Introduction: Intraventricular Hemorrhage (IVH) is a devastating condition mostly in preterm infants at < 30 weeks GA with large morbidities and mortality usually in the first 72 hours after birth. Prevention seems to be the only way to completely deal with this problem. The IVH prevention in this age group has been studied and includes some strategies such as prenatal corticosteroids, cesarean delivery, careful extraction among others, but still, it has an unacceptably high incidence in this population. A protocol with the name Drive to Zero IVH Prevention Project that was presented in one of EpicLatino conferences some years ago. As with any quality improvement in practices, we adapted this project to our unit. Objective: To compare the IVH incidence in our unit after the protocol implementation with and historic cohort from the same unit and with all other units un the epilactino network. Material and method: In October 2017 we begun to implement a neuro protection protocol. For this analysis we include every patient born <30 weeks of GA, inborn or outborn but less than 2 days old, that survived at least three days and had a neuroimaging preformed. We include cases until July 2022, and we use the EpicLatino, a Latin-American database, from 2018 to 2020 excluding our own unit for comparison as well as an historical cohort from our unit from 2010-2017. The protocol consists of: Minimal manipulation, low volume ventilation, one routine fiscal exam a day, neutral head position, one blood pressure measured per shift, no keel stick measurements, continuous dim light and low noise level, minimal touch, no vasoactive therapy except in extreme cases, temperature and humidity at 80%, catheters, when possible, fluid restriction followed with diuresis, no PDA therapy or Echo if possible and routine therapy with hydrocortisone, erythropoietin, caffeine, parenteral nutrition, and trophic feeding. e performed a univariate analysis for IVH and groups and a logistic regression model with variables that had statistical significance in the univariate analysis. Results: The study group included 64 cases, the historic cohort 123 and the EpicLatino 1029. Demographic characteristics were similar with few statistically significant differences. We found four grade 1-2 and six grade 3-4 IVH in the study group (some caused by very traumatic delivery with multiples hematomas in head, body, and extremities), all significantly lower that the other two groups. The logistic regression model confirmed the independent statistically significant result in the study group. Conclusion: The hemorrhage during delivery must be prevented by the obstetric team. Afterwards, a set of interventions like very gentle handling with minimal manipulation and unnecessary strict lab managing seams to decrease the incidence of IVH.

Breastmilk is the only recommended source of nutrition for infants below six-months of age. However, a significant proportion of children are either on supplemental breastfeeding(SBF) or weaned due to the early introduction of solid/semi-solid/soft food and liquids(SSF) before 6 months of age. There is good evidence that Exclusive Breastfeeding(EBF) in infants below six-months of age protects them from preventable illnesses, including malnutrition. The relationship between infant feeding practices and coexisting forms of malnutrition(CFM) has not yet been explored. This study examined the association of different feeding indicators(continuation of breastfeeding, predominant feeding, and SSF) and feeding practices(EBF, SBF, and complete weaning) with CFM in infants aged below six-months of age in Pakistan. National and regional datasets of Pakistan from the last ten years were retrieved from the Demographic Health Surveys(DHS) and UNICEF data repositories. In Pakistan, 34.5%(n=6131) of infants have some form of malnutrition. Among malnourished infants, 44.7%(~15.4% of the total sample) had a CFM. Continuation of breastfeeding was observed in more than 85% of infants, but less than a quarter were on EBF, and the rest were either SBF(65.4%) or weaned infants(13.7%). Compared to EBF, complete weaning increased the odds of coexistence of underweight with wasting and underweight with both wasting and stunting by 1.96(1.12-3.47) and 2.25(1.16-4.36), respectively. Overall, breastfed children had lower odds of various forms of CFM (compared to non-breastfed), except for the coexistence of stunting with overweight/obesity. Continuation of any breastfeeding protects infants in Pakistan from various types of CFM during the first six months of life.

Introduction: Some of the practices in medicine are carried out of habit without proven benefits. This is the case of premature babies from 30 to 34 weeks of gestation who are always given parenteral fluids, even though this practice has been associated with an increase incidence of infection. At the end of 2017, we started a protocol of rationalization in the use of parenteral fluid. To administer nutrition/fluids, we used oral fluids by suction if this was possible or otherwise by oral/nasogastric tube at volumes of 70-80 mL/Kg/day divided every 3 hours, with 5 mL increments every 12-24 hours until 200 mL/K/day was achieved, always using breast milk when possible. Material and methods: The present study sought to compare results before and after this new policy. For this work, we review all premature babies between 30-34 weeks of gestation in two time periods, the first from 01/01/2010 to 12/31/2017 and the second from 01/01/2018 to 08/15/2022. The number of cases with and without parenteral fluids (PF), the incidence of infection, the weight at admission and discharge, and the change in the weight Z score between birth and discharge were compared. Both the anthropometric and outcome variables were compared using the different statistical methods according to each variable. Results: were found 920 cases with the described characteristics. The groups before and after the intervention did not show significant differences in their general demographic characteristics. We observed a decrease use of PF in the second period, from 425 cases (82.0%) before to 297 (26.2%) after implementation, p <0.0001 and fewer days of use (4.1 days/average before vs 1.3 after, p <0.0001) of PF. The weight at discharge and the change in weight Z-score were the same in both groups. Infections went from nine cases before to two cases after but it was not statistically significant. There were no complications due to less use of PF. Discussion: This study showed that the use of PF is not associated with significant changes in outcomes of interest, which reinforces that its use does not generate any benefit for the patient. Larger number of cases is required to detect differences in low incidence events such as infections.

Background: This study describes the attitudes and practices of Brazilian adults regarding the mandatory vaccination for COVID-19 and the hesitancy to children´s vaccination. Methods: The participants answered an online questionnaire disseminated on social networks. An adaptation of the SAGE-WG questionnaire was used to measure the children's vaccination hesitancy. Results: Among 1,007 participants, 677 (67.4%) believed that vaccination for COVID-19 among adults should be mandatory. Just over half of the participants (51.5%) believe that parents and guardians should be free to decide whether their children should be vaccinated against COVID-19, and 9.1% were unsure about this. Younger, non-religious people who have higher self-perceptions of risk for COVID-19, and who evaluate the federal government's performance in combating the disease as bad or very bad, have a higher agreement with mandatory vaccination, a lower agreement that parents and guardians should be free to vaccinate their children, and lower child vaccination hesitancy scores. Conclusion: In Brazil, mandatory COVID-19 vaccination for adults is far from a consensus, and an expressive part of the population believes that parents and guardians should be free to choose whether or not to vaccinate their children. These perceptions and vaccine hesitancy for children are associated with religious and political inclinations.

Background: This study aimed to evaluate whether measles vaccine uptake can be predicted directly or indirectly by parental perceptions about the availability of measles vaccine services with parental hesitancy towards the measles vaccine as a potential mediator. Methods: This was a community-based cross-sectional study conducted at Omdurman locality in Khartoum state, Sudan in February 2019. The study population included parents/ guardians having at least one child aged 2 -3 years old. Mediation analysis was conducted using two models, the ordinary least squares path analysis and multiple logistic regression. Results: a total of 495 responded and the mean age of the mothers who participated in the study was 31.1 (SD=5.73). A half of the respondents (50.1%) completed university education and nearly three-quarters of the respondents (74.7%) were housewives. After controlling for the other factors, including the mother’s age and the number of children, parental perception about the accessibility and availability of the measles vaccine influences the uptake of the measles vaccine indirectly through the mediation effect of measles vaccine hesitancy. Conclusions: We suggest that intervening in measles vaccine hesitancy in addition to measles vaccination access issues will have positive impact on the uptake and coverage of the measles vaccine in Sudan.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents was not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German health care system. (2) Methods: From January 24, 2022 to July 31, 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and need for respiratory support were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day were hospitalized on general wards, whereas a median of 0.1 cases (range 0–0.4 cases) were on intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with need for intensive care treatment and respiratory support due to a symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.

Objective: One of the major causes of cerebral ventricular shunt failure is proximal catheter occlusion. We describe a novel ventricular cerebrospinal fluid (CSF) flow replicating system that assesses pressure and flow responses to varied degrees of catheter occlusion. Methods: Ventricular catheter performance was assessed during conditions of partial and complete occlusion. The catheters were placed into a three-dimensionally printed phantom ventricular replicating system. Artificial CSF was pumped through the ventricular system at a constant rate of 1 ml/min to mimic CSF flow, with the proximal end of the catheter in the phantom ventricle. Pressure transducer and flow rate sensors were used to measure intra-phantom pressure, outflow pressure and CSF flow rates. The catheters were also inserted into silicone tubing and pressure was measured in the same manner for comparison with the phantom. Results: Pressure measured in the phantom ventricle did not change when the outflow of the ventricular catheter was partially occluded. However, the intraventricular phantom pressure significantly increased when the outflow catheter was 100% occluded. Flow through the catheter showed no significant difference in rate with any degree of partial occlusion of the catheter. At the distal end of the partially occluded catheters, there was less pressure compared with the nonoccluded catheters. This difference in pressure in partially occluded catheters correlated with the percentage of catheter hole occlusion. Conclusions: Our model mimics physiological dynamics of the CSF flow in partially and completely obstructed ventricular catheters. We found that partial occlusion of the catheter had no effect on CSF flow rate, but did reduce outflow pressure of the catheter.

Background. It is well established that human milk feeding contributes in limiting lung disease among vulnerable neonates. The primary aim of this research was to compare the need for mechanical ventilation of human milk-fed sick neonates with that of formula-fed sick neonates. Methods. All late preterm and full term infants from a single center with findings of sepsis, from 2002 to 2017, were identified. Data regarding infant feeding during hospital admission were recorded. Multivariate logistic regression analyses were performed to assess the impact of the type of milk on ventilation support and main neonatal morbidities. Results. The total number of participants was 322 (human milk group = 260, exclusive formula group = 62). On bivariate analysis, 72% of human milk-fed neonates did not need oxygen therapy nor respiratory support versus 55% of their formula-fed counterparts (P<0.0001). Accordingly, invasive mechanical ventilation was required by 9.2% of human milk-fed infants versus 32% of their formula-fed counterparts (P=0.0085). These results hold true in multivariate analysis, indeed human milk-fed neonates were more likely to require less respiratory support (OR=0.44; 95% CI: 0.22, 0.89) when compared to those who were exclusively formula-fed. Conclusion. Human milk feeding might minimize exposure to mechanical ventilation.

