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Objective: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae., Study Design: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8 + and CD4 + T lymphocytes (CMV-IFN-γ-CD8 + /CD4 + ) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up., Results: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8 + or CD4 + lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study., Conclusions: CMV-specific IFN-γ-CD4 + and CD8 + T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae., Competing Interests: Declaration of Competing Interest DBG received fees from MSD as speaker in educational activities. JSL received fees from Biomerieux as speaker. None of the remaining authors have any conflict of interests to declare. This work was supported by projects PI 16/00807, PI 19/01333, and PI 22/01540, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and co-funded by the European Regional Development Fund. DBG was supported by the Spanish Ministry of Science and Innovation - Instituto de Salud Carlos III and by Fondos FEDER “Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 INT20/00  086 and 2023 INT23/00  039”. The study was approved by the Ethics Committee of Hospital Universitario 12 de Octubre. Paula Rodríguez-Molino was funded by the Spanish Ministry of Science and Innovation-Instituto de Salud Carlos III and Fondos FEDER (Contrato Río Hortega CM21/00  174)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Prognostic markers for fetal transmission of Cytomegalovirus (CMV) infection during pregnancy are poorly understood. Maternal CMV-specific T-cell responses may help prevent fetal transmission and thus, we set out to assess whether this may be the case in pregnant women who develop a primary CMV infection., Methods: A multicenter prospective study was carried out at 8 hospitals in Spain, from January 2017 to April 2020. Blood samples were collected from pregnant women at the time the primary CMV infection was diagnosed to assess the T-cell response. Quantitative analysis of interferon producing specific CMV-CD8+/CD4+ cells was performed by intracellular cytokine flow cytometry., Results: In this study, 135 pregnant women with a suspected CMV infection were evaluated, 60 of whom had a primary CMV infection and samples available. Of these, 24 mothers transmitted the infection to the fetus and 36 did not. No association was found between the presence of specific CD4 or CD8 responses against CMV at the time maternal infection was diagnosed and the risk of fetal transmission. There was no transmission among women with an undetectable CMV viral load in blood at diagnosis., Conclusions: In this cohort of pregnant women with a primary CMV infection, no association was found between the presence of a CMV T-cell response at the time of maternal infection and the risk of intrauterine transmission. A detectable CMV viral load in the maternal blood at diagnosis of the primary maternal infection may represent a relevant biomarker associated with fetal transmission., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DBG received fees from MSD as speaker in educational activities. None of the remaining authors have any conflict of interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Soriano-Ramos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aimed to assess the applicability of the insertion of small diameter catheters through the femoral vein in extremely low-birth-weight (ELBW) infants., Study Design: All femoral small diameter catheters (Silastic or femoral arterial catheter [FAC]) inserted in ELBW infants in a tertiary level neonatal intensive care unit were retrospectively reviewed. Success rate, dwelling time, and percutaneously inserted central venous catheter-related complications were recorded., Results: Thirteen small diameter catheters were inserted in seven ELBW infants. Mean gestational age at birth was 25 +3  weeks (standard deviation [SD] ± 2.12) and mean birth weight was 686 g (SD ± 204.9). Mean weight at the first time of insertion was 1,044 g (SD ± 376.3). In two occasions, a FAC was used instead of a Silastic. In most cases (11/13, 84.6%), the patient was intubated prior to the procedure. The mean dwelling time was 16.7 days (SD ± 9.8). Most of the inserted small diameter catheters were removed electively (8/12, 66.7%), except for one episode of clinical sepsis from coagulase-negative Staphylococcus and three cases of accidental line extravasation. No other complications were reported. The success rate was 92.3%., Conclusion: Femoral venous catheterization using small diameter catheters in ELBW infants may be promising when other routes have been exhausted. Our results support that it is a feasible technique that can be performed at the bedside with successful results when conducted by experienced personnel., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Up to 15%-20% of infected newborns will develop long-term sequelae such as hearing loss and neurologic abnormalities. The aim of this study was to investigate the prevalence of congenital CMV infection (cCMV) and associated clinical abnormalities in Spain., Methods: A prospective screening for cCMV by viral load in saliva was performed. Saliva samples were obtained within the first 72 hours of life in a maternity ward in Madrid (Spain), during a 1-year period. All positive screening tests were confirmed with viral load in urine. Clinical, laboratory, auditory, visual and cerebral imaging assessments were performed in all children with cCMV., Results: Of the 4097 neonates born during the study period, 3190 (78%) were included. CMV viral load in saliva was detectable in 24/3190 (0.75%) children, and congenital infection was confirmed in 15/3190 (0.47%, CI 95%: 0.29%-0.77%). Positive predictive value was 62.5% (CI 95%: 46.5%-76.1%). Two infants presented symptoms at birth. Eight (53.3%) children showed abnormalities in magnetic resonance imaging; most of them isolated white matter abnormalities. Newborns with abnormalities in magnetic resonance imaging showed higher viral loads in blood and saliva (P = 0.04)., Conclusions: One in 200 neonates born in our hospital presented a cCMV infection. CMV viral load in saliva has been shown to be a simple and highly accepted screening method but should be confirmed by CMV detection in urine. In spite of the fact that half of infected children had abnormalities in cerebral imaging, diagnosis during the neonatal period would have been impossible without a screening program in most cases.

