BACKGROUND:Brain injury, impaired brain growth, and long-term neurodevelopmental problems are common in children with transposition of the great arteries. We sought to identify clinical risk factors ...for brain injury and poor brain growth in infants with transposition of the great arteries undergoing the arterial switch operation, and to examine their relationship with neurodevelopmental outcome.
METHODS:The brains of 45 infants with transposition of the great arteries undergoing surgical repair were imaged pre- and postoperatively using magnetic resonance imaging. Brain weight z scores were calculated based on brain volume and autopsy reference data. Brain injury scores were determined as previously described. Neurodevelopment was assessed at 18 months using the Bayley-III scores of infant development. The relationships between clinical variables, brain injury, perioperative brain growth, and 18-month Bayley-III scores were analyzed.
RESULTS:On preoperative imaging, moderate or severe white matter injury was present in 10 of 45 patients, whereas stroke was seen in 4 of 45. A similar prevalence of injury was seen on postoperative imaging, and we were unable to identify any clinical risk factors for brain injury. Brain weight z scores decreased perioperatively in 35 of 45 patients. The presence of a ventricular septal defect (P=0.009) and older age at surgery (P=0.007) were associated with impaired perioperative brain growth. When patients were divided into those undergoing surgery during the first 2 weeks of life (32/45) versus those being repaired later (13/45), infants repaired later had significantly worse perioperative brain growth (late repair postoperative brain weight z = –1.0±0.90 versus early repair z = –0.33±0.64; P=0.008). Bayley-III testing scores fell within the normal range for all patients, although age at repair (P=0.03) and days of open chest (P=0.03) were associated with a lower composite language score, and length of stay was associated with a lower composite cognitive score (P=0.02).
CONCLUSIONS:Surgery beyond 2 weeks of age is associated with impaired brain growth and slower language development in infants with transposition of the great arteries cared for at our center. Although the mechanisms underlying this association are still unclear, extended periods of cyanosis and pulmonary overcirculation may adversely impact brain growth and subsequent neurodevelopment.
To evaluate whether white matter injury (WMI) volumes and spatial distribution, which are important predictors of neurodevelopmental outcomes in preterm infants, have changed over a period of ...15 years.
Five hundred and twenty-eight infants born <32 weeks’ gestational age from 2 sequential prospective cohorts (cohort 1: 2006 through 2012; cohort 2: 2014 through 2019) underwent early-life (median 32.7 weeks postmenstrual age) and/or term-equivalent-age MRI (median 40.7 weeks postmenstrual age). WMI were manually segmented for quantification of volumes. There were 152 infants with WMI with 74 infants in cohort 1 and 78 in cohort 2. Multivariable linear regression models examined change in WMI volume across cohorts while adjusting for clinical confounders. Lesion maps assessed change in WMI location across cohorts.
There was a decrease in WMI volume in cohort 2 compared with cohort 1 (β = −0.6, 95% CI −0.8, −0.3, P < .001) with a shift from more central to posterior location of WMI. There was a decrease in clinical illness severity of infants across cohorts.
We found a decrease in WMI volume and shift to more posterior location in very preterm infants over a period of 15 years. This may potentially reflect more advanced maturation of white matter at the time of injury which may be related to changes in clinical practice over time.
We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants.
A total of 254 ...infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes.
Greater brain injury volume was associated with lower 18-month Motor scores (β = -5.7, 95% CI -9.2 to -2.2,
= 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: β = 14.5, 95% CI -2.1 to 26.9,
= 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes.
We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.
OBJECTIVETo compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an “early approach” (EA), based on ...ventricular measurements exceeding normal (ventricular index VI <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a “late approach” (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention.
METHODSObservational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18–24 months.
RESULTSForty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>−1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores <−2 SD in 81%.
CONCLUSIONIn preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks.
CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.
To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in ...2008-2013.
Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate.
We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both).
Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.
Dans cette note, nous revenons sur les grandes lignes de la conférence donnée lors des journées de la SAP 2019 concernant le champ actuel de l’ethnogénétique, qui s’intéresse entre autres à ...l’influence des systèmes de parenté sur la diversité génétique des populations humaines. Nous présentons certains des résultats principaux d’une étude ethnogénétique menée en Asie du Sud-Est dans douze populations présentant des systèmes de parenté variés, à filiation patrilinéaire, matrilinéaire et cognatique. Les données ethno-démographiques et génétiques collectées montrent que les processus de résidence, de filiation et d’alliance façonnent la diversité génétique des populations humaines. Ce champ de recherche ouvre ainsi de nouvelles perspectives : mieux connaître, à partir des données génétiques, la dynamique des systèmes de parenté actuels, et retracer leur évolution à travers le temps grâce aux données archéogénétiques. Cependant, les données ethno-démographiques montrent également que le niveau d’observance des règles varie entre populations catégorisées dans un même système de parenté, ce qui module les signatures génétiques laissées par ce système de parenté et invite à une certaine prudence concernant l’inférence des structures sociales du passé à partir des données archéogénétiques. L’impact du « puzzle matrilinéaire » sur la diversité génétique autosomale est également discuté.
