Extrauterine growth restriction in very-low-birthweight infants: prevalence and concordance according to Fenton, Olsen, and INTERGROWTH-21st growth charts in a multicenter Spanish cohort.

Multiple criteria and growth references have been proposed for extrauterine growth restriction (EUGR). We hypothesized that these may impact the diagnosis of EUGR. The objective was to evaluate the prevalence of EUGR with its different definitions and the concordance according to Fenton, Olsen, and INTERGROWTH-21st in very-low-birthweight (VLBW) infants. This is an observational, retrospective, and multicenter study including VLBW infants from the Spanish SEN1500 Network from 2011 to 2020. Patients with major congenital anomalies, embryopathies, and gestational age less than 24 weeks were excluded. EUGR prevalence was calculated at discharge with cross-sectional, longitudinal, "true" cross-sectional, and "true" longitudinal definitions. Concordance was assessed with Fleiss' kappa coefficient. 23582 VLBW infants from 77 NICUs were included. In total, 50.4% were men with a median of gestational age of 29 (4) weeks. The prevalence of EUGR (cross-sectional, longitudinal, and "true") was variable for weight, length, and head circumference. Overall, the prevalence was higher with Fenton and lower with Olsen (cross-sectional and "true" cross-sectional) and INTERGROWTH-21st (longitudinal and "true" longitudinal). Agreement among the charts by weight was good only for cross-sectional EUGR and moderate for longitudinal, "true" cross-sectional, and "true" longitudinal. Concordance was good or very good for EUGR by length and head circumference.Conclusions: The prevalence of EUGR with the most commonly used definitions was variable in the cohort. Agreement among growth charts was moderate for all the definitions of EUGR by weight except cross-sectional and good or very good for length and head circumference. The choice of reference chart can impact the establishment of the diagnosis of EUGR. What is known: • EUGR has been defined in the literature and daily practice considering weight, length and head circumference with multiple criteria (cross-sectional, longitudinal, and "true" definition) • Different growth charts have been used for EUGR diagnosis What is new: • Prevalence of EUGR is variable depending on the definition and growth chart used in our cohort of VLBW infants • For the most frequently EUGR criteria used, traditionally considering weight, concordance among Fenton, Olsen and INTERGROWTH-21st growth charts is only moderate for all the definitions of EUGR by weight except cross-sectional definition. Concordance among the charts is good or very good for the different criteria of EUGR by head circumference and length.

Health care-associated infections in neonatology.

Health care-associated infections are common in neonatology, but there is no consensus on their definitions. This makes it difficult to compare their incidence or assess the effectiveness of prevention bundles. This is why we think it is very important to achieve a consensus on the definitions and diagnostic criteria for one of the most frequent causes of morbidity in hospitalised neonates. This document aims to standardise the definitions for the most frequent health care-associated infections, such as catheter-associated bloodstream infection, ventilator-associated pneumonia and surgical wound infection, as well as the approach to their diagnosis and treatment.

Clinical Utility of the FilmArray® Blood Culture Identification (BCID) Panel for the Diagnosis of Neonatal Sepsis.

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.

Postnatal Growth Faltering: Growth and Height Improvement at Two Years in Children with Very Low Birth Weight between 2002-2017.

The prevalence of postnatal growth faltering (PGF) in preterm infants with very low birth weight (VLBW) (<1500 g) is a universal problem. Growth improvement is expected as neonatal care is optimized. Objectives: To determine if there has been a decrease in the prevalence of PGF and an improvement in height at 2 years in appropriate for gestational age VLBW children in the last two decades. Methods: Clinical descriptive retrospective analysis of neonatal somatometry at birth and at two-year corrected age in VLBW preterm infants. Small for gestational age were excluded. Two cohorts (2002−2006, n = 112; and 2013−2017, n = 92) were compared. Results. In the second five-year period, a decrease in prevalence of PGF was observed (36.6% vs. 22.8%, p = 0.033), an increase in growth rate in the first 28 days (5.22 (4.35−6.09) g/kg/day vs. 11.38 (10.61−12.15) g/kg/day, p < 0.0001) and an increase in height standard deviation (SD) at 2 years (−1.12 (−1.35−−0.91) vs. −0.74 (−0.99−−0.49) p = 0.023). Probability of short stature at 2 years was directly related to daily weight gain in the first 28 days. Conclusions: when comparing two five-year periods in the last two decades, growth in VLBW preterm infants has improved, both during neonatal period and at two years of age.

