Search

Resumen Introduccion No existe consenso sobre que grafica neonatal es mejor utilizar en ninos con muy bajo peso al nacer (MBPN). El objetivo del estudio fue comparar las graficas de Fenton 2013 e Intergrowth-21st (IW-21) con base en su capacidad predictora de la somatometria a los dos anos, asi como analizar factores relacionados con talla baja a los dos anos. Material y metodos Cohorte de ninos con MBPN nacidos entre 2002-2017. Se analizo la asociacion entre la somatometria neonatal (z-score por Fenton e IW-21) y el riesgo de talla baja ( Resultados Se incluyeron 513 ninos con una edad gestacional media de 30,05 ± 2,5 semanas. El z-score del peso al nacimiento y al alta por Fenton y por IW-21 resultaron utiles para predecir riesgo de talla baja y desnutricion a los dos anos (sin diferencias en el AUC de las curvas ROC), siendo el z-score al alta util ademas para predecir perimetro craneal Conclusiones El z-score peso al alta resulta util para predecir riesgo de talla baja, desnutricion y perimetro craneal

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a two-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 h of blood culture incubation (IQR 8–20), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which were Streptococcus epidermidis in neonates with LOS, and there was one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.

Desde que en marzo de 2020 se declarara la pandemia COVID-19 hemos aprendido muchas cosas del coronavirus SARS-CoV-2, y de su papel en la enfermedad pediátrica. Los niños se infectan en un porcentaje bastante similar a los adultos, si bien en la mayoría de las ocasiones sufren cuadros leves o asintomáticos. Alrededor de un 1% de infectados precisan hospitalización, menos de un 0,02% precisan cuidados intensivos, y la mortalidad es muy baja y generalmente en niños con comorbilidades. Los cuadros clínicos más habituales son infecciones respiratorias de vías altas o bajas, cuadros gastrointestinales y con mayor gravedad el síndrome inflamatorio multisistémico (MIS-C). La mayoría de los episodios no precisan tratamiento, salvo el MIS-C. El remdesivir se ha empleado generalmente como tratamiento compasivo y aún está por definir su papel. El recién nacido puede infectarse, si bien la transmisión vertical es muy baja (

The prevalence of postnatal growth faltering (PGF) in preterm infants with very low birth weight (VLBW) (

Background Neonatal sepsis is a condition with high mortality and morbidity that contributes to high rates of antibiotic therapy at birth. In addition, very low birth weight newborns (VLBWN) are particularly vulnerable. Interleukin 6 (IL-6) seems to be an early and effective marker that could help a better selection of patients to be treated. This study aimed to evaluate the use of antibiotics in the first 72 hours of life in VLBW infants before and after using IL-6 as an infection marker. Also, we wanted to analyze the differences in morbidity and mortality during admission and other factors associated with the decision to start antibiotic treatment. Methods We conducted a cohort retrospective study. We included VLBWN born in our hospital or admitted before 72 hours of life in two two-year periods (2007-2008 and 2011-2012). Results Antibiotics use during the first 72 hours of life was analyzed as the primary variable, which was reduced by 20% on the second period (p = 0.002). Regarding the analysis of secondary variables, we found no significant differences in mortality during hospital admission and the incidence of nosocomial sepsis, enterocolitis, or invasive fungal infection. The multivariate analysis indicated extreme prematurity and the study group as the most strongly related factors to the start of antibiotic therapy. Conclusions IL-6 was a useful marker of infection to reduce the use of antibiotic therapy in VLBW infants without increasing mortality.

