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.

Variability in Definitions and Criteria of Extrauterine Growth Restriction and Its Association with Neurodevelopmental Outcomes in Preterm Infants: A Narrative Review.

Extrauterine growth restriction (EUGR) has been used in the literature and clinical practice to describe inadequate growth in preterm infants. Significant variability is seen in the criteria for EUGR, with no standard definition reached to date. Moreover, no consensus on the optimal timing for assessment or the ideal growth monitoring tool has been achieved, and an ongoing debate persists on the appropriate terminology to express poor postnatal growth. To ensure an adequate understanding of growth and early intervention in preterm infants at higher risk, it is critical to relate the diagnostic criteria of EUGR to the ability to predict adverse outcomes, such as neurodevelopmental outcomes. This narrative review was conducted to present evidence that evaluates neurodevelopmental outcomes in preterm infants with EUGR, comparing separately the different definitions of this concept by weight (cross-sectional, longitudinal and "true" EUGR). In this article, we highlight the challenges of comparing various published studies on the subject, even when subclassifying by the definition of EUGR, due to the significant variability on the criteria used for each definition and for the evaluation of neurodevelopmental outcomes in different papers. This heterogeneity compromises the obtention of a single firm conclusion on the relation between different definitions of EUGR and adverse neurodevelopmental outcomes.

[Breastfeeding in Spain and the factors related to its establishment and maintenance: LAyDI Study (PAPenRed)]. / Lactancia materna en España y factores relacionados con su instauración y mantenimiento: estudio LAyDI (PAPenRed).

OBJECTIVE: To find out actual statistics on breastfeeding in Spain, as well as sociocultural and perinatal factors that affect its initiation and maintenance. DESIGN: Prospective, multicentre, longitudinal, nationwide study (XXX study). SITE: Primary care paediatricians' office. PARTICIPANTS: Cohort of newborns born between April 2017 and March 2018 in Spain who were followed up to two years of age in 8 visits. MAIN MEASURES: Rates of different types of breastfeeding were analysed at each visit and variables related to gestation, delivery, neonatal period, social, economic and biological variables were also analysed. RESULTS: Initial sample of 1946 (50.1% male). 90.7% decided to initiate breastfeeding at birth. Exclusive breastfeeding (EBF) was 66.4% at 15days and 35.2% at 6months. Any type of breastfeeding (total breastfeeding [TBF]) at 6months was 61.7%. Median survival from TBF was 6.0months (95%CI: 6.0-6.1). Variables related to EBF at 15days: previous children, mother's level of education, absence of illness during pregnancy, no separation of mother and child at birth, no dummy use, no nipple problems, and time of decision to breastfeed. Variables related to longer duration of TBF: relationship of parents older than 5years, no dummy use, co-sleeping at one month of life, deciding to breastfeed before pregnancy, receiving information on breastfeeding during pregnancy and using support from associations. CONCLUSIONS: Early abandonment of breastfeeding is a major problem in Western societies. There are factors that can be worked on to improve outcomes.

Neonatal Growth, Nutrition, and Neurodevelopment: A Complex Relationship.

Growth in the neonatal period is critical for the neurodevelopment of the individual, both in low- and middle-income countries [...].

Research ethics: From principles to practical aspects.

Any research conducted on human beings or human biological samples requires a prior ethical assessment to avoid risks and problems for all involved parties. The legislation in this regard is very broad and emphasizes the safeguarding of patient rights in relation to the universal principles of autonomy, beneficence and justice. The present article reviews the regulations applicable to clinical trials, observational studies with drugs, biobank projects or any other type of study that may be conducted in the health care field. It also addresses the role of research ethics committees, data protection and the foundations of scientific integrity.

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.

Dexmedetomidine: An Alternative to Pain Treatment in Neonatology.

Infants might be exposed to pain during their admissions in the neonatal intensive care unit [NICU], both from their underlying conditions and several invasive procedures required during their stay. Considering the particularities of this population, recognition and adequate management of pain continues to be a challenge for neonatologists and investigators. Diverse therapies are available for treatment, including non-pharmacological pain management measures and pharmacological agents (sucrose, opioids, midazolam, acetaminophen, topical agents…) and research continues. In recent years one of the most promising drugs for analgesia has been dexmedetomidine, an alpha-2 adrenergic receptor agonist. It has shown a promising efficacy and safety profile as it produces anxiolysis, sedation and analgesia without respiratory depression. Moreover, studies have shown a neuroprotective role in animal models which could be beneficial to neonatal population, especially in preterm newborns. Side effects of this therapy are mainly cardiovascular, but in most studies published, those were not severe and did not require specific therapeutic measures for their resolution. The main objective of this article is to summarize the existing literature on neonatal pain management strategies available and review the efficacy of dexmedetomidine as a new therapy with increasing use in the NICU.

