Motor Delay Research Articles

Evaluating the association between duration of breastfeeding and fine motor development among children aged 20 to 24 months in Butajira, Ethiopia: a case-control study

BackgroundA Suitable environment and proper child nutrition are paramount to a child’s physical and mental development. Different environmental factors contribute to proper child development. Breast milk is an important source of nutrition during the early years of life and contains essential nutrients that are the building blocks for growth and development.ObjectiveTo assess the association between the duration of breastfeeding and fine motor development among children aged 20 to 24 months living in Butajira, southern Ethiopia.MethodCommunity-based case-control study design was employed among mother-child dyads of children aged 20 to 24 months in Butajira Southern Ethiopia. Children were screened for fine motor delay using the Denver II developmental screening and identified as cases and controls. A repeated visit was done to gather the rest of the information and 332 samples, 83 cases, and 249 controls were available and assessed. Epi-data version 4.4.2.1 software was used to prepare a data entry template, which was later exported to and analyzed using STATA version 14 statistical software. Finally, a Multivariable logistic regression model was used to adjust for confounders and estimate the independent effect of breastfeeding duration on fine motor development.ResultWe didn’t find a significant association between the duration of breastfeeding from 21 to 24 months and fine motor delay compared to children who were breastfed less than 18 months[AOR: 0.86, 95% CI: (0.36, 2.05)]. Children who have mothers > 35 years of age were 78% less likely than children who had mothers younger than 25 years, Children who had mothers in secondary school and above were 77% less likely than mothers who didn’t have formal education, Females were 1.86 times more likely than males, and Children who scored 20–29 on the Home score were 51% less likely than Children who scored < 20 to have fine motor delay.ConclusionDuration of breastfeeding was not significantly associated with fine motor delay for children aged 20 to 24 months old. The age of the mother, the educational status of the mother, being female, and Home score were identified to have a significant association with fine motor delay. Improving the educational status and empowerment of women is essential. Further work should be done on avoiding gender differences starting from a young age and creating a conducive environment for child development is crucial.

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.

The Alberta Infant Motor Scale as an Outcomes Measure of Gross Motor Abilities after Early Complex Cardiac Surgery.

To address the research hypothesis that the Alberta Infant Motor Scale (AIMS) completed following complex cardiac surgery (CCS) is a useful outcomes measure this study determined: (1) AIMS scores at age 8months after CCS; (2) predictive validity of AIMS at 8months for Bayley Scales of Infant and Toddler Development-III Gross Motor-scaled scores (GMSS) and diagnosis of cerebral palsy (CP) at 21months; and (3) predictive demographic and surgical variables of AIMS scores. A prospective cohort study of 250/271 (92.3%) surviving children from Northern Alberta (born 2009-2020) who had CCS at age < 6months determined AIMS scores at age mean (SD) 8.6 (2.4) and the GMSS at 21.9 (3.8) months. Gross motor delay was defined as AIMS < 5th percentile and GMSS as < 4 (-2SD). Predictions using multiple logistic regressions were expressed as Odds Ratios (OR) and 95% Confidence Interval (CI). Of children, 100/250 (40%) had AIMS < 5th predicting GMSS < 4 (n = 43); sensitivity, specificity, positive, and negative predictive values were 88%, 71%, 40%, and 97%. Hospitalization days were independently associated with AIMS < 5th, OR 1.02 (95% CI 1.007, 1.032; p = 0.005). Excluding hospital days, ventilation days independently predicted AIMS < 5th, OR 1.08 (95% CI 1.038, 1.125, p < 0.001. Gross motor delay determine by AIMS scores of < 5th percentile occurred in 40% of survivors with good prediction of continued delay. Delay determined by AIMS was predicted by longer hospitalization and ventilation; further investigations about the causes are required. AIMS results provide opportunity for early motor intervention.

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic

BackgroundWe compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. MethodsWe conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. ResultsAt one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6–86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (−13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1–89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (−3.0), p = 0.28] had declining scores. ConclusionThese initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. Level of EvidenceIII.