Postnatal growth restriction has high prevalence in very low birth weight (VLBW) preterm neonates, and this could affect their long-term prognosis. Nowadays, there is no consensus on how to monitor growth in these neonates.Objective:This study aimed to compare prevalence of intra- and extrauterine growth restriction (IUGR and EUGR) in a sample of VLBW infants according to the Fenton 2013 charts and INTERGROWTH-21st (IW-21) standards and to analyze concordance between both in the different EUGR definitions criteria (cross-sectional, dynamic, and true).Patients and Methods:An observational retrospective study of 635 VLBW preterm was performed. The study was carried out in Central University Hospital of Asturias. Body measurements (weight, length, and head circumference) were collected at birth and at hospital discharge and expressed in z-scores for the two references (Fenton 2010 and IW-21). Kappa concordance was calculated.Results:Kappa concordance between Fenton and IW-21 was 0.887 for IUGR and 0.580 for static EUGR. Prevalence was higher according to Fenton in IUGR (36.5 vs. 35.1%), in static EUGR (73.8 vs. 59.3%), and in dynamic EUGR (44.3 vs. 29.3%). Despite observing low prevalence of EUGR when IW-21 was used to define EUGR, a statistical association between neonatal morbidity and diagnosis of EUGR was observed.Conclusion:The Fenton and IW-21 concordance for IUGR is good. IW-21 is more restrictive than Fenton in EUGR. Patients diagnosed by IW-21 as EUGR are more likely to have neonatal morbidity, especially if we use EUGR dynamic definition. In our study, we cannot conclude that one graph is better than the other.

For the first time, the study of iron metabolism and bioavailability, administered as stable iron isotope enriched nanoparticles, was carried out by speciation analysis and isotope pattern deconvolution (IPD) in rat body fluids and tissue. Nanoparticles of Fe(III) oxo-hydroxide were synthesized using a stable iron isotope (57Fe) and administered to lactating rats as a fortifier in formula milk. Quantitative iron speciation analysis in erythrocytes, serum and rat liver was performed by high performance liquid chromatography (HPLC) coupled to post-column isotope dilution and inductively coupled plasma mass spectrometry (ICP-MS). The quantification of endogenous (natural Fe) and exogenous iron (57Fe) was carried out by applying the IPD methodology. The speciation analysis demonstrated that 57Fe was incorporated into the iron compartments (functional, transport and storage) and was associated with the main proteins implicated in iron metabolism (hemoglobin, transferrin and ferritin-like species). Results showed that the iron administered as labeled nanoparticles was incorporated in a high degree (more than 50%), being higher than the degree observed for ferrous sulfate, the most common iron fortifier.

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.

Objective To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). Study design Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. Results Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (−4.8 days less than reference, 95% CI –7.3 to −2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI –12.3 to −11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. Conclusions We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

Introduction: Late prematures (LP) belong to a subgroup of many premature babies with a risk of delayed psychomotor development (PMD). Many subtle changes pass unnoticed if adequate assessment tools are not used. The Ages & Stages Questionnaires 3® (ASQ3®) for parents appears simple and useful for the detection of risk of impairment of PMD, and is recommended by scientific societies that study LP. Objectives: To evaluate the risk of impaired PMD in LP at 5 years-old, and compare them with term newborns (TNB) using the ASQ3. Patients and methods: Data were collected on the LP born in a third level hospital in 2010, as well as 2 TNB of the same gender for each LP. The prenatal and postnatal morbidity variables were compared. At 5 years, their families (excluding those with other neurological risks) were asked to complete the ASQ3. The cut-off point was determined for the total score of the ASQ3 that would discriminate the risk of PMD impairment using ROC analysis. The cut-off point to determine a change in each domain was obtained according to the ASQ3 manual. Results: The ASQ3 was completed for 88 (47%) and 131 (35%) TNB. All the overall mean scores and those for domains were lower in LP, with no significant differences found between the two groups. A risk of PMD impairment (≤253 points) was observed in 7 LP compared to 4 TNB, with no significant difference. More maternal, foetal, and neonatal illnesses were observed in 195 LP than in the 390 TNB. In the univariate analysis, male gender and restricted uterine growth (RUG) were factors associated with a risk of PMD impairment and only RUG in the multivariate analysis. Conclusion: The risk of PMD impairment between LP and TNB at 5 years appears not to be shown, with no significant differences between both, and with the values obtained in the ASQ3 being slightly lower in the LP. Male gender and RUG negatively influence this risk. Resumen: Introducción: Los prematuros tardíos (PT) son un subgrupo de prematuros numeroso con riesgo de déficit en el desarrollo psicomotor (DPM). Muchas alteraciones sutiles pasan desapercibidas si no se emplean herramientas adecuadas de evaluación. El cuestionario para padres Ages & Stages Questionnaires 3® (ASQ3®) parece sencillo y útil para la detección de riesgo en el DPM y está recomendado por sociedades científicas que estudian a los PT. Objetivos: Evaluar el riesgo de déficit en el DPM a los 5 años de edad en PT y compararlos con recién nacidos a término (RNAT) con ASQ3. Pacientes y métodos: Se recogieron los PT nacidos en un hospital de tercer nivel en el año 2010 y 2 RNAT del mismo sexo por cada PT. Se compararon variables de morbilidad prenatal y neonatal. A los 5 años se solicitó a sus familias (excluyendo aquellos con otros riesgos neurológicos) completar ASQ3. Se determinó el punto de corte para la puntuación total de ASQ3 que discriminará el riesgo de déficit del DPM mediante un análisis ROC. El punto de corte para determinar alteración en cada dominio se obtuvo según el manual ASQ3. Resultados: ASQ3 fue completado por 88 PT (47%) y 131 RNAT (35%). Todas las puntuaciones medias globales y por dominios fueron menores en PT, sin encontrar diferencias significativas entre ambos grupos. Siete PT tuvieron riesgo de déficit del DPM (≤253 puntos) frente a 4 RNAT, sin diferencia significativa. Un total de 195 PT tuvieron mayor patología materna, fetal y neonatal que RNAT (n = 390). En el análisis univariante el sexo varón y el crecimiento intrauterino restringido (CIR) fueron factores asociados al riesgo de déficit del DPM y en el multivariante solo CIR. Conclusión: El riesgo de déficit en el DPM entre PT y RNAT a los 5 años parece no evidenciarse con diferencias significativas entre ambos, siendo los valores obtenidos en el ASQ3 ligeramente inferiores en los PT. Sexo varón y CIR parecen influir negativamente en este riesgo.