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.

A Dynamic Approach for Early Risk Prediction of Gram-Negative Bloodstream Infection and Systemic Inflammatory Response Syndrome in Febrile Pediatric Hemato-Oncology Patients.

Background: The aim of this study was to evaluate the usefulness of C-Reactive Protein (CRP), Procalcitonin (PCT), and Interleukine 6 (IL6) biomarkers in predicting the existence of high-risk episodes (HRE) during the first 24 h of fever in pediatric cancer patients. HRE were defined as the presence of Gram-negative bloodstream infections or Systemic Inflammatory Response Syndrome. Methods: The study included 103 consecutive fever episodes in 44 hemato-oncological pediatric patients, from whom samples for biomarkers were taken upon initial evaluation (CRP-1, PCT-1 and IL6-1) and then between 12 and 24 h afterward (CRP-2, PCT-2 and IL6-2). Results: An IL6-1 value higher than 164 pg/mL showed an area under the curve (AUC) of 0.890 (0.791−0.989) and OR of 48.68 (7.92−951.42, p < 0.001) to detect HRE in multivariate analysis. A PCT-1 higher than 0.32 ng/mL showed an AUC of 0.805 (0.700−0.910) and OR of 4.55 (0.90−27.84, p = 0.076). A PCT-2 higher than 0.94 ng/mL showed an AUC of 0.836 (0.725−0.947) and OR of 13.01 (1.82−149.13, p = 0.018), and an increase in CRP between the first and second sample (CRP-2vs1) higher than 291% also showed an AUC of 0.785 (0.655−0.915) and OR of 31.09 (4.87−355.33, p = 0.001). Conclusions: IL6-1, PCT-2, and CRP-2vs1 showed a strong and independent correlation with HREs in pediatric cancer patients. CRP variations over the first 24 h provide an improvement in predictive models that are especially useful if IL-6 and PCT are not available.

Trends and Pattern of Antibiotic Use in Children in Northern Spain, Interpreting Data about Antibiotic Consumption in Pediatric Outpatients.

Monitoring of antibiotic prescription and consumption behavior is crucial. The Access, Watch, and Reserve (AWaRe) classification of antibiotics has been recently introduced in order to measure and improve patterns of antibiotic use. In this study, retrospective data about systemic antibiotic consumption (expressed in defined daily dose per 1000 inhabitants per day (DID)) in pediatric outpatients in a region in northern Spain (around 100,000 children up to 14 years old) from 2005 to 2018 were analyzed and compared with antibiotic consumption in general population in Spain. The pattern of use was analyzed by the percentage of the current AWaRe categories, the Access-to-Watch index, and the amoxicillin index. Data were calculated annually and compared into two periods. Mean antibiotic consumption in pediatric outpatients was 14.0 DID (CI 95% 13.38-14.62). It remained stable throughout the study and was lower than consumption in general population in Spain, particularly from 2016. Changes in the consumption of the main active principles have led to an improvement in the three metrics of the pattern of use. It is important to have a thorough knowledge of the methodology applied in studies about antibiotic consumption. There is a lack of an optimal standardized metric for the pediatric population.

Evolution of antibiotic consumption in pediatric outpatients of Asturias, Spain (2005-2018).

INTRODUCTION: Data about consumption of antibiotics in Spain are worrisome. They are mainly prescribed in the community sector and there is a high exposure to antibiotics in the pediatric population. The aim of this study is to describe the evolution of antibiotic consumption in the pediatric population of Asturias during 2005-2018 period. METHODS: Retrospective and descriptive study using data about consumption of antibacterial agents for systemic use (J01 group of the Anatomical Therapeutic Chemical Classification) in pediatric outpatients in Asturias between 2005 and 2018. Data, expressed as defined daily dose (DDD) per 1000 inhabitants per day (DID), in three periods were compared. RESULTS: Mean antibiotic consumption in pediatric outpatients in Asturias (2005-2018) was 14 DID (CI95% 13.4-14.6). Consumption increased until 2009 (15.2 DID) and decreased from 2015 onwards (11.9 DID in 2018). Remarkable data along the study were: 1) increase in amoxicillin consumption (p = 0.027), that have exceeded that of amoxicillin-clavulanate since 2011; 2) steady consumption of macrolides, with an increase in azithromycin (p < 0.001) and a decrease in clarithromycin (p = 0.001); 3) reduction of cephalosporins consumption (p < 0.001); 4) increase in quinolones consumption (p = 0.002). CONCLUSIONS: Global antibiotic consumption in pediatric outpatients in Asturias between 2005 and 2018 has experienced a constant decrease lately and an improvement in patterns of antibacterial use.

