Pub Date : 2024-06-25DOI: 10.1101/2024.06.24.24309434
Rebecca Jackson, Yue Meng
Accessibility to developmental interventions for children and adolescents could be increased through virtual, at-home delivery of home-based training programs incorporating technology. Virtual childhood training programs and their effects on cognitive outcomes in children and adolescents with developmental delays have not been well studied. To that end, this study examined the effects of the virtual at-home Brain Balance® (BB) program on the cognitive task performance of children and adolescents with baseline developmental and attentional difficulties (aged 4-17 years). The at-home BB program is delivered through: (1) a computer-based format utilizing multimodal program activities previously studied in-center (multisensory stimulation with gross motor, coordination, balance, and timing activities, along with nutritional recommendations); and (2) the BB app (visual motor, auditory and visual processing, and rhythm and timing training) — creating a comprehensive program experience delivered remotely. Cognitive performance was measured by six online cognitive assessments from Creyos Health before and after 3 months of participation in the at-home BB program (N = 316) or in-center BB program (N = 4,232), compared to controls. Results showed that overall cognitive assessment scores (including attention, response inhibition, and working memory) improved after participation in either the at-home or the in-center program, compared to controls. Importantly, significant improvements over the controls were observed for two tasks, Double Trouble and Feature Match, in both programs. Further, two analyses support that the effects on cognitive performance from either delivery format, in-center or at home, are comparable in magnitude. This research: (1) presents new findings demonstrating improved cognitive performance after 3 months of the at-home BB program; (2) replicates previous findings of cognitive improvements after 3 months of the in-center BB program; and (3) suggests that the cognitive effects of virtual at-home BB training are similar to those observed for in-center BB training. Overall, the results demonstrate the effectiveness of the at-home BB program in improving cognitive functioning in pediatric populations with preexisting developmental and attentional difficulties. With virtual delivery and ease of use, at-home programs have the potential to increase access to much-needed developmental and cognitive support, ultimately reaching populations that may otherwise lack easy access to high-quality, evidence-based developmental programs.
{"title":"Cognitive Outcomes of the At-Home Brain Balance Program","authors":"Rebecca Jackson, Yue Meng","doi":"10.1101/2024.06.24.24309434","DOIUrl":"https://doi.org/10.1101/2024.06.24.24309434","url":null,"abstract":"Accessibility to developmental interventions for children and adolescents could be increased through virtual, at-home delivery of home-based training programs incorporating technology. Virtual childhood training programs and their effects on cognitive outcomes in children and adolescents with developmental delays have not been well studied. To that end, this study examined the effects of the virtual at-home Brain Balance<sup>®</sup> (BB) program on the cognitive task performance of children and adolescents with baseline developmental and attentional difficulties (aged 4-17 years). The at-home BB program is delivered through: (1) a computer-based format utilizing multimodal program activities previously studied in-center (multisensory stimulation with gross motor, coordination, balance, and timing activities, along with nutritional recommendations); and (2) the BB app (visual motor, auditory and visual processing, and rhythm and timing training) — creating a comprehensive program experience delivered remotely. Cognitive performance was measured by six online cognitive assessments from Creyos Health before and after 3 months of participation in the at-home BB program (N = 316) or in-center BB program (N = 4,232), compared to controls. Results showed that overall cognitive assessment scores (including attention, response inhibition, and working memory) improved after participation in either the at-home or the in-center program, compared to controls. Importantly, significant improvements over the controls were observed for two tasks, Double Trouble and Feature Match, in both programs. Further, two analyses support that the effects on cognitive performance from either delivery format, in-center or at home, are comparable in magnitude. This research: (1) presents new findings demonstrating improved cognitive performance after 3 months of the at-home BB program; (2) replicates previous findings of cognitive improvements after 3 months of the in-center BB program; and (3) suggests that the cognitive effects of virtual at-home BB training are similar to those observed for in-center BB training. Overall, the results demonstrate the effectiveness of the at-home BB program in improving cognitive functioning in pediatric populations with preexisting developmental and attentional difficulties. With virtual delivery and ease of use, at-home programs have the potential to increase access to much-needed developmental and cognitive support, ultimately reaching populations that may otherwise lack easy access to high-quality, evidence-based developmental programs.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.1101/2024.06.22.24309343