Growth outcome at 2 years using Fenton and Intergrowth-21st charts in infants less than 1500 g.

INTRODUCTION: There is no consensus on which neonatal chart is best to use in very low birth weight (VLBW) infants. The aim of the study was to compare the Fenton 2013 and Intergrowth-21st (IW-21) charts based on their predictive ability for somatometry at 2 years, as well as to analyze factors related to short stature at 2 years. MATERIAL AND METHODS: Cohort of children with VLBW born between 2002 and 2017. Association between neonatal somatometry (z-score by Fenton and IW-21) and risk of short stature (<-2 DS), head circumference <-2 DS and malnutrition at 2 years (BMI < -2 DS) was analyzed (WHO charts). RESULTS: 513 children with a mean gestational age of 30.05 ± 2.5 weeks were included. Birth and discharge weight z-score by Fenton and IW-21 were useful for predicting risk of short stature and malnutrition at 2 years (without differences in the AUC of the ROC curves). Weight z-score at discharge was also useful for predicting head circumference < -2 DS. At 2 years, prevalence of short stature, head circumference < -2 DS, and malnutrition was 17.2, 4.1, and 6.1%, respectively. Low weight for gestational age and length of stay were identified as independent risk factors for short stature at 2 years. CONCLUSIONS: Discharge weight z-score is useful for predicting risk of short stature, malnutrition and head circumference < -2 DS at 2 years in very low birth weight children, with no statistical difference between using Fenton or IW-21 charts.

Near-Infrared Sensors for Onsite and Noninvasive Quantification of Macronutrients in Breast Milk.

Breast milk is an optimal food that covers all the nutritional needs of the newborn. It is a dynamic fluid whose composition varies with lactation period. The neonatal units of hospitals have human milk banks, a service that analyzes, stores, and distributes donated human milk. This milk is used to feed premature infants (born before 32 weeks of gestation or weighing less than 1500 g) whose mothers, for some reason, cannot feed them with their own milk. Here, we aimed to develop near-infrared spectroscopy (NIRS) measures for the analysis of breast milk. For this purpose, we used a portable NIRS instrument scanning in the range of 1396-2396 nm to collect the spectra of milk samples. Then, different chemometrics were calculated to develop 18 calibration models with and without using derivatives and the standard normal variate. Once the calibration models were developed, the best treatments were selected according to the correlation coefficients (r2) and prediction errors (SECVs). The best results for the assayed macronutrients were obtained when no pre-treatment was applied to the NIR spectra of fat (r2 = 0.841, SECV = 0.51), raw protein (r2 = 0.512, SECV = 0.21), and carbohydrates (r2 = 0.741, SECV = 1.35). SNV plus the first derivative was applied to obtain satisfactory results for energy (r2 = 0.830, SECV = 9.60) quantification. The interpretation of the obtained results showed the richness of the NIRS spectra; moreover, the presence of specific bands for fat provided excellent statistics in quantitative models. These results demonstrated the ability of portable NIRS sensors in a methodology developed for the quality control of macronutrients in breast milk.

COVID-19 pandemic. What have we learned?

Since the COVID-19 pandemic was declared in March 2020, we have learned a lot about the SARS-CoV-2 coronavirus, and its role in pediatric pathology. Children are infected in a rate quite similar to adults, although in most cases they suffer mild or asymptomatic symptoms. Around 1% of those infected require hospitalization, less than 0.02% require intensive care, and mortality is very low and generally in children with comorbidities. The most common clinical diagnoses are upper or lower respiratory infections, gastrointestinal infection and, more seriously, multisystemic inflammatory syndrome (MIS-C). Most episodes do not require treatment, except for MIS-C. Remdesivir has been widely used as a compassionate treatment and its role has yet to be defined. The newborn can become infected, although vertical transmission is very low (<1%) and it has been shown that the baby can safely cohabit with its mother and be breastfed. In general, neonatal infections have been mild. Primary care has supported a very important part of the management of the pandemic in pediatrics. There has been numerous collateral damage derived from the difficulty of access to care and the isolation suffered by children. The mental health of the pediatric population has been seriously affected. Although it has been shown that schooling has not led to an increase in infections, but rather the opposite. It is essential to continue maintaining the security measures that make schools a safe place, so necessary not only for children's education, but for their health in general.

