T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study).

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.

Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study.

BACKGROUND: Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. METHODS: Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. RESULTS: We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period. CONCLUSIONS: The use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Architectural design, facilities and family participation in neonatal units in Spain: A multicentre study.

AIM: The architecture of neonatal units plays a key role in developmental strategies and preterm outcomes. The aim was to evaluate the design of Spanish neonatal units and its impact on the participation of parents in neonatal care. METHODS: A web-based survey was sent to all level III Spanish neonatal units, including questions about hospital data, architectural design, facilities and family participation. RESULTS: The study included 63 units. Most units (87%) had part or all the intensive care patients located in open bay units, while 54% had at least one individual patient cubicle. Single family rooms, defined as those including enough space and furniture for family members to stay with the infant without restrictions, were available in 8 units (13%). Eighteen units (29%) had a structured programme of family education. Units with single family rooms were more likely to have parental participation in rounds (p < 0.01), safety protocols (p = 0.02), oxygen management (p < 0.01) and nasogastric tube feeding (p = 0.02), as well as to allow siblings to participate in kangaroo care (p < 0.01). CONCLUSION: Widely variable architectural designs and policies were found in Spanish neonatal units. The presence of single family rooms may have impacted the participation of parents in neonatal care.

XIII International Conference on Kangaroo Mother Care - Different opinions, experiences and related KMC issues: Good practices, stabilisation concept, nutrition and basic respiratory support.

AIM: This study aimed to summarise the views and experiences of the participants in the workshop of the XIII International Conference on Kangaroo Mother Care (KMC). METHODS: The results of the discussions held during the workshop of the XIII International Conference on KMC were summarised. There were 152 participants from 47 countries. Four main KMC topics were discussed: good practices, immediate implementation, nutrition and basic ventilation. RESULTS: Several agreements were reached, namely that professional societies and governments should develop official recommendations to promote KMC as standard care for preterm and low birth weight infants and that parents should be involved as active caregivers in neonatal care units. Moreover, the criteria for referring community-born infants to KMC require standardisation. Important inequalities in resource availability among high-, middle- and low-income countries were recognised for all topics. Specific needs were identified for parenteral nutrition and fortifiers, nasal continuous positive airway pressure (nCPAP) and oxygen blenders, which are rarely available in low- and middle-income countries. Immediate implementation of KMC was discussed as a new concept. Its benefits were recognised, but its application has some variability. CONCLUSION: Adequate preterm care requires a basic neonatal package, including KMC, nCPAP, immediate management protocols and adequate nutrition and feeding strategies. The differences in resources among high-, middle- and low-income countries highlight the wide disparities in neonatal care according to the place of birth.

Clinical outcomes and antibody transfer in a cohort of infants with in utero or perinatal exposure to SARS-CoV-2 (Coronascope Study).

We aimed to describe the outcomes, focusing on the hearing and neurological development, of infants born to mothers with COVID-19 during pregnancy and to evaluate the persistence of maternal antibodies in the first months of life. An observational, prospective study at a tertiary hospital in Madrid (Spain) on infants born to mothers with COVID-19 during pregnancy between March and September 2020 was conducted. A follow-up visit at 1-3 months of age with a physical and neurological examination, cranial ultrasound (cUS), SARS-CoV-2 RT-PCR on nasopharyngeal swab, and SARS-CoV-2 serology were performed. Hearing was evaluated at birth through the automated auditory brainstem response and at six months of age through the auditory steady-state response. A neurodevelopmental examination using the Bayley-III scale was performed at 12 months of age. Of 95 infants studied, neurological examination was normal in all of them at the follow-up visit, as was the cUS in 81/85 (95%) infants, with only mild abnormalities in four of them. Serology was positive in 47/95 (50%) infants, which was not associated with symptoms or severity of maternal infection. No hearing loss was detected, and neurodevelopment was normal in 96% of the infants (median Z score: 0). CONCLUSION: In this cohort, the majority of infants born to mothers with COVID-19 during pregnancy were healthy infants with a normal cUS, no hearing loss, and normal neurodevelopment in the first year of life. Only half of the infants had a positive serological result during the follow-up. WHAT IS KNOWN: • Hearing loss and neurodevelopmental delay in infants born to mothers with COVID-19 during pregnancy has been suggested, although data is inconsistent. Maternal antibody transfer seems to be high, with a rapid decrease during the first weeks of life. WHAT IS NEW: • Most infants born to mothers with COVID-19 during pregnancy had normal hearing screening, cranial ultrasound, and neurodevelopmental status at 12 months of life. Antibodies against SARS-CoV-2 were only detected in 50% of the infants at two months of life.

