Frontiers in Pediatrics

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ISSN / EISSN : 2296-2360 / 2296-2360
Published by: Frontiers Media SA (10.3389)
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Bjarne Vandervoort, Django De Beuckeleer, Elke Huenaerts, Marianne Schulte, François Vermeulen, Marijke Proesmans, Thierry Troosters, Myriam Vreys,
Published: 23 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.858410

Abstract:
Airway clearance therapy (ACT) is one of the cornerstone treatment modalities to improve mucociliary clearance for patients with bronchiectasis. The progression of lung disease in patients with bronchiectasis can be evaluated by spirometry and multiple breath washout (MBW) and it is advised to monitor these on a regular basis. However, the short term effect of ACT on spirometry and MBW parameters is insufficiently clear and this variability may impact standardization. For cystic fibrosis (CF), available literature refutes a short time effect on spirometry and MBW parameters in children, however, for primary ciliary dyskinesia (PCD) no data are available. We performed a single-center, prospective cross-over study to evaluate the short term effect of a single ACT session using positive expiratory pressure mask on forced expiratory volume in 1 s (FEV1) and lung clearance index (LCI), derived from MBW, compared to no ACT (control) in pediatric patients with CF and PCD. A total of 31 children were included: 14 with PCD and 17 with CF. For the whole group, there was no difference in median change of FEV1 pp between the treatment and the control group (p 0.969), nor in median change of LCI (p 0.294). For the CF subgroup, the mean change in FEV1 pp with ACT was −1.4% (range −9 to + 5) versus −0.2% (range −6 to + 5) for no ACT (p 0.271), the mean change in LCI with ACT was + 0.10 (range −0.7 to + 1.2) versus + 0.17 (range −0.5 to + 2.8) for no ACT (p 0.814). In the PCD subgroup, the mean change in FEV1 pp with ACT was + 1.0 (range −7 to + 8) versus −0.3 (range −6 to + 5) for no ACT (p 0.293) and the mean change in LCI with ACT was −0.46 (range −3.7 to + 0.9) versus −0.11 (range −1.4 to + 1.3) for no ACT (p 0.178). There was no difference between PCD and CF for change in FEV1 pp after ACT (p = 0.208), nor for LCI (p = 0.095). In this small group of pediatric patients, no significant short-term effect of chest physiotherapy on FEV1 pp nor LCI in PCD and CF values nor variability was documented.
Jun Lin, Chujun Wu, Dizhou Zhao, Xuhang Du, Wangzhi Zhang, Jieyu Fang
Published: 20 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.865107

Abstract:
Background: Children that need surgery and medical examinations are often uncooperative, and preoperative sedation is necessary. We aimed to assess the safety and efficacy of inhaled nebulized dexmedetomidine in children for sedation that underwent medical examinations or surgery.Methods: We systematically searched PubMed, Web of science, Embase, and Cochrane library, for randomized controlled trials of Intranasal dexmedetomidine using a spray or a mucosal atomization device in children undergoing examination or elective surgery. We included all studies that analyzed the sedation efficiency of intranasal dexmedetomidine in children.Results: Ten studies with 1,233pediatric patients were included. Compared to other sedation treatments, inhaled nebulized dexmedetomidine showed similar sedation satisfaction [risk ratio RR: 1.02; 95% confidence interval (CI): 0.87–1.18; P = 0.83; I2 = 72%]. there was also no statistical difference in the success rate of separation from parents (RR: 0.96; 95% CI: 0.82–1.12; P = 0.58; I2 = 67%), and mask acceptability (RR: 1; 95% CI: 0.83–1.20; P = 0.99; I2 = 35%). But it is worth mentioning that nebulized dexmedetomidine combined with ketamine provided better sedation satisfaction (RR: 0.69; 95% CI: 0.49–0.96; I2 = 49%) and more satisfactory separation from parents (RR: 0.85; 95% CI: 0.74–0.97; I2 = 0%). Moreover, nebulized dexmedetomidine reduced the occurrences of nausea and vomiting (RR: 0.28; 95% CI: 0.15–0.51; P < 0.01; I2 = 10%) and emergence agitation (RR: 0.30; 95% CI: 0.18–0.49; P < 0.01; I2 = 0%). There are no hypotension or arrhythmia reported that required intervention in all articles.Conclusion: Compared to other premedication treatments, inhaled nebulized dexmedetomidine provided equivalent sedation satisfaction for the examination or preoperative sedation of children, but it reduced the occurrences of emergence agitation and postoperative nausea and vomiting.
Enas F. Elngar, Mona A. Azzam, Ayman A. Gobarah, , , Nouran B. AbdAllah
Published: 20 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.779511

