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.

Impact of the Choice of Diagnostic Criteria and Growth Reference on the Prevalence of Extrauterine Growth Restriction in Extremely-Low-Birthweight Infants.

BACKGROUND AND OBJECTIVES: Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. MATERIALS AND METHODS: An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), "true" cross-sectional and "true" longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss' Kappa coefficient. RESULTS: The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). CONCLUSIONS: The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight.

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.

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.

Neonatal unplanned extubations: an unsolved safety issue.

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.

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.

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.

[Nutritional composition of donor human milk according to lactation period]. / Composición nutricional de la leche materna donada según el periodo de lactancia.

INTRODUCTION: Introduction: when own mother´s breast milk is unavailable, donor human milk is the best option to guarantee the nutritional requirements of preterm or ill newborns. Objectives: to analyze the macronutrient composition of donor breast milk and its evolution over lactation periods. Material and methods: we retrospectively analyzed the nutritional composition of 822.423 L of donor breast milk from 160 donors at the human milk bank of a third-level hospital between February 1, 2017 and December 31, 2019. Results: lipid and carbohydrate composition remains constant throughout lactation. However, protein content decreases initially to increase again starting in the second year of lactation. Conclusions: donor human milk banks should be aware of the variations in macronutrient composition donor human milk shows in order to optimize nutrition for preterm newborns.

INTRODUCCIÓN: Introducción: cuando no se dispone de leche materna propia, la leche materna donada es la mejor alternativa para asegurar los requerimientos nutricionales de los recién nacidos prematuros o enfermos. Objetivos: conocer el contenido de macronutrientes de la leche materna donada y cómo varían estos en los distintos periodos de la lactancia. Material y métodos: se analizó de forma retrospectiva la composición nutricional de 822,423 litros de leche materna donada, procedentes de 160 donantes del banco de leche materna de un hospital de tercer nivel entre el 1 de febrero de 2017 y el 31 de diciembre de 2019. Resultados: el contenido en lípidos y carbohidratos se mantiene constante a lo largo de la lactancia; sin embargo, el contenido proteico disminuye inicialmente para luego volver a aumentar a partir del segundo año de lactancia. Conclusiones: los bancos de leche materna deben conocer las variaciones del contenido en macronutrientes de la leche donada para optimizar la nutrición del recién nacido prematuro.

Predicción del crecimiento a los dos años utilizando las gráficas de Fenton e Intergrowth-21 en menores de 1.500 g / Growth outcome at 2 years using Fenton and Intergrowth-21st charts in infants less than 1500 g

Introducción: No existe consenso sobre qué gráfica neonatal es mejor utilizar en niños con muy bajo peso al nacer (MBPN). El objetivo del estudio fue comparar las gráficas de Fenton 2013 e Intergrowth-21st (IW-21) con base en su capacidad predictora de la somatometría a los dos años, así como analizar factores relacionados con talla baja a los dos años. Material y métodos: Cohorte de niños con MBPN nacidos entre 2002-2017. Se analizó la asociación entre la somatometría neonatal (z-score por Fenton e IW-21) y el riesgo de talla baja (< -2 desviación estándar [DS]), perímetro craneal < -2 DS y desnutrición a los 2 años (IMC < -2 DS) (gráficas OMS). Resultados: Se incluyeron 513 niños 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 útiles para predecir riesgo de talla baja y desnutrición a los dos años (sin diferencias en el AUC de las curvas ROC), siendo el z-score al alta útil además para predecir perímetro craneal < -2D. A los dos años, la prevalencia de talla baja, perímetro craneal < -2 DS, y desnutrición fue del 17,2, 4,1 y 6,1%, respectivamente. El bajo peso para la edad gestacional y la duración del ingreso neonatal se identificaron como factores de riesgo independientes para talla baja a los dos años. Conclusiones: El z-score peso al alta resulta útil para predecir riesgo de talla baja, desnutrición y perímetro craneal < -2 DS a los dos años en niños con muy bajo peso al nacer, sin diferencias estadísticas entre utilizar las gráficas de Fenton o IW-21. (AU)

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 in 2002–2017. 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. (AU)

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.

Composición nutricional de la leche materna donada según el periodo de lactancia / Nutritional composition of donor human milk according to lactation period

INTRODUCCIÓN: cuando no se dispone de leche materna propia, la leche materna donada es la mejor alternativa para asegurar los requerimientos nutricionales de los recién nacidos prematuros o enfermos. OBJETIVOS: conocer el contenido de macronutrientes de la leche materna donada y cómo varían estos en los distintos periodos de la lactancia. MATERIAL Y MÉTODOS: se analizó de forma retrospectiva la composición nutricional de 822,423 litros de leche materna donada, procedentes de 160 donantes del banco de leche materna de un hospital de tercer nivel entre el 1 de febrero de 2017 y el 31 de diciembre de 2019. RESULTADOS: el contenido en lípidos y carbohidratos se mantiene constante a lo largo de la lactancia; sin embargo, el contenido proteico disminuye inicialmente para luego volver a aumentar a partir del segundo año de lactancia. CONCLUSIONES: los bancos de leche materna deben conocer las variaciones del contenido en macronutrientes de la leche donada para optimizar la nutrición del recién nacido prematuro

INTRODUCTION: when own mother's breast milk is unavailable, donor human milk is the best option to guarantee the nutritional requirements of preterm or ill newborns. OBJECTIVES: to analyze the macronutrient composition of donor breast milk and its evolution over lactation periods. MATERIAL AND METHODS: we retrospectively analyzed the nutritional composition of 822.423 L of donor breast milk from 160 donors at the human milk bank of a third-level hospital between February 1, 2017 and December 31, 2019. RESULTS: lipid and carbohydrate composition remains constant throughout lactation. However, protein content decreases initially to increase again starting in the second year of lactation. CONCLUSIONS: donor human milk banks should be aware of the variations in macronutrient composition donor human milk shows in order to optimize nutrition for preterm newborns