Similar associations with body measure outcomes were found for stable high and rapid gain trajectories, suggesting that long-term outcomes do not differ greatly between children with consistently high BMI and children with rapid increases in BMI. As the shape and timing of the trajectories differed between studies, it is difficult to draw conclusions.

9.
Eye (Lond) ; 33(7): 1152-1157, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30837711

RESUMO

OBJECTIVES: To investigate the functional and structural impact of neonatal hypoxic ischaemic encephalopathy (HIE) on childhood visual development. METHODS: In a prospective study, the neurocognitive outcomes of 42 children with a history of neonatal HIE were assessed serially up to 5 years. For the ophthalmic component of the study, visual, refractive, orthoptic and ocular biometry measurements were obtained in 32 children, with axial length measurements estimated using the IOLMaster. RESULTS: For the 32 children who completed the ophthalmic component of the study, severity of HIE grade was determined to be mild, moderate, or severe in 18 (56.3%), 13 (40.6%), and 1 (3.1%) cases, respectively. One (3.1%) child was classed as visually impaired. Twelve (37.5%) were found to have ametropia. Mean (±SD) axial length was 22.09 (±0.81) mm, within the normal range for the age of this cohort. Seven of the 42 (16.7%) children who were involved in the larger neurodevelopmental arm of the study had clinical evidence of a squint. There was no correlation between the severity of HIE grade at birth and axial length or occurrence of squint. CONCLUSIONS: Neonatal HIE is associated with a higher incidence of squint compared with the general paediatric population. This occurred irrespective of severity of HIE grade. The ocular biometry measurements were consistent with published normative data, and no significant difference in ocular biometry was demonstrated between HIE severity groups.

10.
BMJ Open ; 9(3): e025051, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878984

RESUMO

OBJECTIVES: To investigate the association between caesarean section (CS) birth and body fat percentage (BF%), body mass index (BMI) and being overweight or obese in early childhood. DESIGN: Prospective longitudinal cohort study. SETTING: Babies After Screening for Pregnancy Endpoints: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints cohort. PARTICIPANTS: Infants born to mothers recruited from the Screening for Pregnancy Endpoints study, Cork University Maternity Hospital between November 2007 and February 2011. OUTCOME MEASURE: Overweight or obese defined according to the International Obesity Task Force criteria. RESULTS: Of the 1305 infants, 362 (27.8%) were delivered by CS. On regression analysis, BF% at 2 months did not differ significantly by delivery mode. Infants born by CS had a higher mean BMI at 6 months compared with those born vaginally (adjusted mean difference=0.24; 95% CI 0.06 to 0.41, p value=0.009). At 2 years, no difference was seen across the exposure groups in the risk of being overweight or obese. At 5 years, the association between prelabour CS and the risk of overweight or obesity was not statistically significant (adjusted relative risk ratio, aRRR=1.37; 95% CI 0.69 to 2.69) and the association remained statistically nonsignificant when children who were macrosomic at birth were excluded from the model (aRRR=0.86; 95% CI 0.36 to 2.08). CONCLUSION: At 6 months of age, children born by CS had a significantly higher BMI but this did not persist into future childhood. There was no evidence to support an association between mode of delivery and long-term risk of obesity in the child.

11.
Pediatr Res ; 85(5): 687-692, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30745570

RESUMO

BACKGROUND: Insulin-like growth factor (IGF)-I and -II play an important role in prenatal growth. During the first 2 months from birth, body fat doubles, and rapid weight gain during this time increases future risk of cardiometabolic disease. The aim of this study was to determine whether IGF measurements at birth associate with body composition and the trajectory of its changes in the first 2 months. METHODS: Umbilical cord IGF-I and -II concentrations were measured in term infants. Air displacement plethysmography was performed at birth and 2 months. Fat mass (FM) and fat-free mass (FFM) were corrected for infant length (L) to FM/L3 and FFM/L2, respectively. RESULTS: In 601 (317 male) infants, IGF-I concentrations at birth were associated with FM/L3 and FFM/L2 Z-scores at birth (R2 = 0.05 and 0.04, respectively, P < 0.001), and IGF-II concentrations were associated with FFM/L2 Z-scores at birth (R2 = 0.01, P = 0.02). Lower IGF-I concentrations were weakly associated with increases in FM/L3 Z-scores over the first 2 months (R2 = 0.01, P = 0.003). CONCLUSION: IGF-I concentrations at birth are associated with adiposity and lean mass at birth and inversely with the trajectory of FM accumulation over the first 2 months. IGF-I measurements only account for a small amount of the variance in these measures.