Abstract:
Background: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury.Aim: To explore for the first time the association of the C1INH rs4926 (Val480Met) variant and circulatory transcript expression levels in the neonates that had evidence of lung disease and the clinic-laboratory data.Methods: A total of 139 unrelated neonates were enrolled in this case-control study. C1INH genotyping and expression analyses were done using TaqMan Genotyping and Real-Time qPCR, respectively.Results: A/A genotype carriers were two times more likely to develop in newborns with lung disease under homozygote (A/A vs. G/G: OR = 2.66, 95%CI = 1.03-6.87, p = 0.039) and recessive (A/A vs. G/G-A/G: OR = 2.42, 95%CI = 1.07-6.06, p = 0.047) models. Also, a higher frequency of A/A genotype was observed in the patient's cohort complicated with sepsis (44.2 vs. 14.3%, p = 0.002). Neonates with lung disease with A variant had more risk for developing sepsis under homozygote (A/A vs. G/G: OR = 5.19, 95%CI = 1.73-15.6, p = 0.002), dominant (A/G-A/A vs. G/G: OR = 2.39, 95%CI = 1.02-5.58, p = 0.041), and recessive (A/A vs. G/G-A/G: OR = 5.38, 95%CI = 1.86-15.5, p < 0.001) models. Regression analysis revealed rs4926*A/A genotype as an independent predictor risk factor for sepsis development in cohorts with lung disease (adjusted OR = 4.26, 95%CI = 1.38-13.1, p = 0.012). The circulatory transcript was significantly downregulated in neonates with lung disease in whom rs4926*A/A carriers had the least expression levels (median: −2.86, IQR: −3.55 to −1.71; p < 0.001). ROC curve analysis revealed C1INH expression could differentiate between cohorts with/without subsequent development of sepsis, and the discrimination ability was enhanced when combined with circulatory IL-6 and CRP levels (AUC = 0.926, 95%CI = 0.87-0.97).Conclusion: The C1INH rs4926 variant might play an essential role in the susceptibility to neonatal lung disease and could predict sepsis development in this cohort. Furthermore, the circulatory expression levels of this gene were downregulated in the neonatal lung disease cohort, supporting its potential role in the pathophysiology of this disorder, and highlighting its promising role in future targeted therapy.
Silvia Bucci, Luana Coltella, Ludovica Martini, Alessandra Santisi, Domenico Umberto De Rose, Livia Piccioni, Francesca Campi, Maria Paola Ronchetti, Daniela Longo, Giulia Lucignani, et al.
Published: 20 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.881516

