Pub Date : 2024-11-09DOI: 10.1007/s00431-024-05869-w
Min Jeong Lee, Ji Soo Park, Kyunghoon Kim, Jung Min Ko, June Dong Park, Dong In Suh
{"title":"Correction to: Congenital central hypoventilation syndrome in korea: 20 years of clinical observation and evaluation of the ventilation strategy in a single center.","authors":"Min Jeong Lee, Ji Soo Park, Kyunghoon Kim, Jung Min Ko, June Dong Park, Dong In Suh","doi":"10.1007/s00431-024-05869-w","DOIUrl":"https://doi.org/10.1007/s00431-024-05869-w","url":null,"abstract":"","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":"184 1","pages":"2"},"PeriodicalIF":3.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08DOI: 10.1007/s00431-024-05838-3
Andrew Limavady, Matko Marlais
{"title":"Nutritional status and paediatric tuberous sclerosis complex-associated kidney angiomyolipomas: reply to the commenting letter by Singhvi M et al.","authors":"Andrew Limavady, Matko Marlais","doi":"10.1007/s00431-024-05838-3","DOIUrl":"https://doi.org/10.1007/s00431-024-05838-3","url":null,"abstract":"","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":"184 1","pages":"1"},"PeriodicalIF":3.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A stepwise approach is currently considered the best choice to manage gastroesophageal reflux (GER) in preterm infants. This study aimed to evaluate the effect of different tube feeding techniques on GER frequency and features in symptomatic tube-fed preterm neonates. Tube-fed infants < 34 weeks' gestation were eligible for this prospective, bicentric, cross-over study if, due to GER symptoms, they underwent a diagnostic 24-h combined pH and multiple intraluminal impedance (pH-MII) monitoring. During the monitoring period, each infant received the same feeding cycle, repeated twice: continuous tube feeding, bolus feeding followed by tube feeding permanence and by tube feeding removal. The impact of these three feeding modalities on pH-MII GER features was assessed. Thirty-one infants were enrolled. Despite a low number of reflux episodes, a significant decrease in total GERs (P < 0.001), in GERs detected by pH monitoring (P < 0.001), and in both acid and non-acid GERs detected by MII (P < 0.001 and P = 0.009, respectively) was observed in association with continuous feeding compared to bolus feeds, followed or not by tube feeding removal. Compared to continuous feeding, both bolus feeding modalities were associated with a significantly higher number of proximal GERs (P < 0.001). No difference in any pH-MII parameter was observed in relation to tube feeding persistence after bolus feeding administration.
Conclusions: Continuous feeding and boluses may have a different impact on pH-MII GER features in symptomatic tube-fed preterm infants, whereas the permanence of the feeding tube across LES did not seem to worsen GER indexes.
What is known: • Due to the functional and anatomical immaturity of the gastrointestinal tract, gastroesophageal reflux (GER) is common in preterm infants. • A stepwise therapeutical approach which firstly undertakes conservative strategies is the most advisable choice to avoid potentially harmful pharmacological overtreatments in the preterm population.
What is new: • Continuous feeding and boluses may have a different impact on GER features assessed by pH-MII monitoring in tube-fed preterm infants. • The permanence of the feeding tube during or after the feeding period did not seem to worsen GER occurrence. • By reducing GER features, especially acid GER, continuous feeding may potentially contribute to limit the need for antiacid medications in this population.