Early childhood neurodevelopmental milestones in children with allergic diseases: the Japan Environment and Children’s Study (JECS)

This study investigated the potential link between early childhood allergic diseases and neurodevelopmental milestone attainment during the first 3 years of life. Utilizing data from a large-scale prospective birth cohort study in Japan, encompassing 87,986 children, we examined physician-diagnosed and caregiver-reported allergic conditions, including atopic dermatitis (AD), asthma, and food allergy (FA). Neurodevelopmental milestones were assessed using the Ages and Stages Questionnaires at 1, 1.5, 2, 2.5, and 3 years of age. Stabilized inverse probability-weighted generalized estimating equation models were employed to estimate odds ratios (ORs). Our analysis revealed no significant association of AD and asthma with delay in communication, gross motor, fine motor, problem-solving, and personal-social skills during the initial 3 years of life. However, children with FA showed an increased likelihood of experiencing gross motor delay compared with that shown by those without FA (weighted adjusted OR: 1.14). Despite this, no significant association of FA with other developmental domains was observed. Early childhood allergies may not influence neurodevelopmental delays. However, there is a potential association between FA and delays, specifically in gross motor skills, that warrants routine developmental monitoring and additional investigations.

POLR3-related leukodystrophy caused by biallelic POLR3A and 1C pathogenic variants: a single-center experience.

This study aimed to investigate the clinical, radiological, and genetic features of POLR3-related leukodystrophy caused by mutations in POLR3A or POLR1C. Fourteen Chinese patients with POLR3-related leukodystrophy were enrolled in this cross-sectional observational study. The clinical manifestations, brain MRI and genetic tests of the patients were evaluated. Thirteen patients had biallelic variants in POLR3A (92.9%), and one had biallelic variants in POLR1C (7.1%). The median age at disease onset was 9 months. A total of 85.7% of the patients presented with motor delay, abnormal gait, and intelligence disability in the first 2 years of life. Intellectual disability can be categorized based on its severity. It varied from mild (which involves difficulty concentrating) to very severe (with no smiling or laughing or never being able to speak since birth). Short stature was observed in all patients, and delayed dentition was observed in 64.3% of them. Furthermore, three out of 14 patients had myopia. Hypomyelination was invariably present in all patients, whereas myelination of the basal ganglia was preserved in only six out of 14 patients. All the mutations were compound heterozygous and included missense (n = 25), deletion (n = 1), and splice site variants (n = 2). A total of 78.6% of the patients with POLR3A were identified as carrying the c.1771-6C>G variant or the c.1771-7C>G variant. The phenotypic diversity of POLR3-HLD associated with pathogenic variants ranges from mild to very severe for neurological and non-neurological symptoms. Most patients presented symptoms in the first 2 years of life. The c.1771-6C>G or c.1771-7C>G variant is the most frequent mutation site in POLR3A in Chinese individuals.

Early childhood development and its association with women's empowerment in the context of urban poverty in Ethiopia

BackgroundEmpowered women, with increased access to and control over resources, stronger social networks, greater decision-making power, and a more positive gender attitude, significantly contribute to better family well-being. While there is ample evidence regarding the association between child nutrition and women's empowerment, studies examining the association between early childhood development (ECD) and women's empowerment are scarce. AimsThe aim of this study was to estimate the prevalence of ECD delays among 12–36 months old and investigate its association with women's empowerment among the urban poor in Ethiopia. MethodsThe study included a sample of 432 women who were unemployed or had irregular employment during the data collection period, along with their children in urban Ethiopia. The ECD was assessed using the Age and Stage Questionnaire (ASQ-3), a tool designed to accurately identify developmental delays in infants and young children and categorized as on track, needs monitoring, and possible delays. Women's empowerment was measured using a multidimensional index that captured access to and control over resources, decision-making power, and social capital, and then categorized into lowest, medium, and highest empowerment levels. The association between ECD domains and women's empowerment was analyzed using ordinal logistic regression, after adjusting for confounders. ResultsThe study found a high prevalence of delays in ECD domains, with fine motor domain accounting for the largest delay (40.6 %). Children of less empowered mothers are more likely to have the highest development delays in communication (OR=2.22; 95 % CI: 1.36; 3.62), gross motor (OR=1.69; 95 % CI: 1.04; 2.76), problem solving (OR=1.85; 95 % CI: 1.15; 2.98), and personal-social (OR=2.59; 95 % CI: 1.62; 4.15) skills compared to children of more empowered mothers. ConclusionsThe study highlights the significance of women's empowerment in promoting ECD, especially in developing countries where ECD programs are fragmented and lacks coordination. Therefore, targeted interventions that improve women's empowerment could lead to improved ECD outcomes.

