Impact: Widening ASD burden disparities between high and low socioeconomic regions require targeted workforce development and resource allocation in underserved areas. With ASD disability projected to rise 58.83% by 2030, healthcare systems must expand developmental screening and early intervention services in primary care. Integration of GBD epidemiological data with causal inference techniques enables evidence-based policy development for children's neurodevelopmental health services.
Background: Prenatal metal exposure and genetics may affect birth size, and genetic factors could modify metal toxicity. However, few studies examined gene-metal interactions on birth size.
Methods: We used data from 324 mother-infant pairs in the Taiwan Birth Panel Study. Cord blood levels of 16 metals were measured with inductively coupled plasma mass spectrometry, and we selected 13 SNPs related to birth size, folate and metal metabolism. Birth weight, birth length and head circumference were abstracted from medical records. Multivariable generalized linear regression was applied to assess single metal-birth size associations and interactions, and quantile g-computation and Bayesian kernel machine regression were applied for metal mixture analyses.
Results: Prenatal barium exposure was negatively associated with birth size, whereas prenatal zinc exposure was positively associated with birth size. We observed several metal-SNP interactions on birth size, particularly between cobalt and multiple genetic variants. Genetic variants also modified the effects of metal mixtures on birth size.
Conclusions: Genetic factors may influence the impact of prenatal metal exposure on birth size. Identifying these gene-environment interactions may help guide precision strategies to reduce metal-related risks in early life.
Impact: Elevated prenatal Ba and Zn levels were associated with birth size in opposite directions. Genetic variants in folate and metal metabolism modified prenatal metal effects, with the strongest interactions seen for cobalt and folate-pathway variants. Metal mixture-birth size associations were most pronounced for the rs10830963 genotype and several other variants. Gene-metal interactions can inform precision prenatal risk reduction strategies for metal exposure.
Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory condition with multi-organ involvement, particularly affecting the cardiac and gastrointestinal systems. Although immunomodulatory therapy is standard, treatment approaches vary. This study aimed to evaluate treatment modalities in MIS-C such as methylprednisolone (MP), intravenous immunoglobulin (IVIG), anakinra and therapeutic plasma exchange (TPE) based on clinical severity and laboratory parameters in a prospectively followed cohort.
Methods: A total of 125 MIS-C patients were included in the study and followed for at least 6 months after discharge. Patients were stratified by severity and treated with various immunomodulatory regimens, including IVIG+MP, IVIG+MP+anakinra, and IVIG+MP+anakinra+TPE.
Results: Patients with mild disease and low inflammatory markers (median CRP 9 mg/dL, ferritin 192 µg/dL) received IVIG+MP. Those with higher inflammation (CRP 20-24 mg/dL, ferritin 308-846 µg/dL) without cardio-pulmonary support were treated with IVIG+low-dose-MP+anakinra. Patients with shock, macrophage activation syndrome, or bicytopenia received IVIG+high-dose-MP+anakinra. TPE was added in cases requiring cardio-pulmonary support. Most were discharged without corticosteroids or anakinra; only 11% received a short outpatient prednisolone taper.
Conclusion: The mid-term longitudinal assessment of MIS-C patients suggests that timely immunomodulatory therapies, guided by laboratory parameters, promote safe resolution of systemic inflammation and cardiac complications, and shorten treatment duration.
Impact: Demonstrates that short-term, biomarker-guided use of anakinra and corticosteroids effectively controls hyperinflammation in MIS-C. Highlights that prolonged corticosteroid therapy may not be necessary, even in severe cases. Provides evidence of early cardiac recovery, including resolution of CAAs, without post-discharge steroids. Supports a steroid-sparing treatment approach, reducing risks of long-term immunosuppression. May inform future MIS-C treatment guidelines by minimizing the need for escalation therapy, ECMO, and related complications.
Background: A growing body of evidence highlights the link between gut microbiome imbalances and constipation. However, the role of gut microbiota and its metabolic interactions in pediatric functional constipation (FC) remains incompletely understood.