12.
PLoS Med ; 16(2): e1002744, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742624

RESUMO

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.


Assuntos
Índice de Massa Corporal , Análise de Dados , Ganho de Peso na Gestação/fisiologia , Obesidade Pediátrica/epidemiologia , Austrália/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , América do Norte/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Fatores de Risco
13.
JAMA Neurol ; 76(3): 333-341, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30592487

RESUMO

Importance: Neonatal hypoxic-ischemic encephalopathy (HIE) remains a significant cause of neurologic disability. Identifying infants suitable for therapeutic hypothermia (TH) within a narrow therapeutic time is difficult. No single robust biochemical marker is available to clinicians. Objective: To assess the ability of a panel of candidate microRNA (miRNA) to evaluate the development and severity of encephalopathy following perinatal asphyxia (PA). Design, Setting, and Participants: This validation study included 2 cohorts. For the discovery cohort, full-term infants with PA were enrolled at birth to the Biomarkers in Hypoxic-Ischemic Encephalopathy (BiHiVE1) study (2009-2011) in Cork, Ireland. Encephalopathy grade was defined using early electroencephalogram and Sarnat score (n = 68). The BiHiVE1 cohort also enrolled healthy control infants (n = 22). For the validation cohort, the BiHiVE2 multicenter study (2013-2015), based in Cork, Ireland (7500 live births per annum), and Karolinska Huddinge, Sweden (4400 live births per annum), recruited infants with PA along with healthy control infants to validate findings from BiHiVE1 using identical recruitment criteria (n = 80). The experimental design was formulated prior to recruitment, and analysis was conducted from June 2016 to March 2017. Main Outcomes and Measures: Alterations in umbilical cord whole-blood miRNA expression. Results: From 170 neonates, 160 were included in the final analysis. The BiHiVE1 cohort included 87 infants (21 control infants, 39 infants with PA, and 27 infants with HIE), and BiHiVE2 included 73 infants (control [n = 22], PA [n = 26], and HIE [n = 25]). The BiHiVE1 and BiHiVE2 had a median age of 40 weeks (interquartile range [IQR], 39-41 weeks) and 40 weeks (IQR, 39-41 weeks), respectively, and included 56 boys and 31 girls and 45 boys and 28 girls, respectively. In BiHiVE1, 12 candidate miRNAs were identified, and 7 of these miRNAs were chosen for validation in BiHiVE2. The BiHiVE2 cohort showed consistent alteration of 3 miRNAs; miR-374a-5p was decreased in infants diagnosed as having HIE compared with healthy control infants (median relative quantification, 0.38; IQR, 0.17-0.77 vs 0.95; IQR, 0.68-1.19; P = .009), miR-376c-3p was decreased in infants with PA compared with healthy control infants (median, 0.42; IQR, 0.21-0.61 vs 0.90; IQR, 0.70-1.30; P = .004), and mir-181b-5p was decreased in infants eligible for TH (median, 0.27; IQR, 0.14-1.41) vs 1.18; IQR, 0.70-2.05; P = .02). Conclusions and Relevance: Altered miRNA expression was detected in umbilical cord blood of neonates with PA and HIE. These miRNA could assist diagnostic markers for early detection of HIE and PA at birth.

14.
PLoS One ; 13(12): e0207952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30507953

RESUMO

MicroRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. MicroRNAs have been identified in various body fluids under normal conditions and their stability as well as their dysregulation in disease has led to ongoing interest in their diagnostic and prognostic potential. Circulating microRNAs may be valuable predictors of early-life complications such as birth asphyxia or neonatal seizures but there are relatively few data on microRNA content in plasma from healthy babies. Here we performed small RNA-sequencing analysis of plasma processed from umbilical cord blood in a set of healthy newborns. MicroRNA levels in umbilical cord plasma of four male and four female healthy babies, from two different centres were profiled. A total of 1,004 individual microRNAs were identified, which ranged from 426 to 659 per sample, of which 269 microRNAs were common to all eight samples. Many of these microRNAs are highly expressed and consistent with previous studies using other high throughput platforms. While overall microRNA expression did not differ between male and female cord blood plasma, we did detect differentially edited microRNAs in female plasma compared to male. Of note, and consistent with other studies of this type, adenylation and uridylation were the two most prominent forms of editing. Six microRNAs, miR-128-3p, miR-29a-3p, miR-9-5p, miR-218-5p, 204-5p and miR-132-3p were consistently both uridylated and adenylated in female cord blood plasma. These results provide a benchmark for microRNA profiling and biomarker discovery using umbilical cord plasma and can be used as comparative data for future biomarker profiles from complicated births or those with early-life developmental disorders.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30472660

RESUMO

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171.