Prenatal Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Promising Way to Change the Impact of Cystic Fibrosis.

INTRODUCTION: Cystic fibrosis (CF) is a potentially severe disease. The development of new therapies with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been a great advance in the management of this condition because they improve the function of the faulty CFTR protein rather than palliate its consequences. CFTR modulator therapy improves pancreatic and lung function and, therefore, quality of life, with greater benefits the sooner treatment is started. For this reason, the use of these therapies is being approved for increasingly younger patients. Only two cases of pregnant women taking CFTR modulator therapy with CF fetuses have been reported, suggesting that it could resolve meconium ileus (MI) prenatally and delay/prevent other consequences of CF. CASE PRESENTATION: We report a case of a healthy pregnant patient who underwent CFTR modulator therapy with elexacaftor-tezacaftor-ivacaftor (ETI) in order to treat her fetus with CF (F508del homozygous CFTR mutation) and MI. Ultrasound findings suggestive of MI were observed at 24 weeks. Both parents were tested for CFTR mutations, and both were carriers of the F508del CFTR mutation. The fetus was diagnosed with CF by amniocentesis at 26+2 weeks. Maternal ETI therapy was initiated at 31+1 weeks, and no dilated bowel was observed at 39 weeks. There were no signs of bowel obstruction after birth. Maternal ETI treatment was continued during breastfeeding, with normal liver function. Immunoreactive trypsinogen in the newborn was 58.1 ng/mL, sweat chloride test was 80 mmol/L, and fecal elastase on the second day of life was 58 µg/g. CONCLUSION: Prenatal ETI treatment, as well as during breastfeeding, could solve, prevent, and/or delay CF complications.

Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice.

BACKGROUND: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. METHODS: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. RESULTS: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. CONCLUSION: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.

Feasibility of three-dimensional nasal imaging and printing in producing customized nasal masks for non-invasive ventilation in extremely low birth weight infant: A pilot study.

72Several studies have been conducted to investigate the feasibility of customized nasal masks produced by three-dimensional (3D) facial imaging and printing for continuous positive airway pressure in adults and in premature mannequin. In addition to replicating the entire process, we applied the customized nasal mask to a premature patient who weighed less than 1,000 g. Facial scanning was performed. The study masks were manufactured using stereolithography with a 3D printer model Form3BL (FormLABS). Elastic 50 resin was used as the material. We verified the feasibility of the correct transmission of non-invasive ventilation and found that the mask improved the respiratory parameters and reduced the need for supplemental oxygen. The fraction of inspired oxygen (FiO2) was lowered from 45%, which was the requirement when the traditional mask is used, to almost 21% when the nasal mask was applied to the premature patient, who was either in incubator or in kangaroo position. In view of these results, a clinical trial is being launched to evaluate the safety and efficacy of 3D-printed masks in extremely low birth weight (ELBW) infants. 3D printing provides an alternative for obtaining customized masks that may be more suitable for non-invasive ventilation in ELBW infants than traditional masks.

Prácticas de lactancia materna en las unidades neonatales de España. Encuesta internacional Neo-IHAN / Breastfeeding practices in neonatal wards in Spain. Neo-BFHI international survey