{"title":"Effect of different tube feeding methods on gastroesophageal reflux features in preterm infants: a pH-impedance monitoring study.","authors":"Silvia Martini, Fabio Meneghin, Arianna Aceti, Nadia Cerchierini, Isadora Beghetti, Gianluca Lista, Luigi Corvaglia","doi":"10.1007/s00431-024-05737-7","DOIUrl":"10.1007/s00431-024-05737-7","url":null,"abstract":"<p><p>A stepwise approach is currently considered the best choice to manage gastroesophageal reflux (GER) in preterm infants. This study aimed to evaluate the effect of different tube feeding techniques on GER frequency and features in symptomatic tube-fed preterm neonates. Tube-fed infants < 34 weeks' gestation were eligible for this prospective, bicentric, cross-over study if, due to GER symptoms, they underwent a diagnostic 24-h combined pH and multiple intraluminal impedance (pH-MII) monitoring. During the monitoring period, each infant received the same feeding cycle, repeated twice: continuous tube feeding, bolus feeding followed by tube feeding permanence and by tube feeding removal. The impact of these three feeding modalities on pH-MII GER features was assessed. Thirty-one infants were enrolled. Despite a low number of reflux episodes, a significant decrease in total GERs (P < 0.001), in GERs detected by pH monitoring (P < 0.001), and in both acid and non-acid GERs detected by MII (P < 0.001 and P = 0.009, respectively) was observed in association with continuous feeding compared to bolus feeds, followed or not by tube feeding removal. Compared to continuous feeding, both bolus feeding modalities were associated with a significantly higher number of proximal GERs (P < 0.001). No difference in any pH-MII parameter was observed in relation to tube feeding persistence after bolus feeding administration.</p><p><strong>Conclusions: </strong>Continuous feeding and boluses may have a different impact on pH-MII GER features in symptomatic tube-fed preterm infants, whereas the permanence of the feeding tube across LES did not seem to worsen GER indexes.</p><p><strong>What is known: </strong>• Due to the functional and anatomical immaturity of the gastrointestinal tract, gastroesophageal reflux (GER) is common in preterm infants. • A stepwise therapeutical approach which firstly undertakes conservative strategies is the most advisable choice to avoid potentially harmful pharmacological overtreatments in the preterm population.</p><p><strong>What is new: </strong>• Continuous feeding and boluses may have a different impact on GER features assessed by pH-MII monitoring in tube-fed preterm infants. • The permanence of the feeding tube during or after the feeding period did not seem to worsen GER occurrence. • By reducing GER features, especially acid GER, continuous feeding may potentially contribute to limit the need for antiacid medications in this population.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4755-4762"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of our study was to show the presence of neurotrophic factors in breast milk that have a significant impact on neurocognitive development of children aged two years and beyond. Mothers expressed at least 5 mL of breast milk into sterile containers when their children 18, 24, and ≥ 25 months of age, and then specimens were transferred to Eppendorf tubes and stored at -20 °C. One day before the analysis, specimens were kept at +4 °C and then thawed at room temperature to prepare them for analysis. Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and S100B neurotrophic growth factor levels were analyzed using the sandwich enzyme-linked immunosorbent assay (ELISA) principles. Sixty-two mothers with children aged 18 months were included in the study. The mean age of the mothers was 33.4 (± 0.71) years. Due to the detection limits of the commercial kits, BDNF and S100B analyses could not be conducted. Therefore, only GDNF was analyzed. The presence of GDNF was found in the breast milk samples taken at 18, 24, and ≥ 25 months, and the median (min max) values were 315,505 ng/mL (193,067 750,718), 316,721 ng/mL (161,278 l-752,252), and 564,577 ng/mL (238,528-781,104) respectively. There were no significant differences between GDNF levels of breast milk samples collected from the same mother at the three different time points (18, 24, and ≥ 25 months) (p = 0.278). Conclusion: Our study was the first to show the presence of neurotrophic factors in the breast milk of mothers with healthy children over one year of age. Our results provide evidence-based data on the importance of breastfeeding until children are at least two years of age. What is Known: • Presence of Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and S100B neurotrophic growth factor have been shown in the breast milk of mothers whose infants are the first year of life. What is New: • Glial Cell Line-Derived Neurotrophic factors continue to present in breast milk of mothers with children aged 18, 24, and ≥ 25 months, without any significant difference in level between months.