16.
J Nutr ; 148(10): 1580-1586, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169669

RESUMO

Background: Although animal studies show evidence for a role of vitamin D during brain development, data from human studies show conflicting signals. Objective: We aimed to explore associations between maternal and neonatal vitamin D status with childhood neurodevelopmental outcomes. Methods: Comprehensive clinical, demographic, and lifestyle data were collected prospectively in 734 maternal-infant dyads from the Cork BASELINE Birth Cohort Study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were quantified at 15 weeks of gestation and in umbilical cord sera at birth via a CDC-accredited liquid chromatography-tandem mass spectrometry method. Children were assessed at age 5 y through the use of the Kaufman Brief Intelligence Test (2nd Edition, KBIT-2) and the Child Behaviour Checklist (CBCL). Linear regression was used to explore associations between 25(OH)D and neurodevelopmental outcomes. Results: 25(OH)D concentrations were <30 nmol/L in 15% of maternal and 45% of umbilical cord sera and <50 nmol/L in 42% of mothers and 80% of cords. At age 5 y, the mean ± SD KBIT-2 intelligence quotient (IQ) composite score was 104.6 ± 8.6; scores were 107.2 ± 10.0 in verbal and 99.8 ± 8.8 in nonverbal tasks. Developmental delay (scores <85) was seen in <3% of children across all domains. The mean ± SD CBCL total problem score was 21.3 ± 17.5; scores in the abnormal/clinical range for internal, external, and total problem scales were present in 12%, 4%, and 6% of participants, respectively. KBIT-2 and CBCL subscale scores at 5 y were not different between children exposed to low antenatal vitamin D status, either at 30 or 50 nmol/L 25(OH)D thresholds. Neither maternal nor cord 25(OH)D (per 10 nmol/L) were associated with KBIT-2 IQ composite scores [adjusted ß (95% CI): maternal -0.01 (-0.03, 0.02); cord 0.01 (-0.03, 0.04] or CBCL total problem scores [maternal 0.01 (-0.04, 0.05); cord 0.01 (-0.07, 0.09)]. Conclusion: In this well-characterized prospective maternal-infant cohort, we found no evidence that antenatal 25(OH)D concentrations are associated with neurodevelopmental outcomes at 5 y. The BASELINE Study was registered at www.clinicaltrials.gov as NCT01498965; the SCOPE Study was registered at http://www.anzctr.org.au as ACTRN12607000551493.

17.
Mol Neurobiol ; 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30178296

RESUMO

Hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neurological disability worldwide. No blood biomarker capable of early detection and classification of injury severity in HIE has been identified. This study aimed to investigate the potential of miRNA-181b (miR-181b) and its downstream target, ubiquitin C-terminal hydrolase-L1 (UCH-L1), to predict the severity of HIE. Full-term infants with perinatal asphyxia were recruited at birth and observed for the development of HIE, along with healthy controls. Levels of miR-181b and messenger UCH-L1 (mUCH-L1) in umbilical cord blood were determined using qRT-PCR. In total, 131 infants; 40 control, 50 perinatal asphyxia without HIE (PA) and 41 HIE, recruited across two separate cohorts (discovery and validation) were included in this study. Significant and consistent downregulation of miR-181b was observed in infants with moderate/severe HIE compared to all other groups in both cohorts: discovery 0.25 (0.16-0.32) vs 0.61 (0.26-1.39), p = 0.027 and validation 0.33 (0.15-1.78) vs 1.2 (0.071-2.09), p = 0.035. mUCH-L1 showed increased expression in infants with HIE in both cohorts. The expression ratio of miR-181b to mUCH-L1 was reduced in those infants with moderate/severe HIE in both cohorts: discovery cohort 0.23 (0.06-0.44) vs 1.59 (0.46-2.54), p = 0.01 and validation cohort 0.41 (0.10-0.81) vs 1.38 (0.59-2.56) in all other infants, p = 0.009. We have validated consistent patterns of altered expression in miR-181b/mUCH-L1 in moderate/severe neonatal HIE which may have the potential to guide therapeutic intervention in HIE.

