Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Mild Hypophosphatemia-Associated Conditions in Children: The Need for a Comprehensive Approach.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

[Infections in early life as risk factor for coeliac disease]. / Infecciones en la primera infancia como factor de riesgo de enfermedad celiaca.

INTRODUCTION: Among the environmental factors that can affect the pathological response to gluten in coeliac disease (CD), the factors that influence the immune response, such as infections and use of antibiotics, are proposed. Our objective is to determine the relationship between infections in early life and the risk of CD. PATIENTS AND METHODS: A retrospective case-control study, including patients aged 0-16 years with a diagnosis of CD was performed between the years 2014-2018. An analysis was made of documented infections in the first 6 months of life, types of infection (respiratory, gastrointestinal, urinary, others), microorganisms involved, and antibiotic therapy used. RESULTS: A total of 93 coeliac patients, 93 controls, and 237 infectious episodes were registered. Documented infections affected 67.7% of coeliac patients and 50.5% of controls (P = .017), with a mean of 1.49 ± 1.53 episodes in the coeliac group and 1.05 ± 1.5 in the controls (P = .016). Documented infections in the first 6 months of life doubles the risk of developing CD (OR 2.05; 95% CI; 1.13-3.73), with this risk being higher for respiratory infections, which multiply the risk by 2.3 (OR 2.30, 95% CI; 1.28-4.14). Also, having 3 or more respiratory infections in the first 6 months of life multiplied the risk by 2.8 (OR 2.79, 95% CI; 1.03-7.54). No differences were found related to the types of involved microorganism or regarding the use of antibiotics. CONCLUSIONS: Infections in the first 6 months of life increase the risk of developing CD, especially for respiratory infections and, to a greater extent, if 3 or more episodes occur. The use of antibiotics in this period of life has not been related to an increased risk of CD.

Modified Serum ALP Values and Timing of Apparition of Knee Epiphyseal Ossification Centers in Preterm Infants with Cholestasis and Risk of Concomitant Metabolic Bone Disease of Prematurity.

The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns <32 weeks. A significant correlation existed between serum ALP and direct bilirubin (DB), expressed by the regression equation: M-ALP (IU/L) = 302.1 + 96.9 (DB (mg/dL)). The ratio ALP/M-ALP > 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis.

[Current diagnosis and management of toddler's fracture]. / Manejo diagnóstico y terapéutico actual de la fractura de los primeros pasos.

INTRODUCTION: Toddler's fracture is an accidental spiral tibial fracture, characteristic of the early childhood. The objective of this study is to determine the incidence and current diagnosis and management of this disorder. PATIENTS AND METHODS: A retrospective study was conducted on a sample of patients aged 0-3 years diagnosed with a toddler's fracture in a tertiary hospital between years 2013 and 2017. RESULTS: A total of 53 patients were registered (10.6 cases per year). The median age was 2 years, with a slight male predominance. The initial radiograph was normal in 24.5% of patients. With the initial approach, 69.8% of patients were diagnosed with fracture, 11.3% with suspected fracture, and 18.9% with contusion. A follow-up was required in 22% required a control test, using radiographs in 10 patients (pathological 90%), and ultrasound in 5 (pathological 80%, 3 of them with normal initial radiography). The large majority (80.8%) of the patients were immobilised with a cast, while flexible immobilisation or non-immobilisation was used in 19.2%. Complications were found in a 21.4% of patients immobilised with splint, mainly skin injuries (19%). These were more frequent in this group than in those that were not immobilised (21.4% vs. 0%, P=.006); with no significant differences in time to weight-bearing. CONCLUSIONS: Radiography has a limited sensitivity for the diagnosis of toddler's fracture. In the group of patients with normal radiography, the use of ultrasound can be helpful to the diagnosis and avoid additional radiation. Even though the most common treatment continues to be immobilisation with a splint, the alternative without rigid immobilisation does not seem to give worse results, even with lower morbidity associated with the treatment.