Background: Fetoscopic laser photocoagulation can directly injure fetal skin and may at birth resemble aplasia cutis congenita (ACC). Case report: A twin monochorionic pregnancy was complicated by twin-to-twin transfusion syndrome requiring in utero laser photocoagulation, resulting in the death of one twin. After birth, the viable baby presented skin lesions in both legs that were congruent with laser-induced burns. Conclusions: Laser-induced burns present as asymmetric superficial non-necrotic or ulcerated lesions, with a geographic outline, which turn into scars with no retraction or contractures and no changes in pain perception or motor limitations over time. ACC lesions are bilateral and symmetric, with a regular outline, an ulcerated or necrotic appearance, a higher degree of skin involvement affecting all skin layers and, over time, they turn into scars with retraction and contractures. These differential features may help clinicians in a challenging approach to the diagnosis of congenital skin defects.

Background: Early hypophosphatemia is common in premature infants ≤1250 g. The aim of this study was to assess the frequency and severity of hypophosphatemia after sodium glycerophosphate supplementation from first day of life in parenteral nutrition and to address the safety of this practice., Methods: Prospective cohort study of infants ≤1250 g birth weight born in a tertiary-care level neonatal intensive care unit and supplied with sodium glycerophosphate from the first day of life. Primary outcome was the presence of hypophosphatemia (<4 mg/dL) on the first week. Data were compared with our 2014 prospective subcohort of infants ≤1250 g receiving phosphate after 48 hours of life and morbidity with that of our 2016 retrospective cohort of ≤1250 g., Results: Fifty-four neonates were included. The frequency of hypophosphatemia was 29.6%. Only 1 patient presented hypophosphatemia <2 mg/dL. Mild hypokalemia was found in 8 patients (50%). No cases of hypernatremia were observed. Patients with hypophosphatemia had significantly lower gestational age (27.4 vs 28.8 weeks, P = .032) and lower z-score birth weight (-1.68 vs -0.47; P = .001). When compared with the 2014 subcohort, we found a lower frequency of hypophosphatemia (29.6% vs 69.2%; P = .008) and a lower rate of samples with hypophosphatemia (20.4% vs 51.4%; P = .0002) and critical hypophosphatemia (0.68% vs 11.4%, P = .0005). No differences were found in morbidity or mortality., Conclusions: Sodium glycerophosphate supplementation in parenteral nutrition from the first day of life significantly decreased the frequency of hypophosphatemia. No adverse events were reported., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Introduction: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Data about the management of CMV infection in pregnant women are scarce, and treatment options are very limited. The aim of the study is to investigate the effectiveness of cytomegalovirus hyperimmune globulin (CMV-HIG) for the prevention and treatment of congenital CMV (cCMV) infection., Materials and Methods: A retrospective observational study was conducted in three tertiary hospitals in Madrid. In the period 2009-2015, CMV-HIG (Cytotect ® CP Biotest, Biotest) treatment was offered to all pregnant women with primary CMV infection and/or detection of CMV-DNA in amniotic fluid in participating centers. Women were divided into prevention and treatment groups (PG and TG, respectively). Those with primary CMV infection who had not undergone amniocentesis comprised the PG and received monthly CMV-HIG (100 UI/kg). If CMV-DNA was subsequently detected in amniotic fluid, one extra dose of CMV-HIG (200 UI/kg) was given 4 weeks after the last dose. Those women were considered to be part of the PG group despite detection of CMV-DNA in amniotic fluid. In the case of a negative result in CMV-DNA detection in amniotic fluid or if amniocentesis was not performed, monthly HIG was given up to the end of the pregnancy., Results: Thirty-six pregnant women were included. Median gestational age at birth was 39 weeks (interquartile range: 38-40) and two children (5.5%) were premature (born at 28 and 34 weeks' gestation). Amniocentesis was performed in 30/36 (83.4%) pregnancies and CMV PCR was positive in 21 of them (70%). One fetus with a positive PCR in amniotic fluid that received one dose of HIG after amniocentesis presented a negative CMV-PCR in urine at birth, and was asymptomatic at 12 months of age. Twenty-four children were infected at birth, and 16/21 (76.2%) presented no sequelae at 12 months, while two (9.5%) had a mild unilateral hearing loss and three (14.3%) severe hearing loss or neurological sequelae. Seventeen women were included in the PG and 19 in the TG. In the PG 7/17 (41%) fetuses were infected, one pregnancy was terminated due to abnormalities in cordocentesis and one showed a mild hearing loss at 12 months of age. In the TG, 18/19 children (95%) were diagnosed with cCMV, while the remaining neonate had negative urine CMV at birth. Eight out of the 19 fetuses (42.1%) showed CMV related abnormalities in the fetal US before HIG treatment. Complete clinical assessment in the neonatal period and at 12 months of age was available in 16 and 15 children, respectively. At birth 50% were symptomatic and at 12 months of age, 4/15 (26.7%) showed a hearing loss and 3/15 (20%) neurologic impairment. Fetuses with abnormalities in ultrasonography before HIG presented a high risk of sequelae (odds ratios: 60; 95%CI: 3-1185; p = .007)., Discussion: Prophylactic HIG administration in pregnant women after CMV primary infection seems not to reduce significantly the rate of congenital infection, but is safe and it could have a favorable effect on the symptoms and sequelae of infected fetuses. The risk of long-term sequelae in fetuses without US abnormalities before HIG is low, so it could be an option in infected fetuses with normal imaging. On the other hand, the risk of sequelae among infected fetuses with abnormalities in fetal ultrasonography before HIG despite treatment is high.