{"title":"Unique content of breastmilk: neurotrophic growth factors in breastmilk at 2 years and beyond.","authors":"Öykü Özbörü Aşkan, Fatma Hande Karpuzoğlu, Alev Bakır Kayı, Tülin Ayşe Özden, Gülbin Gökçay, Gonca Keskindemirci","doi":"10.1007/s00431-024-05732-y","DOIUrl":"10.1007/s00431-024-05732-y","url":null,"abstract":"<p><p>The aim of our study was to show the presence of neurotrophic factors in breast milk that have a significant impact on neurocognitive development of children aged two years and beyond. Mothers expressed at least 5 mL of breast milk into sterile containers when their children 18, 24, and ≥ 25 months of age, and then specimens were transferred to Eppendorf tubes and stored at -20 °C. One day before the analysis, specimens were kept at +4 °C and then thawed at room temperature to prepare them for analysis. Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and S100B neurotrophic growth factor levels were analyzed using the sandwich enzyme-linked immunosorbent assay (ELISA) principles. Sixty-two mothers with children aged 18 months were included in the study. The mean age of the mothers was 33.4 (± 0.71) years. Due to the detection limits of the commercial kits, BDNF and S100B analyses could not be conducted. Therefore, only GDNF was analyzed. The presence of GDNF was found in the breast milk samples taken at 18, 24, and ≥ 25 months, and the median (min max) values were 315,505 ng/mL (193,067 750,718), 316,721 ng/mL (161,278 l-752,252), and 564,577 ng/mL (238,528-781,104) respectively. There were no significant differences between GDNF levels of breast milk samples collected from the same mother at the three different time points (18, 24, and ≥ 25 months) (p = 0.278). Conclusion: Our study was the first to show the presence of neurotrophic factors in the breast milk of mothers with healthy children over one year of age. Our results provide evidence-based data on the importance of breastfeeding until children are at least two years of age. What is Known: • Presence of Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and S100B neurotrophic growth factor have been shown in the breast milk of mothers whose infants are the first year of life. What is New: • Glial Cell Line-Derived Neurotrophic factors continue to present in breast milk of mothers with children aged 18, 24, and ≥ 25 months, without any significant difference in level between months.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4729-4734"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-09-23DOI: 10.1007/s00431-024-05757-3
Estefanía Martínez-Barrios, Oscar Campuzano, Andrea Greco, José Cruzalegui, Georgia Sarquella-Brugada
Cardiac channelopathies are a group of inherited syndromes that can cause malignant arrhythmias and sudden cardiac death, particularly in the pediatric population. Today, a 12-lead electrocardiogram is the most effective tool to diagnose these diseases. Incomplete penetrance and variable expressivity are hallmarks of these syndromes. Some of these malignant entities may remain hidden and only a trigger such as exercise, emotions or fever can unmask the electrical pattern to diagnose the disease. Sudden cardiac death may be the first manifestation of any of these syndromes. The use of complementary tests that allow early diagnosis is strongly recommended, among which we find: pharmacological provocations, exercise tests, and genetic analysis. Genetic testing makes it possible to unravel the origin of the disease, and also identify family members who carry the harmful genetic defect and are therefore at risk. One of the main challenges in this area is the large number of genetic variants of uncertain significance, which prevent effective translation into clinical practice. Early identification of the pediatric population at risk and adequate risk stratification are crucial to adopting personalized preventive measures that reduce the risk of lethal episodes in this population. What is Known: • In the pediatric population, malignant arrhythmias leading to sudden cardiac death are mainly caused by inherited syndromes. • A conclusive genetic diagnosis unravels the origin of the syndrome and allows cascade screening to identify relatives carrying the genetic alteration. What is New: • The use of sequencing technologies allows a broad genetic analysis, helping to unravel new genetic alterations causing inherited arrhythmogenic syndromes. • A periodic reanalysis of genetic variants that currently have an ambiguous role will help discern those that are truly pathogenic.
{"title":"Cardiac channelopathies in pediatrics: a genetic update.","authors":"Estefanía Martínez-Barrios, Oscar Campuzano, Andrea Greco, José Cruzalegui, Georgia Sarquella-Brugada","doi":"10.1007/s00431-024-05757-3","DOIUrl":"10.1007/s00431-024-05757-3","url":null,"abstract":"<p><p>Cardiac channelopathies are a group of inherited syndromes that can cause malignant arrhythmias and sudden cardiac death, particularly in the pediatric population. Today, a 12-lead electrocardiogram is the most effective tool to diagnose these diseases. Incomplete penetrance and variable expressivity are hallmarks of these syndromes. Some of these malignant entities may remain hidden and only a trigger such as exercise, emotions or fever can unmask the electrical pattern to diagnose the disease. Sudden cardiac death may be the first manifestation of any of these syndromes. The use of complementary tests that allow early diagnosis is strongly recommended, among which we find: pharmacological provocations, exercise tests, and genetic analysis. Genetic testing makes it possible to unravel the origin of the disease, and also identify family members who carry the harmful genetic defect and are therefore at risk. One of the main challenges in this area is the large number of genetic variants of uncertain significance, which prevent effective translation into clinical practice. Early identification of the pediatric population at risk and adequate risk stratification are crucial to adopting personalized preventive measures that reduce the risk of lethal episodes in this population. What is Known: • In the pediatric population, malignant arrhythmias leading to sudden cardiac death are mainly caused by inherited syndromes. • A conclusive genetic diagnosis unravels the origin of the syndrome and allows cascade screening to identify relatives carrying the genetic alteration. What is New: • The use of sequencing technologies allows a broad genetic analysis, helping to unravel new genetic alterations causing inherited arrhythmogenic syndromes. • A periodic reanalysis of genetic variants that currently have an ambiguous role will help discern those that are truly pathogenic.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4635-4640"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD).