Abstract:
Background: Non-polio-enteroviruses (EV) and human parechoviruses (HPeV) are small RNA viruses, which in newborns cause infections with a wide range of severity. Today molecular biology tools allow us to diagnose viral meningitis in neonates, sparing patients from useless antibiotics. Data on neurodevelopmental outcome of children who contract enterovirus meningitis in early childhood are still limited in the literature.Aims: To evaluate the neurodevelopmental outcome of newborns with documented enterovirus and parechovirus meningitis contracted within the first months of life.Methods: Enterovirus and parechovirus were detected on cerebrospinal fluid (CSF) and plasma by RT-PCR. The virological typing was done according to WHO recommendations. During the hospitalization each neonate underwent many diagnostic and instrumental examinations, to evaluate any neurological lesions attributable to the infection. After the discharge children entered in an outpatient interdisciplinary assessment process, comprehensive of the administration of Bayley III scales up to 12 months old.Results: We observed longitudinally 30 children, born at term (mean GA 39.7 ± 0.8 weeks, mean birthweight was 3,457 ± 405 grams), who contracted enterovirus and parechovirus meningitis within the first month of life (mean age at diagnosis was 15.8 ± 7.33 days). We were able to perform the genetic typing only on 15/30 (50.0%) cerebrospinal fluid (CSF) samples from 15 neonates. We found MRI anomalies in 9/26 observed neonates (34.6%): one of them presented brainstem abnormality that are specific of enteroviral central nervous system (CNS) involvement. During the follow up children displayed an overall normal neurodevelopment and no deficit in visual and hearing areas. The mean cognitive (105.19 ± 8.71), speech (100.23 ± 8.22) and motor (97.00 ± 8.98) composite scores, assessed by Bayley III, were normal in 29/30 (96.7%). Despite this, children with pathological brain magnetic resonance imaging (MRI) scored significantly lower (p = 0.01) than children with normal brain MRI on cognitive subscale at 12 months of life.Conclusions: Early enterovirus infections can be associated to brain MRI abnormalities, more frequently the earlier the infection. Although within a normal range, our children with pathological brain MRI scored significantly lower than those with normal brain MRI on cognitive subscale at 12 months of life.
Bassam N. AlBassam, , Saleh A. AlQahtani, Elham Hassan
Published: 20 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.907179

Abstract:
Jejunoileal atresia (JIA) is one of the common etiologies of intestinal obtrusion in neonates. However, cases of concomitant ileal atresia and Hirschsprung disease (HD) rarely occur. We report the case of a male infant who had JIA concomitantly with HD that was re-anastomosed. The patient underwent an exploratory laparotomy to resect the dilated terminal ileum. Subsequently, owing to a significantly dilated proximal bowel, he underwent a second exploratory laparotomy. However, he continued to have feeding intolerance postoperatively. He had colonic aganglionosis and was diagnosed with HD. A third laparotomy was then performed. Additionally, he had recurrent episodes of gram-negative bacteremia, especially candida parapsilosis fungemia, despite receiving antibiotics and antifungal, and there were no identifiable underlying genetic or immunological causes. Finally, the patient had recurrent episodes of hypoglycemia, central hypothyroidism, and multiple organ failure and died at the age of 7 months. The concomitant ileal atresia and HD was thought to be due to a common intrauterine vascular accident, together with loss of bowel, thereby acting as a barrier for the caudal migration of neuromeric cells and leading to colonic aganglionosis. In this case, ileal atresia was associated with colonic aganglionosis, central hypothyroidism, and persistent bacteremia, which is a unique finding. In cases of JIA, persistent poor bowel function after surgical correction of concomitant HD should be considered.
Hui Yan, Bo Zhai, Ruiling Feng, Penggao Wang, Yaodong Zhang, Yiran Wang, Yuwei Hou, Yang Zhou
Published: 19 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.828300