COVID-19 infection in the pediatric population usually leads to a mild illness, however, a rare but serious complication of MIS-C has been seen in children. MIS-C usually presents 2-4 weeks after COVID-19 infection or exposure, and rare reports have been documented in neonates. Vaccinations for COVID-19 have been approved for children 6 months and above in the United States, and recent reports suggest significantly low prevalence and risk of complications of MIS-C in vaccinated children compared to unvaccinated children. Vaccinations for COVID-19 are safe and recommended during pregnancy and prevent severe maternal morbidity and adverse birth outcomes. Evidence from other vaccine-preventable diseases suggests that through passive transplacental antibody transfer, maternal vaccinations are protective against infections in infants during the first 6 months of life. Various studies have demonstrated that maternal COVID-19 vaccination is associated with the presence of anti-spike protein antibodies in infants, persisting even at 6 months of age. Further, completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy is associated with reduced risk for COVID-19–associated hospitalization among infants aged 6 months or less. Therefore, it can be hypothesized that maternal COVID-19 vaccination can reduce the risk of and severity of MIS-C in infants. In this article, we review the literature to support this hypothesis.

There is an increasing need for effective anxiety and pain reduction during medical imaging procedures in children. This is a complex issue, addressed by both non-pharmacological or pharmacological approaches. Dexmedetomidine is a fairly recently marketed, selective α2-adrenergic agonist, and can be administered intranasally. To develop an evidence-guided clinical protocol, we investigated its (side)-effects, preconditions and safety aspects following intranasal dexmedetomidine in children (1 month-5 years) for procedural sedation during medical imaging. To do so, a systematic search (PubMed, Embase, CINAHL (12/2021)) was performed to identify clinical studies on intranasal dexmedetomidine for procedural sedation for medical imaging (Computer Tomography, Magnetic Resonance Imaging). Following screening and quality assessment, 8 studies were retained. Nasal nebulization was considered the best administration method, dosing varied between 2 to 4 µg/kg (age-dependent) 30-45 minutes prior to imaging, and contra-indications or restrictions on oral intake were somewhat consistent across studies. Valid sedation scores were routinely used to assess sedation and the need for rescue dosing, while discharge was generally based on the Aldrete score (score ≥9). Heart rate, blood pressure and saturation were routinely monitored, with commonly observed bradycardia or hypotension (decrease by 20%). Based on these findings, a roadmap for evidence-guided clinical protocol was generated.

Hearing loss in infancy leads to preventable speech, language, and cognitive developmental delay [1, 2]. Sensorineural hearing loss (SNHL) is caused by damages, problems, or issues related to the inner ear such as the cochlea with or without the auditory nerve; cranial nerve VIII, involvement. There are three anatomic areas which include the outer ear: composed of the auricle and external auditory canal and the middle ear: which includes the tympanic membrane, ossicles, and the middle ear space, the inner ear: composed of the cochlea, semi-circular canals, and internal auditory canals. The unique anatomical shape of the auricle catches the incoming sound waves to send them down the external auditory canal. Hearing risk assessment should be part of all health visits while regular hearing screening checks are done for all children from 4 to 21 years [1, 2]. Assessment of hearing loss includes history, physical examination and specific hearing assessment tests.

Objective To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure. Method We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant. Results Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. Conclusion The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologist, and neonatal pediatricians.

To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure.We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant.Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologists and neonatal pediatricians.

Despite concerns about the negative effects of social distancing and prolonged school closures on children’s lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the COVID-19 pandemic on children’s wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns and screen time of school-aged children during the different phases of COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (Grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep dairy recording their daily sleep and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (Sep 2019 – Jan 2020; n=577), during school closures (Mar 2020 – Apr 2020; n=146), and after schools partially reopened (Oct 2020 – Jul 2021; n=227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. Our findings illustrate the impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should reinforce the importance of maintaining a physically active lifestyle, good sleep hygiene, and healthy use of electronic devices to parents and school-aged children during the COVID-19 Pandemic.

Objectives: This study assessed the associations between parent intent to have their child receive COVID-19 vaccination, and demographic factors and various child activities including attendance at in-person education or childcare. Methods: Persons undergoing COVID-19 testing residing in Minnesota and Los Angeles County, California with children aged <12 years completed anonymous internet-based surveys between May 10 and September 6, 2021 to assess factors associated with intention to vaccinate their child. Factors influencing parents’ decision to have their child attend in person school or childcare were examined. Estimated adjusted odds rations (AORs, 95% CI) were computed between parents’ intentions regarding children’s COVID-19 vaccination and participation in school and extra-curricular activities using multinomial logistic regression. Results: Compared to parents intending to vaccinate their children (n=4,686 [77.2%]), those undecided (n=874 [14.4%] or without intention to vaccinate (n=508 [8.4%]) tended to be younger, non-White, less educated and themselves not vaccinated against COVID-19. Their children more commonly participated in sports (aOR:1.51 1.17-1.95) and in-person faith or community activities (aOR:4.71 (3.62-6.11). They further indicated that additional information regarding vaccine safety and effectiveness would influence their decision. COVID-19 mitigation measures were the most common factors influencing parents’ decision to have their child attend in-person class or childcare. Conclusions: Several demographic and socioeconomic factors are associated with parents’ decision whether to vaccinate their <12-year-old children for COVID-19. Child participation in in-person activities was associated with parents’ intentions not to vaccinate. Tailored communications may be useful to inform parents’ decisions regarding safety and effectiveness of vaccination.

Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

Human Adenovirus (HAdV) infection occurs in 14-16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk to develop HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical or HLA mismatched parent) and severe lymphopenia (< 0.2 x 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold on blood (> 102-3 copies/ml) and/or on the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3-5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention applicable both in prevention and therapeutic setting.

Running at odds with the timing imposed by the circadian clock plays an important role in the process that leads to communicable and non communicable diseases. The primary objective of this study was to analyse whether early dinner eater children were at lower risks of acute respiratory infections than late dinner eater children, during the COVID-19 pandemic. Methods: This cross sectional study was conducted from July to December 2020 on children attending Majorcan emergency services. Clinical data collected included timing, symptoms, laboratory tests and imaging studies of current illness. Each diagnosis was validated by general paediatricians. Our survey on dinner time habits was carried out by using self-administered questionnaires. Results: A total of 669 children under age 18 were included in the study. The median of dinner time was 8:30 pm. Late dinner eaters accounted for a higher proportion of acute otitis media than early dinner eaters (7% vs 3%; P=0.028). Other infectious diseases were not associated with dinner time habits. Conclusions: We make a preliminary estimate of the link between late dinner habits and acute otitis media in children. However, no conclusions about causality can be established due to the observational design of the study.

Background: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). Methods: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. Results: Sixty-three patients were male, and the median age was 83 (3–205) months. Fifty-nine patients (%59.6) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or &gt;1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). Conclusions: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.

Gilbert Syndrome, is a benign condition characterized by persistent indirect hyperbilirubinemia due to reduced UDP-glucuronyltransferase enzyme activity. Its coexistence with other clinical disorders has important clinical and pharmacological implications. GS is known to coexist with many hemolytic conditions and may lead to diagnostic difficulty and also increased incidence of gallstones. UGT1A1 gene has been shown to be involved in the conjugation of various physiologically important endogenous and exogenous compounds, so individuals with Gilbert mutation (the variant allele UGT1A1*28) have an increased risk of toxicity of various drugs and endogenous compounds like irinotecan, steroid hormones, implicated in various human carcinoma like colorectal and breast carcinoma. Deferiprone (DFP) is an orally available chelator used in the management of iron overload in patients with Transfusion Dependent Thalassemia (TDT). In this study, fifteen out of 275 patients with TDT, had a deferiprone-induced joint deformity. Among these fifteen patients with joint deformity, eleven patients (four patients were homozygous for TA 7 repeats and seven were heterozygous for TA7 repeats) had associated gilbert mutation. Therefore, we hypothesize that patients of TDT who had underlying Gilbert mutation might have decreased enzymatic activity of UGTIA6, which metabolizes the DFP, leading to more prominent adverse effects related to DFP.

The aims of the study are: a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA vaccines (Oxford-AstraZeneca, Sinovac) among lactating mother and baby pairs; and b) compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site; the largest minority of respondents, 43.7% (780/1784), reported experiencing worse symptoms when receiving the second dose compared to the first dose. There were no major reported adverse effects or behavioural changes in the breastfed infants. Among the respondents who received non-mRNA COVID-19 vaccinations, a majority reported no change in lactation but those who did more commonly reported an increase in milk supply, decrease in milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breastmilk supply and pain in the breast) for the non-mRNA vaccines were similar to that of respondents who received mRNA vaccines. Our study, with a large cohort and wide geographical and racial mix, further augments earlier reported findings that COVID-19 vaccines are safe for breastfeeding mothers and her children.

Good child protection systems and processes require reliable and accurate data. A retrospective study of the case records of 452 children referred to a major UK children’s tertiary centre for suspected child maltreatment was undertaken to determine whether routinely collected data on a child’s journey through the child protection system, together with a study of related multidimensional factors, can be used to develop an enhanced dataset to protect children in the UK and in other countries. Child maltreatment was substantiated in 65% of referred cases, with the vast majority of referrals coming from children living in the most deprived neighbourhoods in the country. Domestic violence and abuse, and the child’s previous involvement with statutory bodies was associated with case substantiation. Physical abuse predominated, with soft tissue injuries, including dog bites, and burns. Burns were related almost exclusively to supervisory neglect. There were also cases of medical neglect. Emotional abuse was associated with exposure to domestic violence and abuse, and to self-harm. The strengths and weaknesses for single centre data systems were explored, concluding with a recommendation to establish an agreed national and international minimum data set to protect children from maltreatment.

