RESUMEN
We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.
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Proteinosis Alveolar Pulmonar , Receptores CCR2 , Niño , Humanos , Pulmón/metabolismo , Macrófagos Alveolares/metabolismo , Proteinosis Alveolar Pulmonar/genética , Proteinosis Alveolar Pulmonar/diagnóstico , Receptores CCR2/deficiencia , Receptores CCR2/genética , Receptores CCR2/metabolismo , Reinfección/metabolismoRESUMEN
Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns.
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Melatonina , Nacimiento Prematuro , Femenino , Recién Nacido , Humanos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Melatonina/uso terapéutico , Recien Nacido Prematuro , Especies Reactivas de Oxígeno , Neuroprotección , Estudios ProspectivosRESUMEN
The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices. Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: ⢠Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. ⢠Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: ⢠Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. ⢠Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs.
RESUMEN
Echovirus 11 (E11) has recently been associated with a series of nine neonatal cases of severe hepatitis in France. Here, we present severe hepatitis caused by E11 in a pair of twins. In one of the neonates, the clinical picture evolved to fulminant hepatitis. The E11 genome showed 99% nucleotide identity with E11 strains reported in the cases in France. Rapid genome characterisation using next generation sequencing is essential to identify new and more pathogenetic variants.
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Infecciones por Echovirus , Hepatitis A , Hepatitis , Necrosis Hepática Masiva , Recién Nacido , Humanos , Masculino , Italia/epidemiología , Francia/epidemiología , Enterovirus Humano B/genética , Infecciones por Echovirus/diagnóstico , Infecciones por Echovirus/epidemiologíaRESUMEN
Fresh frozen plasma (FFP) is largely misused in the neonatal setting. The aim of the study is to evaluate the impact of a Thromboelastography (TEG)-based Quality Improvement (QI) project on perioperative FFP use and neonatal outcomes. Retrospective pre-post implementation study in a level-III NICU including all neonates undergoing major non-cardiac surgery before (01-12/2017) and after (01-12/2019) the intervention. In 2018, the intervention included the following: (1) Training on TEG, (2) Implementation of TEG, and (3) Algorithm for TEG-directed FFP administration in surgical neonates. We compared pre- vs post-intervention patient characteristics, hemostasis, and clinical management. Linear and logistic regression models were used to evaluate the impact of the project on main outcomes. We analyzed 139 neonates (pre-intervention: 72/post-intervention: 67) with a mean (± SD) gestational age (GA) 34.9 (± 5) weeks and birthweight 2265 (± 980) grams which were exposed to 184 surgical procedures (pre-intervention: 91/post-intervention: 93). Baseline characteristics were similar between periods. In 2019, prothrombin time (PT) was longer (14.3 vs 13.2 s; p < 0.05) and fibrinogen was lower (229 vs 265 mg/dl; p < 0.05), if compared to 2017. In 2019, the intraoperative exposure to FFP decreased (31% vs 60%, p < 0.001), while the pre-operative FFP use did not change. The reduction of intraoperative FFP did not impact on mortality and morbidity. Intraoperative FFP use was lower in the post-intervention even after controlling for GA, American Society of Anesthesiologists score, PT, and fibrinogen (Odds ratio: 0.167; 95% CI: 0.070, 0.371). Conclusion: The TEG-based QI project for the management of FFP during neonatal surgery reduced intraoperative FFP exposure. What is Known: ⢠PT and aPTT are poor predictors of bleeding risk in acquired neonatal coagulopathy, leading to likely unnecessary fresh frozen plasma (FFP) transfusion in the Neonatal Intensive Care Setting. ⢠As neonatal hemostasis is a delicate balance between the concomitant reduction of pro- and anti-coagulants drivers, thromboelastography (TEG) is a promising alternative for coagulation monitoring. What is New: ⢠The implementation of TEG, training, and shared protocols contributed to reduced intraoperative FFP use, which was not associated with increased mortality or bleeding events. ⢠These findings inform future research showing that there is clinical equipoise to allow for larger studies to confirm the use of TEG in NICUs and to identify TEG cut-offs for transfusion practice.