Abstract:
Objective: This study aimed to examine the prevalence and the related risk factors of congenital heart disease (CHD) in children with different birth weights in China and the relationship between the subtypes of CHD and birth weight (BW).Methods: This study conducted a cross-sectional survey on the data collected in the children’s congenital heart disease database (CHDD) established in China. This database contained data from one Grade A, Level III Children’s Public Hospital in Zhengzhou, Henan. The study included all the children and their parents in the database from 2014 to 2020 as the study subjects, and the missing data were processed by means of imputation. Diagnoses of CHD were coded using the International Classification of Diseases version 10 (ICD-10), and subtypes were classified by the codes Q20 to Q26. We reported the prevalence of CHD based on birth weight and gestational age and analyzed the related risk factors for children with CHD in different birth weight groups and factors for children of the same birth weight groups between the CHD groups and the non-CHD groups. The generalized linear model was used to assess the association between the subtypes of CHD and BW by establishing three adjusting models, and the data were stratified for further analysis by urban-rural and infant gender.Results: A total of 42,814 children were identified as having CHD among 5,071,799 live children; the overall prevalence of CHD was 8.44 per 1,000 live births during 2014–2020; and the three subtypes with the highest prevalence of CHD were atrial septal defect (ASD) (2.75‰), ventricular septal defect (VSD) (2.57‰), and patent foramen ovale (PFO) (1.12‰). The prevalence of CHD was 18.87‰ in the group with BW <1,500 g, 12.84‰ in the group with BW 1,500–2,500 g, 8.24‰ in the group with BW 2,500–4,000 g, and 4.80‰ in the group with BW ≥4,000 g. The prevalence of CHD was 16.62‰ in the small for gestational age (SGA) group, 6.99‰ in the appropriate for gestational age (AGA) group, and 6.40‰ in the larger for gestational age (LGA) group. Parental factors such as drinking, smoking, viral infections, peri-pregnancy exposure to radioactive substances, low family monthly expenditure, and low Apgar scores at 1 and 5 min were related to the increased risk of CHD in the offspring. Parental supplementation of folic acid and exercise during the peri-pregnancy period could reduce the risk of CHD in the offspring. The results of Model 3 adjusting for confounding variables showed that infants with ASD had a birth weight 461 g lower (95% CI: −1,085, –128), infants with VSD had a birth weight 426 g lower (95% CI: –932, –120), infants with tetralogy of Fallot (TOF) had a birth weight 532 g lower (95% CI: –987, –168), and without classification, infants with CHD had a birth weight 973 g lower (95% CI: –1,502, –204).Conclusion: In very low birth weight (VLBW) and low birth weight (LBW) infants, CHDs are more prevalent than in the general live-born population. Moreover, some peri-pregnancy factors of parents are closely related to the occurrence of CHD in offspring; different types of heart defects can lead to LBW. Therefore, if the fetus is found to have a heart defect during the prenatal examination, the mother should pay more attention to maintaining weight and ensuring that the fetus is within the normal weight range, thereby increasing the postpartum survival rate, reducing complications, and promoting children’s health.
, Harris P. Baden, Emily R. Berkman, Erica Bourget, Thomas V. Brogan, Jane L. Di Gennaro, Ardith Z. Doorenbos, D. Michael McMullan, Joan S. Roberts, Jessica M. Turnbull, et al.
Published: 19 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.896232

Abstract:
Technological advancements and rapid expansion in the clinical use of extracorporeal life support (ECLS) across all age ranges in the last decade, including during the COVID-19 pandemic, has led to important ethical considerations. As a costly and resource intensive therapy, ECLS is used emergently under high stakes circumstances where there is often prognostic uncertainty and risk for serious complications. To develop a research agenda to further characterize and address these ethical dilemmas, a working group of specialists in ECLS, critical care, cardiothoracic surgery, palliative care, and bioethics convened at a single pediatric academic institution over the course of 18 months. Using an iterative consensus process, research questions were selected based on: (1) frequency, (2) uniqueness to ECLS, (3) urgency, (4) feasibility to study, and (5) potential to improve patient care. Questions were categorized into broad domains of societal decision-making, bedside decision-making, patient and family communication, medical team dynamics, and research design and implementation. A deeper exploration of these ethical dilemmas through formalized research and deliberation may improve equitable access and quality of ECLS-related medical care.
Jiayu Miao, Zhuxiao Ren, Zhicheng Zhong, Fang Xu, Jianlan Wang, Jie Yang
Published: 19 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.903319