Antibiotherapy at birth in very low birth weight infants before and after the use of interleukin 6 as an infectious biomarker in a tertiary level unit.

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.

[COVID-19 pandemic. What have we learned?] / Pandemia COVID-19. ¿Qué hemos aprendido en este tiempo?

Since the COVID-19 pandemic was declared in March 2020, we have learned a lot about the SARS-CoV-2 coronavirus, and its role in pediatric pathology.Children are infected in a rate quite similar to adults, although in most cases they suffer mild or asymptomatic symptoms. Around 1% of those infected require hospitalization, less than 0.02% require intensive care, and mortality is very low and generally in children with comorbidities. The most common clinical diagnoses are upper or lower respiratory infections, gastrointestinal infection and, more seriously, multisystemic inflammatory syndrome (MIS-C). Most episodes do not require treatment, except for MIS-C. Remdesivir has been widely used as a compassionate treatment and its role has yet to be defined.The newborn can become infected, although vertical transmission is very low (<1%) and it has been shown that the baby can safely cohabit with its mother and be breastfed. In general, neonatal infections have been mild.Primary care has supported a very important part of the management of the pandemic in pediatrics. There has been numerous collateral damage derived from the difficulty of access to care and the isolation suffered by children. The mental health of the pediatric population has been seriously affected. Although it has been shown that schooling has not led to an increase in infections, but rather the opposite. It is essential to continue maintaining the security measures that make schools a safe place, so necessary not only for children's education, but for their health in general.

Extrauterine Growth Restriction in Very Low Birth Weight Infants: Concordance Between Fenton 2013 and INTERGROWTH-21st Growth Charts.

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.

Neonates Born to Mothers With COVID-19: Data From the Spanish Society of Neonatology Registry.

OBJECTIVES: To describe neonatal and maternal characteristics of the largest prospective cohort of newborns from mothers with coronavirus disease 2019 (COVID-19), the data of which were prospectively collected from the nationwide registry of the Spanish Society of Neonatology. METHODS: Between March 8, 2020, and May 26, 2020, the data of 503 neonates born to 497 mothers diagnosed with COVID-19 during pregnancy or at the time of delivery were collected by 79 hospitals throughout Spain. RESULTS: Maternal symptoms were similar to that of the general population, with 5% of severe forms. In 45.8% of asymptomatic women at the time of delivery, severe acute respiratory syndrome coronavirus 2 infection was detected because of recommendations established in Spain to perform COVID-19 screening in all women admitted to the hospital for labor. The rate of preterm deliveries was 15.7% and of cesarean deliveries, 33%. The most common diagnostic test was detection of viral RNA by polymerase chain reaction of nasopharyngeal swabs at a median age of 3 hours after delivery (1-12 hours). Almost one-half of neonates were left skin-to-skin after delivery, and delayed clamping of umbilical cords was performed in 43% of neonates. Also, 62.3% of asymptomatic neonates were managed with rooming-in. Maternal milk was received by 76.5% of neonates, 204 of them as exclusive breastfeeding. CONCLUSIONS: The current study indicates that there is no need for separation of mothers from neonates, allowing delayed cord clamping and skin-to-skin contact along with maintenance of breastfeeding in a high percentage of newborns from mothers with COVID-19.

[Psychomotor development in late premature newborns at five years. Comparison with term newborns using the ASQ3®]. / Desarrollo psicomotor en prematuros tardíos a los cinco años de edad: comparación con recién nacidos a término mediante ASQ3®.

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 5years-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 2TNB of the same gender for each LP. The prenatal and postnatal morbidity variables were compared. At 5years, 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 7LP compared to 4TNB, with no significant difference. More maternal, foetal, and neonatal illnesses were observed in 195LP than in the 390TNB. 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 5years 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.

Neonatal Infection Due to SARS-CoV-2: An Epidemiological Study in Spain.