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Trastornos de la Coagulación Sanguínea , Tromboelastografía , Transfusión de Componentes Sanguíneos , Fibrinógeno , Humanos , Lactante , Recién Nacido , Plasma , Mejoramiento de la Calidad , Estudios Retrospectivos , Tromboelastografía/métodosRESUMEN
In newborns with congenital diaphragmatic hernia (CDH), the mediastinal shift caused by the herniated organs negatively affects lung development. Assessment of the fetal magnetic resonance imaging (MRI) mediastinal shift angle (MSA) was shown to have an inverse correlation with the total fetal lung volume (TFLV), being associated with neonatal survival. However, a possible association with postnatal morbidity has never been investigated. We hypothesize that the degree of the mediastinal shift could be associated with higher respiratory and cardiocirculatory impairment, requiring intensive treatments and extended hospitalization in survivors. We retrospectively consider a cohort of isolated, left-sided CDH, for whom we calculated the MSA and the observed/expected (O/E) TFLV at fetal MRI. We performed a data collection regarding inotropic or vasoactive support, treatment with pulmonary vasodilators, mechanical ventilation, and length of stay. General linear models were performed. The MSA and O/E TFLV were inversely correlated (Pearson's coefficient - 0.65, p < 0.001), and deceased patients showed higher MSA values then survivors (p = 0.011). Among survivors, an increase in MSA was associated with longer pharmacological treatments (dobutamine: p = 0.016; dopamine: p = 0.049; hydrocortisone: p = 0.003; nitric oxide: p = 0.002; sildenafil: p = 0.039; milrinone: p = 0.039; oxygen: p = 0.066), and mechanical ventilation (p = 0.005), with an increasing trend in the length of hospitalization (p = 0.089).Conclusion: The MSA indirectly reflects lung hypoplasia and is associated with a higher neonatal intensity of cares. However, further studies are needed to consolidate the results.Trial registration: The study is an exploratory post hoc analysis of the registered NeoAPACHE protocol at ClinicalTrials.gov with the identifier NCT04396028. What is Known: ⢠In congenital diaphragmatic hernia, the lung size, liver position, and defect side are the most common prenatal prognostic parameters used in clinical practice for morbidity and mortality prediction. ⢠Lung hypoplasia, strictly associated with lung size, is estimated by observed/expected lung to head ratio and observed/expected total fetal lung volume with prenatal ultrasound and fetal magnetic resonance imaging, respectively. What is New: ⢠A new, faster, more straightforward, and less operator-dependent tool to assess CDH severity could be the mediastinal shift angle calculation with fetal magnetic resonance imaging. ⢠Postnatal clinical severity, considered as a postnatal cardiovascular and respiratory impairment that indirectly reflects lung hypoplasia, is associated with an increased mediastinal shift angle calculation.
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Hernias Diafragmáticas Congénitas , Femenino , Edad Gestacional , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Humanos , Recién Nacido , Pulmón/diagnóstico por imagen , Mediciones del Volumen Pulmonar , Imagen por Resonancia Magnética , Embarazo , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
BACKGROUND: Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nu- cleocapsid (NCP) IgG, was investigated. METHODS: A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnan- cy and newborn parameters were evaluated in comparison with 200 uninfected controls. RESULTS: Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mount- ed significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and new- born parameters were not significantly different from those observed in uninfected controls. CONCLUSION: Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.
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COVID-19 , Neumonía , Complicaciones Infecciosas del Embarazo , Anticuerpos Antivirales , Formación de Anticuerpos , Femenino , Humanos , Inmunoglobulina A , Inmunoglobulina G , Recién Nacido , Embarazo , Estudios Prospectivos , SARS-CoV-2RESUMEN
Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indirectly. Inherited forms are due either to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease. Our recommendations are based on a systematic literature search. A series of questions regarding the key signs and symptoms, the methods for diagnosis, the clinical management in neonatal/childhood/adulthood period, and the therapeutic approach of methemoglobinemia were formulated and the relative recommendations were produced. An agreement was obtained using a Delphi-like approach and the experts panel reached a final consensus >75% of agreement for all the questions.