Methods: This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥ + 5) 30 days or later after KD onset.
Results: Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91-2.46).
Conclusions: Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients.
What is known: • Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events. • Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA.
What is new: • Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis. • The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group.
{"title":"Regression effect of renin-angiotensin-aldosterone system inhibitors on Kawasaki disease patients with coronary artery aneurysm: a prospective, observational study.","authors":"Eisuke Suganuma, Masaru Miura, Yutaro Koyama, Tohru Kobayashi, Tetsuji Kaneko, Tatsunori Hokosaki, Fujito Numano, Kenji Furuno, Junko Shiono, Shigeto Fuse, Ryuji Fukazawa, Yoshihide Mitani","doi":"10.1007/s00431-024-05765-3","DOIUrl":"10.1007/s00431-024-05765-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD).</p><p><strong>Methods: </strong>This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥ + 5) 30 days or later after KD onset.</p><p><strong>Results: </strong>Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91-2.46).</p><p><strong>Conclusions: </strong>Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients.</p><p><strong>What is known: </strong>• Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events. • Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA.</p><p><strong>What is new: </strong>• Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis. • The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4817-4825"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 ± 0.8) compared to the placebo group (2.4 ± 0.7, p < 0.001). Changes in CBCL total score and CBCL internalizing score were also better in the folinic acid group (19.7 ± 9.5 vs. 12.6 ± 8.4 and 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001 for both). High-titer anti-folate receptor autoantibodies were positive in 32/40 and 33/40 cases in the folinic acid and placebo groups, respectively (p = 0.78). In the placebo group, improvement in CARS score was comparable regardless of autoantibody status (p = 0.11), but in the folinic acid group, improvement was more pronounced in the high-titer autoantibody group (p = 0.03). No adverse reactions were reported in either group.
Conclusions: Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate receptor autoantibodies.
What is known: • Folate receptor autoantibodies are more prevalent in children with autism spectrum disorder (ASD) compared to typically developing children. • Folate receptor autoantibodies play a significant role in the neuropathogenesis of autism spectrum disorder.
What is new: • Add-on oral folinic acid supplementation is safe and effective in reducing the severity of symptoms in children with ASD. • The clinical benefits are more pronounced in children with high titers of folate receptor autoantibodies.
{"title":"Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial.","authors":"Prateek Kumar Panda, Indar Kumar Sharawat, Sarama Saha, Diksha Gupta, Achanya Palayullakandi, Kiran Meena","doi":"10.1007/s00431-024-05762-6","DOIUrl":"10.1007/s00431-024-05762-6","url":null,"abstract":"<p><p>Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 ± 0.8) compared to the placebo group (2.4 ± 0.7, p < 0.001). Changes in CBCL total score and CBCL internalizing score were also better in the folinic acid group (19.7 ± 9.5 vs. 12.6 ± 8.4 and 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001 for both). High-titer anti-folate receptor autoantibodies were positive in 32/40 and 33/40 cases in the folinic acid and placebo groups, respectively (p = 0.78). In the placebo group, improvement in CARS score was comparable regardless of autoantibody status (p = 0.11), but in the folinic acid group, improvement was more pronounced in the high-titer autoantibody group (p = 0.03). No adverse reactions were reported in either group.</p><p><strong>Conclusions: </strong>Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate receptor autoantibodies.</p><p><strong>Trial registration: </strong> CTRI/2021/07/034901, dated 15-07-2021.</p><p><strong>What is known: </strong>• Folate receptor autoantibodies are more prevalent in children with autism spectrum disorder (ASD) compared to typically developing children. • Folate receptor autoantibodies play a significant role in the neuropathogenesis of autism spectrum disorder.</p><p><strong>What is new: </strong>• Add-on oral folinic acid supplementation is safe and effective in reducing the severity of symptoms in children with ASD. • The clinical benefits are more pronounced in children with high titers of folate receptor autoantibodies.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4827-4835"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous research has assessed the effects of caesarean delivery (CD) on child neurodevelopment; however, whether the effects stem from the surgical procedure itself or its related medical conditions has not been conclusively determined. This study aimed to evaluate the associations among delivery mode, CD-related medical conditions and early childhood neurodevelopment. A total of 3829 maternal-infant pairs from a longitudinal birth cohort in Wuhan City, China, were included in the primary analysis. The neurodevelopment of the children was assessed by the Bayley Scales of Infant Development (BSID), the Conners Comprehensive Behaviour Rating Scale and the Chinese version of the Autism Behavior Checklist. Data on delivery mode and medical conditions were collected via medical records from the study hospital. Among the 3829 children for whom the BSID test was completed at two years of age, 50%, 27%, and 23% were delivered vaginally, by necessary CD, and by elective CD, respectively. Compared with vaginally delivered children, Necessary CD was associated with a 16.67% decrease in Mental Development Index (MDI) scores and a 13.37% decrease in Psychomotor Development Index (PDI) scores, while elective CD showed a 20.63% and 20.99% decrease after FDR correction, respectively. Similarly, among the 2448 children for whom the CBRS was completed, necessary CD was found to be associated with conduct disorders (adjusted β: 0.06; 95% CI: 0.02, 0.09), hyperactivity (adjusted β: 0.06; 95% CI: 0.02, 0.11), and hyperactivity index (adjusted β: 0.07; 95% CI: 0.03, 0.11), while elective CD was significantly associated with hyperactivity problem scores (adjusted β: 0.08, 95% CI: 0.03, 0.13). However, no significant association was found between CD and symptoms of autism in children, as assessed by the Autism Behavior Checklist (ABC).