Gieng Thi My Tran, Nhat Phan Minh Nguyen, Long Phuoc Nguyen, Duc Ninh Nguyen, Thu-Tinh Nguyen
Background: Pulmonary hemorrhage (PH) is a catastrophic event associated with significant morbidity and mortality among preterm infants. Understanding PH risk factors in preterm newborns, particularly those in low-to-middle-income countries like Vietnam, remains limited. This study aimed to investigate the risk factors and short-term outcomes of PH in very preterm infants. Methods: We conducted an observational study of newborns aged < 72 hours with gestational age < 32 weeks, admitted to our unit from April 1, 2018 to March 31, 2019. Results: Of 118 recruited newborns, 28 (23.7%) had PH. The logistic regression analysis showed that intubation within 24 first hours, blood transfusion, and coagulation disorders within the first 3 days were risk factors for PH (aOR = 4.594, 95% CI = 1.200-17.593; aOR = 5.394, 95% CI = 1.243-23.395 and aOR = 7.242 95% CI = 1.838-28.542, respectively). Intra-ventricular hemorrhage (IVH) and mortality rates were higher in patients with PH compared to those without (p<0.001). The length of invasive ventilation was longer in the PH group (p<0.001). Conclusion: We have identified intubation, blood transfusion, and coagulation disorders shortly after birth as risk factors for PH in very preterm infants, which was associated with increased mortality and occurrence of IVH.
{"title":"Risk Factors and Outcomes of Pulmonary Hemorrhage in Preterm Infants born before 32 weeks.","authors":"Gieng Thi My Tran, Nhat Phan Minh Nguyen, Long Phuoc Nguyen, Duc Ninh Nguyen, Thu-Tinh Nguyen","doi":"10.1101/2024.06.22.24309343","DOIUrl":"https://doi.org/10.1101/2024.06.22.24309343","url":null,"abstract":"Background: Pulmonary hemorrhage (PH) is a catastrophic event associated with significant morbidity and mortality among preterm infants. Understanding PH risk factors in preterm newborns, particularly those in low-to-middle-income countries like Vietnam, remains limited. This study aimed to investigate the risk factors and short-term outcomes of PH in very preterm infants. Methods: We conducted an observational study of newborns aged < 72 hours with gestational age < 32 weeks, admitted to our unit from April 1, 2018 to March 31, 2019. Results: Of 118 recruited newborns, 28 (23.7%) had PH. The logistic regression analysis showed that intubation within 24 first hours, blood transfusion, and coagulation disorders within the first 3 days were risk factors for PH (aOR = 4.594, 95% CI = 1.200-17.593; aOR = 5.394, 95% CI = 1.243-23.395 and aOR = 7.242 95% CI = 1.838-28.542, respectively). Intra-ventricular hemorrhage (IVH) and mortality rates were higher in patients with PH compared to those without (p<0.001). The length of invasive ventilation was longer in the PH group (p<0.001). Conclusion: We have identified intubation, blood transfusion, and coagulation disorders shortly after birth as risk factors for PH in very preterm infants, which was associated with increased mortality and occurrence of IVH.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141514912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.1101/2024.06.23.24307757
Alice Kuhn, Maren Hackenberg, Anna-Lena Klauser, Antonia Herrmann, Julia Matilainen, Simone Mayer, Saskia Froelich, Ingeborg Kraegeloh-Mann, Samuel Groeschel, Wibke G. Janzarik
Introduction: Pontocerebellar hypoplasia type 2A (PCH2A) is a rare, autosomal recessive disease, caused by a homozygous pathogenic variant in the gene TSEN54 (c.919G>A, p.A307S). Apart from the characteristic pontocerebellar hypoplasia in MRI, PCH2A is clinically characterized by a dyskinetic movement disorder, severe neurodevelopment delay, progressive microcephaly, and, less well recognized, failure to thrive. Additional symptoms such as seizures, gastrointestinal or respiratory problems are common. The aim of this study was to document growth data of PCH2A patients, calculate growth charts for height, weight, body mass index (BMI) and head circumference (hc), and compare these to German reference charts. Patients and methods: In total, data of 65 patients with genetically confirmed PCH2A were included in the study. Growth data were collected retrospectively from medical reports and a parent questionnaire. Disease-specific growth charts were prepared using gamlss package in R. Sex-disaggregated growth charts for PCH2A were compared to German reference data from the KiGGs study. Results: Height and weight of patients with PCH2A were within the normal range at birth. Mean weight was significantly lower from the age of 3 months onwards, and mean height at the age of 6 months in patients with PCH2A, both, females and males. Mean BMI was statistically lower in patients at the age 4 months. Compared to reference values, mean head circumference of patients with PCH2A was significantly below average at birth, and all patients showed severe and progressive microcephaly in the further course. Conclusion: In line with previous reports, patients with PCH2A typically exhibit progressive microcephaly, and frequently fail to thrive during infancy. Disease-specific growth charts of pediatric patients with PCH2A are provided as a helpful tool to monitor height, weight, BMI and head circumference of affected children.
