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Yellow fever vaccine (YFV) is a live attenuated vaccine that can cause a mild infection in immunocompetent patients. However, it may not be self-limiting in patients with inborn errors of immunity (IEI) and may be the first and most severe presentation in these patients. A 10-month-old female infant sought emergency care presenting fever for three days and diffuse exanthema. She was a previous healthy child of consanguineous parents. The child had received YFV 28 days before the onset of symptoms. Upon hospital admission, petechial rash on the limbs and hepatosplenomegaly were noted on physical exam. Laboratory tests showed thrombocytopenia, increased serum aminotransferases and elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase levels. During hospitalization she developed hypoactivity, drowsiness, and hypotonia. The possibility of viscerotropic and neurotropic vaccine associated disease was suspected and a possible primary immunodeficiency disease considered. The patient was tested for antibodies against the yellow fever virus (MAC ELISA) on serum and cerebrospinal fluid (CSF) samples, showing positive IgM results. Immunophenotyping showed low levels of lymphocytes and absence of T-cell receptor excision circles (TREC), leading to diagnose of severe combined immunodeficiency disease (SCID). Despite treatment, after 35 days of hospitalization, she evolved to cardiorespiratory arrest and death. Serious adverse events after administration of the YFV are rare and associated with neurological or visceral involvement in most cases. The unfavorable outcome highlights the importance of neonatal screening for SCID and the clinical suspicion of primary immunodeficiencies in infants who have serious adverse events to live virus vaccines.

Objectives: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB., Methods: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18 years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation., Results: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients., Conclusions: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To evaluate the rates of exclusive breastfeeding (EBF) and growth of preterm and/or low birth weight newborns during the third stage of the Kangaroo Method (TSKM), at discharge., Methods: Retrospective study in a reference public maternity hospital between Jan/2014 and Dec/2017, including the preterm (less than 37 weeks) and/or low birth weight (less than 2500 g) newborn infants. Information was collected from medical records. Statistics analysis was done in SPSS software., Results: 482 infants were included and followed up at the TSKM ambulatory. The average gestational age was 33 weeks (variation: 24-39 weeks) and birth weight, 1715g (variation: 455-2830 g). EBF occurred in 336 (70.1%) infants at hospital discharge, and in 291 (60.4%) at TSKM discharge. Each additional day of hospital stay increased the chance of infant formula (IF) use by 9.3% at hospital discharge and by 10.3% at TSKM discharge. Staying in the Kangaroo Neonatal Intermediate Care Unit (KNICU) favored EBF at hospital discharge and TSKM discharge (p<0.001). Not performing the kangaroo position increased the chance formula administration to the newborn infant at hospital discharge by 11%. Weight gain and head circumference growth were higher in infants using formula (p<0.001)., Conclusions: The length of hospital stay and not performing the kangaroo position favored the use of infant formula at hospital and TSKM discharge. Staying in the KNICU favored exclusive breastfeeding at hospital and TSKM discharge. Weight gain and HC growth were higher in newborns receiving infant formula.

Background: A handheld optical device was developed to evaluate a newborn's skin maturity by assessing the photobiological properties of the tissue and processing it with other variables to predict early neonatal prognosis related to prematurity. This study assessed the device's ability to predict respiratory distress syndrome (RDS)., Methods: To assess the device's utility we enrolled newborns at childbirth in six urban perinatal centers from two multicenter single-blinded clinical trials. All newborns had inpatient follow-up until 72 h of life. We trained supervised machine learning models with data from 780 newborns in a Brazilian trial and provided external validation with data from 305 low-birth-weight newborns from another trial that assessed Brazilian and Mozambican newborns. The index test measured skin optical reflection with an optical sensor and adjusted acquired values with clinical variables such as birth weight and prenatal corticoid exposition for lung maturity, maternal diabetes, and hypertensive disturbances. The performance of the models was evaluated using intrasample k-parts cross-validation and external validation in an independent sample., Results: Models adjusting three predictors (skin reflection, birth weight, and antenatal corticoid exposure) or five predictors had a similar performance, including or not maternal diabetes and hypertensive diseases. The best global accuracy was 89.7 (95% CI: 87.4 to 91.8, with a high sensitivity of 85.6% (80.2 to 90.0) and specificity of 91.3% (95% CI: 88.7 to 93.5). The test correctly discriminated RDS newborns in external validation, with 82.3% (95% CI: 77.5 to 86.4) accuracy. Our findings demonstrate a new way to assess a newborn's lung maturity, providing potential opportunities for earlier and more effective care., Trial Registration: RBR-3f5bm5 (online access: http://www.ensaiosclinicos.gov.br/rg/RBR-3f5bm5/), and RBR-33mjf (online access: https://ensaiosclinicos.gov.br/rg/RBR-33rnjf/)., Competing Interests: The authors declare a patent deposit on behalf of the Universidade Federal de Minas Gerais and Fundação de Amparo a Pesquisa de Minas Gerais, Brazil (http://www.fapemig.br/en/). BR1020170235688 (CTIT-PN862)., (© 2023 Reis, Pappa, Nader, do Vale, Silveira Neves, Vitral, Mussagy, Norberto Dias and Romanelli.)