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Metahemoglobinemia/diagnóstico , Metahemoglobinemia/terapia , Consenso , Diagnóstico Diferencial , Manejo de la Enfermedad , Humanos , Metahemoglobinemia/fisiopatologíaRESUMEN
BACKGROUND: Phlebotomy is among the main determinants of anemia of prematurity. Blood sparing policies endorsed umbilical cord blood (here called placental) as an alternative source for laboratory testing. Little is known on the suitability of placental blood to evaluate neonatal hemostasis of newborn infants. We aimed to compare the hemostatic profile of paired placental and infant venous blood, by means of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, protein C, thromboelastography (TEG) and thrombin generation assay (TGA). STUDY DESIGN: This was an observational single-center study. METHODS: We collected at birth venous citrated blood from both placental and infant venous source and performed PT, APTT, fibrinogen, antithrombin, protein C, TEG (reaction time-R; kinetics-K alpha angle-α, maximum amplitude-MA and lysis at 30 minutes-LY30), and TGA (endogenous thrombin potential-ETP). RESULTS: We enrolled 60 neonates with a median gestational age (range) of 37 weeks (28+1 -41) and birth-weight 2417 g (950-4170). Based on TEG and TGA, placental blood showed a procoagulant imbalance as indicated by lower median R (4.0 vs. 6.1 min; p < 0.001) and K (1.3 vs. 2.2 min; p < 0.001); higher α-angle (69.7 vs. 57.4°; p < 0.001) and ETP (1260 vs. 1078; p = 0.002) than those observed for infant venous blood. PT and APTT did not differ significantly between the two groups. CONCLUSIONS: While placental and neonatal blood samples are equally suitable to measure the standard coagulation tests PT and APTT, placental blood leads to a procoagulant imbalance when testing is performed with TEG or TGA. These effects should be considered when interpreting results stemming from investigation of neonatal hemostasis.
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Trastornos de la Coagulación Sanguínea/diagnóstico , Hemostasis/fisiología , Enfermedades del Recién Nacido/diagnóstico , Tamizaje Neonatal/métodos , Placenta/irrigación sanguínea , Trastornos de la Coagulación Sanguínea/sangre , Pruebas de Coagulación Sanguínea , Femenino , Sangre Fetal/fisiología , Fibrinógeno/análisis , Edad Gestacional , Humanos , Recién Nacido , Enfermedades del Recién Nacido/sangre , Masculino , Tiempo de Tromboplastina Parcial , Parto/sangre , Flebotomía/métodos , Flebotomía/normas , Embarazo , Tiempo de Protrombina , Reproducibilidad de los Resultados , Trombina/análisisRESUMEN
It is well known that the nephron endowment of healthy subjects is highly variable and that individual nephron mass has potentially important implications both in health and disease. However, nephron count is technically impossible in living subjects. Based on the observation of an increase in serum creatinine (sCr) in otherwise healthy newborns with solitary kidney during the physiological perinatal dehydration, we hypothesized that perinatal sCr might be helpful in identifying healthy subjects with a reduced nephron mass. In the framework of a study on blood pressure in babies (NeoNeph), sCr of normal Caucasian neonates was determined 48-96 h after birth and their association with a family history of arterial hypertension (AH) was analyzed. SCr was determined in 182 normal newborns (90 males) at a mean of 61 ± 8 h after birth (range 46-82). Newborns with paternal AH had a higher mean sCr (0.97 + 0.28 mg/dL) then newborns without paternal AH (0.73 + 0.28 mg/dL; p = 0.006). No differences in mean sCr were found in relation with mother or grandparent's history of AH. CONCLUSION: The association between parental AH and high sCr during perinatal dehydration supports the hypothesis that the latter is a promising tool for identifying normal subjects with a reduced nephron mass with potential important implications in prevention and in understanding the individual outcome of renal and extrarenal diseases (including AH). What is Known: ⢠Nephron endowment of healthy subjects is highly variable and individual nephron mass has potentially important implications both in health and disease however nephron count is not feasible in living subjects. What is New: ⢠Serum creatinine during perinatal dehydration is a possible biomarker for identifying normal subjects with a reduced nephron mass.