{"title":"Growth charts for pontocerebellar hypoplasia type 2A","authors":"Alice Kuhn, Maren Hackenberg, Anna-Lena Klauser, Antonia Herrmann, Julia Matilainen, Simone Mayer, Saskia Froelich, Ingeborg Kraegeloh-Mann, Samuel Groeschel, Wibke G. Janzarik","doi":"10.1101/2024.06.23.24307757","DOIUrl":"https://doi.org/10.1101/2024.06.23.24307757","url":null,"abstract":"Introduction:\u0000Pontocerebellar hypoplasia type 2A (PCH2A) is a rare, autosomal recessive disease, caused by a homozygous pathogenic variant in the gene TSEN54 (c.919G>A, p.A307S). Apart from the characteristic pontocerebellar hypoplasia in MRI, PCH2A is clinically characterized by a dyskinetic movement disorder, severe neurodevelopment delay, progressive microcephaly, and, less well recognized, failure to thrive. Additional symptoms such as seizures, gastrointestinal or respiratory problems are common. The aim of this study was to document growth data of PCH2A patients, calculate growth charts for height, weight, body mass index (BMI) and head circumference (hc), and compare these to German reference charts.\u0000Patients and methods:\u0000In total, data of 65 patients with genetically confirmed PCH2A were included in the study. Growth data were collected retrospectively from medical reports and a parent questionnaire. Disease-specific growth charts were prepared using gamlss package in R. Sex-disaggregated growth charts for PCH2A were compared to German reference data from the KiGGs study.\u0000Results:\u0000Height and weight of patients with PCH2A were within the normal range at birth. Mean weight was significantly lower from the age of 3 months onwards, and mean height at the age of 6 months in patients with PCH2A, both, females and males. Mean BMI was statistically lower in patients at the age 4 months. Compared to reference values, mean head circumference of patients with PCH2A was significantly below average at birth, and all patients showed severe and progressive microcephaly in the further course.\u0000Conclusion:\u0000In line with previous reports, patients with PCH2A typically exhibit progressive microcephaly, and frequently fail to thrive during infancy. Disease-specific growth charts of pediatric patients with PCH2A are provided as a helpful tool to monitor height, weight, BMI and head circumference of affected children.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-23DOI: 10.1101/2024.06.22.24309339
Lisette M Harteveld, Lisanne M van Leeuwen, Sjoerd M Euser, Lucy Smit, Karlijn C Vollebregt, Debby Bogaert, Marlies A van Houten
Objectives: To investigate the perception and willingness of pregnant women and their partners to accept maternal vaccination or neonatal immunization against respiratory syncytial virus (RSV). Design: A cross-sectional survey study Setting: Pregnant women and their partners were recruited through healthcare professionals (midwives, gynaecologists, and Youth Health care), social media platforms (Instagram, LinkedIn, Facebook via institutions like the Spaarne Hospital), and the 9-Months Fair in the Netherlands. Main outcome measures: Willingness and motivation in decision-making for both maternal RSV vaccination or neonatal RSV immunization among pregnant women and their partners, including strategy preferences, and informational needs. Results: In total 1001 pregnant women (mean age: 31.1 years) and their partners (mean age: 33.2 years) completed the survey. On average, they were 24 weeks pregnant at the time, and 54.6% had no other children yet. The majority was Dutch-born (95.2% of women); with 68.3% of women having completed higher education and with overall strong pro-vaccination attitudes (93.9% of partners intended to vaccinate their expected newborn). The overall acceptability to vaccination and immunization was high, with 87% of respondents indicating they would (likely) accept both strategies. A positive attitude towards both methods was associated with previous experience with severity of RSV, intention to vaccinate the newborn and parental vaccination status during childhood and current pregnancy. When the choice was given, the majority of participants, in particular those with children and the intention to breastfeed, favoured maternal vaccination over passive immunization of infants (75.3% of the pregnant and 71.6% of the partners). A majority of the respondents cited optimal protection for the child and knowledge of RSV as important factors for accepting RSV prophylaxis. Conclusions: While most participants would accept both strategies for RSV protection of their infant, a majority, especially those with other children, favored maternal vaccination, due to concerns about infant safety and awareness of RSV severity.