IntroducciónEn 2017 se realizó una encuesta a nivel mundial sobre el cumplimiento de las prácticas que promueve la Neo-IHAN (Iniciativa para la Humanización de la Asistencia al Nacimiento y la Lactancia en las unidades neonatales).Objetivo: Presentar los resultados de las unidades españolas que participaron en la encuesta mundial y compararlos con los obtenidos internacionalmente.Material y métodos: Estudio transversal mediante una encuesta sobre el cumplimiento de los requisitos de la Neo-IHAN («Tres principios básicos», «Diez pasos adaptados a unidades neonatales» y el «cumplimiento del Código internacional de comercialización de sucedáneos de leche materna»). El cumplimiento se calculó como la media en cada indicador y una puntuación media final para cada unidad neonatal. Para las puntuaciones parciales y finales de cada país y a nivel internacional se utilizó la mediana. Las puntuaciones van de 0 a 100.Resultados: La tasa de respuesta en España fue del 90% de las unidades de nivel 2 y 3. El rango de la media para las unidades neonatales fue de 37 a 99, sin diferencias según el nivel asistencial. La puntuación global de España (72) está por debajo de la mediana internacional (77), así como en 8 de los 14 requisitos de la Neo-IHAN. Las unidades neonatales de hospitales con maternidades acreditadas IHAN obtuvieron una puntuación media final significativamente mayor, así como en 9 de los 14 requisitos frente a las no acreditadas.Conclusiones: Los resultados, tanto internacionales como nacionales, indican una mejora de las prácticas de la lactancia materna en las unidades neonatales. Los beneficios de la acreditación IHAN de las maternidades alcanzan a las unidades neonatales. España tiene varios puntos clave por debajo de la puntuación internacional. (AU)

Introduction: In 2017, a worldwide survey was conducted on compliance with the practices promoted by Neo-BFHI (Baby-friendly Hospital Initiative expansion to neonatal wards).Objective: Present the results of the Spanish wards that participated in the global survey and compare them with those obtained internationally.Material and methods: Cross-sectional study through a survey on compliance with the Neo-BFHI (“Three basic principles”, “Ten steps adapted to neonatal wards” and “the compliance with the International Code of Marketing of Breast-milk Substitutes” and subsequent relevant World Health Assembly resolutions). Compliance was calculated as the mean in each indicator and a final mean score for each neonatal unit. For the partial and final scores for each country and at the international level, the median was used. All score ranged between 0 and 100.Results: The response rate in Spain was 90%. The range of the national mean for neonatal wards were from 37 to 99, with no differences in the final score according to the level of care. The global score for Spain (72) is below the international median (77) and this also occurs in 8 of 14 items. The neonatal wards from BFHI designated hospitals, obtained a significantly higher mean global score, and in 9 of 14 items than the non-accredited ones.Conclusions: Both international and national results indicate an improvement in breastfeeding practices in neonatal units. The benefits of the BFHI accreditation of maternity reach neonatal wards. Spain has several key points below the international score. (AU)

[Breastfeeding practices in neonatal wards in Spain. Neo-BFHI international survey]. / Prácticas de lactancia materna en las unidades neonatales de España. Encuesta internacional Neo-IHAN.

INTRODUCTION: In 2017, a worldwide survey was conducted on compliance with the practices promoted by Neo-BFHI (Baby-friendly Hospital Initiative expansion to neonatal wards). OBJECTIVE: Present the results of the Spanish wards that participated in the global survey and compare them with those obtained internationally. MATERIAL AND METHODS: Cross-sectional study through a survey on compliance with the Neo-BFHI ("Three basic principles", "Ten steps adapted to neonatal wards" and "the compliance with the International Code of Marketing of Breast-milk Substitutes" and subsequent relevant World Health Assembly resolutions). Compliance was calculated as the mean in each indicator and a final mean score for each neonatal unit. For the partial and final scores for each country and at the international level, the median was used. All score ranged between 0 and 100. RESULTS: The response rate in Spain was 90%. The range of the national mean for neonatal wards were from 37 to 99, with no differences in the final score according to the level of care. The global score for Spain (72) is below the international median (77) and this also occurs in 8 of 14 items. The neonatal wards from BFHI designated hospitals, obtained a significantly higher mean global score, and in 9 of 14 items than the non-accredited ones. CONCLUSIONS: Both international and national results indicate an improvement in breastfeeding practices in neonatal units. The benefits of the BFHI accreditation of maternity reach neonatal wards. Spain has several key points below the international score.

Severe Acute Respiratory Syndrome Coronavirus 2 Vertical Transmission from an Asymptomatic Mother.

In utero transmission of severe acute respiratory syndrome coronavirus 2 infection is a point of debate. We report a case of severe acute respiratory syndrome coronavirus 2 vertical transmission from asymptomatic mother, with molecular detection in mother's blood at delivery and neonatal nasopharyngeal swabs at 5 and 28 hours of life and later IgG seroconversion. The newborn was asymptomatic.

