Bone mineral density, body composition, and metabolic health of very low birth weight infants fed in hospital following current macronutrient recommendations during the first 3 years of life

The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required.This research was partially funded by the ‘Fondo de Investigación Sanitaria’ (grant number PI041631

Identification of clinical variants beyond the exome in inborn errors of metabolism

Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency. Eight novel variants in six genes were identified: six (four of them deep intronic) located in GALE, IDUA, PTS, ASS1 and OTC, all affecting the splicing process, and two located in the promoters of IDUA and PTS, thus affecting these genes’ expression. All the new variants were subjected to functional analysis to verify their pathogenic effects. This work underscores how the combination of different omics technologies and functional analysis can solve elusive cases in clinical practic

Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p < 0.001) and glutamine levels (from 791.4 ± 289.8 to 648.6 ± 247.41 μmol/L, p < 0.001) was observed. After one year of GPB treatment (411 ± 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 ± 0.7 to less than 0.1 ± 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.This study was funded by AECOM (Spanish Association for the Study of Inborn Errors of Metabolism). Immedica Pharma Spain funded medical writing support and article processing charges

Chemical probes for the recognition of cannabinoid receptors in native systems.

Receptors made visible: The described biotin-tagged small-molecule probes with excellent affinities for the CB(1) and CB(2) cannabinoid receptors (CB(1)R and CB(2)R) enable direct visualization of these receptors in native cellular systems, including neurons, microglia, and immune cells. This method could overcome some of the limitations of current methodologies and may help to dissect the complexity of the endogenous cannabinoid system.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

Parto domiciliario: un fenómeno creciente con potenciales riesgos.

Home birth is a controversial issue that raises safety concerns for paediatricians and obstetricians. Hospital birth was the cornerstone to reduce maternal and neonatal mortality. This reduction in mortality has resulted in considering pregnancy and childbirth as a safe procedure, which, together with a greater social awareness of the need for the humanisation of these processes, have led to an increase in the demand for home birth. Studies from countries such as Australia, the Netherlands, and United Kingdom show that home birth can provide advantages to the mother and the newborn. It needs to be provided with sufficient material means, and should be attended by trained and accredited professionals, and needs to be perfectly coordinated with the hospital obstetrics and neonatology units, in order to guarantee its safety. Therefore, in our environment, there are no safety data or sufficient scientific evidence to support home births at present