Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux.

BACKGROUND: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported.

Corrigendum: Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

[This corrects the article DOI: 10.3389/fendo.2021.641543.].

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

Vitamin D-Resistant Rickets and Cinacalcet-One More Favorable Experience.

Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by early onset of severe rickets, with a complete triad of clinical, biochemical and skeletal abnormalities. Homozygous or heterozygous mutations in the vitamin D receptor (VDR) gene leading to complete or partial target organ resistance to the action of 1α, 25-dihydroxyvitamin D3 (the active form of vitamin D) are responsible for HVDRR. Theoretically the therapeutic goal is to overcome this tissue resistance, and to normalize calcium and phosphate homeostasis. Practically, the treatment could be oriented to correct the secondary hyperparathyroidism to avoid long-term negative impact on bone health. The conventional therapeutic strategy (high-dose calcium plus active vitamin D metabolites) gives variable responses in magnitude and duration. We report a case of HVDRR with heterozygous mutation in the VDR gene, neonatal alopecia, and a severe clinical phenotype diagnosed at the age of 30 months who showed unsatisfactory response to traditional therapy. The short-term responsiveness to cinacalcet was encouraging, with adequate correction of phosphate-calcium homeostasis and significant improvement of clinical and radiological status at 6 months of treatment.

Malignancy-Induced Hypercalcemia-Diagnostic Challenges.

Hypercalcemia in children is a rare metabolic finding. The clinical picture is usually non-specific, and the etiology includes several entities (metabolic, nutritional, drug-induced, inflammatory, cancer-associated, or genetic) depending on the age at presentation, but severe hypercalcemia is associated mainly with malignancy in childhood and sepsis in neonates. Severe parathyroid hormone (PTH)-suppressed hypercalcemia is challenging and requires multidisciplinary diagnostic and therapeutic approaches to (i) confirm or rule out a malignant cause, (ii) treat it and its potentially dangerous complications. We report a case of severe and complicated PTH-independent hypercalcemia in a symptomatic 3-year-old boy. His age, severity of hypercalcemia and its complicated course, and the first imaging reports were suggestive of malignancy. The first bone and kidney biopsies and bone marrow aspiration were normal. The definitive diagnosis was a malignant-induced hypercalcemia, and we needed 4 weeks to assess other differential diagnoses and to confirm, on histopathological and immunochemical base, the malignant origin of hypercalcemia. Using this case as an illustrative example, we suggest a diagnostic approach that underlines the importance of repeated histology if the clinical suspicion is malignancy-induced hypercalcemia. Effective treatment is required acutely to restore calcium levels and to avoid complications.

Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene.

We report a 16-year-old girl with neonatal progeroid features and congenital lipodystrophy who was considered at birth as a possible variant of Wiedemann-Rautenstrauch syndrome. The emergence of additional clinical signs (marfanoid habitus, severe myopia and dilatation of the aortic bulb) lead to consider the diagnosis of the progeroid variant of Marfan syndrome. A de novo donor splice-site mutation (c.8226+1G>A) was identified in FBN1. We show that this mutation leads to exon 64 skipping and to the production of a stable mRNA that should allow synthesis of a truncated profibrillin-1, in which the C-terminal furin cleavage site is altered. FBN1 mutations associated with a similar phenotype have only been reported in four other patients. We confirm the correlation between marfanoid phenotype with congenital lipodystrophy and neonatal progeroid features (marfanoid-progeroid-lipodystrophy syndrome) and frameshift mutations at the 3' end of FBN1. This syndrome should be considered in differential diagnosis of neonatal progeroid syndromes.

The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium.

OBJECTIVE: To determine mortality and morbidity at discharge from the hospital of a large population-based cohort of infants who were born at

Heart rate response profiles to tilting in healthy and unhealthy neonates.

BACKGROUND: Clinical observations suggest the immaturity of the neonate's ability to respond appropriately to cardio-respiratory challenges and tilt test could help in detecting autonomic dysfunction in neonates. MATERIAL/METHODS: Heart rate (HR) responses following a 45 degrees head-up tilt during sleep were measured within the first week of adjusted age in 7 healthy full-term neonates, 7 healthy preterm infants and 5 neonates with abstinence syndrome. RESULTS: The tilt and the return to the horizontal position generally provoked a sustained or transient tachycardia, or a flat response in healthy full-term neonates and in preterm neonates, but a sustained or transient bradycardia in neonates with abstinence syndrome. CONCLUSIONS: When compared to previous studies in older infants, our data point to the immaturity of the neonate's ability to respond appropriately to cardio-respiratory challenges. No difference is noted between full-term and preterm neonates. The altered HR response in neonates with abstinence syndrome suggests an autonomic dysregulation in this group.

The flow-pressure plot: a new look on the patient-ventilator interaction in neonatal care.

Most modern neonatal ventilators have now a built-in flow sensor and, as a spin-off of their mechanical action, provide some information about lung function characteristics as compliance and resistance after computation of the flow and pressure signals. Additionally, respiratory graphics as volume-pressure and flow-volume plots can be displayed. In clinical practice, however, they are rarely used to refine the ventilator setting. A nonconventional flow-pressure plot is presented in this article, constructed from the volume or flow, and pressure outputs of a Babylog 8000 (Dräger, Lübeck, Germany). This flow-pressure diagram appears to be useful in the real-time computation of respiratory mechanics based on the Rahn's law of respiratory motion. Its major advantage, however, is the easy pattern recognition of subtle changes in infant-ventilator interaction, ie, excessive triggering, fighting against the ventilator, augmented breath, tube subobstruction. It may be useful to add the flow-pressure plot to the classical respiratory graphics allowing to monitor mechanical ventilation more accurately and to fine tune the ventilator setting accordingly.