Abstract:
Umbilical cord blood from singleton preterm infants was collected during delivery, and the concentration of LL37 was measured. C-reactive protein (CRP), white blood cell count (WBC), platelets (PLT), and mean platelet volume (MPV) were determined within 3 days after birth. The differences in LL37, CRP, WBC, PLT, and MPV levels between the two groups were compared. Pearson correlation method was used to analyze the correlation between these factors. The early individual value of each detected index for early onset sepsis was analyzed by ROC curve. The level of LL37 in umbilical cord blood of sepsis group was significantly higher than those in the control group (383.85 ± 46.71 vs. 252.37 ± 83.30 ng/ml). Meanwhile, the levels of CRP, WBC, and MPV in the sepsis group were significantly higher than those in the control group (CRP:5.73 ± 4.19 vs. 2.50 ± 2.77 mg/L; WBC: 13.47 ± 12.35 vs. 6.83 ± 3.55 × 109/L; MPV: 11.20 ± 1.11 vs. 8.90 ± 0.68 fL), the level of PLT was significantly lower than those in the control group (PLT: 161.00 ± 38.51 vs. 241.50 ± 49.85 × 109/L) (P < 0.05). Pearson correlation analysis showed that the expression of LL37 was negatively correlated with PLT level (r = −0.9347, P < 0.0001), and positively correlated with MPV level (r = 0.9463, P < 0.0001). ROC curve analysis showed that the area under curve of LL37 for diagnosis of early onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.
, Robin T. Saggers, Rossella M. Bandini, Yoliswa Magadla, Aripfani V. Mphaphuli, Daynia E. Ballot
Published: 19 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.902263

Abstract:
Background: Improved survival in extremely low birth weight infants (ELBWI) in Sub-Saharan Africa has raised the question whether these survivors have an increased chance of adverse neurodevelopmental outcomes.Objectives: To describe neurodevelopmental outcomes of ELBWI in a neonatal unit in South Africa.Methods: This was a prospective follow-up study. All ELBWI who survived to discharge between 1 July 2013 and 31 December 2017 were invited to attend the clinic. Bayley Scales of Infant and Toddler Development (version III) were conducted at 9 to 12 months and 18 to 24 months.Results: There were 723 ELBWI admissions during the study period, 292 (40.4%) survived to hospital discharge and 85/292 (29.1%) attended the neonatal follow up clinic. The mean birth weight was 857.7 g (95% CI: 838.2–877.2) and the mean gestational age was 27.5 weeks (95% CI 27.1–27.9). None of the infants had any major complication of prematurity. A total of 76/85 (89.4%) of the infants had a Bayley-III assessment at a mean corrected age of 17.21 months (95% CI: 16.2–18.3). The mean composite scores for cognition were 98.4 (95% CI 95.1–101.7), language 89.9 (95% CI 87.3–92.5) and motor 97.6 (95% CI 94.5–100.6). All mean scores fell within the normal range, The study found 28 (36.8%) infants to be “at risk” for neurodevelopmental delay.Conclusion: Our study demonstrates good neurodevelopmental outcome in a small group of surviving ELBWI, but these results must be interpreted in the context of the high mortality in this group of infants.
Qi-Liang Zhang, Shi-Hao Lin, Wen-Hao Lin, Hua Cao,
Published: 19 May 2022
Frontiers in Pediatrics, Volume 10; https://doi.org/10.3389/fped.2022.888375

Abstract:
Objective: This study is aimed to explore the effect of short-term nutritional support for infants with unrestricted ventricular septal defects on improving preoperative nutritional status and promoting postoperative recovery.Methods: The clinical data of 35 infants with unrestricted ventricular septal defects who were treated with 2 weeks of nutritional support in our hospital from December 2020 to March 2021 were analyzed retrospectively. The clinical data of 38 infants with unrestricted ventricular septal defects who were treated in our hospital from May 2020 to October 2020 were selected as controls.Results: The preoperative body weight, preoperative albumin, preoperative prealbumin, and preoperative hemoglobin in the intervention group were significantly higher than those in the control group (P < 0.05). The postoperative ventilator time, intensive care time, and discharge time in the intervention group were significantly shorter than those in the control group (P < 0.05).Conclusion: Performing 2 weeks of nutritional support for infants with unrestricted ventricular septal defects can improve their preoperative nutritional status and promote postoperative recovery.
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