Tanning beds have been classified as carcinogenic to humans. As a result, many countries have enacted laws regulating the use of commercial tanning beds, including bans for minors. However, there is no international overview of the current legal status of access restrictions for minors that provides details on their specific design regarding age limits and possible exceptions to the statutory regulation. Therefore, we performed a comprehensive web search of current tanning bed legislation for minors on the three continents North America, Australia, and Europe. Our findings regarding existence and concrete design of access restrictions are presented graphically using maps. We found a wide variety of different legislations. In Australia, a total ban on tanning beds exists, while in New Zealand tanning bed use is banned for minors. In Europe about half of the countries have implemented a strict ban for minors. In North America we found differences in the age limit for access restrictions between the states, provinces and territories for those regions that implemented a ban for minors. In the United States, some states have rather ‘soft bans’ that allow use by minors with different types of parental consent. The patchwork in legislation calls for harmonization. Therefore, our comparison is an important starting point for institutions such as the World Health Organization or the European Commission to advance their goals towards a harmonization of tanning bed legislation in general and for minors in particular.

Lethal congenital contracture syndrome 11 (LCCS11) is a form of arthrogryposis multiplex congenita (AMC) which is associated with mutations in the gliomedin gene (GLDN) and has been known to be severely life-shortening, mainly due to respiratory insufficiency. Patients with this condition have been predominantly treated by pediatricians as they usually do not survive beyond childhood. In this case report we present a young adult who developed severe progressive respiratory insufficiency as a teenager due to diaphragmatic hypomotility and was diagnosed with LCCS11 following the finding of compound heterozygous pathogenic variants in GLDN. This case demonstrates the importance of screening for neuromuscular diseases in well-child visits and follow-ups of patients at risk for gross and fine motor function developmental delay. It also underscores the significance of including LCCS11 and other axonopathies in the differential diagnosis of juvenile onset of respiratory insufficiency, highlights that patients with this condition may present to adult practitioners and questions whether the nomenclature of this condition with various phenotypes should be reconsidered due to the stigmatizing term ‘lethal’.

Screen viewing time is the total time spent by a child on any digital/electronic device. The objective of the present study was to determine the incidence and predictors of excessive screen viewing time in children in Ujjain, India. This cross-sectional, community-based study was conducted through house-to-house survey by using the three-stage cluster sampling method in 36 urban wards and 36 villages of Ujjain district, India. Excessive screen viewing time was defined as screen viewing for &gt; 2 h/day. The prevalence of excessive screen viewing time was 17.83%. Risk factors identified using the multivariate logistic regression model were: age (OR: 1.5, P &lt; 0.001); mobile phone use before bedtime (OR: 3.17, P = 0.008); parents’ perception about the child habituated to screen (OR: 14.03, P &lt; 0.001); television in bedroom (OR: 48.69, P &lt; 0.001); morning mobile screen viewing time (OR: 9.27, P &lt; 0.001); not reading books other than textbooks (OR: 9.71, P &lt; 0.001); and lack of outdoor play for &gt;2 h (OR: 4.20, P &lt; 0.001). Presence of eye pain was a protective factor for excessive screen viewing time (OR: 0.12, P = 0.011). The study identified multiple modifiable risk factors for excessive screen viewing time.

Background: This work aimed to undertake a bibliometric analysis of the Rubella virus. Medical studies were conducted between 2000 and 2022 to discover trends, dynamics, and research outputs in the industry. Methods:A bibliometric study was performed using R software to determine research characteristics indexed worldwide and published in Rubella research in medical studies. The Rubella virus was chosen as the subject in the PUBMED database, and 374 papers from the previous two decades were reviewed. Results: There was an increase in the number of publications after 2003. The United States was the most essential countryamong all which had the most contributions on Rubella Virus. Conclusion:Rubella research has increased in the medical profession over the previous decade, with the United States leading to publications in this field.

A growing body of literature suggests a causative relationship between severe adverse neurological outcomes and early life exposure to paracetamol (acetaminophen) in the presence of oxidative stress. Review of the literature revealed that, although its use is not regularly monitored, paracetamol has achieved near universal acceptance, with exposure in some pediatric populations exceeding 90%. In addition, use of the drug as well as associated adverse outcomes may have risen as a result of pharmaceutical advertising rather than need, and inappropriate use of the drug, both in terms of dose and indication, is widespread. These findings indicate that many clinicians and patients do not, at the present time, evenly weigh the potential risks with the potential benefits of paracetamol exposure early in life. Although retrospective studies might be envisioned to further address the neurodevelopmental risks of paracetamol use during early development, in silico simulations demonstrated that such studies can be thwarted by very high rates of use of the drug combined with associations between paracetamol use and oxidative stressors that act as cofactors in the induction of neurodevelopmental injury. These findings suggest that, despite persistent uncertainty, clinicians and patients should be more aware of available information pointing toward the potential dangers for neurodevelopment of early life exposure to paracetamol. Most importantly, health care workers need to provide a more balanced view, weighing both risks and benefits, when providing advice for patients regarding paracetamol use during periods of brain development.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of 1 year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age 1. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age 1 year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β and IL-6. Conclusion: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of 1 year

(1)Background: When the COVID-19 pandemic arrived, changes had to be made to several management aspects at our Pediatric Oncology Center. We investigated how the families per-ceived these changes. (2) Methods: Two questionnaires were developed at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan, to explore how the pandemic has affected the experience of patients who had been or were being treated at our hospital, and their families. These were administered to three samples of individuals. (3) Results: Between July and October 2020, 120 questionnaires were administered to parents of patients. The impact of school closures and the impossibility of attending sports and social activities outside the hospital were regarded as im-portant. 77.5% of parents judged the social distancing to have affected their children. Regarding the changes introduced in the management of the ward and outpatient clinic, most parents’ opinions were positive. Differences in the opinions expressed by Groups 2 and 3 were statistically significant on the topic of relationships on the ward and staff workload. The aspect most negatively affected by the pandemic was the support that patients’ parents were able to give each other. Regardless of whether patients were treated before the pandemic or after the first lockdown, their parents of all indicated a strong degree of satisfaction with the care received, and with the organizational ar-rangements. (4) Conclusions: The results of our study point us in the right direction to further improve our daily work and better respond to the needs of our patients and their families.

In Japan, the prevalence of low birth weight (LBW) has been estimated to be approximately 10%, which is the highest among developed countries. This high prevalence might affect the prevalence of LBW-associated diseases in the adult population of Japan. Recently, LBW has been recognized as a contributing factor to post-adaptive focal segmental glomerulosclerosis (FSGS) in adulthood; however, few reports to date have evaluated the clinical and pathological characteristics of post-adaptive FSGS. A 13-year-old girl was referred to our hospital owing to mild proteinuria, which was detected at a school urinary screening. She was born at a gestational age of 23 weeks, with a very LBW of 630 g. Dipstick urinalysis revealed grade (2+) proteinuria. Her serum creatinine level was 1.02 mg/dL, and she was diagnosed as having stage 2 chronic kidney disease (CKD). Her serum uric acid level was 7 mg/dL. Her mother and 16-years old brother had hyperuricemia, too. A percutaneous renal biopsy leads to a diagnosis of FSGS. After 3 years of treatment with an angiotensin receptor blocker, her proteinuria decreased. However, her serum creatinine level was 1.07 mg/dL, and she still had stage 2 CKD. We considered that in this patient, the first hit was her LBW, and the second hit was hyperuricemia. The second hit might be associated with the development of CKD. The birth history of patients is not usually confirmed by nephrologists. Our case demonstrates that obtaining information regarding the preterm birth and LBW of patients is important in the diagnosis of noncommunicable diseases, because school urinary screening is not routinely performed in countries other than Japan.

Acetaminophen use during pregnancy and early childhood was accepted in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on false assumptions and ignorance of the impact of the drug on brain development. Fourteen studies now indicate that prenatal exposure to acetaminophen is associated with neurodevelopmental problems. Based on corrections for confounding factors applied to the analyses of available data, it can be concluded that prenatal exposure to acetaminophen causes statistically significant risks of one subtype of autism spectrum disorder (ASD), developmental delays, and attention deficit hyperactivity disorder. In contrast, data regarding postnatal exposure to acetaminophen are limited, and several factors impede a classic multivariate analysis of data to resolve the issue. However, circumstantial evidence regarding postnatal exposure to the drug is abundant, and it can be concluded beyond a reasonable doubt that postnatal exposure to acetaminophen in susceptible children is responsible for many if not most cases of ASD. Circumstantial evidence includes at least three otherwise unexplained temporal relationships, data from laboratory animal studies, several miscellaneous and otherwise unexplained correlations, and the lack of alternative suspects that fit the evidence-derived profile.

Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalizations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.

Background: Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy characterized by the presence of a two-layer myocardium with prominent trabeculation and deep intertrabecular recesses. The diagnosis of LVNC can be challenging because the diagnostic criteria are not uniform. The aim of our study was to evaluate echocardiographic and CMR findings in a group of children with isolated LVNC. Methods: From February 2008 to July 2021, pediatric patients under 18 years of age at the time of diagnosis with echocardiographic evidence of isolated LVNC were prospectively enrolled. The patients underwent echocardiography and contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement to assess myocardial noncompaction, ventricular size, and function. Results: A total of 34 patients with a median age of 11.9 years were recruited. Patients were followed prospectively for a median of 5.1 years. Of the 31 patients who met Jenni’s criteria in echocardiography, CMR was performed in 27 (79%). Further comprehensive analysis was performed in the group of 25 patients who met the echocardiographic and CMR criteria for LVNC. In echocardiography, the median NC/C ratio in systole was 2.60 and in diastole 3.40. In 25 out of 27 children (93%), LVNC was confirmed by CMR according to Petersen’s criteria, with a median NC/C ratio of 3.27. Conclusions: 1) Echocardiography precisely identifies patients with LVNC. 2) Echocardiography is a good method for monitoring LV systolic function, but CMR is indicated for the precise assessment of LV remodeling and RV size and function as well as for the detection of myocardial fibrosis.