In this note, we summarize the talk given at the SAP conference 2019 regarding the field of ethnogenetics, that studies the influence of kinship systems on the genetic diversity of human populations.We will present some of the main results of an ethnogenetic study led in twelve Southeast Asian populations exhibiting various kinship systems, with matrilineal, patrilineal and cognatic descent. This study contributes to highlight that processes of residence, descent and alliance shape the genetic diversity of human populations. This opens new perspectives, notably understanding better the present dynamics of kinship systems thanks to genetic data, and tracing back their evolution through time thanks to archeogenetic data. However, this work also shows that the signatures left by a given type of social organization are variable depending on the extent to which the rule is observed, inviting to be careful when inferring past social systems from archeogenetic data. The genetic impact of the « matrilineal puzzle » is also discussed.
Children with hypoxic-ischemic encephalopathy (HIE) are at high risk of neurodevelopmental delay despite the widespread adoption of therapeutic hypothermia. Thus, consideration of both biological and ...psychosocial factors is warranted to better predict outcomes. We examined the associations between various child neurodevelopmental outcomes and potentially influential factors such as brain imaging, parent mental health, previous intervention, and social risk. Qualitative themes in the parent experience were also identified from free-text questionnaire responses. Methods: Parents of 54 children with HIE (ages 6 months-6.5 years) completed questionnaires capturing sociodemographic factors, qualitative perceptions of clinical outcome, parent mental health, and ratings of child adaptive and psychosocial functioning. Neurodevelopmental assessment scores at 18 and 36 months were extracted retrospectively from the medical chart for a subset of children. Results: Linear regression analyses showed significant associations between poorer parent mental health and child psychosocial and language outcomes. In multivariable analyses, social risk served as a significant predictor of 18 and 36 month cognitive and language functioning. Qualitative analyses of parents' written reflections revealed themes of hopefulness and ongoing concern. Conclusion: In children with HIE, social context and parent mental health are strong contributing factors in the pathway of neurodevelopmental outcomes.
Estimation and correlation of the Hildebrand solubility parameter (δ) of polymers and small molecules is a common practice in membrane material science and is accomplished by experimental and ...numerical routes. In this paper, we revisit, update, and compare both routes to enhance the accuracy in the determination of δ. Best practices for the experimental determination of polymer solubility parameters are provided, and the viability of Dynamic Light Scattering (DLS) was demonstrated as an alternative to conventional time- and material-consuming techniques, such as Ubbelohde viscometry and swelling measurements. Glassy and rubbery polymers, including high fractional free volume (FFV) microporous polymers such as PIM-1 and poly(1-trimethylsilyl-1-propyne) (PTMSP), are among the samples included in this study with great relevance to membrane science. In an attempt to enhance the accuracy of numerical estimate of polymer solubility parameters via the group contribution method, we provide updated group contribution parameters, along with their uncertainty, according to the technique recently reported by Smith et al. These updated group contribution parameters result in a mean absolute relative error of 9.0% in predicting the solubility parameter on a test set of 40 polymers, which is on par with the average 10% error reported previously. We also show, using machine learning techniques, that augmenting the group contribution model with extra parameters or non-linear relationships does not improve its accuracy. Results of the updated group contribution technique and dynamic light scattering measurements were compared to experimental viscometry on four test polymers, and the difference between the three techniques is compared.
To compare neurodevelopmental and visual outcomes in preterm infants treated with intravitreal bevacizumab (IVB) to laser ablation at 18-24 months corrected age.
A retrospective study was performed. ...The primary outcome was neurodevelopmental impairment (NDI). Secondary neurodevelopmental outcomes were significant NDI (sNDI), cerebral palsy, hearing loss, and composite scores of the Bayley Scales of Infant Development, Third edition. Visual outcomes included structural and refractive outcomes. Adjusted odds ratios (AOR) were calculated controlling for GA, sex, and ROP severity and confounding baseline characteristics using a cutoff of p < 0.20.
Thirty-four (60 eyes) infants receiving IVB and 30 (51 eyes) laser were included. No significant differences were identified in NDI (AOR 1.77, 95% CI 0.46, 6.73) or sNDI (AOR 2.31, 95% CI 0.75, 7.14). There were no other differences in outcomes.
Larger randomized trials are required to establish long-term efficacy and safety of IVB in preterm neonates.
This study investigated the diagnostic utility of nontargeted genomic testing in patients with pediatric heart disease.
We analyzed genome sequencing data of 111 families with cardiac lesions for ...rare, disease-associated variation.
In 14 families (12.6%), we identified causative variants: seven were de novo (ANKRD11, KMT2D, NR2F2, POGZ, PTPN11, PURA, SALL1) and six were inherited from parents with no or subclinical heart phenotypes (FLT4, DNAH9, MYH11, NEXMIF, NIPBL, PTPN11). Outcome of the testing was associated with the presence of extracardiac features (p = 0.02), but not a positive family history for cardiac lesions (p = 0.67). We also report novel plausible gene-disease associations for tetralogy of Fallot/pulmonary stenosis (CDC42BPA, FGD5), hypoplastic left or right heart (SMARCC1, TLN2, TRPM4, VASP), congenitally corrected transposition of the great arteries (UBXN10), and early-onset cardiomyopathy (TPCN1). The identified candidate genes have critical functions in heart development, such as angiogenesis, mechanotransduction, regulation of heart size, chromatin remodeling, or ciliogenesis.
This data set demonstrates the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test. The genetic heterogeneity will necessitate large-scale genomic initiatives for delineating novel gene-disease associations.
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