{"title":"Respiratory syncytial virus (RSV) prevention: perception and willingness of expectant parents in the Netherlands","authors":"Lisette M Harteveld, Lisanne M van Leeuwen, Sjoerd M Euser, Lucy Smit, Karlijn C Vollebregt, Debby Bogaert, Marlies A van Houten","doi":"10.1101/2024.06.22.24309339","DOIUrl":"https://doi.org/10.1101/2024.06.22.24309339","url":null,"abstract":"Objectives: To investigate the perception and willingness of pregnant women and their partners to accept maternal vaccination or neonatal immunization against respiratory syncytial virus (RSV). Design: A cross-sectional survey study Setting: Pregnant women and their partners were recruited through healthcare professionals (midwives, gynaecologists, and Youth Health care), social media platforms (Instagram, LinkedIn, Facebook via institutions like the Spaarne Hospital), and the 9-Months Fair in the Netherlands. Main outcome measures: Willingness and motivation in decision-making for both maternal RSV vaccination or neonatal RSV immunization among pregnant women and their partners, including strategy preferences, and informational needs. Results: In total 1001 pregnant women (mean age: 31.1 years) and their partners (mean age: 33.2 years) completed the survey. On average, they were 24 weeks pregnant at the time, and 54.6% had no other children yet. The majority was Dutch-born (95.2% of women); with 68.3% of women having completed higher education and with overall strong pro-vaccination attitudes (93.9% of partners intended to vaccinate their expected newborn). The overall acceptability to vaccination and immunization was high, with 87% of respondents indicating they would (likely) accept both strategies. A positive attitude towards both methods was associated with previous experience with severity of RSV, intention to vaccinate the newborn and parental vaccination status during childhood and current pregnancy. When the choice was given, the majority of participants, in particular those with children and the intention to breastfeed, favoured maternal vaccination over passive immunization of infants (75.3% of the pregnant and 71.6% of the partners). A majority of the respondents cited optimal protection for the child and knowledge of RSV as important factors for accepting RSV prophylaxis. Conclusions: While most participants would accept both strategies for RSV protection of their infant, a majority, especially those with other children, favored maternal vaccination, due to concerns about infant safety and awareness of RSV severity.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"352 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141514913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-10DOI: 10.1101/2024.06.09.24307243
Santiago Vasco-Morales, Mercedes Elina Yanez Valencia, Paola Toapanta-Pinta
Introduction: In 1983, the Latin American Center for Perinatology/Women's Health and Reproductive Health published the Perinatal Information System, which records perinatal information of the mother and newborn. At the Hospital Gineco Obstetrico Isidro Ayora, there has been an electronic record of this database since 2008. In 2016, the Ministerio de Salud Publica adapted and added registration variables to this medical history. Similarly, at the Hospital General docente de Calderon and the Hospital Gineco Obstetrico Pediatrico de Nueva Aurora Luz Elena Arismendi, there are records of neonatal care such as neonatal anthropometry, perinatal risk factors, admission diagnoses, and length of hospital stay. These variables can be integrated with the database of the Hospital Gineco Obstetrico Isidro Ayora. Objectives: Analyze the variables of the perinatal clinical history to identify factors associated with changes in fetal-neonatal morbidity and mortality. Methods: Descriptive, analytical, observational study using secondary sources. Frequentist and Bayesian statistical analyses will be applied. To determine the association between qualitative variables, the Chi-square test and logistic regression models will be used. The t-test and linear regression will be used to analyze numerical