Objectives: The aim of this study was to compare the performance of the EQ-5D-Y-3L (Y-3L) and the expanded five level version, the EQ-5D-Y-5L (Y-5L). Methods: Children/adolescents with an acute or chronic health condition and from the general population completed the Y-5L and Y-3L self-report questionnaires. Performance of the Y-5L and Y-3L was determined by comparing feasibility, redistribution of dimension responses, discriminatory power, validity, and test-retest reliability. Results. Five hundred and fifty children/adolescents completed baseline measures and 173 completed repeat measures. The ceiling effect decreased by 15% from the Y-3L to Y-5L. Informativity of dimensions improved by 0.094 on the Y-5L. There was a range of 4-9% inconsistent responses moving from the Y-3L to Y-5L. Convergent validity of the Visual Analogue Scale (VAS) and Y-3L, Y-5L dimensions was similar, weak to moderate (r_s range: 0.18 – 0.38) but similar and strong on paired Y-3L and Y-5L dimensions: Kendall Tau B (range 0.69 – 0.80) and Gamma (range 0.92 – 0.98). The Y-5L and Y-3L showed moderate to substantial agreement for test-retest reliability across dimensions and VAS scores in stable chronic health conditions and fair agreement for the general population. Conclusion: The EQ-5D-Y-5L is a valid, reliable extension of the Y-3L for children/adolescents across health conditions and healthy children/adolescents. The expanded levels reduced the ceiling effect. The relative informativity of report across dimensions increased on the Y-5L compared to the Y-3L with retention of the evenness of reporting. The convergent validity and test-retest reliability of the Y-5L was comparable to the Y-3L.

Pneumonia is the leading cause of hospitalization in pediatric patients. Disease severity greatly influences pneumonia progression and adverse health outcomes such as hospital readmission. Hospital readmissions have become a measure of healthcare quality to reduce excess expenditures. The aim of this study was to examine 30-day all-cause readmission rates and evaluate the association between pneumonia severity and readmission among pediatric pneumonia hospitalizations. Using 2018 Nationwide Readmissions Database (NRD), we conducted a cross-sectional study of pediatric hospitalizations for pneumonia. Pneumonia severity was defined by the presence of respiratory failure, sepsis, mechanical ventilation, dependence on long-term supplemental oxygen, and/or respiratory intubation. Outcomes of interest were 30-day all-cause readmission, length of stay, and cost. The rate of 30-day readmission for the total sample was 5.9%, 4.7% for non-severe pneumonia, and 8.7% for severe pneumonia (p&lt;0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p&lt;0.01) and higher daily cost ($3,246 vs. $2,679, p&lt;0.01) than admissions for non-severe pneumonia. Factors associated with 30-day readmission were pneumonia severity, immunosuppressive conditions, length of stay, and hospital case volume. To reduce potentially preventable readmissions, clinical interventions to improve the disease course and hospital system interventions are necessary.

Purpose: ETV is indicated for treating obstructions of major CSF pathways. The outcome evaluation often yields success rates of only +- 70% for shunt independency. Hence, compromised CSF absorption seems to occur more often than expected. We searched for parameters suitable to assess the involved CSF dynamics. Material and Methods: This was a prospective study in 58 paediatric patients (7.7 yrs. mean age) between 2000 and 2020 with aqueductal stenosis (11/58), obstruction of the aqueduct due to tumor growth (22/58),and connatal hydrocephalus (9/58). The average follow-up interval was 4.7 years. Head circumferences, Evans- and fronto-occipital horn ratios before and 3 months after ETV were obtained as Delta-indices. Furthermore ETV success score (ETVSS), the patency of the aqueduct pre- and postoperatively as well as of the stoma were assessed by flow void signs on MRI. Evaluation on MRI also included the shape of the floor of the 3^rd ventricle and whether or not the septum pellucidum showed signs of perforation. Four patients were analysed pre- and postoperatively via real-time MRI. At least the educational status regarding protected or unprotected education was analyzed. Results:The prevalence of a bowing of the floor of the 3^rd ventricle was 72%, and the ETVSS was 71.0%. In 26 children a septal perforations or an open aqueduct prior to ETV (19) could be identified. Mean ER and FOHR were reduced by 0.03 and 0.05 , respectively. Maintained open (flow void on postop MRI) or perforation could successfully be carried out during endoscopic surgery in 44 patients (79%). The disproportionate increase of head circumference abated in 79.4% of patients. New shunt insertion occurred in 16 patients (27.5%). Intraoperatively upward CSF flow was detected in all cases. Statistical analyses(ANOVA) showed significant results for unprotected education, postoperative ER and FOHR but not for open stoma. Conclusion: The identification of flow through the stoma on postoperative MRI seems to be a necessary but not sufficient condition for ETV success. In our study, ventricular volumes were used as parameters to determine success rates as well as unprotected education. Furthermore, enabling upward CSF flow driven by inspiration seems crucial for successful ETV.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most of children diagnosed with isolated GHD presents with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

More than twenty-five years ago the Global Solar UV index (UVI) has been introduced as a simple means of visualizing the intensity of ultraviolet radiation and to alert people to the need for sun protection. In our survey among directors of 436 kindergartens in southern Germany we investigated the level of awareness and knowledge about the UVI as well as the practical consequences for sun protection in kindergartens. Less than half of the directors (n=208, 47.7%) had ever heard of the UVI, and only a small minority of them (n=34, 8.7%) used the daily UVI information to adapt sun protective measures in their kindergartens. Detailed knowledge about the UVI was a rarity among the respondents. The proportion of respondents with self-perceived detailed UVI knowledge was five times higher than actual knowledge assessed by an in-depth structured interview using open-ended questions about the UVI (14.2% vs. 2.8%). No clear relationship of UVI awareness, knowledge, and use to directors' age and gender was found. The UVI-related variables also showed no association with directors' knowledge of risk factors for skin cancer and their attitudes towards tanned skin. Overall, the results paint a sobering picture regarding the penetration of the UVI into sun protection policies of German kindergartens. Future public health campaigns should target increasing awareness and understanding of the UVI as well as its importance for sun protection of children.

Context: CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia cases (CAH), a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provides critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Objective: Analyze the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of the CYP21A2. Methods: SNVs of the CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of the CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. Results: SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews' correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). Conclusion: From our analysis, we identified four predictors of CYP21A2 pathogenicity with good performance. These results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP21A2.

Stunting in children is a serious problem of nutritional disorders and is strictly monitored by the Indonesian government, it is not only cause physical but also cognitive abnormalities in the form of less intelligence in children so that when they grow up, their productivity will decrease. The incidence of stunting in 2018 in Indonesia was 30.8 %, while in West Java was 29.92%, still at a moderate to high level, consequently, prevention and early detection efforts need to be carried out by various parties, including health professionals and health cadres. Therefore, the aim of this study was to examine the association between the socio demographic characteristics factors as well as the knowledge and motivation of health cadres in the stunting prevention in West Java. A correlational study with a cross-sectional approach was employed with the samples of health cadres from 8 districts/cities in West Java Province: Karawang, Tasikmalaya, Garut, Bandung, Subang, Sukabumi, Cianjur, and West Bandung. A total of 363 health cadres participated and the sampling technique used is the stratified method. The data were collected using a questionnaire developed specifically for this study and were analyzed using a correlation with Chi-Square test and presented in the form of a frequency distribution. The study findings found that majority of the health cadres have good knowledge of 81.27%, which was significantly influenced by education level and marital status with p &lt;0.05. Meanwhile, approximately half of the respondents had moderate motivation with 47.66%, while one-third or 39.12% had high motivation. This motivation was significantly influenced by education level, marital status, and age with p &lt;0.05. It was concluded that health cadres need to further enhance the roles and functions in the prevention and early detection of stunting in West Java by providing continuous guidance, stunting training prevention and award presentations.

The incidence and prevalence of food allergy (FA) are increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants particularly in those at high or low risk of atopy are still unclear. This 1-year study evaluated the safety of early introduction of single foods (milk, egg, or peanut), vs. two foods (milk/egg, egg/peanut, milk/peanut), vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/fish/soy at low, medium, or high doses) vs no early introduction in infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity with standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixture was 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least 6 months of age. Results demonstrate that infants at either high or low risk for atopy were able to tolerate early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that early introduction of foods, particularly simultaneous mixtures of many allergenic foods is efficacious for preventing FA and can occur safely.

Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

Deficiency of Cytochrome P450 Steroid 21-hydroxylase (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction along with functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in the Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of 21OH deficiency.

AbstractIn the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from static functional to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.Impact StatementWhile functional connectivity has elucidated much MN properties with relation to age, disease, and behavior, effective connectivity has been shown to be useful in MN-informed therapies in adults. Thus, effective connectivity may have potential to impact childhood movement disorder therapies, given the lower to no patient demand.

Overweight/obesity is one of the most important health problem worldwide. Birth by cesarean section has been shown to influence long-term health outcome including obesity. The aim of this systematic review-meta-analysis is to examine whether cesarean section increases the risk of offspring’ s overweight/obesity. The study follows the PRISMA and MOOSE guidelines. A systematic literature search was con-ducted on Scopus, PubMed, and WoS until December 2020. For inclusion, studies must have re-ported either (I) both Birth by cesarean section and adult (≥ 18 years) offspring BMI, (II) cohort or case–control study design and (III) a risk estimate. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger’s test and Begg’s test. Me-ta-analysis was performed through a random effect model. Eleven studies with a combined population of 180.408 subjects were included in the meta-analysis. The overall analysis (n = 18) yielded a combined risk estimate for overweight/obesity of 1.19 (95% CI 1.08-1.31) and the test of heterogeneity resulted Q=53,37 (I2 = 70,37 %, P≤0•0001). The risk of offspring obesity is 1.23 (95% CI 1.09-1.39) and the test of heterogeneity resulted Q=39.50 (I2= 72,15%, P≤0•0001). Children born by cesarean section have an increased risk of developing obesity in adulthood

Adverse childhood experiences are known to program children for disrupted biological cycles, premature aging, microbiome dysbiosis, immune-inflammatory misregulation, and chronic disease multimorbidity. To date, the microbiome has not been a major focus of deprogramming efforts despite its emerging role in every aspect of ACE-related dysbiosis and dysfunction. This article examines: 1) the utility of incorporating microorganism-based, anti-aging approaches to combat ACE-programmed chronic diseases (also known as noncommunicable diseases and conditions, NCDs) and 2) microbiome regulation of core systems biology cycles that affect NCD comorbid risk. In this review microbiota influence over three key cyclic rhythms (circadian cycles, the sleep cycle, and the lifespan/longevity cycle) as well as tissue inflammation and oxidative stress are discussed as an opportunity to deprogram ACE-driven chronic disorders. Microbiota, particularly those in the gut, have been shown to affect host-microbe interactions regulating the circadian clock, sleep quality, as well as immune function/senescence and regulation of tissue inflammation. The microimmunosome is one of several systems biology targets of gut microbiota regulation. Furthermore, correcting misregulated inflammation and increased oxidative stress is key to protecting telomere length and lifespan/longevity and extending what has become known as the healthspan. This review article concludes that to reverse the tragedy of ACE-programmed NCDs and premature aging, managing the human holobiont microbiome should become a routine part of healthcare and preventative medicine across the life course.