18.
Dev Neurosci ; 40(3): 271-277, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205414

RESUMO

The role of inflammation is an important factor in the progression of hypoxic-ischaemic encephalopathy (HIE). We have previously shown that interleukin-16 (IL-16) is increased in infants with moderate and severe HIE and relates to poor neurodevelopmental outcomes. We aimed to validate IL-16 as a cord blood-based biomarker for HIE and to examine its relationship to long-term outcomes. The study sample consisted of 105 full-term infants who experienced perinatal asphyxia (PA) (with and without an encephalopathy) along with healthy, gestational age-matched newborn controls. Umbilical cord blood serum was processed and biobanked at delivery. Infants were assigned a modified Sarnat score at 24 h. Analysis of IL-16 cytokine cord blood levels was performed using the sandwich-based enzyme-linked immunosorbent assay (ELISA) technique. Cord blood-based IL-16 was increased in infants with PA and HIE relative to controls (p = 0.025). IL-16 was also increased in the HIE group relative to controls (p = 0.042). There was no significant difference in IL-16 across grades of HIE or in those with abnormal outcomes at 2 years of age. This study validates findings that cord blood-based IL-16 levels are increased in infants with PA, including those who go on to develop HIE.

19.
Allergy ; 73(11): 2182-2191, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30085352

RESUMO

BACKGROUND: Prospective studies of antenatal and infant vitamin D exposure and atopic disease from extensively characterised, disease-specific, maternal-infant cohorts with gold standard analysis of vitamin D status and clinically validated atopic outcomes are lacking. This study aimed to investigate associations between intrauterine vitamin D status and atopic outcomes in an extensively characterised, disease-specific, maternal-infant cohort. METHODS: Circulating 25-hydroxyvitamin D (25(OH)D) was measured in maternal sera at 15 weeks of gestation (n = 1537) and umbilical cord blood (n = 1050) using a CDC-accredited LC-MS/MS platform, and the association with clinically validated atopic disease outcomes (eczema, food allergy, asthma, allergic rhinitis) at 2 and 5 years was explored using multivariable logistic regression. RESULTS: Persistent eczema in the first 2 years of life was present in 5% of infants. Food allergy at 2 years was confirmed in 4%. The prevalence of aeroallergen sensitisation at 2 years was 8%. Asthma at 5 years was reported in 15% and allergic rhinitis in 5% of 5-year-olds. There were no significant differences in the distributions of maternal 25(OH)D at 15 weeks of gestation (mean [SD] 58.4 [26.2] and 58.5 [26.1] nmol/L) and cord 25(OH)D concentrations (mean [SD] 35.2 [17.8] and 35.4 [18.3] nmol/L) between children with and without atopic disease. Neither maternal (aOR [95% CI]: 1.02 [0.97, 1.08], P = 0.450) nor cord 25(OH)D (aOR [95% CI]: 1.00 [0.91, 1.09], P = 0.991) were significant predictors of atopic disease outcomes in fully adjusted models. CONCLUSION: These data in a disease-specific cohort with prospectively collected, validated atopic outcomes do not support an association between antenatal exposure to vitamin D and atopic disease outcomes in childhood.

20.
Nutrients ; 10(8)2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061547

RESUMO

: Obesity in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ≥ 30 kg/m²) and normal weight (n = 245, BMI < 25 kg/m²) age matched pregnant women collected at approximately 15 weeks' gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.


Assuntos
Anemia Ferropriva/etiologia , Sangue Fetal/metabolismo , Inflamação/etiologia , Ferro/sangue , Troca Materno-Fetal , Obesidade/complicações , Complicações na Gravidez/metabolismo , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/etnologia , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Grupos Étnicos , Feminino , Ferritinas/sangue , Hepcidinas/sangue , Humanos , Recém-Nascido , Inflamação/sangue , Interleucina-6/sangue , Ferro/deficiência , Masculino , Mães , Estado Nutricional , Obesidade/sangue , Gravidez , Estudos Prospectivos , Receptores da Transferrina/sangue
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