Conclusion: This study suggested that the adverse impact of CD on child neurodevelopment stems from the procedure itself rather than CD-related medical conditions. It is important to minimize the use of CD when there is no medical necessity.
What is known: • Caesarean delivery (CD) may influence child neurodevelopment and other long-term outcomes. • In China, approximately one-quarter of CD are performed due to maternal request without medical indications.
What is new: • The negative impact of CD on the neurodevelopmental outcomes of children may be primarily attributed to the procedure itself, as opposed to related medical conditions. • In the absence of medical indications, unnecessary CD may have adverse impacts on children's neurodevelopment.
以往的研究曾评估过剖腹产(CD)对儿童神经发育的影响,但这些影响究竟是源于手术本身还是与之相关的医疗条件,目前尚无定论。本研究旨在评估分娩方式、剖腹产相关疾病和儿童早期神经发育之间的关联。主要分析对象包括来自中国武汉市纵向出生队列的 3829 对母婴。通过贝利婴儿发育量表(BSID)、康纳斯综合行为评定量表和中文版自闭症行为核对表评估了患儿的神经发育情况。有关分娩方式和医疗状况的数据来自研究医院的医疗记录。在3829名两岁时完成BSID测试的儿童中,阴道分娩、必要的剖宫产和选择性剖宫产的比例分别为50%、27%和23%。与阴道分娩的婴儿相比,必要的剖宫产婴儿的智力发育指数(MDI)得分下降了16.67%,精神运动发育指数(PDI)得分下降了13.37%,而选择性剖宫产婴儿的智力发育指数(MDI)得分在经过FDR校正后分别下降了20.63%和20.99%。同样,在完成 CBRS 的 2448 名儿童中,发现必要 CD 与行为障碍(调整后 β:0.06;95% CI:0.02,0.09)、多动(调整后 β:0.06;95% CI:0.02,0.11)和多动指数(调整后β:0.07;95% CI:0.03,0.11),而选择性 CD 与多动问题评分显著相关(调整后β:0.08,95% CI:0.03,0.13)。然而,根据自闭症行为核对表(ABC)的评估,CD与儿童自闭症症状之间并无明显关联:本研究表明,CD对儿童神经发育的不良影响源于手术本身,而非与CD相关的疾病。在没有医疗必要性的情况下,尽量减少使用剖腹产非常重要:- 剖腹产(CD)可能会影响儿童的神经发育和其他长期结果。- 在中国,约有四分之一的剖腹产是在无医学指征的情况下根据产妇的要求进行的:- 新发现:剖宫产对儿童神经发育的负面影响可能主要归因于手术本身,而非相关的医疗条件。- 在没有医学指征的情况下,不必要的 CD 可能会对儿童的神经发育造成不良影响。
{"title":"Association between mode of delivery and early neurodevelopment: A prospective birth cohort study.","authors":"Yun Huang, Zhenxian Jia, Xinmei Chen, Yin Wang, Aifen Zhou, Huaicai Zeng, Wei Xia, Yuanyuan Li, Shunqing Xu, Hongxiu Liu","doi":"10.1007/s00431-024-05758-2","DOIUrl":"10.1007/s00431-024-05758-2","url":null,"abstract":"<p><p>Previous research has assessed the effects of caesarean delivery (CD) on child neurodevelopment; however, whether the effects stem from the surgical procedure itself or its related medical conditions has not been conclusively determined. This study aimed to evaluate the associations among delivery mode, CD-related medical conditions and early childhood neurodevelopment. A total of 3829 maternal-infant pairs from a longitudinal birth cohort in Wuhan City, China, were included in the primary analysis. The neurodevelopment of the children was assessed by the Bayley Scales of Infant Development (BSID), the Conners Comprehensive Behaviour Rating Scale and the Chinese version of the Autism Behavior Checklist. Data on delivery mode and medical conditions were collected via medical records from the study hospital. Among the 3829 children for whom the BSID test was completed at two years of age, 50%, 27%, and 23% were delivered vaginally, by necessary CD, and by elective CD, respectively. Compared with vaginally delivered children, Necessary CD was associated with a 16.67% decrease in Mental Development Index (MDI) scores and a 13.37% decrease in Psychomotor Development Index (PDI) scores, while elective CD showed a 20.63% and 20.99% decrease after FDR correction, respectively. Similarly, among the 2448 children for whom the CBRS was completed, necessary CD was found to be associated with conduct disorders (adjusted β: 0.06; 95% CI: 0.02, 0.09), hyperactivity (adjusted β: 0.06; 95% CI: 0.02, 0.11), and hyperactivity index (adjusted β: 0.07; 95% CI: 0.03, 0.11), while elective CD was significantly associated with hyperactivity problem scores (adjusted β: 0.08, 95% CI: 0.03, 0.13). However, no significant association was found between CD and symptoms of autism in children, as assessed by the Autism Behavior Checklist (ABC).