Nanoparticles (NPs) of 57Fe(III) oxo-hydroxide have been investigated for formula milk iron fortification. The body iron status of lactating rats was evaluated by analyzing iron content in all iron compartments (functional, transport and storage). Results were compared with a non‑iron fortified rat group (NF) and a rat group fortified with FeSO4. Intestinal iron (57Fe) absorption observed in rats using the synthesized NPs was 91% (similar to the obtained for FeSO4), and their total iron levels in the functional compartment were the highest, while similar values were observed in the other iron compartments for both iron fortified groups. Exogenous 57Fe incorporation from NPs was always higher than 56% in all the analyzed iron compartments. Interestingly, higher than those observed for other physicochemical forms assayed for formula milk fortification. This work has shown that 57Fe from the assayed NPs is efficiently incorporated keeping appropriate iron levels, protecting from possible body iron deficiency.

Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography - mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points. The analysis of plasma samples from newborns with HIE revealed a decrease of lactate, pyruvate and β-hydroxybutyrate concentrations, whereas rising malate concentrations were observed. In healthy control newborns (N = 19) significantly lower levels of pyruvate and lactate were found in comparison to age-matched newborns with HIE undergoing TH, whereas acetoacetate and β-hydroxybutyrate levels were clearly increased. Access to a validated analytical method and a controlled cohort of newborns with HIE undergoing hypothermia treatment for the first time allowed the in-depth study of the evolution of key metabolites of metabolic junctions in this special population., MV acknowledges the EC11-244 grant from the Instituto Carlos III. ANR acknowledges a research contract by the Spanish Maternal, Neonatal and Developmental Network SAMID RETICS funded by the PN 2018–2011 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (FEDER), reference RD12/0026. JK, MCe and ASI are grateful for their personal grants from the Instituto Carlos III (grant numbers CP16/00034, JR16/00038 and FI16/00380, respectively). APL acknowledges her personal grant from the Health Research Institute La Fe (CPR2015/0371)