Towards an AI-driven soft toy for automatically detecting and classifying infant-toy interactions using optical force sensors.

Introduction: It is crucial to identify neurodevelopmental disorders in infants early on for timely intervention to improve their long-term outcomes. Combining natural play with quantitative measurements of developmental milestones can be an effective way to swiftly and efficiently detect infants who are at risk of neurodevelopmental delays. Clinical studies have established differences in toy interaction behaviors between full-term infants and pre-term infants who are at risk for cerebral palsy and other developmental disorders. Methods: The proposed toy aims to improve the quantitative assessment of infant-toy interactions and fully automate the process of detecting those infants at risk of developing motor delays. This paper describes the design and development of a toy that uniquely utilizes a collection of soft lossy force sensors which are developed using optical fibers to gather play interaction data from infants laying supine in a gym. An example interaction database was created by having 15 adults complete a total of 2480 interactions with the toy consisting of 620 touches, 620 punches-"kick substitute," 620 weak grasps and 620 strong grasps. Results: The data is analyzed for patterns of interaction with the toy face using a machine learning model developed to classify the four interactions present in the database. Results indicate that the configuration of 6 soft force sensors on the face created unique activation patterns. Discussion: The machine learning algorithm was able to identify the distinct action types from the data, suggesting the potential usability of the toy. Next steps involve sensorizing the entire toy and testing with infants.

The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%) and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%) and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%) and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P = 0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%), motor delay with non-ambulance (64%), and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P = 0.003), non-ambulance (P = 0.035), ongoing enteral feeds (P < 0.001) and cortical visual impairment (P = 0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs, provide insights into their neurological basis, and vitally, enable meaningful genetic counselling for affected individuals and their families.

Early childhood development and nutritional status in urban Ethiopia.

Early childhood development (ECD) is crucial for better health and well-being throughout life, but few studies have examined how ECD relates to child malnutrition. This is mainly due to lack of reliable and disaggregated data on ECD. We estimated the prevalence of ECD delays (communication, fine motor, gross motor, problem-solving and personal-social) and examined how different ECD domains were associated with child nutritional status in urban Ethiopia. Using a community-based cross-sectional survey design, 627 mother-child (12-36 months old) pairs were included in the study. The ECD was assessed using the Age and Stage Questionnaire (ASQ-3), and the nutritional status was assessed using anthropometric measurements. The association between the ECD domains and nutritional status was analysed using ordinal logistic regression, adjusting for confounding variables. Delays in ECD domains were common, especially in fine motor domain (41.9%); and more than half of the children were stunted (52.8%). Stunting and underweight were associated with ECD delays, while wasting was not. Accordingly, stunted children were more likely to have worst ECD delays in fine motor (odds ratios [OR] = 1.54; 95% confidence interval [CI]: 1.11; 2.15), gross motor (OR = 1.47; 95% CI: 1.05; 2.04) and problem-solving (OR = 1.41; 95% CI: 1.02; 1.96) domains compared to non-stunted children. Similarly, underweight children were more likely to have worse ECD delays in gross motor (OR = 1.91; 95% CI: 1.20; 3.04) and fine motor (OR = 1.90; 95% CI: 1.15; 3.15) domains compared to normal children. Coordinated and targeted ECD interventions, such as nurturing care, should be promoted and implemented widely to improve ECD outcomes and child nutrition.

