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.

Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23.

Fibroblast growth factor 23 (FGF23) was identified at the turn of the century as the long-sought circulating phosphatonin in human pathology. Since then, several clinical and experimental studies have investigated the metabolism of FGF23 and revealed its relevant pathogenic role in various diseases. Most of these studies have been performed in adult individuals. However, the mineral metabolism of the child is, to a large extent, different from that of the adult because, in addition to bone remodeling, the child undergoes a specific process of endochondral ossification responsible for adequate mineralization of long bones' metaphysis and growth in height. Vitamin D metabolism is known to be deeply involved in these processes. FGF23 might have an influence on bones' growth as well as on the high and age-dependent serum phosphate concentrations found in infancy and childhood. However, the interaction between FGF23 and vitamin D in children is largely unknown. Thus, this review focuses on the following aspects of FGF23 metabolism in the pediatric age: circulating concentrations' reference values, as well as those of other major variables involved in mineral homeostasis, and the relationship with vitamin D metabolism in the neonatal period, in vitamin D deficiency, in chronic kidney disease (CKD) and in hypophosphatemic disorders.

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.

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)

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.

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.