variables. Statistical significance will be set at p<0.05, and Odds Ratios with a 95% confidence interval will be calculated. Neonatal growth curves stratified by sex and gestational age will be developed. The statistical program R will be used. Expected Results: The characteristics of the population served in the hospitals in the north, central, and south of Quito, as well as the demographic and obstetric data of the mothers and their neonates, will be known. Perinatal characteristics associated with an increase or decrease in neonatal morbidity and mortality will be identified. Trends in maternal and child health will be detected and compared with national and international standards.
导言：1983 年，拉丁美洲围产期医学/妇女健康和生殖健康中心发布了围产期信息系统，该系 统记录了母亲和新生儿的围产期信息。Gineco Isidro Ayora 产科医院自 2008 年起就建立了该数据库的电子记录。2016 年，公共卫生部对这一病历进行了调整，增加了登记变量。同样，在卡尔德隆医生总医院（Hospital General docente de Calderon）和新奥罗拉-卢斯-埃莱娜-阿里斯门迪产科儿科医院（Hospital Gineco Obstetrico Pediatrico de Nueva Aurora Luz Elena Arismendi），也有新生儿护理记录，如新生儿人体测量、围产期风险因素、入院诊断和住院时间。这些变量可以与 Gineco Isidro Ayora 产科医院的数据库进行整合：分析围产期临床病史变量，找出与胎儿-新生儿发病率和死亡率变化相关的因素：方法：利用二手资料进行描述性、分析性、观察性研究。将采用频数和贝叶斯统计分析。为确定定性变量之间的关联，将使用卡方检验和逻辑回归模型。数字变量将采用 t 检验和线性回归分析。统计显著性将设定为 p<0.05，并将计算带有 95% 置信区间的比率。将绘制按性别和胎龄分层的新生儿生长曲线。将使用 R 统计程序：将了解基多北部、中部和南部医院服务人群的特征，以及母亲和新生儿的人口和产科数据。将确定与新生儿发病率和死亡率增减相关的围产期特征。还将发现孕产妇和儿童健康的趋势，并与国家和国际标准进行比较。
{"title":"Multicenter Analysis on Morbidity, Mortality, and Medical Care in Neonates at the Hospital Gineco Obstetrico Isidro Ayora, Hospital General Docente de Calderon, and Hospital Gineco Obstetrico Pediatrico de Nueva Aurora Luz Elena Arismendi, January 2008 - June 2024, Quito-Ecuador (clinical research design protocol)","authors":"Santiago Vasco-Morales, Mercedes Elina Yanez Valencia, Paola Toapanta-Pinta","doi":"10.1101/2024.06.09.24307243","DOIUrl":"https://doi.org/10.1101/2024.06.09.24307243","url":null,"abstract":"Introduction: In 1983, the Latin American Center for Perinatology/Women's Health and Reproductive Health published the Perinatal Information System, which records perinatal information of the mother and newborn. At the Hospital Gineco Obstetrico Isidro Ayora, there has been an electronic record of this database since 2008. In 2016, the Ministerio de Salud Publica adapted and added registration variables to this medical history. Similarly, at the Hospital General docente de Calderon and the Hospital Gineco Obstetrico Pediatrico de Nueva Aurora Luz Elena Arismendi, there are records of neonatal care such as neonatal anthropometry, perinatal risk factors, admission diagnoses, and length of hospital stay. These variables can be integrated with the database of the Hospital Gineco Obstetrico Isidro Ayora.\u0000Objectives: Analyze the variables of the perinatal clinical history to identify factors associated with changes in fetal-neonatal morbidity and mortality.\u0000Methods: Descriptive, analytical, observational study using secondary sources. Frequentist and Bayesian statistical analyses will be applied. To determine the association between qualitative variables, the Chi-square test and logistic regression models will be used. The t-test and linear regression will be used to analyze numerical variables. Statistical significance will be set at p<0.05, and Odds Ratios with a 95% confidence interval will be calculated. Neonatal growth curves stratified by sex and gestational age will be developed. The statistical program R will be used.\u0000Expected Results: The characteristics of the population served in the hospitals in the north, central, and south of Quito, as well as the demographic and obstetric data of the mothers and their neonates, will be known. Perinatal characteristics associated with an increase or decrease in neonatal morbidity and mortality will be identified. Trends in maternal and child health will be detected and compared with national and international standards.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"165 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141530740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.30.24308230
Vani Taluja, Sanaz Nazari, Javad Zahiri, Lana Garmire, Karen Pierce, Yaqiong Xiao, Eric Courchesne