Iron fortification in infant formulas is a common practice for providing iron to newborns in order to avoid its deficiency (anemia). Depending on the physicochemical species used, its bioavailability might be insufficient to meet iron requirements. In this vein, the influence of Lactoferrin (Lf) presence on iron bioavailability in 2-week-old wistar rats fed with formula milk fortified with 57 Fe(III)2 -Lf or 57 Fe(II)SO4 (in presence of Lf) using quantitative speciation (by HPLC-ICP-MS) and Isotope Pattern Deconvolution (IPD) is studied here. Results obtained were compared among fortifiers and also with the maternal group. In RBCs, iron was mainly bound to hemoglobin in all the assayed groups in the same extent. Regarding serum samples, several iron-proteins were observed (such as transferrin and albumin). In both samples, iron content in the fractions studied was similar in all groups compared and exogenous 57 Fe incorporation of intaked iron was always above 50%, showing no significative differences between physicochemical forms but related to the dose administered. Regarding iron stores (liver) the group fed with formula milk fortified with the higher dose of 57 FeSO4 in presence of Lf presented the highest values of total iron even superior than those found in the maternal group, and also the highest exogenous (57 Fe) incorporation. In conclusion, it was proved that iron fortification is required to ensure proper iron levels in all body compartments. No significative differences were observed between different physicochemical species when iron is administered at low doses. However, higher iron doses lead to a greater incorporation in all the iron-proteins studied.

In this work, the absorption and/or bioavailability of iron from two chemical species, 57Fe-Lf (apo-lactoferrin) complex and 57FeSO4 at low and high dose, and in Lf excess were investigated in lactating wistar rats. The methodology used is based on the use of stable isotopes in combination with the approach “isotope pattern deconvolution” and ICP-MS for detection. This approach provides quantitative information about exogenous (57Fe) and endogenous iron (natFe) distribution in fluids and tissues in the iron-supplemented rat groups. The observed results with supplemented rats were compared with those found in rats receiving maternal feeding. Interestingly, differences were found between groups in iron for transport and storage compartments, but not in the functional one, depending upon the dose of iron administered and the chemical species. Considering the results obtained, supplementation with iron salts in excess of Lf appears to be the best way of iron supplementation of formula milk.

This paper summarises results of zinc content and its speciation in human milk from mothers of preterm and full-term infants at different stages of lactation and from synthetic formula milks. Human milk samples (colostrum, 7th, 14th, and 28th day after delivery) from Spanish and Brazilian mothers of preterm and full-term infants (and also formula milks) were collected. After adequate treatment of the sample, total Zn was determined, while speciation analysis of the Zn was accomplished by size exclusion chromatography coupled online with the ICP-MS. It is observed that total zinc content in human milk decreases continuously during the first month of lactation, both for preterm and full term gestations. All infant formulas analysed for total Zn were within the currently legislated levels. For Zn speciation analysis, there were no differences between preterm and full term human milk samples. Moreover Zn species elute mainly associated with immunoglobulins and citrate in human milk whey. Interestingly the speciation in formula milk whey turned out to be completely different as the observed Zn(2+) was bound almost exclusively to low molecular weight ligands (citrate) and only comparatively very low amounts of the metal appeared to be associated with higher mass biomolecules (e.g. proteins).

Holder pasteurization is a thermal treatment commonly applied to milk in human milk banks. However, the application of heating processes can affect the actual composition of milk. In this work, the effect of Holder pasteurization on essential elements in donor human breast milk was studied, including total contents and protein-binding profile of Cu, Fe, Se and Zn. The total contents were determined by inductively coupled plasma mass spectrometry (ICP-MS) and chemical speciation studies were conducted by size exclusion chromatography (SEC) coupled to an ICP-MS and to an UV–vis detector. Total concentrations (μg/L) of Cu (0.19 ± 0.01), Fe (0.35 ± 0.01), Se (0.010 ± 0.003) and Zn (0.57 ± 0.01) were obtained before pasteurization and concentrations of Cu (0.19 ± 0.01), Fe (0.36 ± 0.02), Se (0.008 ± 0.002) and Zn (0.57 ± 0.01) were obtained after pasteurization. Their protein-binding profiles did not change significantly for the majority of the species, indicating a low degree of interconversion due to the elevation of the temperature. However, protein profiles changed after pasteurization, indicating that the losses occurred mainly in the apo form (metal-free form) of proteins rather than in their holo forms (metallo-species).