</p><p><strong>Conclusion: </strong>This study suggested that the adverse impact of CD on child neurodevelopment stems from the procedure itself rather than CD-related medical conditions. It is important to minimize the use of CD when there is no medical necessity.</p><p><strong>What is known: </strong>• Caesarean delivery (CD) may influence child neurodevelopment and other long-term outcomes. • In China, approximately one-quarter of CD are performed due to maternal request without medical indications.</p><p><strong>What is new: </strong>• The negative impact of CD on the neurodevelopmental outcomes of children may be primarily attributed to the procedure itself, as opposed to related medical conditions. • In the absence of medical indications, unnecessary CD may have adverse impacts on children's neurodevelopment.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4867-4875"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-08-23DOI: 10.1007/s00431-024-05734-w
Neiva Leite, Maiara Cristina Tadiotto, Francisco Jose de Menezes-Junior, Tatiana A Affornali Tozo, Patricia Ribeiro Paes Corazza, Frederico Bento de Moraes-Junior, Maria de Fátima Aguiar Lopes, Juliana Pizzi, Kátia Sheylla Malta Purim, Manuel J Coelho-E-Silva, Beatriz de Oliveira Pereira, Jorge Mota
Strategies for controlling hypertension include reducing excess fat and increasing muscle mass. However, the effects of exercise interventions on hypertension in adolescents have been little investigated. The purpose was to evaluate the effect of 12 weeks of aerobic exercise on systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the cardiometabolic profile of overweight hypertensive and non-hypertensive boys. The sample included 107 boys diagnosed as overweight, aged between 12 and 17, divided into two non-hypertension groups, one control (GCN, n = 14) and one with exercise (GEN, n = 55), as well as two groups of hypertensives, one control (GCH, n = 12) and one with exercise (GEH, n = 26). The boys were assessed at the study baseline and after 12 weeks in terms of anthropometric parameters, biological maturation, SBP, DBP and mean blood pressure (MBP), lipid, and metabolic profile. The aerobic training programs lasted 12 weeks and were carried out in three weekly sessions at different intensities. The high-intensity interval training session lasted around 35 min at an intensity of 80-100% of the reserve heart rate, and the moderate-intensity of continuous training session lasted 60 min at an intensity of 35-75% of the reserve heart rate. Caloric expenditure was equivalent between the exercises (p = 0.388). CGN and CGH participated only in school physical activities. Repeated measures analysis of variance and clinical effect analysis using Cohen's effect size were used, with a significance level established at p < 0.05. After 12 weeks, all groups increased their height (p < 0.05), but only the exercise groups showed a reduction in anthropometric variables (p < 0.05), with a possibly beneficial effect in GEN (d = - 0.203; p = 0.003). No differences were found in the variables for the GCN. The GCH and GEH groups reduced SBP (p < 0.05), but only GEH showed a reduction in DBP (p = 0.005) and MBP (p = 0.001). In relation to the lipid profile, GEH maintained HDL-c close to baseline values, while GCH showed a reduction in HDL-c (p = 0.021). Regarding the clinical effect of exercise on hypertension, GEH showed a large and very beneficial effect size on DBP (d = - 0.916; p = 0.006) and MBP (d = - 0.926; p = 0.005).Conclusion: Hypertensive boys who practiced physical exercise showed greater effects in reducing blood pressure, indicating the importance of non-drug therapeutic management in overweight adolescents.Trial registration:Brazilian Registry of Clinical Trials RBR-4v6h7b / RBR-6343y7.