Social affective and communication symptoms stand at the center of autism, and usually become apparent within the first 1-3 years of life. Symptom severity differs widely across toddlers and clinical outcomes, ranging from near-neurotypical to poor. The biological bases of this early and wide symptom diversity are largely unknown. While more than two dozen studies have attempted to subgroup early-age clinical heterogeneity, most studies fail to rigorously validate discovered subtypes using multiple methods, and none linked observed clinical subtypes with underlying functional neural signatures. Using a well-established approach for precision medicine patient subtyping (Similarity Network Fusion) and multiple rigorous validation methods, we integrated thoroughly replicated measures of social neurofunctional activation and social and language ability in 137 toddlers at early ages. Results identified three distinct social neural-clinical ASD subtypes, validated using multiple methods. One subtype was consistent with a ‘profound’ autism profile with negligible social neural activation, severe social and language symptoms, low social interest, and little clinical improvement. Another ASD subtype had a contrasting pattern with only mildly reduced social neural activity, near neurotypical social and language abilities, and substantial age-related clinical improvement. One principal implication of these results is that the “spectrum” of ASD heterogeneity is not truly a continuous spectrum from the neurobiological and clinical perspective. The profound autism subtype is the neurofunctional, clinical and developmental opposite of the mild ASD subtype, suggesting different etiological mechanisms. A second implication is that neurobiological and clinical subtype differences highlight the need to develop subtype-specific treatments, particularly for the profound subtype. Third, treatment studies with an undetermined mix of subtypes could fail or succeed based on how many patients from each subtype are included in the mix.
{"title":"Multimodality Integration of Neural Social Activation and Social and Language Scores Reveals Three Replicable Profound and Milder Autism Subtypes With Divergent Clinical Outcomes","authors":"Vani Taluja, Sanaz Nazari, Javad Zahiri, Lana Garmire, Karen Pierce, Yaqiong Xiao, Eric Courchesne","doi":"10.1101/2024.05.30.24308230","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308230","url":null,"abstract":"Social affective and communication symptoms stand at the center of autism, and usually become apparent within the first 1-3 years of life. Symptom severity differs widely across toddlers and clinical outcomes, ranging from near-neurotypical to poor. The biological bases of this early and wide symptom diversity are largely unknown. While more than two dozen studies have attempted to subgroup early-age clinical heterogeneity, most studies fail to rigorously validate discovered subtypes using multiple methods, and none linked observed clinical subtypes with underlying functional neural signatures. Using a well-established approach for precision medicine patient subtyping (Similarity Network Fusion) and multiple rigorous validation methods, we integrated thoroughly replicated measures of social neurofunctional activation and social and language ability in 137 toddlers at early ages. Results identified three distinct social neural-clinical ASD subtypes, validated using multiple methods. One subtype was consistent with a ‘profound’ autism profile with negligible social neural activation, severe social and language symptoms, low social interest, and little clinical improvement. Another ASD subtype had a contrasting pattern with only mildly reduced social neural activity, near neurotypical social and language abilities, and substantial age-related clinical improvement. One principal implication of these results is that the “spectrum” of ASD heterogeneity is not truly a continuous spectrum from the neurobiological and clinical perspective. The profound autism subtype is the neurofunctional, clinical and developmental opposite of the mild ASD subtype, suggesting different etiological mechanisms. A second implication is that neurobiological and clinical subtype differences highlight the need to develop subtype-specific treatments, particularly for the profound subtype. Third, treatment studies with an undetermined mix of subtypes could fail or succeed based on how many patients from each subtype are included in the mix.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.30.24308257
Lars Dinkelbach, Triinu Peters, Corinna Grasemann, Anke Hinney, Raphael Hirtz