In the current Sars-CoV-2 pandemic, wearing a face mask was mandatory and is still desired during school lessons. There are no controlled studies in children to date indicating an effect on cognitive performance wearing face masks. In a randomized controlled trial, we analysed the influence of face masks on cognitive performance of pupils during regular school lessons. Pupils (n=133, 5th to 7th grade) were randomized by alternating allocation into control (with masks, n=65) and intervention groups (without mask, n=68). After two school lessons with (control) and without (intervention) face masks in class all pupils performed digital tests for cognitive performance regarding attention and executive functions (Switch, CORSI block tapping, 2-back and flanker task). Overall, there were no significant differences in cognitive performance between both groups, masks vs. no masks. Wearing face masks has no significant influence on attention and executive functions of pupils and can still be recommended during school lessons.

The main aim of the present study was to explore health professionals’ reported experiences and approaches to managing children who receive a designation of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive inconclusive diagnosis following a positive NBS result for cystic fibrosis. An online questionnaire was distributed via Qualtrics Survey Software and circulated to a purposive, international sample of health professionals involved in managing children with this designation. In total, 101 clinicians completed the online survey; 39 from the US, six from Canada and 56 from Europe (including the UK). Results indicated that while respondents reported minor deviations in practice, they were cognizant of recommendations in the updated guidance and for the most part, attempted to implement these into practice consistently internationally. Where variation was reported, the purpose of this appeared to be to enable clinicians to respond to either clinical assessments or parental anxiety in order to improve outcomes for the child and family. Further research is needed to determine if these findings are reflective of both a wider audience of clinicians and actual (rather than reported) practice.

We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants < 12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients under-went clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 hours of hospital admission. The existence of significant correlation between car-diac and respiratory parameters was the primary outcome. The association of different cardio-pulmonary variables with the need of respiratory support higher than O2, the length of stay hos-pitalization, the PICU stay, and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5-3) months; 62% males) hospitalized with acute bron-chiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction. Up to 36 (32%) infants required respira-tory support during the hospitalization. This group presented with higher lung ultrasound score (p<0.001), and increased values of Tei index (p<0.001) and pulmonary artery pressures (p<0.001). All the analyzed respiratory and cardiac variables showed moderate to strong correlations with the LOS hospitalization and the time of respiratory support. Lung ultrasound and echocardiog-raphy showed a moderate to strong predictive accuracy for the need of respiratory support in the ROC analysis, with AUC varying from 0.74 to 0.87. Conclusion: Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ul-trasonography could be a good strategy to easily identify high-risk population for a complicated acute bronchiolitis hospitalization.

In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.

Juvenile idiopathic arthritis (JIA) is a disease with unknown causes within all forms of arthritis in children under 16 years of age. The diagnosis is made when another joint pathology is excluded. Difficulties in early and differential diagnosis lead to the rapid disability of patients and an unfavourable life prognosis. Therefore, timely diagnosis is necessary to prevent irreversible damage to the joints and preserve their function. Due to the widespread use of new technologies, modern multimodal imaging has gained recognition, which includes X-ray, ultrasound, and MRI. The combination of methods plays a key role in confirming the diagnosis, monitoring disease activity, prognosis during the course, and outcome in children with JIA. Each method has its own advantages and disadvantages. The introduction of the method of passive microwave radiometry (MWR), in combination with other imaging methods, makes it possible to expand the possibilities of screening the disease in the preclinical and early clinical phases.

Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.

Excessive intake of fat and fatty acids is associated with major health hazards such as obesity or chronic diseases. The aim of this study was to provide the first data on total fat, saturated fatty acids (SFA) and trans fatty acids (TFA) intakes and their major food sources in Tunisian children. A total of 1200 children, aged 3 to 9 years old (yo), were randomly selected from primary schools and kindergarten under a cross-sectional design. The 24-hour recall method and food frequency questionnaire were used to assess dietary intake. The energy percentages of total fat, SFA and TFA in Tunisian children were respectively 29.6, 11.4 and 0.15. No sex differences were found. The WHO recommendations for total fat, SFA and TFA were adopted by 58 %, 39 % and 89 % of the study population, respectively. The leading food groups of fat and fatty acids were ultra-processed foods, breakfast cereals and dairy products. The meat, fish, eggs and fish alternatives were the fifth main contributors to the total fat and SFA intakes in Tunisian children. The implementation of a relevant strategy for fat reduction, especially from ultra-processed foods, considered as low nutrient energy-dense products, is needed to promote health among children and prevent diet-related chronic diseases.

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [ΔFEV1 (% pred.) =18.3, and similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p<0.0001) with Omalizumab. Conclusions: Treatment with Omalizumab can be an effective and safe therapeutic option for Romanian children with severe allergic asthma, providing clinically relevant in-formation on asthma control and exacerbation rate in children and adolescents. The results highlighted the effect of Omalizumab in young patients, starting from the first year of treatment.

Infectious disease is the leading cause of mortality in children under five. This study has investigated environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM study in Matiari, Pakistan. Publicly available map data was used to compile coordinates of healthcare facilities. A Pearson correlation coefficient (r) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found participants living closer to secondary hospitals had lower prevalence of ARI (r=0.154, p&lt;0.010) and diarrhea (r=0.228, p&lt;0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI (r=0.185, p&lt;0.002) and diarrhea (r=0.223, p&lt;0.001) compared to those living near primary facilities. Our random forest model showed distance to have high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.

I Introduction: Pneumothorax is a pathological condition characterized by the presence of air between the visceral and parietal pleura. Objectives: To investigate incidence, clinical characteristics, risk factors, management and perinatal outcome among newborns with pneumothorax in a tertiary care center. Materials and Methods: A prospective observational study was conducted in Maternity hospital with tertiary NICU from 2015-2019. We included all neonates with pneumothorax born in our hospital and compared demographic characteristics, perinatal risk factors, anthropometric parameters, concurrent diseases, clinical course and method of chest drainage between full term (≥37 GW) and preterm (<37GW) newborns. Results: Mong 30.378 neonates, 74 developed pneumothorax (2, 4/1000 newborns). The incidence of neonatal pneumothorax (NP) was higher in preterm group (59, 5%), with a mean age 34,62 GW in whole group. The mode of delivery was c. section in 68.9%. NP occurred mostly on the right side (47,3%), on the second day of life , in males (67,6%). Chest drainage was performed in 64,9% of cases. Of 74 NP cases, 64 (85.1%) recovered, 6 (8,1%) died. Conclusion: Pneumothorax is a pathological condition of the newborn, which, if not diagnosed in time and treated adequately, leads to a fatal outcome.ads to a

Congenital heart defects (CHD) are the most common birth anomaly affecting approximately 1% of births and have a prevalence of about 5.8 per 1000 people. CHD is the most common congenital anomaly in newborn babies. Management of the newborn with CHD represents a frontier of clinical pediatric cardiology. Progress in diagnosis and surgical treatment of the individuals with a heart defect has progressed to the point that almost all heart defects can be significantly improved and treated. Cardiovascular malformations account for about 10% of infant deaths and nearly half of all deaths from malformations

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

Congenital deafness is a major pediatric problem, affecting about 1.5-3 per 1000 newborns. The early treatment through cochlear implantation and auditory rehabilitation has been a historic milestone. Early diagnosis of congenital deafness is an essential requirement to obtain the best results, which is achieved through neonatal screening, a diagnostic practice that we began systematically at the Hospital Clínico in Valencia (Spain) 30 years ago.

A widely accepted concept is that boys are more susceptible than girls to oxidative stress related complications of prematurity, including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL). We aimed to quantify the effect size of this male disadvantage by performing a systematic review and meta-analysis of cohort studies exploring the association between sex and complications of prematurity. Risk ratios (RRs) and 95% CIs were calculated by a random-effects model. Of 1365 potentially relevant studies, 41 met the inclusion criteria (625680 infants). Male sex was associated with decreased risk of hypertensive disorders of pregnancy, fetal distress, and C-section, but increased risk of low Apgar score, intubation at birth, respiratory distress, surfactant use, pneumothorax, postnatal steroids, late onset sepsis, any NEC, NEC&gt;stage 1 (RR 1.12, CI 1.06-1.18), any IVH, severe IVH (RR 1.28, CI 1.22-1.34), severe IVH or PVL, any BPD, moderate/severe BPD (RR 1.23, CI 1.18-1.27), severe ROP (RR 1.14, CI 1.07-1.22), and mortality (RR 1.23, CI 1.16-1.30). In conclusion, preterm boys have higher clinical instability and greater need for invasive interventions than preterm girls. This leads to a male disadvantage in mortality and short-term complications of prematurity.

Several factors enhance the possibility of vertical HIV transmission in the pediatric population. Unfortunately, the data of the prevalence of HIV and associated risk factors in these populations remain limited in Rwanda. The study aimed to assess HIV prevalence and risk factors for infants born to mothers on ARV treatment at CHUB/Rwanda. MethodsA cross-sectional study was carried out on infants who were born to mothers under ARV treatment at CHUB. The associated risk factors were retrospectively assessed using prevention vertical HIV transmission records, and Dried Blood spots (DBS) were prospectively tested using Polymerase Chain Reaction (PCR). Data were analyzed by logistic regression. Ethical clearance (Ref: CMHS/IRB/198/2017) was issued by University of Rwanda to fulfill research ethical consideration.ResultsAmong 185(100%) infants born to HIV-positive mothers under ARV treatment, 5(2.7%) were HIV positive. The most associated risk factors were increased to over 1log copies/ml mother’s viral load (OR 9.3, 95% CI 1.01-85.45, P= 0.04) and mother’s CD4 count lower than 350 cells/µl (OR 6.4, 95% CI 1.03-40.06, P=0.04). The factors found to reduce the rate of vertical transmission of HIV were health facility as a delivery place (P=0.03), exclusive breastfeeding for 6 months (P= 0.006), and attending the antenatal care (P=0.01) while feeding children and vaginal delivery were associated risks but not statistically significant.ConclusionThe current study supports that the more mothers’ viral load and CD4 count decrease, so does the risk of HIV to their infants. A fact which indicates that both prevalence and risk factors remain an alarming issue. Much effort and multi-disciplinary approach are highly recommended.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

The two major global immunisation agenda framings (Missed Opportunity for Immunisation, MOI vs Immunisation Defaulting) are interchangeably and inappropriately used in public health research and practice with flawed or misleading strategies recommended and adopted in various settings globally. This is evident in the fact that many opportunities to adopt evidence/findings from immunisation coverage research in policy are grossly missed. Ineffectiveness of inappropriate interventions from biased evidence can discourage and mislead the governance to make radical decisions by discretion. This could be the reason for the inability of low-and middle-income countries to vaccinate 80% of their children and otherwise; this also poses a global health threat to capable nations. The current guideline and information on MOI and immunisation defaulting appear insufficient and a little clarification on it would assist forerunners in immunisation to achieve measurable progress in ensuring good coverage especially in low-and middle-income countries. Consequently, this paper is aimed at addressing this issue in immunisation practice with appropriate recommendations. Optimistically, this will stimulate further discussions, streamline differences, and gear global immunisation governance on the subject matter, to achieve the target coverage by 2030 in low-and middle-income countries.

