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Lung involvement in children with congenital cytomegalovirus infection has been scarcely described. We describe three new cases of persistent pulmonary hypertension in children with congenital cytomegalovirus and review the other seven cases reported in the literature since 1988. All children had a symptomatic infection, including severe central nervous system or visceral findings. Morbidity and mortality were high. Persistent pulmonary hypertension may be a rare complication in severely symptomatic congenital cytomegalovirus infants. It is important to screen for congenital cytomegalovirus in cases of idiopathic refractory persistent pulmonary hypertension. Intensive treatment should be undertaken to treat this potentially rare lung involvement in combination with antiviral treatment., (© 2024 Japanese Teratology Society.)

Purpose: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center., Methods: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO., Results: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032)., Conclusions: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited., Research Question: What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era?, Study Design and Methods: We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 ± 1.05 years)., Results: Thirty-seven children aged 15.73 ± 1.31 years, mean gestational age 26 weeks ( ± 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean V̇O 2 peak of 91% predicted. The BPD and non-BPD subgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 ± 18.99 vs. 26.58 ± 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 ± 0.13 vs. 0.37 ± 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 ± 0.13 vs. 1.11 ± 0.10, p = 0.021)., Interpretation: In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

To evaluate the effectiveness of a novel protocol, adopted in our institution, as a quality improvement project for congenital diaphragmatic hernia (CDH). A maximal lung protection (MLP) protocol was implemented in 2019. This strategy included immediate use of high-frequency oscillatory ventilation (HFOV) after birth, during the stay at the Neonatal Intensive Care Unit (NICU), and during surgical repair. HFOV strategy included low distending pressures and higher frequencies (15 Hz) with subsequent lower tidal volumes. Surgical repair was performed early, within 24 h of birth, if possible. A retrospective study of all inborn neonates prenatally diagnosed with CDH and without major associated anomalies was performed at the NICU of Schneider Children's Medical Center of Israel between 2009 and 2022. Survival rates and pulmonary outcomes of neonates managed with MLP were compared to the historical standard care cohort. Thirty-three neonates were managed with the MLP protocol vs. 39 neonates that were not. Major adverse outcomes decreased including death rate from 46 to 18% (p = 0.012), extracorporeal membrane oxygenation from 39 to 0% (p < 0.001), and pneumothorax from 18 to 0% (p = 0.013)., Conclusion:  MLP with early surgery significantly improved survival and additional adverse outcomes of neonates with CDH. Prospective randomized studies are necessary to confirm the findings of the current study., What Is Known: • Ventilator-induced lung injury was reported as the main cause of mortality in neonates with congenital diaphragmatic hernia (CDH). • Conventional ventilation is recommended by the European CDH consortium as the first-line ventilation modality; timing of surgery is controversial., What Is New: • A maximal lung protection strategy based on 15-Hz high-frequency oscillatory ventilation with low distending pressures as initial modality and early surgery significantly reduced mortality and other outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis., Methods: We performed a retrospective population-based cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network., Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis., Conclusions: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background and Objectives: Late-onset sepsis is associated with significant morbidity and mortality among very low birth weight (VLBW) infants. Our objective was to determine risk factors associated with late-onset sepsis and to present temporal trends in overall and pathogen-specific rates., Methods: Population-based study by the Israel Neonatal Network on VLBW infants (≤1500 g) born between 1995 and 2019. Late-onset sepsis required clinical symptoms and microbiologic confirmation. Bivariate and multivariable analyses were performed to identify risk factors. The study period was divided into 4 epochs. Overall and pathogen-specific late-onset sepsis rates for each epoch were compared., Results: The study population comprised 31 612 VLBW infants, of whom 7423 (23.5%) had late-onset sepsis. An increased adjusted risk of late-onset sepsis was associated with gestational age <27 w (odds ratio [OR] 8.90, 95% confidence interval [CI] 7.85-10.09) and delivery room resuscitation (OR 1.43, 95% CI 1.34-1.52) and a decreased adjusted risk among infants born between 2013 and 2019 (OR 0.32, 95% CI 0.29-0.35). Late-onset sepsis rates declined from 29.5% in 1995 to 2000 to 13.0% in 2013 to 2019. Gram-negative and fungal rates decreased in all epochs, whereas gram-positive rates decreased only in the last epoch. The adjusted hazard ratios (95% CI) decreased in the 2013 to 2019 versus 1995 to 2000 epochs and were: all late-onset sepsis, 0.40 (0.37-0.43); gram-positive, 0.47 (0.37-0.59); gram- negative, 0.54 (0.48-0.61); fungal, 0.17 (0.12-0.22)., Conclusions: The strongest risk factor for late-onset sepsis was gestational age <27 w. Over a 25-year period, the pathogen-specific rates of late-onset sepsis among VLBW infants decreased approximately twofold for gram-positive and gram-negative bacterial infections and sixfold for fungal infections., (Copyright © 2023 by the American Academy of Pediatrics.)

Introduction: Perianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry., Materials and Methods: A retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test., Results: Sixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038)., Conclusions: Perianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed "the self-regulation clock" and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the "clock" circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.