Objective: Coronavirus disease 2019 (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to increase worldwide. Although some data from pediatric series are available, more evidence is required, especially in neonates, a group with specific characteristics that deserve special attention. This study aimed to describe general and clinical characteristics, management, and treatment of postnatal-acquired (community and nosocomial/hospital-acquired) COVID-19 neonatal cases in Spain. Methods: This was a national prospective epidemiological study that included cases from a National Registry supported by the Spanish Society of Neonatology. Neonates with postnatal SARS-CoV-2 infection were included in this study. General data and infection-related information (mode and source of transmission, age at diagnosis, clinical manifestations, need for hospitalization, admission unit, treatment administered, and complementary studies performed, hospital stay associated with the infection) were collected. Results: A total of 40 cases, 26 community-acquired and 14 nosocomial were registered. Ten were preterm newborns (2 community-acquired and 8 nosocomial COVID-19 cases). Mothers (in both groups) and healthcare workers (in nosocomial cases) were the main source of infection. Hospital admission was required in 22 community-acquired cases [18 admitted to the neonatal intermediate care unit (NIMCU) and 4 to the neonatal intensive care unit (NICU)]. Among nosocomial COVID-19 cases (n = 14), previously admitted for other reasons, 4 were admitted to the NIMCU and 10 to the NICU. Ten asymptomatic patients were registered (5 in each group). In the remaining cases, clinical manifestations were generally mild in both groups, including upper respiratory airways infection, febrile syndrome or acute gastroenteritis with good overall health. In both groups, most severe cases occurred in preterm neonates or neonates with concomitant pathologies. Most of the cases did not require respiratory support. Hydroxychloroquine was administered to 4 patients in the community-acquired group and to 2 patients in the nosocomial group. Follow-up after hospital discharge was performed in most patients. Conclusions: This is the largest series of COVID-19 neonatal cases in Spain published to date. Although clinical manifestations were generally mild, prevention, treatment, and management in this group are essential.

The Spanish National Network "Grupo Castrillo": 22 Years of Nationwide Neonatal Infection Surveillance.

OBJECTIVE: This study aimed to describe the epidemiology of vertically transmitted sepsis (VS) and nosocomial sepsis (NOS) in very low birth weight (VLBW) neonates (birth weight ≤ 1,500 g) over the past 22 years in Spain. STUDY DESIGN: This is a retrospective analysis of prospectively collected VS and NOS in neonates from 1996 to 2018 in the 44 neonatal units integrated in the Spanish Neonatal Network Grupo Castrillo. RESULTS: A total of 2,676 episodes of VS were recorded in 2,196,129 live births (LBs; 1.2/1,000 LBs) over the study period (1996-2018). The incidence declined from 2.4 to 1 to 1.2/1,000 LBs (p < 0.0001). Of the 2,676 episodes, 95.7% were early onset (≤72 hours) and 4.3% cases late onset VS. Group B streptococcus (GBS) (33.1%) and E. coli (29.3%) were the most frequently isolated pathogen. The GBS incidence declined significantly from 1.25 to 0.21/1,000 LBs (p < 0.0001). E. coli incidence showed a significant increase trend in VLBW infants (p < 0.05). The global mortality per 1000 LBs decreased from 0.21 to 0.13/1,000. A total of 7,036 episodes of NOS involving 5,493 VLBW infants were registered over 20,935 neonatal admissions (NAs) in the study period (2006-2018). The incidence was 26.2 per 100 NAs. The median postnatal age at onset was 13 days (interquartile range [IQR]: 9-23 days). Around 80% of cases occurred in infants with a central line in place. Gram positive (GP) bacteria accounted for 66.2% with Staphylococcus epidermidis as the most frequently isolated pathogen, gram negative (GN) bacteria entailed 27.4%, and fungi 6.2%. Klebsiella sp. was the most common GN isolated and Candida albicans the most prevalent fungus. The overall mortality was 8.3%. CONCLUSION: The causative pathogen of neonatal sepsis may change over time and between countries, therefore a national surveillance network based on a consensus definition could be essential to provide accurate information. KEY POINTS: · Grupo Castrillo is a Spanish network for neonatal infections surveillance.. · A neonatal sepsis definition based on epidemilogical and not only chronological criteria was established.. · Epidemiology of neonatal sepsis may change over time; therefore, a national surveillance network is essential to provide accurate information..

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.

In vivo study of the effect of lactoferrin on iron metabolism and bioavailability from different iron chemical species for formula milk fortification.

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.

[Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy]. / Estrés oxidativo en la asfixia perinatal y la encefalopatía hipóxico-isquémica.

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.

Evolution of Energy Related Metabolites in Plasma from Newborns with Hypoxic-Ischemic Encephalopathy during Hypothermia Treatment.

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 ß-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 ß-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.