Lactoferrin is a multifunctional protein and one of the most abundant proteins in human milk. Holder pasteurisation, commonly applied in human milk banks, can reduce the levels of this iron-binding protein. However, there are no studies available about the effects of Holder pasteurisation on holo-lactoferrin (iron-bound form). In this study, we synthesised a isotopically labelled iron-lactoferrin complex [57Fe(III)2-Lf] and used it to fortify donor milk samples, which were submitted to pasteurisation. The total contents of lactoferrin and iron-lactoferrin complex were determined by ELISA and elemental speciation was performed by size exclusion chromatography coupled to inductively coupled plasma mass spectrometry. The results showed that the levels of lactoferrin was reduced 61 ± 11% after pasteurisation. Nevertheless, the decrease was significantly lower in the samples spiked with 57Fe(III)2-Lf, suggesting that the binding with iron could protect lactoferrin from the effects of the heat during pasteurisation.

Total and speciation analyses of iron in human milk from mothers of preterm and full-term infants at different stages of lactation and formula milk were performed by ICP-MS and SEC-ICP-MS respectively. Total iron content of preterm human milk samples was 0.5 μg/ml as compared with 0.4 μg/ml of full-term samples. Breast milk iron concentration did not vary significantly during the first month of lactation nor according to preterm or full-term gestations. Pre-term and full-term formulas from different manufacturers showed a media total iron content (9.5 μg/ml and 6.0 μg/ml, respectively) significantly higher than the iron content of human milk samples. Only 3 preterm and 2 full-term formulas had total iron contents higher than the minimum recommended level of fortification. Iron distribution patterns in milk proteins for human and formula milk samples were obtained. Whereas iron was mostly spread over the high molecular mass region of biomolecules in human milk samples, iron was mostly spread over fractions eluting at low molecular mass in formulas and these differences were statistically significant. Thus, speciation of iron is clearly different in formula milk than in natural milk.

OBJECTIVE To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN We included 58 004 infants born weighing

Objective To identify the variables associated with sepsis-associated mortality, as well as to develop a severity risk score to predict death in very low-birth-weight (VLBW) neonates affected by nosocomial sepsis. Study Design Retrospective cohort study. Infants weighing ≤1500 g with neonatal sepsis of nosocomial origin were included. Epidemiological, clinical, and laboratory variables were recorded at onset (0 hours), at 12 hours, and at 24 hours. Bivariate and multivariate analyses were performed. Result The study population included 95 VLBW infants who presented 129 episodes of nosocomial sepsis. In the bivariate analysis, gram-negative bacilli as the etiology of sepsis, seizures, age, postconceptional age, weight, serum procalcitonin (24 hours), platelet count (24 hours), blood urea nitrogen (0 and 24 hours), creatinine (24 hours), diuresis (12 and 24 hours), mean blood pressure (12 and 24 hours), pH, base excess (0, 12, and 24 hours), and SpO 2 (pulse oximetric saturation):F io 2 (fraction of inspired oxygen) ratio (12 and 24 hours) were significantly associated with mortality. In the multivariate analysis, weight at the onset of sepsis, base excess (0 hours), and SpO 2 :F io 2 ratio (12 hours) were independent predictors of mortality. Conclusion A lower weight at the onset of sepsis, base excess, and SpO 2 :F io 2 ratio are useful to predict nosocomial sepsis-associated mortality in VLBW infants.

Iodine is an essential trace element, required for brain development of the foetus and in early postnatal life. This paper evaluates the effect of iodine supplementation during lactation in women living in Asturias (north of Spain). The iodine contents in breast milk (BMI) of premature and full term mothers, receiving during their pregnancy and lactation an iodine supplement (200 μg of KI/day), were compared with those of non-supplemented mothers. The iodine contents in premature and full term formula milks were also evaluated. Furthermore, the urine iodine (UI) in mothers and in both breast- and formula-fed children was also measured. Results showed that extra iodine supplementation with KI during lactation, as recommended by WHO/UNICEF and ICCIDD, is appropriate, and appears to be safe for mothers and neonates. Moreover, breast milk appears to be a better source of iodine for the babies than are formula milks, especially for premature infants.