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

Background: Little information exists regarding the differences in the clinical and laboratory characteristics of Kikuchi-Fujimoto disease (KFD) according to age. Objective: To evaluate the clinical and laboratory characteristics of KFD according to age. Methods: We retrospectively evaluated patients diagnosed with KFD at Pusan National University Hospital between 2010 and 2020. Results: Eighty patients (46 children and 34 adults) with a mean age of 21.5 ± 11.8 years (range, 3–49 years) were included in the study. Among children, the male sex ratio was higher, in adults, the female sex ratio was higher. Fever, tenderness in the lymph node, and skin rashes were more common in children, while myalgia and weight loss were more common in adults. In children, the recurrence rate was significantly higher among boys than among girls (15.8% vs 0.0%, P=0.001). EBV and ANA positivity rates were higher in boys than in girls. In adults, the recurrence rate was significantly higher in women than in men (18.2% vs 0.0%, P=0.005). ANA positivity rates were higher in women than in men. Conclusion: The clinical features, laboratory findings, and recurrence of KFD may differ depending on age and sex. Clinicians should be aware of this.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

Background: The purpose of this article is to update the diagnostic assessment, therapeutic approach, and 12-18 month follow up of patients added in the Italian Lombardy ADHD Register. Methods: Data on patients evaluated by the 18 Regional ADHD Reference Centres in the ten year period from 2011 to April 2021 were analysed. Results: 4091 of 5934 added patients received a diagnosis of ADHD. In 20.3% of cases, there was a family history of ADHD. 2879 children (70.4%) had at least one comorbidity disorder, the most common of which was learning disorder (39%). Nearly all (95.9%) received at least one psychological prescription, 17.9% of them almost one pharmacological treatment, and 15.6% a combination of both. Values of ≥5 of the Clinical Global Impressions- Severity (CGI-S) are more commonly presented by patients with a pharmacological prescription than with a psychological treatment (p < .0001). A significant improvement was reported in half of the patients followed after 1 year, with Clinical Global Impressions- Improvement (CGI-I ≤ 3). In all, 233 of 4091 are 18 year old patients. Conclusion: A ten year systematic monitoring of models of care was a fruitful shared and collaborative initiative in order to promote significant improvement in clinical practice, providing effective and continuous quality of care. The unique experience here reported should spread.

The goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease, and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease-specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2,200 with a range from 69 to 7,944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of new discoveries into clinical practice.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

Background: Recent years have seen chaos in the neonatology use of antibiotics with diverse opinions and recommendations in international guidelines and societies. This has created great uncertainty in which cases to use, for how long, and which tests apply to make these decisions. We conducted a retrospective cohort study about the use of antibiotics in the EpicLatino neonatal units and a Latin American network database, after noting these variations in the 2019 report. Methods: For the year 2019 using the EpicLatino database, we included cases (only first admission) ≤32 weeks gestational age at birth, excluding one unit that did not accept to participate. The number of cases and days receiving antibiotics were recorded as well as the progression for each unit. Inappropriate use of antibiotics was defined as greater than 3 days in patients with negative cultures (blood/CSF cultures) excluding: major malformations, urinary tract infections, necrotizing enterocolitis (NEC) and cases with suspected chorioamnionitis in the mother (the latter two only during the course of diagnosis of NEC or chorioamnionitis). This study was approved by the EpicLatino board of directors and by the participating units. Results: A total of 6,543 days of antibiotics were observed, 49.5% of cases had at least one positive blood/CSF culture. A total of595 days of antibiotics without justification were found in 72 courses in 61 cases; 14/72(19.4%) had no diagnosis of infection in the database, 7/72(9.7%) did not document any culture throughout their stay, and 37/72(51,4%) obtained only one blood/CSF culture during their entire stay. Most diagnosis were clinical sepsis and in 24/58(41%) curses, a diagnosis of pneumonia with a poor positive culture correlation was found. Furthermore, 74% of the units didn´t use pneumonia as a justification to use antibiotics. Other diagnosis found: Conjunctivitis, NEC 1A and rotavirus NEC. Conclusions: Although the method of reviewing the use of antibiotics in a database has a number of limitations, especially the cause that motivated the use of antibiotics and other tools used for diagnosis of infections, the notable differences between units is striking. Although it is difficult to make recommendations to all units, it is important to control infections in some units and in others to reduce the excessive use of antibiotics, especially with diagnosis of pneumonia in neonates and negative blood/CSF cultures.

Background: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. If reference sickle cell centers have been implemented in capital-cities of African countries and have proven to be beneficial for SCD patients, it has never been set up ina rural area for families with very low sources of income. Method: A cohort of 143 children with SCD aged 10 years old (IQR [inter quartile range]: 6–15 years) (sex ratio male: female = 1.3) were clinically followed for 12 months without any specific intervention, outside management of acute events ,and then 12 months with a monthly medical visit , a biological follow-up and regular prophylaxis. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). The implementation of standardized and regular follow-up in a new sickle cell referral center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease of the lymphocytes count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. Conclusions: Creation of a sickle cell referral center and a regular follow-up of children with SCD are possible and applicable in the context of a remote city of an African country. Those simple and accessible measures can reduce the morbimortality of the sickle cell children.

Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19). Most of reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (a country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On May 25th, we have launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4th March 2020) and prospective data collection. Up to 28th July, 39 reported children met inclusion criteria. We stratified them according to age (&lt;5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and 9 children had COVID-19 confirmation. This is the first to our knowledge report of PIMS register from the country with low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g. older age should be considered in the differential diagnosis of inflammatory syndromes in children.

Context: bullying among schoolchildren is a serious phenomenon and a leading health concern. Aim: to determine the prevalence of bullying, its forms, and its effect on academic abilities and school attendance, as well as associated sociodemographic, physical, and dentofacial features among Saudi schoolchildren. Methods: this cross-sectional study recruited a sample of 1131 parents of schoolchildren 8-18 years old and requested them to complete internationally accepted questionnaires for their children. Chi-square test and logistic regression analysis were used to analyze the data (p<0.05). Results: a majority (89.2%) of schoolchildren were bully victims. Physical bullying (48.9%) was the most common form of bullying. The youngest schoolchildren (8-11 years), those who disliked school classes or neither liked nor hated them, as well as those who were truant from school were more likely to be victims. In addition, those who had worse grades because of bullying, and those who were very often bullied because of good grades or because they showed an interest in school were more likely to be victims. With regards to targeted physical features, teeth were the number one target, followed by the shape of the lips and strength, while teeth shape and color was the most common dentofacial target, followed by anterior open bite and protruded anterior teeth. Boys and the youngest schoolchildren were more often subjected to bullying because of these features (p<0.05). Conclusions: the prevalence of bullying, mainly in a physical form, was high among Saudi schoolchildren, with a negative influence on students’ academic abilities. Problems related to teeth, in particular, which can be treated, were targets, mainly for boys and the youngest schoolchildren. More studies are required in Saudi Arabia to explore the issue further among schoolchildren, themselves.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal and postnatal period. Alveolar oxygen tension (PAO2) and pulmonary arterial PO2 are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen is the mainstay of PPHN management. However, optimal monitoring of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimize oxygen delivery to vital organs is not known. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and ranges 91-95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial oxygen tension, especially with variations in hemoglobin type (transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, and mixed venous oxygen tension and SpO2 in the management of PPHN. Translation and clinical studies suggest maintaining an arterial oxygen tension of 50-80 mmHg to help decrease PVR and optimize pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN based on targeting SpO2 or PO2. However, most critically ill patients have umbilical arterial catheters and postductal arterial oxygenation may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 ranges and compare outcomes in PPHN.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

The prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyze the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.5%. At the time of this writing, 17 of the patients have celebrated their 10th birthdays with good quality of life and no indications for LT. The obtained results underscore the critical importance of surgical correction of BA by Kasai surgery during the first 60 days of life and subsequent dynamic follow-up of the patients for the purpose of the early detection and timely correction of possible complications.

The popularity of multiparticulate formulations (MPs) as a paediatric dosage form continues to increase. MPs comprise of multiple small units that are easy-to-swallow. Currently, MPs are commonly manufactured into unit doses that are either swallowed whole or opened prior to administration. While this is an acceptable approach, dosing is envisioned to be optimized with a ‘standard’ paediatric device which can better harness the flexible dosing potential of MPs. We evaluated a novel oral syringe (SympfinyTM) that is being developed as a tool to dispense and administer MPs to children. Forty children, 4-12 years old, received 0.5, 1.2, and 2.0 mL doses of placebo MPs using the oral syringe with spring water or a drink of choice to complete sample intake. Acceptability was recorded as those able to completely swallow the dose and participants also rated dose acceptability on a 5-point scale. The ability to completely swallow the dose decreased as dose volume increased; the smallest dose was completely swallowed by 87.5% (35/40) children, and 69.4% (27/39) of children confirmed their willingness to take the sample as a daily medicine. Larger doses, 1.2 and 2.0 mL, gave values of 55% and 57.5% for the doses completely swallowed and 58.8% and 51.72% for willingness to take the sample as a daily medicine, respectively. Use of a drink of choice showed no increase in swallowability as compared with water. The novel oral syringe being developed is an appropriate device for dispensing doses flexibly and administering neutral tasting MPs directly to the mouth in the lower dose range without the need for a co-administration vehicle in children aged 4-12 years.

Background: Elevated respiratory rates (RR) have been described in several disease states, such as pneumonia, asthma and bronchiolitis. Despite this, there are few studies defining the range of RR found in healthy children. Available age percentiles for RR have been generated using methods that have the potential themselves to alter the rate. Aim: The aim of this study was to develop accurate percentile charts of RR specific for age in healthy children for potential use in pre-hospital care (first-aid), clinical medicine and for reference in respiratory research. Method: A newly developed optical respiratory sensor was used to measure RR which placed no restrictions on respiratory excursion. This technique enabled recording in awake children without the artefact of the observer’s presence on the subject’s RR. A cross-sectional sample of healthy children was obtained from maternity wards, childcare centres and schools in Brisbane, Queensland, Australia. Results: RR were observed in 560 awake and 103 sleeping children of which data from 343 awake and 94 sleeping children was used to create reference ranges for healthy children from newborn to 13 years of age. The recorded rates were significantly higher when children were awake compared to asleep. During quiet sleep, RR decreased from 40 (interquartile range 7) bpm at one month to 20 (interquartile range 3) in children aged 3 years. In awake children, RR ranged from a median of 40 bpm (interquartile range 18) at 1 year to 12 bpm (interquartile range 11) at 13 years respectively. Conclusion: The optical sensor was found to be an appropriate respiratory transducer, capable of measuring RR and reducing artefact by the subjective responses of alert children. The centile charts will be helpful as an aid to detecting abnormal RR in children and will contribute to further systematic reviews related to this vital sign.

Objectives: To investigate the value of early lactate dynamic monitoring index in predicting prognosis of patients with sepsis and septic shock. Methods: We performed our test on 50 patients. Out of 50 patients, 28 are male, and 22 are female. Prospectively studied pediatric patients with septic shock were performed. Vital signs, Lactate clearance, were obtained at presentation 6 h, 12 h, 24 h over the first 48 h of hospitalization. The therapy received, outcome parameters of mortality and duration of hospitalization were recorded. Results: The statistical data and comparative analysis showed that an average of 16.88 days after admission, 5 patients have died, 17 patients are poorly prognosis leaves the hospital, and the remaining 28 are recovered and discharged. The primary outcome variable of mean 16 days hospitalization mortality rate was 10%. Poor prognosis 34% and fully recovery 56 % were observed. In this retrospective cohort study, a lactate level of more than 2.5mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. In our research, we found mean LC 6 h 3.08mmol/L, and after 48 h mean it is 1.79mmol/L. Significant LC 6 h found, which is 8.08mmol/L in the death group patient where 48 h mmol/L shows significant high. Poor prognosis also presents a clinical increase of lactate level high in the LC 6 h analysis, which is 3.32mmol/L. Recovered patients showed a significant improvement after administering treatment depending on the patient organ involvement and good decrease of lactate reports achieved, which is 1.20mmol/L, where admission reports show it was 1.91mmol/L in LC 6 h. Mean Heart rate 94/51mmhg, pulse 119, temperature 39℃, respiratory rate 32.26, and urine output 456 ml recorded during our study. Death patient shows a remarkable detonation of those reports but has a significant clinical report with the recovered patients. Conclusion: The early lactate dynamic monitoring index has a high value in predicting sepsis and septic shock patients' prognosis, thus worth popularizing.

The objective of the study was to report the health-related quality of life (HRQOL) following road traffic accidents (RTAs) among children. A community-based survey using EuroQol five-dimension questionnaire (EQ-5D-5L) in Hindi was used to collected data from community. The survey included 2620 households from urban and rural areas of Ujjain, India. From these households 229 children aged 5–18 years with a history of RTA in the last 1 year were identified, with 27%, 63%, and 10% children reporting mild, moderate, and severe injury based on length of hospitalization. Motorcycles, bicycles, and pedestrians constituted most RTAs. Helmet use was low (12%). EQ-5D-5L revealed that the most severe and extreme problem was pain and discomfort, whereas the least severe problem was usual activity and self-care. The most common (65%) injuries were either abrasion or fracture and dislocation. EQ-5D-5L severity index was maximum (mean 72) for lower extremity injuries. The results of the present study highlight the ability and requirement for quality of life measurement using EQ-5D-5L among children post-RTA.

The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.

Objective: To assess the functionality of the affected upper limb in children diagnosed with hemiplegia aged between 4 and 8 years after applying low-intensity modified constraint-induced movement therapy(mCIMT). Methods: Prospective case series study. A mCIMT protocol was applied for five weeks, with two hours of containment per day. The study variables were: quality of movement of the upper limb, spontaneous use, participation of the affected upper limb in activities of daily living, dynamic joint position, grasp-release action, grasp strength, supination and extension elbow movements. Four measurements were performed, using the QUEST scale, the SHUEE Evaluation, a hand dynamometer and a goniometer. Results: The sample was composed of 8 children with moderate manual ability. Statistically significant differences were detected in all the studied variables (p&lt;0.05). The greatest increase occurred in spontaneous use from assessment 1-4 (p = 0.01), reaching 88.87% active participation in bimanual tasks. The quality of movement of the upper limb obtained a significant value due to the increase in dissociated movements and grasp (p = 0.01). Conclusion: A low dose (50 hours) of mCIMT increased the functionality of children diagnosed with congenital hemiplegia between 4 and 8 years of age with moderate manual ability.

BACKGROUND AND OBJECTIVES. Suicide is a topical issue in Lithuania and all around the world. It is the second common cause of death among young people. There’s a lack of research studies on the psychosocial aspects of adolescents’ suicide in Lithuania. The study aimed to evaluate the demography, life circumstances, health conditions as possible suicide causes in adolescents. MATERIALS AND METHODS: a retrospective study was performed in the Children’s Hospital (Vilnius University Santara Clinics). Medical documentation of adolescents, treated in this hospital after the suicidal attempt, from January 2011 till April 2018 were analyzed. RESULTS: there were 117 cases of suicide attempts included into the study: 83.8% female and 16.2% male with an average age 15.02 ± 1.9 years; 40.6% of patients lived in divorced families, 21.9% - in the orphanage; 36.4% suffered from parental alcoholism, 17,2% experienced suicide in their close surroundings. They hade comorbidities (girls 72.5%, boys 68.8%), mostly - depression (31.3%), were suffering from bullying (54,1%), or violence (26.0%), hade signs of other self-harm (85.4%, girls more often (p 0.000)). Most of them chose to cut for suicide attempts (86.0% girls, 56.2% boys), in 52.8% of cases attempt was spontaneous, 34% - relapsed. Even 34% of events were done in March (18.9%). CONCLUSIONS: Our study revealed the possible circumstances related to adolescents’ suicide: female gender for an attempt, male – for more potentially lethal method, lack of prosperity in family life, comorbidity, experienced bullying, violence, and early spring period. The signs of any self-harm could be an indicator before the suicidal attempt.

Necrotizing pneumonia due to Methicillin-Resistant Staphylococcus Aureus (MRSA) is devastating and difficult to treat in preterm infants. We report a case of severe MRSA necrotizing pneumonia in a preterm infant. As an add-on rescue therapy to vancomycin, linezolid rapidly cured this case after the failure of vancomycin plus rifampicin. This rapid cure suggests that adjunctive rather than rescue linezolid may be considered in such cases.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a newly described condition. It has a spectrum of presentations related to hyperinflammation and cytokine storm. We report the first case of PIMS-TS in a child on established anti-Tumor Necrosis Factor-alpha (anti-TNF-α) therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6-weeks of daily fever with mucocutaneous, gastrointestinal, renal and hematologic involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia (up to 691 µ/L; normal 15-80 µg/L), C-reactive protein (CRP) (>100mg/L for >10 days, normal 0-5 mg/L), erythrocyte sedimentation rate (ESR) consistently >100mm/hr (normal 0-15 mm/hr), raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase (LDH), anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin (PUO) were negative. The condition was refractory to treatment with intravenous immunoglobulin (IVIG) but improved within 24hrs of high dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow up. Polymerase chain reaction (PCR) and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock or organ failure. It is postulated that prior anti-TNF-α therapy attenuated the disease course. Infliximab therapy may interfere with serology testing and produce false negative results. This case supports the need for investigation into infliximab as primary therapy for PIMS-TS.

Background: Adiposity rebound (AR) refers to the second rise of the BMI curve that usually occurs physiologically between 5 and 7 years of age. AR timing has a great impact on children´s health, being the early adiposity rebound (EAR) associated with the development of metabolic disease later in life. Aim: We aimed to investigate the prevalence of EAR in a cohort of preterm newborns. Secondary outcomes evaluated if some determinants such as (1) gender (male/female), (2) type of delivery (caesarean/vaginal), (3) birth weight (SGA/NGA/LGA), (4) type of feeding (5) duration of breastfeeding, (6) timing of introduction of solid food, (7) parental education and (8) parental pre-pregnancy BMI can influence EAR in this cohort. Tertiary aim was to evaluate the prevalence of obesity or overweight at 7 years of age in children according to early versus timely AR. Methods: This is a perspective, population-based longitudinal study, where infants born preterm were evaluated at birth and at 1, 3, 6, 9, 12, 15, 18, 24 months and 3, 4, 5, 6, 7 years of gestational-corrected age. Weight and height data were analyzed, and BMI was calculated. AR was assessed in the growth trajectory in a body mass index (BMI) plot. Results: Of the 250 preterm newborns included, 100 completed the 7 years follow-up and entered in the final analysis. The prevalence of EAR in our cohort of preterm newborns was 54%. EAR was associated with being LGA at birth. No other factors were associated to EAR. Early adiposity rebounders have a significant higher BMI at 7 years compared to children with timely AR (17.2 ±2.7 vs 15.6 ± 2.05, p=0.021). No significant differences were found in the prevalence of obesity or overweight at 7 years of age in children with early or timely AR (29% vs 14% p=0.202). Conclusions: Clinical management of preterm infants should focus on reducing excess weight gain to prevent long-term metabolic risk. Others neonatal factors are not associated to an higher risk of EAR.

We report the first case of COVID 19 pneumonia in a preterm neonate in Mayotte, an overseas department of France. The respiratory distress with typical thoracic imaging lesions appears at 14 days of life. This case-report emphasizes the need for a cautious and close up follow-up for asymptomatic neonates born to mothers with COVID-19 infection. Vertical transmission cannot be excluded in this case.

Recent reports suggest that the clinical course of coronavirus disease 2019 (COVID-19) in previously healthy children is usually milder as compared to adults. However, children with comorbid conditions such as diabetes are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as morbidity and mortality due to COVID-19. Experience in adults with diabetes shows that they are prone to faster metabolic decompensation, develop diabetes-related complications, and have a poor prognosis when hospitalized with COVID-19. Data on children are limited. The aim of this mini-review is to discuss the possible risks to children and adolescents with diabetes during the current pandemic and the special considerations in management in those affected with COVID-19. The challenges for children who develop new-onset type 1 diabetes during the COVID-19 lockdown, especially in accessing healthcare, are also discussed.

Background: Cancer has been one of the most critical health problems during the past decades which require serious consideration, especially in developing countries. Methods: 80 parents of the children with different types of cancers were studied via both questionnaire and person-to-person interview after announcing their informed consent. Results: The highest delay in patients' initial referral was due to the following factors: lack of attention or ignoring the first symptoms, delay in referring to the physician, low economic status and even lack of family support for the patient. In addition, visiting several doctors after the initial diagnosis, uncertainty about the first proposed method, and high cost of treatment can be mentioned as the main causes of delays in the start of treatment. Conclusion: Education plays an important role in identifying the signs of cancer. In addition, proper relationship and cooperation between the health system and physicians as well as provision of adequate information to patients could lead to the long-term cooperation of these patients in continuing their treatment.

In the end of April nearly 100 cases of children aged between 6 month and 9 years with Kawasaki like disease were reported (mostly in Europe) probably linked to COVID-19. With the increasing awareness of this condition the number of cases reported is increasing worldwide. We aim to sum up the known data about this new entity based on published data (in a case report, a series of 8 cases and in newspapers and society statement) and using our knowledge of classical Kawasaki disease. It seems to be a post infectious disease with an onset between 2-4 weeks after the infection, probably in genetically predisposed children aged between 6 month to 17 years. A very rough estimation of incidence based on current data from Bergamo, Italy, and New York State and a lot assumption is between 0.016% (95% CI:0.013-0.02%) - 0.31% (95% CI: 0.2-0.47%) of infected children. Clinical signs overlaps with Kawasaki disease in some children, but another feature is prominent gastrointestinal manifestations. For the 9 detailed patients most had incomplete presentation for Kawasaki disease (with a mean 1.7 (+/-1.2) criteria per patient for the 5 non fever criterion) and only one had a classical form. In some cases, presentation is closer to toxic shock syndrome or isolated myocarditis. Persistent fever seems to be constant and biological exploration are consistent with inflammation (elevated CRP, ferritin and D-Dimers). Management is described as supportive and children seem to improve rapidly, but can require cardiac or respiratory support. In date of 11 may 2020 there is 4 deaths confirmed linked to these new entities (1 in UK and 3 in New York). Paediatricians and general practitioners need to be aware of these possible evolution following COVID-19 infection. However it seems to be rare and children are probably still spared from most morbidities and mortality linked to COVID-19 infection .There are need of published detailed cohorts to better delineate these entities.

The microbiota of human breast milk (HBM) contributes to infant gut colonization; however, whether bacterial extracellular vesicles (EVs) are present in HBM or might contribute to this process remains unknown. In the present study, we characterized the HBM microbiota of healthy Korean mothers and measured the key bacteria likely affecting infant gut colonization by analyzing both the microbiota and bacterial EVs. A total of 22 HBM samples were collected from lactating mothers. The DNA of bacteria and bacteria-derived EVs was extracted from each sample. Gene analysis was performed using Illumina MiSeq. Firmicutes accounted for the largest portion among the phyla, followed by Proteobacteria, Bacteroides, and Actinobacteria in both bacteria and bacterial EV samples. At the genus level, Streptococcus (25.1%) and Staphylococcus (10.7%) were predominant in bacterial samples, whereas Bacteroides (9.1%), Acinetobacter (6.9%), and Lactobacillaceae(f) (5.5%) were prevalent in bacterial EV samples. Several genera including Bifidobacterium were significantly positively correlated between the two samples. Our findings reveal the diverse bacterial communities in HBM of healthy lactating mothers and suggest the presence of key bacteria with metabolic activity in HBM and that EVs derived from these bacteria may contribute to the vertical transfer of gut microbiota from mother to infant.

At least one ultrasound is recommended to predict fetal growth restriction and low birthweight earlier in pregnancy. However, in low-income countries imaging equipment and trained manpower are scarce. Hence, we developed and validated a model and risk score to predict low birthweight using maternal characteristics during pregnancy, for use in resource limited settings. We conducted a prospective cohort study among 379 pregnant women in South Ethiopia. A step-wise multivariable analysis was done to develop the prediction model. To improve clinical utility, we developed a simplified risk score to classify pregnant women at high- or low-risk of low birthweight. The accuracy of the model was evaluated using the area under the receiver operating characteristics curve (AUC) and calibration plot. We evaluated the clinical impact of the model using a decision curve analysis across various threshold probabilities. Age at pregnancy, underweight, anemia, height, gravidity, and presence of comorbidity remained in the final multivariable prediction model. The area under the receiver operating characteristics curve (AUC) of the model was 0.83 (95% confidence interval: 0.78 to 0.88). The decision curve analysis shows the model provides a higher net benefit across ranges of threshold probabilities. In general, this study showed the possibility of predicting low birthweight using maternal characteristics during pregnancy. The model could help to identify those at higher risk of having a low birthweight baby. This feasible prediction model would offer an opportunity to reduce obstetric-related complications and thus improving the overall maternal and child healthcare in low- and middle-income countries.

The aim of the study was to assess the relationship between the shape of the anterior-posterior curvature of the spine and body composition in school-children. The study included 257 children, aged 11-12. Correct spinal curvature was established in 106 (41.08%) subjects. Other types included: decreased kyphosis and correct lordosis - 40 participants (15.50%), correct kyphosis and decreased lordosis - 24 individuals (9.30%), increased kyphosis and correct lordosis - 17 subjects (6.59%), correct kyphosis and increased lordosis - 22 children (8.53%), decreased kyphosis and decreased lordosis - 32 people (12.40%), decreased kyphosis and increased lordosis - 4 of the examined subjects (1.55%), increased kyphosis and lordosis - 13 people (5.04%). In addition, 134 (51.94%) demonstrated scoliotic posture and 8 (3.10%) scoliosis. There were significant relationships between the shape of the anterior-posterior curvatures and body composition in school-children. Those with a strong body build (predominance of mesomorphs) were generally characterised by the correct formation of these curvatures. In contrast, lean people (with the predominance of ectomorphic factors) were more likely to experience abnormalities. No correlations with body composition were observed in the group with scoliotic posture or scoliosis.

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.

Objective: Racial/ethnic disparities in infant mortality (IM) continue to persist in the United States, with Black/African Americans (AA) being disproportionally affected with threefold increase in mortality compared to Whites. Epidemiologic data have identified maternal characteristics as risk IM such as eclampsia, maternal education, smoking, maternal weight, maternal SES, and family structure. Understanding the cause of causes including the method of labor and delivery and the racial heterogeneity may facilitate intervention mapping in narrowing the Black White IM risk differences. We aimed to assess the temporal/racial trends and the methods of delivery, mainly vaginal versus cesarean section (C-section) as exposure function of IM. Methods: The United States linked Birth/Infant Death records (2007-2016) were used with a cross-sectional ecologic design. The analysis involved chi squared statistic, incidence rate estimation, and period percent change. Results: Of the 40,445,070 births between 2007 and 2016, cumulative mortality incidence was 249,135 (1.16 per 1000). The IM rate was highest among Black/AA (11.41 per 1000), intermediate among Whites (5.19 per 1000), and lowest among Asian /Pacific Islanders (4.24 per 1000). The cumulative incidence rate difference, comparing vaginal to cesarean procedure was 1.73 per 1000 infants, implying excess IM with C-section. Compared to C-section, there was a 31% decreased risk of IM among mothers with vaginal delivery, rate ratio (RR) = 0.69, 95% CI 0.64-0.74. Racial disparities was observed in the method of delivery associated with IM. Black/AA mothers with vaginal delivery had a 6% decreased risk of IM compared to C-section, RR = 0.94, 95%CI 0.92-0.95, while Whites with vaginal delivery had a 38% decrease risk of IM relative to C-section, RR= 0.68, 95%CI 0.67-0.69, p<0.001. Conclusion: Infant mortality varied by race, with Black/AA disproportionally affected which is explained in part by labor and delivery procedures, suggesting reliable and equitable intrapartum assessment of Black/AA mothers during labor.

Congenital heart disease (CHD) is among the 4 more common causes of infant mortality in Latin America. Pulse oximetry screening (POS) is useful for early diagnosis and improved outcomes of critical CHD. We describe POS implementation efforts in Latin American countries guided and/or coordinated by the Ibero American Society of Neonatology (SIBEN) as well as the unique challenges that are faced for universal implementation. SIBEN collaborates to improve neonatal quality of care and outcomes. A few years ago, a Clinical Consensus on POS was finalized. Since then, we participated in 12 Latin American countries to educate neonatal nurses and neonatologists on POS and to help with its implementation. The findings reveal that despite wide disparities in care that exist between and within countries, and the difficulties and challenges for implementing POS, significant progress was made. We conclude that universal POS is not easy to implement in Latin America but, when executed, not only it has been of significant value for babies with CHD but also for many with other hypoxemic conditions. The successful and universal implementation of POS in the future is essential to reduce the mortality associated with CHD and other hypoxemic conditions and will ultimately lead to the survival of many more Latin American babies. POS saves newborns’ lives in Latin America.

Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed murine thrombocytosis in the absence of functional TRPV4, but no prior reports have described platelet count abnormalities in the context of human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4-associated metatropic dysplasia that was lethal in the infantile period.