Introduction: Febrile neutropenia (FN) is a serious complication of cancer chemotherapy. The present study aimed to identify risk factors for documented infection in pediatric patients with FN and cancer., Methods: This prospective cohort study included patients under 18 years from 2016 to 2018. Infection was defined according to the Centers for Disease Control and Prevention criteria., Results: A total of 172 febrile neutropenic episodes were evaluated. From univariate analysis, the risk factors were: female gender; monocyte count < 100 cell/mm³, platelets < 50,000, C-reactive protein (CRP) > 90 mg/dl and hemoglobin < 7mg/dl at the onset of an episode; two or more episodes of FN, and; fever onset; positive blood culture at the fever onset. Independent risk factors according to the multivariate analysis were: CRP at the onset of a febrile episode > 90mg/dl, fever onset and first blood culture with a positive result. The lowest probability of infection was related to first episode and to platelets > 50,000 at the onset of fever., Conclusion: A CRP > 90 at the onset of a febrile episode, platelets < 50,000, second episode or more, first fever episode during hospitalization and positive first blood culture were found to be associated with a higher risk of infection and they could be useful for the establishment of risk scores for infection in neutropenic children., Competing Interests: Conflicts of interest The authors report no conflict of interest., (Copyright © 2021. Published by Elsevier España, S.L.U.)

Introduction: A new medical device was previously developed to estimate gestational age (GA) at birth by processing a machine learning algorithm on the light scatter signal acquired on the newborn's skin. The study aims to validate GA calculated by the new device (test), comparing the result with the best available GA in newborns with low birth weight (LBW)., Methods: We conducted a multicenter, non-randomized, and single-blinded clinical trial in three urban referral centers for perinatal care in Brazil and Mozambique. LBW newborns with a GA over 24 weeks and weighing between 500 and 2,500 g were recruited in the first 24 h of life. All pregnancies had a GA calculated by obstetric ultrasound before 24 weeks or by reliable last menstrual period (LMP). The primary endpoint was the agreement between the GA calculated by the new device (test) and the best available clinical GA, with 95% confidence limits. In addition, we assessed the accuracy of using the test in the classification of preterm and SGA. Prematurity was childbirth before 37 gestational weeks. The growth standard curve was Intergrowth-21st, with the 10th percentile being the limit for classifying SGA., Results: Among 305 evaluated newborns, 234 (76.7%) were premature, and 139 (45.6%) were SGA. The intraclass correlation coefficient between GA by the test and reference GA was 0.829 (95% CI: 0.785-0.863). However, the new device (test) underestimated the reference GA by an average of 2.8 days (95% limits of agreement: -40.6 to 31.2 days). Its use in classifying preterm or term newborns revealed an accuracy of 78.4% (95% CI: 73.3-81.6), with high sensitivity (96.2%; 95% CI: 92.8-98.2). The accuracy of classifying SGA newborns using GA calculated by the test was 62.3% (95% CI: 56.6-67.8)., Discussion: The new device (test) was able to assess GA at birth in LBW newborns, with a high agreement with the best available GA as a reference. The GA estimated by the device (test), when used to classify newborns on the first day of life, was useful in identifying premature infants but not when applied to identify SGA infants, considering current algohrithm. Nonetheless, the new device (test) has the potential to provide important information in places where the GA is unknown or inaccurate., Competing Interests: The authors declare a patent deposit on behalf of the Universidade Federal de Minas Gerais and Fundação de Amparo a Pesquisade Minas Gerais, Brazil. The inventors were ZSNR, RNG, and BR1020170235688 (CTIT-PN862). BirthTech, a spin-off company, received a license to produce and commercialize this technology, and RG is its founder. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Vitral, Romanelli, Reis, Guimarães, Dias, Mussagy, Taunde, Neves, de São José, Pantaleão, Pappa, Gaspar and de Aguiar.)