{"title":"Reduction in blood pressure and metabolic profile in overweight hypertensive boys participating in a 12-week aerobic exercise program.","authors":"Neiva Leite, Maiara Cristina Tadiotto, Francisco Jose de Menezes-Junior, Tatiana A Affornali Tozo, Patricia Ribeiro Paes Corazza, Frederico Bento de Moraes-Junior, Maria de Fátima Aguiar Lopes, Juliana Pizzi, Kátia Sheylla Malta Purim, Manuel J Coelho-E-Silva, Beatriz de Oliveira Pereira, Jorge Mota","doi":"10.1007/s00431-024-05734-w","DOIUrl":"10.1007/s00431-024-05734-w","url":null,"abstract":"<p><p>Strategies for controlling hypertension include reducing excess fat and increasing muscle mass. However, the effects of exercise interventions on hypertension in adolescents have been little investigated. The purpose was to evaluate the effect of 12 weeks of aerobic exercise on systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the cardiometabolic profile of overweight hypertensive and non-hypertensive boys. The sample included 107 boys diagnosed as overweight, aged between 12 and 17, divided into two non-hypertension groups, one control (GCN, n = 14) and one with exercise (GEN, n = 55), as well as two groups of hypertensives, one control (GCH, n = 12) and one with exercise (GEH, n = 26). The boys were assessed at the study baseline and after 12 weeks in terms of anthropometric parameters, biological maturation, SBP, DBP and mean blood pressure (MBP), lipid, and metabolic profile. The aerobic training programs lasted 12 weeks and were carried out in three weekly sessions at different intensities. The high-intensity interval training session lasted around 35 min at an intensity of 80-100% of the reserve heart rate, and the moderate-intensity of continuous training session lasted 60 min at an intensity of 35-75% of the reserve heart rate. Caloric expenditure was equivalent between the exercises (p = 0.388). CGN and CGH participated only in school physical activities. Repeated measures analysis of variance and clinical effect analysis using Cohen's effect size were used, with a significance level established at p < 0.05. After 12 weeks, all groups increased their height (p < 0.05), but only the exercise groups showed a reduction in anthropometric variables (p < 0.05), with a possibly beneficial effect in GEN (d = - 0.203; p = 0.003). No differences were found in the variables for the GCN. The GCH and GEH groups reduced SBP (p < 0.05), but only GEH showed a reduction in DBP (p = 0.005) and MBP (p = 0.001). In relation to the lipid profile, GEH maintained HDL-c close to baseline values, while GCH showed a reduction in HDL-c (p = 0.021). Regarding the clinical effect of exercise on hypertension, GEH showed a large and very beneficial effect size on DBP (d = - 0.916; p = 0.006) and MBP (d = - 0.926; p = 0.005).Conclusion: Hypertensive boys who practiced physical exercise showed greater effects in reducing blood pressure, indicating the importance of non-drug therapeutic management in overweight adolescents.Trial registration:Brazilian Registry of Clinical Trials RBR-4v6h7b / RBR-6343y7.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4659-4670"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-08-27DOI: 10.1007/s00431-024-05721-1
Tal Ben-Ami, Anna Trotskovsky, Chani Topf-Olivestone, Michal Kori
Iron deficiency (ID) without anemia is common in children with newly diagnosed celiac disease (CD). We aimed to assess the effect of iron supplementation versus no treatment on ferritin levels in newly diagnosed CD patients with ID adhering to a gluten-free diet (GFD). A retrospective review of children < 18 years, with low ferritin (≤ 10 ng/mL) and normal hemoglobin levels diagnosed between 12.2018 and 12.2021. We compared hemoglobin and ferritin levels between patients who received supplemental iron to those who did not. Data, including demographics, laboratory tests, and anthropometrics, were collected at baseline, and at 6 and 12 months following the initiation of the GFD. Adherence to GFD was assessed at each visit. Among 304 children diagnosed during the study period, 43 (14.1%) had iron deficiency anemia and 60 (19.7%) ID without anemia. Among children with ID, 29 (48%) were female, mean age 7.3 ± 3.9 years. Twenty-nine (48%) children received iron supplementation, and 31 (52%) did not. At the 12-month follow-up visit, tissue transglutaminase levels decreased significantly (p < 0.001), from a mean baseline level of 226.6 ± 47.8 to 34.5 ± 46 U/mL in children that received iron supplementation and from 234.2 ± 52.4 to 74.5 ± 88.7 U/mL in non-treated children, with no significant difference between the groups p = 0.22. Ferritin levels increased significantly (p < 0.001), from 9.0 ± 4.7 to 25.2 ± 20.8 ng/mL in patients who received supplementation and from 8.9 ± 3.8 to18.6 ± 9.5 ng/mL in patients who did not, with no significant difference between the groups (p = 0.46).