Biomarkers and Fever in Children with Cancer: Kinetics and Levels According to Final Diagnosis.

We investigated the kinetics of CRP, PCT, IL-6 and MR-proADM in a cohort of consecutive febrile patients with cancer in order to test the hypothesis that higher plasma concentrations and the absence of a rapid decrease in peak values would be associated with disease severity. (1) Method: A prospective descriptive and analytical study of patients with cancer and fever (≤18 years of age) at a University Hospital was carried out between January 2018 and December 2019. Information collected: sex, age, diagnosis, date and symptoms at diagnosis and medical history. The episodes were classified into three groups: bacterial infection, non-bacterial infection and systemic inflammatory response syndrome (SIRS). (2) Results: One hundred and thirty-four episodes were included. Bacterial infection criteria were met in 38 episodes. Biomarkers were measured at four different points: baseline, at 12-24 h, at 25-48 h and at 49-72 h. All the biomarkers evaluated decreased after the peak level was reached. IL-6 and MR-proADM showed a trend towards higher levels in the SIRS group although this rise was statistically significant only for IL-6 (p < 0.005). Bacterial infections more frequently presented values of PCT above the cut-off point (>0.5 ng/mL) at 12-24 h. (3) Conclusion: In our experience, IL-6 kinetics is faster than PCT kinetics and both are faster than CRP in patients with fever and cancer who present a good outcome. Patients with a good evolution show a rapid increase and decrease of PCT and particularly of IL-6 levels.

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.

Neonatal unplanned extubations: an unsolved safety issue / Extubaciones neonatales no programadas: un problema de seguridad no resuelto

Abstract Background: Unplanned extubations are safety events relatively frequent in the neonatal intensive care units (NICU). This study aimed to describe the frequency and characteristics of unplanned extubations in a NICU. Methods: We conducted a retrospective observational study of unplanned extubations in the NICU of a tertiary regional referral hospital. We reviewed medical records for data collection and performed the statistical analysis, comparing the cases of unplanned extubations with those in which it did not occur among all the cases that received intubation and invasive neonatal mechanical ventilation. Results: A total of 958 newborns were admitted to the NICU, of which 174 required assistance with invasive mechanical ventilation (18.1%) and 28 experienced unplanned extubations (16.1%): 25 patients with one episode, one with two episodes, and two with three episodes. The rate was 2.93 unplanned extubations for every 100 days of invasive mechanical ventilation in 5 years, with a significant decrease in the last three years (p = 0.0158). We found a statistically significant correlation between a weight < 1500 g and unplanned extubation in the multivariate analysis, although sedation appears to affect its interaction. Conclusions: Unplanned extubations are a relatively frequent problem, although with a tendency to decrease in recent years. The weight of the patients at birth and sedation during ventilation are important factors in this safety problem.

Resumen Introducción: La extubación no programada es un evento de seguridad relativamente frecuente en las unidades de cuidados intensivos neonatales (UCIN). El objetivo de este estudio fue conocer la frecuencia y las características de las extubaciones no programadas en una UCIN. Métodos: Se realizó un estudio observacional retrospectivo de las extubaciones no programadas en la UCIN de un hospital regional de referencia de tercer nivel. Se revisaron las historias clínicas y se realizó el análisis estadístico de los datos, comparando los casos de extubación no programada con aquellos en los que no sucedió entre todos los pacientes que recibieron intubación y ventilación mecánica invasiva neonatal. Resultados: Ingresaron en la UCIN 958 neonatos, de los cuales 174 precisaron asistencia con ventilación mecánica invasiva (18.1%) y 28 tuvieron una extubación no programada (16.1%). De estos, 25 presentaron un episodio, uno presentó dos episodios y dos presentaron tres episodios de extubación no programada. La tasa fue de 2.93 extubaciones no programadas por cada 100 días de ventilación mecánica invasiva en 5 años, con una importante disminución en los últimos 3 años (p = 0.0158). El peso < 1500 g se relacionó con las extubaciones no programadas de forma estadísticamente significativa en el análisis multivariante, aunque la sedación aparece como un factor modificador de efecto a través de su interacción. Conclusiones: Las extubaciones no programadas son un problema relativamente frecuente, aunque con tendencia a disminuir en los últimos años. El peso de los pacientes al nacimiento y la sedación son factores importantes en este problema de seguridad.

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.