Assessment of Barriers to Referral and Appointment Wait Times for the Evaluation of Spinal Muscular Atrophy (SMA): Findings from a Web-Based Physician Survey.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Clinical trial data suggest early diagnosis and treatment are critical. The purpose of this study was to evaluate neurology appointment wait times for newborn screening identified infants, pediatric cases mirroring SMA symptomatology, and cases in which SMA is suspected by the referring physician. Approaches for triaging and expediting referrals in the US were also explored. Cure SMA surveyed healthcare professionals from two cohorts: (1) providers affiliated with SMA care centers and (2) other neurologists, pediatric neurologists, and neuromuscular specialists. Surveys were distributed directly and via Medscape Education, respectively, between July 9, 2020, and August 31, 2020. Three hundred five total responses were obtained (9% from SMA care centers and 91% from the general recruitment sample). Diagnostic journeys were shorter for infants eventually diagnosed with SMA Type 1 if they were referred to SMA care centers versus general sample practices. Appointment wait times for infants exhibiting "hypotonia and motor delays" were significantly shorter at SMA care centers compared to general recruitment practices (p = 0.004). Furthermore, infants with SMA identified through newborn screening were also more likely to be seen sooner if referred to a SMA care center versus a general recruitment site. Lastly, the majority of both cohorts triaged incoming referrals. The average wait time for infants presenting at SMA care centers with "hypotonia and motor delay" was significantly shorter when initial referrals were triaged using a set of "key emergency words" (p = 0.036). Infants directly referred to a SMA care center versus a general sample practice were more likely to experience shorter SMA diagnostic journeys and appointment wait times. Triage guidelines for referrals specific to "hypotonia and motor delay" including use of "key emergency words" may shorten wait times and support early diagnosis and treatment of SMA.

A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities

BackgroundAutosomal recessive intellectual developmental disorder-3 is caused by homozygous or compound heterozygous mutations in the CC2D1A gene. The disorder is characterized by intellectual disability (ID) and autism spectrum disorder (ASD). To date, 39 patients from 17 families with CC2D1A -related disorders have been reported worldwide, in whom only six pathogenic or likely pathogenic loss-of-function variants and three variants of uncertain significance (VUS) in the CC2D1A gene have been identified in these patients. MethodsWe described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene. ResultsThe patient presented with severe ID and ASD, speech impairment, motor delay, hypotonia, slight facial anomalies, and finger deformities. Threatened abortion and abnormal fetal movements occurred during pregnancy with the proband but not his older healthy sister. WES analysis identified a homozygous nonsense variant, c.736C > T (p.Gln246Ter), in the CC2D1A gene. In addition, six novel likely pathogenic CC2D1A variants were identified by a retrospective review of the in-house database. ConclusionsThis study expands the genetic and clinical spectra of CC2D1A-associated disorders, and may aid in increasing awareness of this rare condition. Our findings have provided new insights into the clinical heterogeneity of the disease and further phenotype-genotype correlation, which could help to offer scope for more accurate genetic testing and counseling to affected families.

Fine Motor Skills, a Surrogate of Motor Planning Ability, at Age 2 Predict Social Skills at Age 6.

Motor planning is the cognitive process of planning necessary steps for achieving a purposeful movement and is specifically reflected through object manipulation. This study aimed to investigate whether fine motor skills, a surrogate of the motor planning ability of object manipulation, in early childhood are associated with later social skills, in a general-population birth cohort. A total of 913 children, participating in the Hamamatsu Birth Cohort for Mothers and Children, were enrolled. Social skills were measured using the Vineland Adaptive Behavior Scales-II, Socialization domain, at age 6 years. Fine motor skills were measured using the Mullen Scales of Early Learning at 14, 24, and 32 months. The associations between fine motor skills at ages 14, 24, and 32 months and social skills at age 6 years were tested separately through multivariable linear regression after adjusting for covariates, including gross motor and language skills at the contemporaneous age, autistic symptoms at age 6 years, and demographic factors. Fine motor skills at 24 and 32 months were significantly associated with social skills at age 6 years (at 24 months: nonstandardized regression coefficient = 1.38 [95% CI, 0.50-2.26], p = 0.002; at 32 months: 1.47 [0.56-2.38], p = 0.001). Fine motor skills in early childhood predicted social skills at age 6 years, indicating an association between the complex motor planning ability of object manipulation and later social skills. Children who demonstrate fine motor delay at as early an age as 2 years should be closely monitored by child professionals.