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Creatinina/sangre , Deshidratación/sangre , Hipertensión/complicaciones , Nefronas/fisiopatología , Biomarcadores/sangre , Deshidratación/complicaciones , Femenino , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
Objective Delayed umbilical cord clamping and cord milking are placental transfusion strategies that produce higher iron stores and better hemodynamic conditions in a newborn. We aimed to evaluate their current practice in tertiary-care delivery wards in Italy. Study Design A multiple-choice questionnaire was e-mailed to all the 101 Italian tertiary-care delivery wards. The comparative analysis between categorical variables was performed by the χ2 test. Result We obtained an 85% (86/101) response rate. Where placental transfusion strategies were applied, in 61% of cases they were performed in less than half of deliveries. Obstetric-neonatal guidelines were available in 21% of the centers. Where they were available, application of delayed clamping and milking was significantly more frequent and clamping time was longer. Conclusion This first Italian nationwide survey on placental transfusion strategies showed low application rate and variability in knowledge and execution. Availability of obstetric-neonatal guidelines, knowledge of benefits, and cooperation within the delivery team were associated with enhanced implementation.
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Transfusión Sanguínea/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Atención Perinatal/normas , Circulación Placentaria , Cordón Umbilical/irrigación sanguínea , Transfusión Sanguínea/métodos , Constricción , Femenino , Humanos , Recién Nacido , Italia , Atención Perinatal/organización & administración , Guías de Práctica Clínica como Asunto , Embarazo , Encuestas y Cuestionarios , Factores de Tiempo , Cordón Umbilical/cirugíaRESUMEN
Background The aim of this study was to evaluate the association between red blood cell (RBC) transfusions on the risk of death, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Study Design and Methods This is an observational study. Data were entered prospectively into the study database at the time of the first transfusion. Clinical characteristics, adverse events, and outcomes of the patients transfused in the first 28 days of life were compared with the population of VLBW infants not transfused during the same period. The association among birth weight, gestational age, comorbidities, and the number of transfusions was estimated with a Poisson regression model. The association between the composite outcome and the occurrence of death, ROP, or BPD separately considered and a set of covariates was estimated with a logistic regression model. Results We enrolled 641 VLBW infants, 42% of whom were transfused. Transfusions were associated with the risk of developing the composite outcome, independently from other conditions; this risk correlated with several transfusions ≥ 3 (odds ratio: 5.88, 95% confidence interval: 2.74-12.6). ROP and BPD were associated with several transfusions ≥ 3. Conclusion We observed an association between RBC transfusions and the composite risk of death or ROP, BPD, and NEC.
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Anemia Neonatal/terapia , Displasia Broncopulmonar/epidemiología , Enterocolitis Necrotizante/epidemiología , Transfusión de Eritrocitos/estadística & datos numéricos , Muerte Perinatal , Retinopatía de la Prematuridad/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recien Nacido Extremadamente Prematuro , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Modelos Logísticos , Masculino , Factores de RiesgoRESUMEN
Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06-0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock.
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Recambio Total de Sangre/métodos , Sepsis Neonatal/terapia , Choque Séptico/terapia , Recambio Total de Sangre/efectos adversos , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Masculino , Sepsis Neonatal/mortalidad , Choque Séptico/mortalidadRESUMEN
OBJECTIVE: To determine the evolution of congenital hypothyroidism in preterms and the clinical features of permanent forms. STUDY DESIGN: We retrospectively evaluated 24 preterm children detected by newborn screening for congenital hypothyroidism: first screening with blood-thyroid stimulating hormone cutoff ≥10 mU/L and second screening with blood-thyroid stimulating hormone cutoff ≥5 mU/L. After the age of 2 years, patients with eutopic thyroid had diagnostic reevaluations, including thyroid function testing and thyroid ultrasonography after L-thyroxine therapy withdrawal. RESULTS: The first screening identified 21.7% of patients with thyroid stimulating hormone elevation, and the second screening identified 73.9% of patients. One patient (4.4%) was identified with a third screening test; 21 patients had an eutopic thyroid and 3 patients a thyroid dysgenesis. At reevaluation, 5 patients (23.8%) showed permanent hypothyroidism (serum-thyroid stimulating hormone [s-TSH] >10 mU/L) resulting in the need to reintroduce therapy, 5 patients (23.8%) showed persistent hyperthyrotropinemia (s-TSH 5-10 mU/L), and 11 infants (52.4%) transient hypothyroidism (s-TSH <5 mU/L). The main clinical features of patients affected by permanent hypothyroidism were 1 case of assisted reproduction, 2 twins, 2 small for gestational age, 1 maternal thyroiditis, and 2 patients with malformations/syndromes. CONCLUSIONS: Premature birth is a significant risk for congenital hypothyroidism with eutopic thyroid. In preterm infants, the evolution of congenital hypothyroidism remains difficult to predict. Our data emphasizes the high incidence of transient hypothyroidism in preterm infants, and the importance of diagnostic reevaluation to determine the definitive diagnosis.