Introduction: Pyridoxine-dependent epilepsy (PDE) is a rare disorder of the lysine metabolism, characterized by a pharmacoresistant epileptic encephalopathy that usually begins in the neonatal period. However, its phenotypic spectrum is wide and not limited to seizures. We report a new case of PDE who developed hydrocephalus, along with an exhaustive review of the literature., Case Report: Our patient presented with seizures at 13 h of life. Antiepileptic drugs, vitamins and cofactors were required to achieve seizure control. Laboratory tests were congruent with PDE. She remained seizure-free until age five months, when seizures reappeared in the context of increasing head size and irritability. A cranial ultrasound showed hydrocephalus, for which she underwent ventriculoperitoneal shunting., Discussion: Seven other patients with same features have been previously reported. Seizure onset occurred within the first 7 days in all patients. Most of the children developed hydrocephalus at 6-7 months of age. In 4 out of 7 a genetic mutation was identified, despite the accurate etiology of hydrocephalus was unknown in most of them. The case we report behaved similarly to the others previously described. We postulate that the pathogenesis of this complication could be related to the high expression of antiquitin in choroid plexus epithelium, where the cerebrospinal fluid is produced., Conclusions: patients with PDE should be closely monitored, since they may present severe complications. We highlight the development of hydrocephalus, an uncommon but potentially life-threatening problem reported in 8 patients up to present time., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Langerhans cell histiocytosis in infants is a rare condition, and presentation as an isolated cervical adenitis is exceptional at this age. We describe the case of a 3-month-old female infant presenting with a neck mass in the right mandibular angle with poor response to antibiotic treatment. Fine needle aspiration was performed and confirmed the diagnosis of Langerhans cell histiocytosis with complementary tests showing no features of systemic involvement. Langerhans cell histiocytosis should be considered in the differential diagnosis of subacute neck masses with poor outcome in infants and physicians should consider performing a fine needle aspiration to establish the diagnosis., (Sociedad Argentina de Pediatría.)

Introduction: Kawasaki disease refers to systemic vasculitis with risk of coronary artery disease. Our objective is to identify risk factors associated with coronary artery disease in patients with complete and incomplete Kawasaki disease., Material and Methods: Descriptive, retrospective study conducted in patients diagnosed with Kawasaki disease in a tertiary-care hospital between 2008 and 2014. The American Heart Association diagnostic criteria were used to define complete and incomplete Kawasaki disease., Results: Thirty-one children were diagnosed with Kawasaki disease; 24 met the criteria for the complete form, and 7, for the incomplete form of this condition. Five had coronary artery disease. One of them had incomplete Kawasaki disease (1/7= 14.3%), and the remaining four had the complete form (4/24= 16.7%). No significant differences were found between both groups (p= 1.0). Patients with coronary artery involvement had a higher C-reactive protein level (median: 16.2 mg/dL versus 8.4 mg/dL, p= 0.047) and lower albuminemia (median: 3.2 mg/dL versus 3.99 mg/dL, p= 0.002)., Conclusions: The risk of coronary artery involvement in incomplete Kawasaki disease is similar to that in complete Kawasaki disease; therefore, in patients with the incomplete form, immunoglobulin therapy should not be delayed. In our population, C-reactive protein and albumin levels were related to a higher risk of coronary artery involvement., (Sociedad Argentina de Pediatría.)