Rancang Bangun Akuarium Dengan Pengkondisian PH Air Otomatis Berbasis PLTS

Many people in Indonesia keep freshwater ornamental fish, including guppy fish (Poecilia reticulata), green growth fish (Gyrinocheilus aymonieri), neon tetra fish (Paracheirodon innesi). Neon tetra fish are popular because of their distinctive striking and bright body lines, while guppy fish are kept because of their ease of care and beautiful color variations, especially in male guppies. Guppy fish can grow well at temperatures of 22°C - 27°C and pH 6.5-7.2. Because managers are busy, this becomes an obstacle in fish cultivation, because the water quality that determines fish development becomes unstable. The results of the PLTS output test for 7 days 7 hours per day from 09.00 – 15.00 WIB can charge the battery with an average voltage of 13.89 V and an average current of 1.2 A and an average power of 14.15 W and can run for 24 hours. O'clock. Testing the battery for 7 days and 7 hours from 09.00 – 15.00 WIB can meet power needs for 24 hours with an average battery voltage of 13.36 V and an average current of 0.71 A. Meanwhile, the test results for the servo motor with a feed weight of 2, 45 grams and a servo motor delay of 2 seconds. Testing the pH of the water using a pH pump showed a change from the initial value of 8.06 to 6.91 and was measured with the PH4502C sensor. Tests without a PH pump showed an increase in changes from the initial pH value of 7.76 to 8.05.

Two Chinese Patients of Auriculocondylar Syndrome 2: A Novel PLCB4 Splicing Variant and 5-Year Follow-up.

Auriculocondylar syndrome (ARCND) is a set of rare craniofacial malformations characterized by variable micrognathia, ear malformations, and mandibular condyle hypoplasia, and other accompanying features with phenotypic complexity. ARCND2 caused by pathogenic variants in the PLCB4 gene is a very rare disease with less than 50 patients reported and only 36 different variants of the PLCB4 gene recorded in HGMD. This study aims to enrich the patient resources, clinical data and mutational spectrum of ARCND2. Case series study. Guangzhou Women and Children's Medical Center and Guangdong Women and Children Hospital. Two Chinese patients with ARCND2. Clinical, radiological and molecular findings. Both the two patients presented with craniofacial and ear malformations, and feeding difficulties. Whole exome sequencing identified two different variants of the PLCB4 gene in these two patients with a heterozygous allele and a de novo mode of inheritance respectively. Patient 1 carried a known pathogenic c.1861C > T(p.Arg621Cys) missense variant, whereas Patient 2 had a novel c.225 + 1G > A splicing variant. Sanger sequencing confirmed the presence of PLCB4 variants in the proband and absence in the unaffected parents. These two PLCB4 variants were suggested as disease-causing candidates for these two patients. During a 5-year follow-up, Patient 2 gradually manifested crowded teeth, underweight, motor delay and intellectual disability. In this study, we report two Chinese patients with ARCND2, describe their clinical and mutational features, and share a 5-year follow-up of one patient. Our study adds two additional patients to ARCND2, reveals a novel PLCB4 variant, and expands the phenotypic and genotypic spectrum.