[EN] Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis., [ES] La asfixia intraparto es una de las causas más frecuentes de muerte neonatal precoz pero también puede, en los supervivientes, evolucionar a una encefalopatía hipóxico-isquémica responsable de una elevada morbilidad neurológica. La presencia de episodios de hipoxia-isquemia prolongados conduce a un rápido agotamiento energético en los tejidos exclusivamente dependientes del metabolismo aeróbico, como el sistema nervioso central. El déficit energético conlleva una paralización de las bombas ATP-dependientes y subsiguiente pérdida del potencial neuronal transmembrana. La población neuronal de las regiones más sensibles del SNC mueren por necrosis, mientras que en otras áreas se produce una hiperexcitabilidad neuronal con entrada masiva de calcio iónico, activación de NO-sintasa, generación de radicales libres que alteran el funcionamiento mitocondrial, provocando un fallo energético secundario y muerte neuronal por apoptosis. Recientemente se ha propuesto una tercera fase en la que factores como la inflamación persistente y los cambios epigenéticos causarían un bloqueo de la maduración de los oligodendrocitos, alteración de la neurogénesis, del crecimiento axonal y de la sinaptogénesis. En este contexto, el estrés oxidativo va a tener un papel protagonista como responsable tanto en causar daño directo al SNC como en activar cascadas metabólicas conducentes a la apoptosis e inflamación. La hipotermia moderada precoz, al preservar las reservas energéticas y disminuir la formación de especies reactivas de oxígeno, atenuará el daño cerebral posreanimación. La combinación de la hipotermia con terapias coadyuvantes para modular el estrés oxidativo podría contribuir a mejorar el pronóstico.

Resumen: La asfixia intraparto es una de las causas más frecuentes de muerte neonatal precoz pero también puede, en los supervivientes, evolucionar a una encefalopatía hipóxico-isquémica responsable de una elevada morbilidad neurológica. La presencia de episodios de hipoxia-isquemia prolongados conduce a un rápido agotamiento energético en los tejidos exclusivamente dependientes del metabolismo aeróbico, como el sistema nervioso central. El déficit energético conlleva una paralización de las bombas ATP-dependientes y subsiguiente pérdida del potencial neuronal transmembrana. La población neuronal de las regiones más sensibles del SNC mueren por necrosis, mientras que en otras áreas se produce una hiperexcitabilidad neuronal con entrada masiva de calcio iónico, activación de NO-sintasa, generación de radicales libres que alteran el funcionamiento mitocondrial, provocando un fallo energético secundario y muerte neuronal por apoptosis. Recientemente se ha propuesto una tercera fase en la que factores como la inflamación persistente y los cambios epigenéticos causarían un bloqueo de la maduración de los oligodendrocitos, alteración de la neurogénesis, del crecimiento axonal y de la sinaptogénesis. En este contexto, el estrés oxidativo va a tener un papel protagonista como responsable tanto en causar daño directo al SNC como en activar cascadas metabólicas conducentes a la apoptosis e inflamación. La hipotermia moderada precoz, al preservar las reservas energéticas y disminuir la formación de especies reactivas de oxígeno, atenuará el daño cerebral posreanimación. La combinación de la hipotermia con terapias coadyuvantes para modular el estrés oxidativo podría contribuir a mejorar el pronóstico. Abstract: Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis.