Preexisting epidemiological studies suggest that early pubertal development in males is associated with externalizing (e.g., conduct problems, risky behavior, and aggression) and internalizing (e.g., depression and anxiety) traits and disorders. However, due to problems inherent to observational studies, especially of reverse causation and residual confounding, it remains unclear whether these associations are causal. Mendelian randomization (MR) studies take advantage of the random allocation of genes at conception and can establish causal relationships. In the current study, N=76 independent genetic variants for male puberty timing (MPT) were derived from a large genome-wide association study (GWAS) on 205,354 participants and used as an instrumental variable in MR studies on 17 externalizing and internalizing traits and psychopathologies utilizing outcome GWAS with 16,400 to 1,045,957 participants. In these MR studies, earlier MPT was significantly associated with higher scores for the overarching phenotype of ‘Externalizing Traits’ (beta=-0.03, 95%-CI [-0.06, -0.01]). However, this effect was likely driven by an earlier age at first sex (beta=-0.17, 95%-CI [-0.21, - 0.13]), without evidence for an effect on further externalizing phenotypes. Regarding internalizing phenotypes, earlier MPT was associated with higher levels of the ‘Depressed Affect’ subdomain of neuroticism (beta=-0.04, 95%-CI [-0.07, -0.01]). Late MPT was related to higher scores of internalizing traits in early life (beta=0.04, 95%-CI [0.01, 0.08]). In conclusion, this MR study supports a causal effect of MPT on specific traits and behaviors. However, no evidence for an effect of MPT on long-term clinical outcomes (depression, anxiety disorders, alcohol dependency, cannabis abuse) was found.
{"title":"The causal role of male pubertal timing for the development of externalizing and internalizing traits: results from Mendelian randomization studies","authors":"Lars Dinkelbach, Triinu Peters, Corinna Grasemann, Anke Hinney, Raphael Hirtz","doi":"10.1101/2024.05.30.24308257","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308257","url":null,"abstract":"Preexisting epidemiological studies suggest that early pubertal development in males is associated with externalizing (e.g., conduct problems, risky behavior, and aggression) and internalizing (e.g., depression and anxiety) traits and disorders. However, due to problems inherent to observational studies, especially of reverse causation and residual confounding, it remains unclear whether these associations are causal. Mendelian randomization (MR) studies take advantage of the random allocation of genes at conception and can establish causal relationships. In the current study, N=76 independent genetic variants for male puberty timing (MPT) were derived from a large genome-wide association study (GWAS) on 205,354 participants and used as an instrumental variable in MR studies on 17 externalizing and internalizing traits and psychopathologies utilizing outcome GWAS with 16,400 to 1,045,957 participants. In these MR studies, earlier MPT was significantly associated with higher scores for the overarching phenotype of ‘Externalizing Traits’ (beta=-0.03, 95%-CI [-0.06, -0.01]). However, this effect was likely driven by an earlier age at first sex (beta=-0.17, 95%-CI [-0.21, - 0.13]), without evidence for an effect on further externalizing phenotypes. Regarding internalizing phenotypes, earlier MPT was associated with higher levels of the ‘Depressed Affect’ subdomain of neuroticism (beta=-0.04, 95%-CI [-0.07, -0.01]). Late MPT was related to higher scores of internalizing traits in early life (beta=0.04, 95%-CI [0.01, 0.08]). In conclusion, this MR study supports a causal effect of MPT on specific traits and behaviors. However, no evidence for an effect of MPT on long-term clinical outcomes (depression, anxiety disorders, alcohol dependency, cannabis abuse) was found.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1101/2024.05.31.24308185
Gustaf Håkansson, Katarina Robertsson Grossmann, Ulrika Ådén, Mats Blennow, Peter Fransson
Aim Neonatal hypoxic-ischemic encephalopathy (HIE) injures the infant brain during the basic formation of the developing functional connectome. This study aimed to investigate long-term changes in the functional connectivity (FC) networks of the adolescent brain following neonatal HIE treated with therapeutic hypothermia (TH).