Background: Recognizing premature newborns and small-for-gestational-age (SGA) is essential for providing care and supporting public policies. This systematic review aims to identify the influence of the last menstrual period (LMP) compared to ultrasonography (USG) before 24 weeks of gestation references on prematurity and SGA proportions at birth., Methods: Systematic review with meta-analysis followed the recommendations of the PRISMA Statement. PubMed, BVS, LILACS, Scopus-Elsevier, Embase-Elsevier, and Web-of-Science were searched (10-30-2022). The research question was: (P) newborns, (E) USG for estimating GA, (C) LMP for estimating GA, and (O) prematurity and SGA rates for both methods. Independent reviewers screened the articles and extracted the absolute number of preterm and SGA infants, reference standards, design, countries, and bias. Prematurity was birth before 37 weeks of gestation, and SGA was the birth weight below the p10 on the growth curve. The quality of the studies was assessed using the New-Castle-Ottawa Scale. The difference between proportions estimated the size effect in a meta-analysis of prevalence., Results: Among the 642 articles, 20 were included for data extraction and synthesis. The prematurity proportions ranged from 1.8 to 33.6% by USG and varied from 3.4 to 16.5% by the LMP. The pooled risk difference of prematurity proportions revealed an overestimation of the preterm birth of 2% in favor of LMP, with low certainty: 0.02 (95%CI: 0.01 to 0.03); I 2 97%). Subgroup analysis of USG biometry (eight articles) showed homogeneity for a null risk difference between prematurity proportions when crown-rump length was the reference: 0.00 (95%CI: -0.001 to 0.000; I 2 : 0%); for biparietal diameter, risk difference was 0.00 (95%CI: -0.001 to 0.000; I 2 : 41%). Only one report showed the SGA proportions of 32% by the USG and 38% by the LMP., Conclusions: LMP-based GA, compared to a USG reference, has little or no effect on prematurity proportions considering the high heterogeneity among studies. Few data (one study) remained unclear the influence of such references on SGA proportions. Results reinforced the importance of qualified GA to mitigate the impact on perinatal statistics., Trial Registration: Registration number PROSPERO: CRD42020184646., (© 2023. The Author(s).)

Background: Early access to antenatal care and high-cost technologies for pregnancy dating challenge early neonatal risk assessment at birth in resource-constrained settings. To overcome the absence or inaccuracy of postnatal gestational age (GA), we developed a new medical device to assess GA based on the photobiological properties of newborns' skin and predictive models., Objective: This study aims to validate a device that uses the photobiological model of skin maturity adjusted to the clinical data to detect GA and establish its accuracy in discriminating preterm newborns., Methods: A multicenter, single-blinded, and single-arm intention-to-diagnosis clinical trial evaluated the accuracy of a novel device for the detection of GA and preterm newborns. The first-trimester ultrasound, a second comparator ultrasound, and data regarding the last menstrual period (LMP) from antenatal reports were used as references for GA at birth. The new test for validation was performed using a portable multiband reflectance photometer device that assessed the skin maturity of newborns and used machine learning models to predict GA, adjusted for birth weight and antenatal corticosteroid therapy exposure., Results: The study group comprised 702 pregnant women who gave birth to 781 newborns, of which 366 (46.9%) were preterm newborns. As the primary outcome, the GA as predicted by the new test was in line with the reference GA that was calculated by using the intraclass correlation coefficient (0.969, 95% CI 0.964-0.973). The paired difference between predicted and reference GAs was -1.34 days, with Bland-Altman limits of -21.2 to 18.4 days. As a secondary outcome, the new test achieved 66.6% (95% CI 62.9%-70.1%) agreement with the reference GA within an error of 1 week. This agreement was similar to that of comparator-LMP-GAs (64.1%, 95% CI 60.7%-67.5%). The discrimination between preterm and term newborns via the device had a similar area under the receiver operating characteristic curve (0.970, 95% CI 0.959-0.981) compared with that for comparator-LMP-GAs (0.957, 95% CI 0.941-0.974). In newborns with absent or unreliable LMPs (n=451), the intent-to-discriminate analysis showed correct preterm versus term classifications with the new test, which achieved an accuracy of 89.6% (95% CI 86.4%-92.2%), while the accuracy for comparator-LMP-GA was 69.6% (95% CI 65.3%-73.7%)., Conclusions: The assessment of newborn's skin maturity (adjusted by learning models) promises accurate pregnancy dating at birth, even without the antenatal ultrasound reference. Thus, the novel device could add value to the set of clinical parameters that direct the delivery of neonatal care in birth scenarios where GA is unknown or unreliable., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2018-027442., (©Zilma Silveira Nogueira Reis, Roberta Maia de Castro Romanelli, Rodney Nascimento Guimarães, Juliano de Souza Gaspar, Gabriela Silveira Neves, Marynea Silva do Vale, Paulo de Jesus Nader, Martha David Rocha de Moura, Gabriela Luíza Nogueira Vitral, Marconi Augusto Aguiar dos Reis, Marcia Margarida Mendonça Pereira, Patrícia Franco Marques, Silvana Salgado Nader, Augusta Luize Harff, Ludmylla de Oliveira Beleza, Maria Eduarda Canellas de Castro, Rayner Guilherme Souza, Gisele Lobo Pappa, Regina Amélia Pessoa Lopes de Aguiar. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.09.2022.)

Objectives: To identify the prevalence of viral congenital infections in newborns classified as premature, low-birthweight, small for gestational age or intrauterine growth restriction., Methods: The definition considered for selecting papers were: P as newborns younger than 28 days; V as low-birthweight, prematurity and intrauterine growth restriction; O as frequency of congenital infections with Cytomegalovirus, Parvovirus B19, Herpes Simplex, and Zika virus. The research was performed using EMBASE, LILACS, SCOPUS and MEDLINE databases, with no limitations on date and language., Results: Eight studies were included. Manuscripts including Herpes Simplex, Zika virus or Parvovirus B19 did not fulfill the defined criteria. A wide variation in the frequency of CMV congenital infection (0-4.8%) was found, which might be attributed to regional and methodological differences between investigations., Conclusions: Newborn characteristics associated with CMV congenital infections may direct investigations towards these patients with a higher probability of infection. However, as data are controversial, studies concerning screening of infection are important to define recommendations of diagnosis., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Since the introduction of Haemophilus influenzae type b vaccines, invasive disease due to Haemophilus influenzae serotype a (Hia) has been reported with increasing frequency., Methods: This study is based on hospital-based surveillance for Hia meningitis over a 5-year period., Results: Thirty-five patients with H. influenzae meningitis were hospitalized and 12 were serotype a. Hia was detected in blood and cerebrospinal fluid by culture or reverse transcription polymerase chain reaction. Patients' median age was 10 months, 7 (58%) boys and 5 (41%) girls. Ten (83%) children had received at least 1 vaccine dose against Haemophilus influenzae type b. All patients were treated with ceftriaxone for a median period of 11 days. The main complications described were empyema in 5 (41%) and seizures in 3 (25%) patients. Two (16.6%) patients died due to cerebral damage and shock., Conclusions: Invasive disease due to Hia affecting young children accounts for considerable morbidity and mortality., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The high prevalence and severity of congenital toxoplasmosis in Brazil, with several affected individuals progressing to low vision, emphasize the importance of evaluating their quality of life. In this study, the Children's Visual Function Questionnaire (CVFQ) was adapted to the sociocultural context of Brazilian children, and its psychometric properties were investigated for evaluating the vision-related quality of life of these individuals., Methods: This was a nested cross-sectional epidemiological study that prospectively monitored a cohort of 142 preschool children at a single referral university hospital in Belo Horizonte, Brazil. All children underwent complete ophthalmological examination, including visual acuity testing and binocular indirect ophthalmoscopy. Questionnaires were applied to their parents and caregivers to evaluate quality of life perception, as well as socioeconomic status of their families. Psychometric properties of the quality of life scale were evalua-ted by multivariate statistical analyses., Results: Adaptation to the Brazilian version of CVFQ-7 resulted in CVFQ-BR-toxo, a questionnaire for evaluating the perception of parents/caregivers about the vision-related quality of life of preschool children with congenital toxoplasmosis. The following six subscales were identified based on description, variability structure, and interpretation/grouping of items: general health, visual acuity, visual performance/functional vision, personal and social behavior, impact on family, and treatment. Children with low vision related to congenital toxoplasmosis had significantly lower scores for the following subscales: visual acuity (p=0.004), visual performance/functional vision (p=0.008), impact on family (p=0.001), and overall health (p=0.001)., Conclusion: Psychometric properties were appropriate concerning the validity of the quality of life construct. CVFQ-BR-toxo could demonstrate the impact of vision impairment on families of children with congenital toxoplasmosis.

Background: Patients undergoing solid organ transplantation, particularly those who live or have lived in tuberculosis (TB) endemic areas, are at a high risk of developing TB. The majority of post-transplantation TB cases are associated with reactivation of latent TB infection (LTBI). Brazil is in a single position with overlapping areas of high TB endemicity and high transplant activity. In liver transplant (LT), one should be aware of the potential hepatotoxicity associated with the treatment regimens for LTBI., Aim: To evaluate the frequency of LTBI in LT patients and treatment-related issues., Methods: This was a retrospective analysis of a cohort of cirrhotic patients aged ≥ 18 years, who underwent LT at a high-complexity teaching hospital from January 2005 to December 2012., Results: Overall, 429 patients underwent LT during the study period. Of these, 213 (49.7%) underwent the tuberculin skin test (TST) during the pre-transplant period, and 35 (16.4%) of them had a positive result. The treatment for LTBI was initiated after LT in 12 (34.3%) of the TST-positive patients; in 3 (25.0%), treatment was maintained for at least 6 mo., Conclusion: The prevalence of LTBI was lower than expected. Initiation and completion of LTBI treatment was limited by difficulties in the management of these special patients., Competing Interests: Conflict-of-interest statement: The authors declare there is no potential conflict-of-interest in this study., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)