Methods: We recruited a total of 40 children with FC and 40 healthy children (CONT). 16SrRNA and metagenomic sequencing were used to evaluate the changes in the gut microbiota structure and gene function in FC patients. Differences in serum metabolite levels were analyzed via targeted metabolomic sequencing.
Results: The FC group exhibited a decrease in gut microbiota diversity, an increase in Bacteroides and Prevotella abundances, depletion of genera such as Lactobacillus and Bifidobacterium and an imbalance of related metabolic activities. Metabolomic analysis revealed that the levels of several metabolites, including taurine and glycochenodeoxycholic acid, which are involved in bile acid (BA) metabolic pathways, differed between the FC and CONT groups. Differences in metabolite levels were associated with changes in the abundances of specific bacteria and with intestinal dysfunction in FC patients.
Conclusion: FC in children is associated with distinct gut microbiota alterations and dysregulated BA metabolism. These findings provide potential therapeutic targets for modulating the gut microbiome and metabolic pathways in FC management.
Impact: This study offers a comprehensive perspective on the intricate relationship between microbial composition and metabolic pathways in the context of functional constipation in children. This study focuses on children, highlighting how disruptions in bile acid metabolism due to gut microbiota disorders are linked to the occurrence of functional constipation. These findings suggest that disturbances in bile acid metabolism may play a role in the mechanisms underlying functional constipation by impairing intestinal secretion and transport functions. This study offers a new way to study the effects of the gut microbiota, bile acid metabolism, and the gut‒brain axis.
Background: Neonatal encephalopathy (NE) is a leading cause of neonatal mortality and disability. The study aims to analyze the condition's global burden and temporal trends.
Methods: Data were extracted from the Global Burden of Disease (GBD) 2021 database, mainly on the cases and rate of prevalence, disability-adjusted life years (DALYs), and deaths of NE from 1991 to 2021. We analyzed prevalence, DALYs, and mortality at different levels. Trends were quantified using percentage change and estimated annual percentage change (EAPC).
Results: Globally, the prevalence of NE has increased from 1991 to 2021, while DALYs and deaths rates decreased. Low Socio-Demographic Index (SDI) regions had the highest prevalence cases in 2021 (15432, 95%UI: 12884-18173). The largest increase of prevalence occurred in South Asia over 31 years, with an EAPC of 2.11 (95%CI: 1.99-2.22). Ethiopia exhibited the largest increase in prevalent cases and rates, with a percentage of 248.51% and an EAPC of 3.56 (95%CI: 3.33-10.92). The burden of NE was consistently higher in males than in females.
Conclusion: Despite global improvements in DALYs and mortality, the increasing prevalence of NE in certain regions highlights the need for targeted public health strategies, particularly in low SDI regions.
Impact statement: We estimated the temporal trends of prevalence, disability-adjusted life years (DALYs), and death following neonatal encephalopathy (NE). The results demonstrated that NE increased, while DALYs and death decreased globally from 1991 to 2021. The prevalence, DALYs, and death rates for NE exhibited a negative correlation with the Socio-Demographic Index (SDI), suggesting a progressive reduction in disease burden as regional socioeconomic conditions improve. Targeted public health strategies are required to implemented in different SDI regions, improving the burden of NE.
Monitoring lung gas volumes of ventilated infants is important. Gas in Scattering Media Absorption Spectroscopy (GASMAS) can estimate gas volume inside tissues by measuring oxygen absorption. We hypothesized that GASMAS can detect different tidal volumes (TV) delivered to mechanically ventilated lungs in a neonatal mannequin model breath-by-breath.
Methods: A neonatal mannequin was ventilated with a set range of TVs (2-6 ml), different inspired fractional oxygen (FiO2) (0.21 and 1.00), and respiratory rate settings (10-60 breaths per minute), and GASMAS measurements were acquired.
Results: For both FiO2 levels, the mean O2 projected concentration (PC) was significantly higher during inspiration compared to expiration for all TV values (p < 0.05). However, the difference in mean O2 PC between the inspiration and expiration phases depended on the TV (p < 0.001 for phase*TV interaction). The differences between the inspiration and expiration phases increased progressively with rising TV values. The oxygen absorption difference between inspiration and expiration differed by respiratory rate (p < 0.001).