Aim: To assess trends in the epidemiology of culture-proven and clinical neonatal sepsis of vertical transmission in the era of intrapartum antibiotic prophylaxis. Methods: Since 1995, the neonatal services of 28 acute-care teaching hospitals in Spain ("Grupo de Hospitales Castrillo") have been involved in the prospective surveillance of neonatal infection of vertical transmission. We here report the comparison of the incidence for the periods 1996-1997 and 2000-2001, and look separately at two groups of hospitals according to the time at which the official hospital policy to provide intrapartum antibiotic prophylaxis for group B Streptococcus (GBS) prevention was adopted. In 16 hospitals the policy was adopted in 1999 and in 10 before 1998 (nine hospitals in 1996, one in 1997). Results: The incidence of proven sepsis decreased significantly by 22% and 54% in the hospitals that started prophylaxis in 1999 and before 1998, respectively. The incidence of GBS sepsis also declined significantly by 36.4% and 65.4% in both groups of hospitals, respectively. Significant variations in the incidence of clinical vertical sepsis as well as in the incidence of sepsis caused by Haemophilus influenzas and Klebsiella were not found. Sepsis caused by Escherichia coli increased in the hospitals with prophylaxis from 1999 and decreased in those that began prophylaxis before 1998, in which the mortality rate of proven and clinical sepsis also decreased significantly by 58.6%. Conclusions: There was a substantial decline in the incidence of proven vertical sepsis, with a significant reduction of GBS sepsis, although decreases were more marked when antibiotic prophylaxis was started before 1998. In this group of hospitals, there was also a decrease in the mortality rate. Fluctuations in the incidence of E. coli infection suggest the need for continuing epidemiological surveillance. © 2005 Taylor & Francis Group Ltd.

A prospective multicenter study was conducted to assess the epidemiology of neonatal invasive candidiasis in Spain. In a total of 20,565 admissions to the 27 participating neonatal units over an 18-month period, systemic candidiasis was diagnosed in 118 (0.57%) neonates. Candida species were isolated from the blood in 79 infants, from the urine in 33, and from the cerebrospinal fluid in 4; in 2 cases, histologic evidence of deep tissue candidiasis was found at autopsy. Very-low-birth-weight (VLBW) infants (or = 1500 g) showed a significantly higher incidence of systemic candidiasis (4.8%) than infants weighing1500 g (0.2%) ( p0.001). Candida albicans was the most frequent species (52.5%) followed by C. parapsilosis (23.7%), and C. tropicalis (7.6%). Only seven infants were treated with amphotericin B (initial dose 0.18 +/- 0.3 mg/kg, maximal daily dose 1.7 +/- 0.9 mg/kg) but treatment was stopped in three of them (43%) due to nephrotoxicity. Liposomal amphotericin B was given to 81 neonates and amphotericin B lipid complex to 29. There were no differences in mortality rate and in the incidence of adverse effects in relation to treatment with liposomal amphotericin B or amphotericin B lipid complex. The mortality rate was 10.2% and all deaths occurred in the VLBW cohort with candidemia.

The psychometric properties of the d2 Selective Attention Test are analyzed in two samples of premature ( n = 63) and born-at-term ( n = 78) children. The reliability coefficients (internal consistency) reached values of around .90. Principal components analysis revealed a three-factor structure, which accounts for 58% of the variance, and thus coincides with the number of factors presented in the manual of the Spanish adaptation of the test but not with their composition. Results suggest that the d2 test has adequate psychometric properties both for the global sample and for each sub-sample.

Background The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission. Methods PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results. Results 169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%). Conclusion Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life.

The objective of this study was to assess clinical characteristics and results of radio imaging studies and compare community-acquired urinary tract infection (UTI) with nosocomial UTI in 301 neonates with UTI consecutively admitted to 28 neonatal units in Spain over 3 years (community-acquired UTI, n = 250; nosocomial UTI, n = 51). UTI was diagnosed in the presence of symptoms of infection together with any colony growth for a single pathogen from urine obtained by suprapubic aspiration, or ≥104 CFU/ml for a single pathogen from urine obtained by urethral catheterization. Abnormal renal ultrasound was present in 37.1% of cases (34% in community-acquired UTI and 54.5% in nosocomial UTI, P < 0.01). The voiding cystourethrography (VCUG) showed vesicoureteral reflux (VUR) in 27% of cases (23.8% in community-acquired UTI and 48.6% in nosocomial UTI, P < 0.01). In patients with abnormal renal ultrasound and VUR, renal scan with dimercaptosuccinic acid (DMSA) performed early after UTI revealed cortical defects in 69.5% of cases. However, in patients with abnormal renal ultrasound and normal VCUG, DMSA also revealed cortical defects in 39% of cases. The absence of VUR in neonates with UTI and abnormal renal ultrasound does not exclude the presence of cortical defects suggestive of pyelonephritis.

Background It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated. Results The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%). Conclusion Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation.