Cognitive Developmental Delay Research Articles

Risk factors for PDA ligation and neurodevelopmental outcomes at corrected 18–24 months in very low birth weight infants

BackgroundPatent ductus arteriosus (PDA) is commonly encountered morbidity which often occurs as up to 60% of extremely preterm infants born at < 29 weeks gestational age (GA).PurposeThis study aims to assess the clinical risk factors associated with PDA ligation among very low birth weight infants (VLBWI) and evaluate the neurodevelopmental outcomes of those who underwent PDA ligation.MethodsA total of 540 VLBWI were initially diagnosed with PDA in our 50-bed level IV NICU at Seoul St. Mary’s Hospital, The Catholic University of Korea, between January 2015 and June 2023. Among these 540 VLBWI with PDA, only 221 had consistent hemodynamically significant (hs) PDA which required intervention including fluid restriction, medical treatment, or surgical ligation. In this study, only those 221 VLBWI with hsPDA who underwent neurodevelopmental assessment at corrected 18–24 months of age were included in this study analysis.ResultsOut of 221 VLBWI diagnosed with hemodynamically significant (hs) PDA, 133 (60.2%) underwent PDA ligation, while the remaining 88 (39.8%) had their hs PDAs closed either medically or with fluid restriction. The mean gestational age and birth weight were significantly lower in PDA ligation group compared to no PDA ligation group (27.02 ± 2.17 vs. 27.98 ± 2.36, 907.31 ± 258.36 vs. 1006.07 ± 283.65, p = 0.001, 0.008). Resuscitation including intubation at delivery and intraventricular hemorrhage (IVH) (grade ≥ 3) were significantly higher in PDA ligation group. The clinical outcomes in the PDA ligation group revealed significantly worse oucomes compared to the no PDA ligation group. Both resuscitation, including intubation at delivery, and IVH (grade ≥ 3), consistently exhibited an increased risk for PDA ligation in a multivariable logistic regression analysis. Concerning neurodevelopmental outcomes, infants who underwent PDA ligation demonstrated significantly lower cognitive scores. However, only IVH (grade ≥ 3) and PVL were consistently associated with an increased risk of abnormal neurodevelopment at the corrected age of 18–24 months.ConclusionIn our study, despite the consistent association between cognitive developmental delays in VLBWI who underwent PDA ligation, we observed that sicker and more vulnerable VLBWIs, specifically those experincing severe IVH, consistently exhibited an increased risk for both PDA ligation and abnormal neurodevelopment at the corrected age of 18–24 months.

Understanding emotion dysregulation from infancy to toddlerhood with a multilevel perspective: The buffering effect of maternal sensitivity.

Challenges with childhood emotion regulation may have origins in infancy and forecast later social and cognitive developmental delays, academic difficulties, and psychopathology. This study tested whether markers of emotion dysregulation in infancy predict emotion dysregulation in toddlerhood, and whether those associations depended on maternal sensitivity. When children (N = 111) were 7 months, baseline respiratory sinus arrhythmia (RSA), RSA withdrawal, and distress were collected during the Still Face Paradigm (SFP). Mothers' reports of infant regulation and orientation and maternal sensitivity were also collected at that time. Mothers' reports of toddlers' dysregulation were collected at 18 months. A set of hierarchical regressions indicated that low baseline RSA and less change in RSA from baseline to stressor predicted greater dysregulation at 18 months, but only for infants who experienced low maternal sensitivity. Baseline RSA and RSA withdrawal were not significantly associated with later dysregulation for infants with highly sensitive mothers. Infants who exhibited low distress during the SFP and who had lower regulatory and orienting abilities at 7 months had higher dysregulation at 18 months regardless of maternal sensitivity. Altogether, these results suggest that risk for dysregulation in toddlerhood has biobehavioral origins in infancy but may be buffered by sensitive caregiving.

Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Molecular basis of neurocognitive dysfunction and psychosis in Alpha-Mannosidosis

A significant portion of patients who are afflicted with lysosomal storage diseases (LSDs) encounter neurological manifestations, including cognitive issues and developmental delay, seizures, psychiatric issues, and an overall neurodegenerative decline. In order to enhance the development of effective therapies for these symptoms, it is imperative that we allude to the neuropathophysiology that underlies these manifestations. These distinct neurological and developmental features are particularly evident in patients with Alpha-Mannosidosis (AM), a type of LSD. However, there is limited published information regarding the mechanisms and pathophysiology of these presentations in patients with this condition. Although the precise impact of lysosomal storage on the biogenesis and functioning of neuronal cells has not been clearly defined, recent studies have placed emphasis on the significance of synaptic defects influencing this dysfunction. These defects encompass changes in synaptic spines, proteins, and vesicles, as well as postsynaptic densities that potentially precipitate functional disruptions in synaptic transmission and neurodegeneration. Ultimately, this cascade is thought to result in extensive neuronal loss and, consequently, the onset of cognitive manifestations. Uncovering the effects on synaptic components in LSDs with neurological symptoms like AM will enable a better understanding of disease progression. It will also allow us to identify critical targets for therapeutic intervention and the determination of optimal time frames for targeted treatments, as well as the effects of these treatments on mitochondrial function. The available therapeutic modalities in AM are not a definitive cure for affected patients, but rather an attempt to reduce the symptomatic severity in their presentation, while aiming to regress/slow down disease progression. This review will aim to discuss and rationalize the current treatment approaches in place for AM patients in relation to their effects on the improvement of neurocognitive symptoms in affected AM individuals.

Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis

BackgroundLamotrigine has become one of the most commonly prescribed antiseizure medications (ASM) in epileptic women during pregnancy and therefore requires regular updates regarding its safety. The aim of this study was to estimate the association between in utero exposure to lamotrigine monotherapy and the occurrence of neurodevelopmental outcomes.MethodsAll comparative studies assessing the occurrence of neurodevelopmental outcomes after epilepsy-indicated lamotrigine monotherapy exposure during pregnancy were searched. First, references were identified through a snowballing approach, then, through electronic databases (Medline and Embase) from 2015 to June 2022. One investigator evaluated study eligibility and extracted data and a second independent investigator reviewed the meta-analysis (MA). A systematic review and random-effects model approach were performed using a collaborative WEB-based meta-analysis platform (metaPreg.org) with a registered protocol (osf.io/u4gva).ResultsOverall, 18 studies were included. For outcomes reported by at least 4 studies, the pooled odds ratios and 95% confidence interval obtained with the number of exposed (N1) and unexposed children (N0) included were: neurodevelopmental disorders as a whole 0.84 [0.66;1.06] (N1 = 5,271; N0 = 22,230); language disorders or delay 1.16 [0.67;2.00] (N1 = 313; N0 = 506); diagnosis or risk of ASD 0.97 [0.61;1.53] (N1 = at least 5,262; N0 = 33,313); diagnosis or risk of ADHD 1.14 [0.75;1.72] (N1 = at least 113; N0 = 11,530) and psychomotor developmental disorders or delay 2.68 [1.29–5.56] (N1 = 163; N0 = 220). The MA of cognitive outcomes included less than 4 studies and retrieved a significant association for infants exposed to lamotrigine younger than 3 years old but not in the older age groups.ConclusionPrenatal exposure to lamotrigine monotherapy is not found to be statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of ASD and diagnosis or risk of ADHD. However, the MA found an increased risk of psychomotor developmental disorders or delay and cognitive developmental delay in less than 3 years old children. Nevertheless, these findings were based exclusively on observational studies presenting biases and on a limited number of included children. More studies should assess neurodevelopmental outcomes in children prenatally exposed to lamotrigine.

Screen-Printed Sensors Modified with Nafion and Mesoporous Carbon for Electrochemical Detection of Lead in Blood

Lead (Pb) has long been acknowledged as a systemic toxicant, with pronounced health impacts observed even at low exposure levels, particularly in children. Adverse effects include diminished cognitive function, altered behavior, and developmental delays. Consequently, it is imperative to conduct regular monitoring of Blood Lead Levels (BLLs). In this work, we report on an electrochemical sensor based on screen-printed carbon electrode (SPCE) coated with Nafion and mesoporous carbon (MC). The sensor system uses simple sample preparation (acidification and dilution of whole blood), minimal sample volume (a few blood drops, 200 μl), and swift time-to-results (1 h). A limit of quantitation (LOQ) of 0.3 μg dL−1 Pb was achieved in whole blood. To demonstrate the practical utility of our sensor system, we evaluated its performance in the analysis of blood samples collected from children (n = 25). Comparative analysis with the laboratory-based gold standard method of inductively coupled plasma mass spectrometry (ICP-MS) demonstrated approximately 77% accuracy and 94% precision. We anticipate that our approach will serve as a valuable tool for more frequent BLL monitoring, particularly in communities where access to laboratory testing is impractical or expensive.

Short-term neonatal and long-term neurodevelopmental outcome of children born term low birth weight

This study aimed to examine the impact of term LBW on short-term neonatal and long-term neurodevelopmental outcomes in children 5–7 years of age. This is a population-based cohort study that merged national data from the Korea National Health Insurance claims and National Health Screening Program for Infants and Children. The participants were women who gave birth at a gestational age of ≥ 37 weeks between 2013 and 2015 in the Republic of Korea, and were tracked during 2020 for the neurodevelopmental surveillance of their children. Among 830,806 women who gave birth during the study period, 31,700 (3.8%) of their babies weighed less than 2500 g. By Cox proportional hazard analysis, children aged 5–7 years who had LBW were associated with any developmental, motor developmental delay, cognitive developmental delay, autism spectrum, attention deficit hyperactivity disorders, and epileptic and febrile seizures.Children born with term LBW were more vulnerable to neurodevelopmental disorders at 5–7 years of age than those with normal and large birth weights. This study further substantiates counseling parents regarding the long-term outcomes of children being born underweight.

Tracheotomy in children older than two years: Analysis of discharge trends from 2015 to 2020

ObjectiveIn light of increasingly complex patients being discharged with tracheostomies, we aimed to evaluate discharge trends over time in pediatric tracheotomy patients. We hypothesized that there would be delays in discharge from increased focus on preparing families for at-home care of critically ill pediatric patients. Materials and methodsWe conducted a cross-sectional analysis of pediatric patients who underwent tracheotomy (Current Procedural Terminology code 31600) between 2015 and 2020 using the American College of Surgeons National Surgical Quality Improvement Program Pediatric database (ACS NSQIP-P). Univariate and multivariate regression analyses were performed to assess patient demographics, comorbidities, perioperative factors, postoperative complications, and discharge information. Data were analyzed using Stata 15. ResultsA total of 1552 patients were identified. There were 868 (56 %) males and 684 (44 %) females with a mean age of 7.3 ± 5.7 years. At least one comorbidity was seen in 1282 (83 %) patients, with 907 (58 %) having impaired cognitive status or developmental delay. Thirty-six (2.3 %) patients experienced mortality within 30 days, while 710 (46 %) were still in the hospital at 30 days. The odds of remaining in the hospital after 30 days were positively correlated with the year (p=.001). Other factors associated with an increased likelihood of remaining in the hospital after 30 days included younger patient age (p <.001), any complication (p <.001), and a higher American Society of Anesthesiologists classification (p <.001). ConclusionAs years have progressed, fewer children were discharged from the hospital after 30 days following tracheotomy. Further research may identify socioeconomic factors contributing to the increasing length of hospital stays associated with a need for tracheotomy.

Parental Involvement in the Transition from Paediatric to Adult Care for Youth with Chronic Illness: A Scoping Review of the North American Literature.

With medical advancements and improvements in medical technology, an increasing number of children with chronic conditions survive into adulthood. There is accordant growing interest toward supporting adolescents throughout the transition from paediatric to adult care. However, there is currently a paucity of research focusing on the role that these patients' parents should play during and after the transition to adult care and if maintained parental involvement is beneficial during this transition within a North American context. Accordingly, this scoping review utilized Arksey and O'Malley's five-step framework to consider parental roles during chronically ill children's transition to adult care. APA PsycInfo, CINAHL, EMBASE, MEDLINE, ProQuest, and Scopus were searched alongside advanced Google searches. Thematic content analysis was conducted on 30 articles meeting the following inclusion criteria: (1) published in English between 2010 and 2022, (2) conducted in Canada or the United States, (3) considered adolescents with chronic conditions transitioning to adult care, (4) family being noted in the title or abstract, and (5) patient populations of study not being defined by delays in cognitive development, nor mental illness. Three themes emerged from the literature: the impacts of maintaining parental involvement during transition to adult care for patients, parents experiencing feeling loss of stability and support surrounding the transition of their child's care, and significant nonmedical life events occurring for youths at the time of transition of care. Parents assuming supportive roles which change alongside their maturing child's needs were reported as being beneficial to young peoples' transition processes, while parents who hover over or micromanage their children during this time were found to hinder successful transitions. Ultimately, the majority of reviewed articles emphasized maintained parental involvement as having a net positive impact on adolescents' transitions to adult care. As such, practice and policies should be structured to engage parents throughout the transition process to best support their chronically ill children during this time of change.

Early-life exposure to unimproved sanitation and delayed school enrollment: Evidence from Bangladesh

Exposure to environmental stressors during early childhood can significantly impact a child’s development and educational outcomes. In this paper, we examine the effects of exposure to unimproved sanitation in the surrounding environment during early childhood on primary school enrollment later in life in Bangladesh between 2007 and 2014. While Bangladesh has made significant progress towards eradicating open defecation, the country still suffers from inadequate access to improved sanitation. Additionally, although policies aiming at improving primary school enrollment have been in place since the 1990s, many children of school age were not enrolled at the appropriate time during the period studied. Using a pseudo-panel dataset for children aged six to nine compiled from the 2007, 2011, and 2014 DHS surveys, we find that children exposed to a higher proportion of unimproved sanitation in their community early in their life are less likely to be enrolled in primary school at the time of survey by about five percentage points on average, indicating delayed school enrollment. This effect is more pronounced for children aged six and seven than those eight and nine, likely because parents of children experiencing poor health or cognitive development delay enrolling their children in school until they are slightly older or healthier. Our results are robust to potential omitted variable biases and are further supported by additional analyses on matched samples. Taken all together, our findings highlight that increasing coverage of improved sanitation facilities can help improve school enrollment rates. However, this should not only occur at the household level alone but also should extend to cover all households in the community to ensure achieving maximum benefits. The findings indicate that the provision of safer sanitation facilities is not only good by itself but also is crucial for achieving improvements throughout the human capital development cycle, including health and nutrition, as well as education.

Prenatal Lead Exposure, Genetic Factors, and Cognitive Developmental Delay

Although the effects of lead (Pb) exposure on neurocognition in children have been confirmed, the individual associations of prenatal Pb exposure and its interaction with genetic factors on cognitive developmental delay (CDD) in children remain unclear. To investigate the association of prenatal Pb exposure and its interaction with genetic factors with CDD risk. Women in Wuhan, China, who had an expected delivery date between March 2014 and December 2017, were recruited for this prospective cohort study. Children were assessed for cognitive development at approximately 2 years of age (March 2016 to December 2019). Maternal venous blood, cord blood, and venous blood from children were collected in a longitudinal follow-up. Data analysis was performed from March 2022 to February 2023. Prenatal Pb exposure, and genetic risk for cognitive ability evaluated by polygenic risk score constructed with 58 genetic variations. Cognitive developmental delay of children aged approximately 2 years was assessed using the Chinese revision of the Bayley Scale of Infant Development. A series of multivariable logistic regressions was estimated to determine associations between prenatal Pb exposure and CDD among children with various genetic backgrounds, adjusting for confounding variables. This analysis included 2361 eligible mother-child pairs (1240 boys [52.5%] and 1121 girls [47.5%]; mean [SD] ages of mothers and children, 28.9 [3.6] years and 24.8 [1.0] months, respectively), with 292 children (12.4%) having CDD. Higher maternal Pb levels were significantly associated with increased risk of CDD (highest vs lowest tertile: odds ratio, 1.55; 95% CI, 1.13-2.13), adjusting for demographic confounders. The association of CDD with maternal Pb levels was more evident among children with higher genetic risk (highest vs lowest tertile: odds ratio, 2.59; 95% CI, 1.48-4.55), adjusting for demographic confounders. In this cohort study, prenatal Pb exposure was associated with an increased risk of CDD in children, especially in those with a high genetic risk. These findings suggest that prenatal Pb exposure and genetic background may jointly contribute to an increased risk of CDD for children and indicate the possibility for an integrated strategy to assess CDD risk and improve children's cognitive ability.