Conclusion: GASMAS detects the difference between inspiration, expiration, and tidal volume gas changes, suggesting a potential clinical application of GASMAS for respiratory monitoring of ventilated neonates.
Impact: What is the key message of your article? An experimental study demonstrating the feasibility of the GASMAS technique for detecting changes in lung gas volume. What does it add to the existing literature? GASMAS detects the difference between inspiratory and expiratory breath phases, various tidal volumes, oxygen concentration, and respiratory rate. What is the impact? This suggests a potential clinical application of GASMAS for respiratory monitoring of neonates.
Background: We aimed to evaluate the effects of a probiotic preparation containing Lacticaseibacillus rhamnosus MP108 on the improvement of clinical symptoms and gut microbiota in children with Functional Constipation (FC).
Methods: This 4-week randomized, double-blind, placebo-controlled trial assigned 6 to 36-month-old children with FC to supplementation with Lacticaseibacillus rhamnosus MP108 (intervention group, n = 77) or maltodextrin supplementation (control group, n = 77). An electronic questionnaire was used to obtain the defecation status, and 16S rRNA sequencing technology was used to extract the characteristics of gut microbiota. The primary outcomes were treatment success rate (defined as average of ≥3 spontaneous stools movements per week), weekly defecation frequency, and stool hardness. The secondary outcomes included constipation-related symptoms and changes in the gut microbiota. The analysis was performed on an intention-to-treat basis.
Results: After the intervention, the treatment success rate in the intervention group was significantly higher than that in the control group (83.1% vs. 63.6%, P = 0.006). The intervention group demonstrated significantly higher weekly defecation frequency (4.99 ± 2.88 vs. 3.71 ± 2.86, P = 0.002) and Bristol Stool Form Scale (BSFS) scores (3.75 ± 1.04 vs. 2.99 ± 1.17, P = 0.002) compared to the control group. There were significant differences in the gut microbiota, and the intervention group had a higher diversity of gut microbiota Alpha (P = 0.047) and a higher relative abundance of Lacticaseibacillus, Bifidobacteriaceae, Parabacteroides_B_862066; while Erysipelatoclostridium and Eggerthella had lower relative abundance.
Conclusion: Lacticaseibacillus rhamnosus MP108 can effectively improve some constipation symptoms and gut microbiota structure in children with FC.
Impact: This is the first study to evaluate the effects of Lacticaseibacillus rhamnosus MP108 on Functional Constipation (FC) in children under 3 years old. The study shows that probiotics containing Lacticaseibacillus rhamnosus MP108 can improve some clinical symptoms and gut microbiota structure in children with FC. The positive results of Lacticaseibacillus rhamnosus MP108 intervention provide new insights for the treatment of FC in children.
Background: Antibiotic exposure in neonatal intensive care units (NICU) is high. This study describes antibiotic use in very preterm infants and examines the association between duration of exposure and outcomes in blood culture negative (CN) infants.
Methods: Infants <32 weeks' gestation admitted between January 2012 and June 2022 were included in this retrospective cohort study. Data were extracted from electronic databases. Antibiotic exposure was calculated as duration of treatment (DOT) and antibiotic utilisation rate (AUR) and compared with neonatal outcomes including mortality, late onset sepsis (LOS), necrotising enterocolitis (NEC), chronic lung disease (CLD), severe retinopathy of prematurity (ROP) and/or severe brain injury.
Results: There were 3235 CN infants included in the study; 1601 (49.5%) received antibiotics for ≤ 2 days of which 266 (8.2%) received no antibiotics; 841 (26.0%) received antibiotics for ≥ 5 days. DOT decreased from 78.0 to 61.9 per 1000 and AUR from 0.07 (IQR 0.04-0.11) to 0.05 (IQR 0.03-0.10) from 2012 to 2022. Higher AUR and/or prolonged antibiotic exposure was associated with increased mortality, brain injury, NEC, ROP, LOS, and CLD.
Conclusion: Antibiotics are critical for infants with sepsis but can cause harm in those without. Strategies to reduce antibiotic exposure are needed to improve preterm infant outcomes.