The Relationship of Body Weight, Exclusive Breastfeeding, MP-ASI and Energy Intake with Stunting in Toddlers

The incidence of stunting in toddlers is a global nutritional problem. Stunting causes delays in fine motor and gross motor development, increases morbidity and mortality rates, and increases the risk of metabolic disorders in adulthood. The aim of this study was to determine the relationship between body weight, exclusive breastfeeding, MP-ASI (weaning foods) and energy intake with stunting in toddlers aged 24-59 months. This research is descriptive analytical with a cross sectional design. The sample consisted of 92 participants selected using simple random sampling technique. Data collected with body weight measurements for birth weight, exclusive breastfeeding and MP-ASI questionnaires, energy intake calculate using daily energy requirements calculator, and stunting incidence questionnaire. Data analysis was carried out using the Chi-square test (P&lt;0.05). The results of the study explain that there is a relationship between body weight (p=0.000), exclusive breastfeeding (p=0.003), MP-ASI (p=0.004) and energy intake (p=0.000) with the incidence of stunting in toddlers aged 24–59 months. The research conclusion is that there is a relationship between body weight, exclusive breastfeeding, complementary foods and energy intake with the incidence of stunting in toddlers aged 24-59 months.

Structural models of genome-wide covariance identify multiple common dimensions in autism.

Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.

Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study

BackgroundFollow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability.MethodsWe developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine.ResultsOne thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4–10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76–0.81(95% CI, 0.73–0.83) for cognitive regress with 4 variables and 0.79–0.83 (95% CI, 0.76–0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75–0.78 (95% CI, 0.72–0.82) for cognitive delay with 10 variables and 0.73–0.82 (95% CI, 0.72–0.85) for motor delay with 4 variables.ConclusionsOur EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Investing in disadvantaged children for common prosperity in China

Despite rapid economic growth in China since 1978, rural-urban inequality has widened. High levels of socioeconomic inequality can have profound implications for child development and lifelong educational equity. Using a dataset containing early childhood development (ECD) outcomes of 0- to 3-year-olds (N = 9,053) from study sites in Eastern, Central, and Western China, the study finds that the risks of cognitive, language, and motor delay are, respectively, 43.2, 18.3, and 20.7 percentage points higher in rural study sites than in urban Shanghai (ps < .01). Impact evaluation of cluster-randomized experiments shows that parental training (focusing on child psychosocial stimulation and caregiver-child interaction) can improve parenting beliefs and practices (or investments) and ECD outcomes of disadvantaged rural children (p<.01). Such programs can play an important role in advancing progress toward more social equality and economic equity, the stated goals of China’s “Common Prosperity” policy.

Postnatal growth and neurodevelopment at 2 years’ corrected age in extremely low birthweight infants

BackgroundFaltering postnatal growth in preterm babies is associated with adverse neurodevelopment. However, which growth reference is most helpful for predicting neurodevelopment is unknown. We examined associations between faltering growth and developmental delay in extremely low birthweight (ELBW) infants.MethodsWe categorized faltering growth (z-score decrease ≥0.8 for weight/length, >1 for head circumference) between birth, 4 weeks, 36 weeks’ postmenstrual age and 2 years’ corrected age using fetal (Fenton, UK-WHO and Olsen) and healthy preterm (INTERGROWTH-21st) references. Associations between faltering growth and developmental delay were examined using binary logistic regression and area under the receiver operating curve (AUC).ResultsIn 327 infants, Olsen charts identified the highest prevalence of faltering growth (weight 37%, length 63%, head 45%). Agreement in classification was higher amongst fetal references (kappa coefficient, ĸ = 0.46–0.94) than between INTERGROWTH-21st and fetal references (ĸ = 0.10–0.81). Faltering growth in all measures between 4–36 weeks (odds ratio, OR 2.0–4.7) compared with other time intervals (OR 1.7–2.7) were more strongly associated with developmental delay, particularly motor delay (OR 2.0–4.7). All growth references were poorly predictive of developmental delay at 2 years (AUC ≤ 0.62).ConclusionsFaltering postnatal growth in ELBW infants is associated with, but is poorly predictive of, developmental delay at 2 years.ImpactIn babies born preterm, different growth references result in wide variation in categorization of faltering postnatal growth.Faltering growth in weight, length, and head circumference from 4 weeks to 36 weeks’ postmenstrual age are associated with developmental delay at 2 years’ corrected age, particularly motor delay.However, postnatal growth is a poor predictor of later developmental delay in extremely low birthweight infants irrespective of the growth reference used.