Conclusion: Most children with newly diagnosed celiac disease and iron deficiency, who adhere to GFD, will normalize ferritin levels within 12 months without the need of iron supplementation.
What is known: • Iron deficiency and iron deficiency anemia are common in newly diagnosed celiac disease. • Improved iron absorption may follow mucosal healing process in patients adhering to a strict gluten-free diet.
What is new: • This single-center, retrospective cohort study evaluated the effect of iron supplementation versus no treatment on ferritin levels in children with newly diagnosed celiac disease with iron deficiency adhering to a gluten-free diet. • Most children with newly diagnosed celiac disease and iron deficiency, who adhere to gluten-free diet, will normalize ferritin levels within 12 months without the need of iron supplementation.
{"title":"Iron deficiency without anemia in children with newly diagnosed celiac disease: 1-year follow-up of ferritin levels, with and without iron supplementation.","authors":"Tal Ben-Ami, Anna Trotskovsky, Chani Topf-Olivestone, Michal Kori","doi":"10.1007/s00431-024-05721-1","DOIUrl":"10.1007/s00431-024-05721-1","url":null,"abstract":"<p><p>Iron deficiency (ID) without anemia is common in children with newly diagnosed celiac disease (CD). We aimed to assess the effect of iron supplementation versus no treatment on ferritin levels in newly diagnosed CD patients with ID adhering to a gluten-free diet (GFD). A retrospective review of children < 18 years, with low ferritin (≤ 10 ng/mL) and normal hemoglobin levels diagnosed between 12.2018 and 12.2021. We compared hemoglobin and ferritin levels between patients who received supplemental iron to those who did not. Data, including demographics, laboratory tests, and anthropometrics, were collected at baseline, and at 6 and 12 months following the initiation of the GFD. Adherence to GFD was assessed at each visit. Among 304 children diagnosed during the study period, 43 (14.1%) had iron deficiency anemia and 60 (19.7%) ID without anemia. Among children with ID, 29 (48%) were female, mean age 7.3 ± 3.9 years. Twenty-nine (48%) children received iron supplementation, and 31 (52%) did not. At the 12-month follow-up visit, tissue transglutaminase levels decreased significantly (p < 0.001), from a mean baseline level of 226.6 ± 47.8 to 34.5 ± 46 U/mL in children that received iron supplementation and from 234.2 ± 52.4 to 74.5 ± 88.7 U/mL in non-treated children, with no significant difference between the groups p = 0.22. Ferritin levels increased significantly (p < 0.001), from 9.0 ± 4.7 to 25.2 ± 20.8 ng/mL in patients who received supplementation and from 8.9 ± 3.8 to18.6 ± 9.5 ng/mL in patients who did not, with no significant difference between the groups (p = 0.46).</p><p><strong>Conclusion: </strong>Most children with newly diagnosed celiac disease and iron deficiency, who adhere to GFD, will normalize ferritin levels within 12 months without the need of iron supplementation.</p><p><strong>What is known: </strong>• Iron deficiency and iron deficiency anemia are common in newly diagnosed celiac disease. • Improved iron absorption may follow mucosal healing process in patients adhering to a strict gluten-free diet.</p><p><strong>What is new: </strong>• This single-center, retrospective cohort study evaluated the effect of iron supplementation versus no treatment on ferritin levels in children with newly diagnosed celiac disease with iron deficiency adhering to a gluten-free diet. • Most children with newly diagnosed celiac disease and iron deficiency, who adhere to gluten-free diet, will normalize ferritin levels within 12 months without the need of iron supplementation.</p>","PeriodicalId":11997,"journal":{"name":"European Journal of Pediatrics","volume":" ","pages":"4705-4710"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}