Impact: Prolonged antibiotic exposure is common in culture-negative, very preterm infants. Although antibiotics are critical for infants with culture-positive sepsis, they can cause harm in those who are culture-negative. This study adds to the small pool of evidence examining antibiotic use and its association with increased morbidity and mortality in very preterm infants. The study findings will impact antibiotic prescribing practices significantly and result in strategies to reduce antibiotic exposure in these at-risk infants.
Background: To assess whether administering hydrocortisone in the perinatal period is associated with subsequent adverse cardiovascular outcomes.
Methods: The children/adolescents enrolled in the PREMILOC trial underwent resting blood pressure (BP) measurement, tonometry evaluation (pulse wave velocity (PWV), aortic systolic BP), continuous BP and ECG measurements (supine and standing), and ambulatory BP monitoring. Heart rate variability (HRV) indices, baroreflex sensitivity (BRS), and orthostatic systolic BP (SBP) response were calculated.
Results: Fifty-two subjects (median [25th; 75th percentile] birth weight: 892 g [750; 982]; gestational age: 26+3 [25+1; 27+4]; age at assessment: 11.7 years [10.5; 12.7]; z-score of body mass index: 0.23 [-0.65; 1.27]; 27 girls) who received hydrocortisone (n = 28) or placebo (n = 24) were enrolled. The PWV was not different (hydrocortisone: 4.84 m/s [4.40; 5.48] vs. placebo: 5.00 m/s [4.48; 5.34], p = 0.969), and similar results were observed for HRV and BP measurements. Overweight/obese children (n = 17) vs. other children (n = 35) were characterized by higher office SBP, lower supine descending BRS, and higher orthostatic SBP response.
Conclusion: Early hydrocortisone administration after extremely preterm birth in a randomized trial is not associated with detrimental cardiovascular indices in children/adolescents, while overweight/obesity is already associated with cardiovascular morbidity. The study has been registered, ClinicalTrials.gov ID NCT05451264: https://clinicaltrials.gov/study/NCT05451264?cond=NCT05451264&rank=1 .
Impact: A meta-analysis on the effects of early postnatal administration of corticosteroids concluded that the hypertensive risk was increased in infants, but that long-term studies should be carried out. We show that early hydrocortisone administration after extremely preterm birth in a randomized trial is not associated with detrimental cardiovascular indices in children/adolescents, at least in one center of the trial Thus, our study suggests that early markers of the risk of hypertension are not altered by hydrocortisone.
Background: Preterm birth increases the risk of neurodevelopmental impairments, emphasizing the need for early interventions. This study aimed to assess the feasibility and effectiveness of a General Movement (GM)-based intervention on infant neurodevelopment and parental mental health.
Method: In a prospective, randomized-controlled trial, very preterm infants (gestational age <32 weeks or birth weight <1500 g) were enrolled between October 1, 2021, and June 6, 2023. Infants received a three times daily GM-based treatment by trained parents over 10 weeks starting at 34 weeks PMA or standard care. Primary outcome was neurodevelopment until 2 years' corrected age, secondary outcomes included parental mental health and serum levels of brain damage biomarkers.
Results: Sixty-six infants were randomized (32 control, 34 intervention). The median birth weight was 1243 g (IQR, 919-1623 g) in the control group and 1035 g (IQR, 853-1230 g) in the GM group. No significant group differences were observed for neurodevelopment outcome and parental mental health. Interestingly, all three infants displaying poor neuromotor features in the intervention group before treatment showed good neurodevelopment in the follow-up.
Conclusion: Our findings suggest a potential role of GM-based intervention in high-risk preterm infants. Future research should focus on improved participant selection and adherence.
Impact: A General Movement (GM)-based early intervention starting at 34 weeks PMA, led by parents with telehealth support over 10 weeks from pediatric physiotherapists, was both feasible and well-received. Infant neurodevelopment until 2 years' corrected age and parental mental health were similar in both the intervention and control groups. The approach may be especially helpful for preterm infants who show early signs of neurodevelopmental challenges. As one of the first studies of its kind, this RCT adds valuable knowledge about GM-based therapy for very preterm infants. The results support the importance of personalized early interventions to meet the unique needs of each infant.
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