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Hipotiroidismo Congénito/diagnóstico , Recien Nacido Prematuro , Tamizaje Neonatal/métodos , Tirotropina/sangre , Estudios de Cohortes , Hipotiroidismo Congénito/tratamiento farmacológico , Hipotiroidismo Congénito/epidemiología , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Masculino , Estudios Retrospectivos , Medición de Riesgo , Pruebas de Función de la Tiroides , Tiroxina/uso terapéutico , Resultado del TratamientoRESUMEN
The early emergence of social smiles is an important milestone of infants' socio-emotional development. Our aim was to assess how the use of protective facemasks by adults affects the display of social smiles in preterm (PT) and full-term (FT) infants at 3 months (corrected age for prematurity). We enrolled 30 FT and 30 PT infants (gestational age ≤ 32 weeks). Infants' social smiles displays were assessed at 2-3-month-age (corrected) across a three-episode (masked mother; unmasked mother; masked adult female stranger) videotaped interactive task. During each episode, the adult was instructed to maintain specific facial expressions (happy-smiling, sad-frowning, neutral-unresponsive) for 15 second windows and then instructed to interact spontaneously for 45 s (of which the first 15 s were coded). FT and PT infants did not differ in the display of social smiles. In both groups, social smiles were mostly exhibited in response to happy/smiling and spontaneously interacting partners. Overall, no effect of wearing a protective facemask emerged. The use of protective facemasks did not result in a lower display of social smiles. The findings suggest that FT and PT might be equally sensitive to their adult interactive partners in terms of social smiles displays at 2-3-month-age.
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Expresión Facial , Recien Nacido Prematuro , Máscaras , Sonrisa , Humanos , Femenino , Sonrisa/psicología , Masculino , Recien Nacido Prematuro/fisiología , Recien Nacido Prematuro/psicología , Adulto , Lactante , Conducta Social , Recién Nacido , Desarrollo Infantil/fisiología , Conducta del Lactante/fisiologíaRESUMEN
Newborns admitted to neonatal intensive care units (NICU) are at increased risk of health care-associated infections. Serratia marcescens represent the third most common pathogen in NICU outbreaks. Here we present an outbreak investigation performed using Whole Genome Sequencing (WGS) analyses and the control measures implemented to limit the spread of S. marcescens in the NICU of an Italian hospital. In February 2023 S. marcescens was isolated from six newborns, when in 2022 this pathogen was isolated only from two samples in the same ward. Measures for infection prevention were adopted. Routinary surveillance screening, performed with rectal swabs collected at admission and weekly thereafter, was implemented to search for S. marcescens presence. Environmental samples were collected. All the isolates, obtained from the conjunctival swab of six newborns, from rectal swab of two newborns who did not develop infections, as well as from the aerators of two faucets, were sequenced. WGS analyses showed no correlation between the isolates from newborns and environmental isolates. The implementation of the measures for infection prevention and control had enabled us to successfully control the outbreak within a short period. WGS analyses proved to be crucial in outbreak investigation to limit the spreading of the pathogens.
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Infección Hospitalaria , Infecciones por Serratia , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Serratia marcescens/genética , Infecciones por Serratia/diagnóstico , Infección Hospitalaria/prevención & control , Brotes de Enfermedades/prevención & control , Secuenciación Completa del GenomaRESUMEN
Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.
Asunto(s)
Plaquetas , Sangre Fetal , Transfusión de Plaquetas , Humanos , Recién Nacido , Transfusión de Plaquetas/métodos , Sangre Fetal/citología , Plaquetas/citología , Plaquetas/metabolismo , Recien Nacido Prematuro , Trombocitopenia Neonatal Aloinmune/terapia , Femenino , Hemorragia/terapia , Hemorragia/etiologíaRESUMEN
BACKGROUND: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. METHODS: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. RESULTS: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.