A New Computer-Aided Method for Assessing Children's Cognition in Bioengineering Systems for Diagnosing Developmental Delay

This pilot study (n = 19) examines fidelity rates of the new computer-aided method of diagnosing cognitive development delay in 3-to-6-year-old children. The small-scale research repeats the methodological components of the previous two studies, only changing the data collection process by introducing the baseline value (BV). Experimental data show a significant increase of 9.4 times in the shared intentionality magnitude in neurodivergent children. The results support the hypothesis that the bioengineering system (computer-mother-child) can encourage shared intentionality in the dyad by emulating the mother-newborn communication model. The outcome shows the association between the shared intentionality magnitude and children's diagnosis. However, the bioengineering diagnostic paradigm and the new BV method still need more evidence since the pilot study observes the effect in a small sample size. The pilot study evaluates the fidelity rates of this new BV method through nine markers. It shows the feasibility (with the limitations) of testing this new BV method in further research with a large sample size.

Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants.

Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants.

Group well child care and risk for developmental delay: Preliminary findings among Asian immigrants

Group well-child care (GWCC) may promote interactive caregiving and prevent developmental delay. Method: This cross-sectional study explored the association between GWCC attendance and odds for suspected developmental delay among low-income Asian immigrants as measured by the Ages and Stages Questionnaire (ASQ)-III at age 18 months. Results: Odds for suspected developmental delay (OR=0.81, 95 % CI 0.40–1.62) were not significantly lower for GWCC infants. However, odds for developmental risk were significantly lower for GWCC infants in the ASQ’s problem-solving domain (OR= 0.40, 95 % CI 0.17–0.92). Conclusion: Among low-income Asian immigrants, GWCC participation may be associated with lower odds for cognitive developmental delay.

Factors associated with cognitive and communication delay in children aged 0 to 3 years using the Battelle-Developmental Inventory, 2nd edition

Background The first years of life are crucial in cognitive and communication development. Delayed functional development impedes children’s future academic and occupational performance. Therefore, early detection is important for effective resolution in order to minimize further impairment.&#x0D; Objective To evaluate cognitive and communication developmental delay in children under 3 years of age in Jakarta using the Battelle Developmental Inventory, 2nd edition (BDI-2).&#x0D; Methods A cross-sectional study was conducted in Jakarta in 2020, including children aged under 3 years of age without chronic medical conditions that hinder cognitive and speech function. We collected subjects’ demographic characteristics, evaluated their communication and cognitive development using the BDI-2, and analyzed for risk factors of delays.&#x0D; Results Of 121 children, 34 (28.1%) had cognitive delay and 21 (17.4%) had communication delay. Bivariate analysis revealed that male gender (P=0.048) and non-exclusive breastfeeding (P=0.003) were significantly associated with communication delay, while only male gender was associated with cognitive delay (P=0.015). Multivariate analysis revealed that significant risk factors for communication delay were male gender (P=0.043) and non-exclusive breastfeeding (P=0.023).&#x0D; Conclusion Male gender and non-exclusive breastfeeding are significant risk factors for delayed communication development, and only male gender was a significant risk factor for cognitive delay. Socioeconomic status, primary caregiver, and breastfeeding duration, were not found to be risk factors for delays.

Brain cell type specific proteomics approach to discover pathological mechanisms in the childhood CNS disorder mucolipidosis type IV.

Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations in MCOLN1, the gene encoding the lysosomal cation channel TRPML1. The disease primarily affects the central nervous system (CNS) and manifests in the first year with cognitive and motor developmental delay, followed by a gradual decline in neurological function across the second decade of life, blindness, and premature death in third or fourth decades. Brain pathology manifestations in MLIV are consistent with hypomyelinating leukodystrophy with brain iron accumulation. Presently, there are no approved or investigational therapies for MLIV, and pathogenic mechanisms remain largely unknown. The MLIV mouse model, Mcoln1-/- mice, recapitulates all major manifestations of the human disease. Here, to better understand the pathological mechanisms in the MLIV brain, we performed cell type specific LC-MS/MS proteomics analysis in the MLIV mouse model and reconstituted molecular signatures of the disease in either freshly isolated populations of neurons, astrocytes, oligodendrocytes, and neural stem cells, or whole tissue cortical homogenates from young adult symptomatic Mcoln1-/- mice. Our analysis confirmed on the molecular level major histopathological hallmarks of MLIV universally present in Mcoln1-/- tissue and brain cells, such as hypomyelination, lysosomal dysregulation, and impaired metabolism of lipids and polysaccharides. Importantly, pathway analysis in brain cells revealed mitochondria-related alterations in all Mcoln1-/- brain cells, except oligodendrocytes, that was not possible to resolve in whole tissue. We also report unique proteome signatures and dysregulated pathways for each brain cell population used in this study. These data shed new light on cell-intrinsic mechanisms of MLIV and provide new insights for biomarker discovery and validation to advance translational studies for this disease.

Child neurodevelopmental disorders in armed conflict country, case of DR Congo: long-term trauma impact on brain development in childhood: review

Child neurodevelopmental disorders in armed conflict country, case of DR Congo: long-term trauma impact on brain development in childhood: review

Clinical and Molecular Aspects Associated with Defects in the Transcription Factor POU3F4: A Review.

X-linked deafness (DFNX) is estimated to account for up to 2% of cases of hereditary hearing loss and occurs in both syndromic and non-syndromic forms. POU3F4 is the gene most commonly associated with X-linked deafness (DFNX2, DFN3) and accounts for about 50% of the cases of X-linked non-syndromic hearing loss. This gene codes for a transcription factor of the POU family that plays a major role in the development of the middle and inner ear. The clinical features of POU3F4-related hearing loss include a pathognomonic malformation of the inner ear defined as incomplete partition of the cochlea type 3 (IP-III). Often, a perilymphatic gusher is observed upon stapedectomy during surgery, possibly as a consequence of an incomplete separation of the cochlea from the internal auditory canal. Here we present an overview of the pathogenic gene variants of POU3F4 reported in the literature and discuss the associated clinical features, including hearing loss combined with additional phenotypes such as cognitive and motor developmental delays. Research on the transcriptional targets of POU3F4 in the ear and brain is in its early stages and is expected to greatly advance our understanding of the pathophysiology of POU3F4-linked hearing loss.

Changes in the early communicative behaviors of young children with significant cognitive and motor developmental delays in a two-year span

IntroductionThis study examines longitudinal changes in communicative behavior of young children with significant cognitive and motor developmental delays (SDD) and determines their individual communicative trajectories. A second focus of this study is the relation of changes in communicative behavior with motor skills. MethodsData consists of codes resulting from a self-developed coding scheme used on observations of 23 children in three different settings and responses on a questionnaire. First, group trends were determined to find out whether communication-related variables tend to significantly change over the course of two years. Furthermore, these findings were contrasted with the individual trajectories of the children. Next, the association of initial communicative skills and (the acquisition of) specific motor skills with the change in their communicative functioning was studied. Wilcoxon Signed Ranks and correlational analyses were used to answer the research questions. ResultsOut of sixteen different variables related to communicative behavior, ten changed significantly over the course of two years. Children with more focus on prompt on the first datapoint showed a significantly larger increase of signs of functionality. Still, all children showed highly individual trajectories. Children with better motor skills on the first datapoint showed a significantly larger increase in communication rate. ConclusionsResults show that if a myriad of detailed variables are taken into account children with significant cognitive and motor developmental disabilities do change regarding their communicative functioning, but that they tend to all show unique developmental trajectories. Children with stronger skills in some aspects of communication and motor functioning, can be considered advantaged regarding their communicative development.

Long-term adverse neurodevelopmental outcomes of discordant twins delivered at term: A nationwide population-based study.

To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. Retrospective cohort study. Nationwide (Republic of Korea). All twin children delivered at term between 2007 and 2010. The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. Long-term adverse neurodevelopmental outcome. Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.