{"title":"Functional brain connectivity in early adolescence after hypothermia-treated neonatal hypoxic-ischemic encephalopathy","authors":"Gustaf Håkansson, Katarina Robertsson Grossmann, Ulrika Ådén, Mats Blennow, Peter Fransson","doi":"10.1101/2024.05.31.24308185","DOIUrl":"https://doi.org/10.1101/2024.05.31.24308185","url":null,"abstract":"<strong>Aim</strong> Neonatal hypoxic-ischemic encephalopathy (HIE) injures the infant brain during the basic formation of the developing functional connectome. This study aimed to investigate long-term changes in the functional connectivity (FC) networks of the adolescent brain following neonatal HIE treated with therapeutic hypothermia (TH).","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141256298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-29DOI: 10.1101/2024.05.29.24307906
Jelte Kelchtermans, Michael E. March, Frank Mentch, Yichuan Liu, Kenny Nguyen, Hakon Hakonarson
Background The relationship between ambient air pollution (AAP) exposure and asthma exacerbations is well-established. However, mitigation efforts have yielded mixed results, potentially due to genetic variability in the response to AAP. We hypothesize that common single nucleotide polymorphisms (SNPs) are linked to AAP sensitivity and test this through a Genome Wide Association Study (GWAS).
{"title":"GWAS reveals Genetic Susceptibility to Air Pollution-Related Asthma Exacerbations in Children of African Ancestry","authors":"Jelte Kelchtermans, Michael E. March, Frank Mentch, Yichuan Liu, Kenny Nguyen, Hakon Hakonarson","doi":"10.1101/2024.05.29.24307906","DOIUrl":"https://doi.org/10.1101/2024.05.29.24307906","url":null,"abstract":"<strong>Background</strong> The relationship between ambient air pollution (AAP) exposure and asthma exacerbations is well-established. However, mitigation efforts have yielded mixed results, potentially due to genetic variability in the response to AAP. We hypothesize that common single nucleotide polymorphisms (SNPs) are linked to AAP sensitivity and test this through a Genome Wide Association Study (GWAS).","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-28DOI: 10.1101/2024.05.28.24308012
Simone Paulson, Alasdair PS Munro, Katrina Cathie, Helen Bedford, Christine E Jones
Introduction Maternal vaccination and infant monoclonal antibodies are promising avenues to protect young infants from respiratory syncytial virus (RSV) infection. Successful inclusion into the UK immunisation schedule depends on parental acceptability, among other factors.
{"title":"Protecting against Respiratory Syncytial Virus: An online questionnaire study exploring UK parents’ acceptability of vaccination in pregnancy or monoclonal antibody administration for infants","authors":"Simone Paulson, Alasdair PS Munro, Katrina Cathie, Helen Bedford, Christine E Jones","doi":"10.1101/2024.05.28.24308012","DOIUrl":"https://doi.org/10.1101/2024.05.28.24308012","url":null,"abstract":"<strong>Introduction</strong> Maternal vaccination and infant monoclonal antibodies are promising avenues to protect young infants from respiratory syncytial virus (RSV) infection. Successful inclusion into the UK immunisation schedule depends on parental acceptability, among other factors.","PeriodicalId":501549,"journal":{"name":"medRxiv - Pediatrics","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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