Safety of tocilizumab in COVID-19 pregnant women and their newborn: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab is an IL-6 receptor inhibitor agent which has been proposed as a candidate to stop the inflammatory phase of infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, safety data of tocilizumab in pregnant women and their newborn are scarce. We aimed to describe maternal and neonatal safety outcomes associated with tocilizumab treatment in pregnant women with severe COVID-19. METHODS: This is a retrospective study of severe COVID-19 pregnant women, treated with tocilizumab in two Spanish hospitals between 1 March and 31 April 2020. Demographics, medical history, clinical and radiologic findings, treatment information and laboratory data of mothers and their newborns were collected from electronic medical records. RESULTS AND DISCUSSION: A total of 12 pregnant women were identified to have received tocilizumab during pregnancy in the two hospitals. Median gestational age at admission was 27.7 weeks (interquartile range, 18.0-36.4). Most of them received lopinavir/ritonavir, azithromycin and hydroxychloroquine, two patients received corticosteroids and one received interferon beta 1B. All 12 pregnancies resulted in live births. Somatometric values were normal for all newborns, and evolution at 14 and 28 days was favourable for all of them. Hepatotoxicity was observed in 2 patients, which improved or resolved at discharge. Cytomegalovirus reactivation was detected in another patient who had also received corticosteroids for 15 days, causing a congenital infection in her newborn. Both hepatotoxicity and viral reactivation adverse events were classified as possibly related to tocilizumab administration according to Naranjo's causality algorithm. WHAT IS NEW AND CONCLUSIONS: It does not appear that tocilizumab has detrimental effects for the mother and newborn. Close monitoring of infections should be considered, especially if other immunosuppressive agents are used.

Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis.

OBJECTIVE: Patent ductus arteriosus (PDA) approach remains controversial. We aim to evaluate whether echocardiography-guided (EchoG) PDA closure (to reduce drug exposure) and 24-h continuous ibuprofen infusion (24 h-IB) (to reduce peak concentration), compared with EchoG PDA closure plus conventional bolus (bolus-IB), reduces severe bowel adverse event rate in preterm infants with hemodynamically significant (hs) PDA. STUDY DESIGN: The study design is a multicenter, blinded, randomized controlled trial. Infants with <28 weeks of gestation underwent routine echocardiographic assessment (18-72 h of birth); infants with 28-33 weeks were screened only in cases where PDA was clinically suspected. HsPDA was considered if ductal diameter >1.5 mm and indicators of pulmonary overflow, systemic hypoperfusion, or both were present. Pharmacodynamic effect of CYP450 genotypes was also analyzed. RESULTS: One hundred forty-six infants [median gestational age 26 (25-28) weeks; median birth weight 881 (704-1,100) g] were randomized to 24 h-IB (n = 70) or bolus-IB (n = 76) study group at 86 (58-140) h from birth. Groups were comparable regarding perinatal and neonatal clinical data, but higher prevalence of male sex in the bolus-IB group was found. Neither severe bowel adverse event rate [10% (24 h-IB) and 2.6% (bolus-IB), p = 0.1] nor ductal closure rate was different between the study groups. Postnatal age and peripheral SaO2 at treatment start and pulmonary hemorrhage were associated with severe bowel events, independent of treatment group allocation. CYP2C8 genetic polymorphisms were associated with ibuprofen efficacy (p = 0.03). CONCLUSIONS: Ibuprofen intravenous continuous infusion compared with bolus infusion in preterm infants with hsPDA shows similar rates of success and does not reduce the prevalence of severe bowel events.

Primer caso de infección neonatal por SARS-CoV-2 en España / First case of neonatal infection due to SARS-CoV-2 in Spain

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Percutaneous Inserted Venous Catheter via Femoral Vein in Extremely Low-Birth-Weight Infants: A Single-Center Experience.

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.

Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial.

BACKGROUND AND OBJECTIVES: Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence. STUDY DESIGN: Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs' cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage. RESULTS: Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 [25.9%] vs. placebo, n = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, n = 5 [9.2%] vs. placebo, n = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found. CONCLUSIONS: Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.