BMP8 and activated brown adipose tissue in human newborns.

The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates. Here, we have applied non-invasive infrared thermography (IRT) to investigate neonatal BAT activity. Our data show that BAT temperature correlates with body temperature and that mild cold stimulus promotes BAT activation in newborns. Notably, a single short-term cold stimulus during the first day of life improves the body temperature adaption to a subsequent cold event. Finally, we identify that bone morphogenic protein 8B (BMP8B) is associated with the BAT thermogenic response in neonates. Overall, our data uncover key features of the setup of BAT thermogenesis in newborns.

Human Milk Concentrations of Minerals, Essential and Toxic Trace Elements and Association with Selective Medical, Social, Demographic and Environmental Factors.

This study aims to quantify concentrations of minerals and trace elements in human milk (HM) and infant formula (IF) and evaluate associations with medical, social, environmental, and demographic variables. A prospective, case series study of 170 nursing mothers was made. HM samples were obtained from full-term (colostrum, intermediate and mature HM) and preterm (mature HM) mothers. Variables of interest were assessed by a questionnaire. For comparison, IF samples (n = 30) were analyzed in a cross-sectional study. Concentrations of 35 minerals, essential and toxic trace elements were quantified, 5 for the first time: thallium in HM and IF; strontium in preterm HM; and gallium, lithium and uranium in IF. In preterm and full-term HM, levels of selenium (p < 0.001) were significantly lower than recommended and were associated with low birth weight (p < 0.002). Cesium and strontium concentrations were significantly higher than recommended (p < 0.001). Associations were observed between arsenic and residence in an urban area (p = 0.013), and between lead and smoking (p = 0.024) and well-water consumption (p = 0.046). In IF, aluminum, vanadium, and uranium levels were higher than in HM (p < 0.001); uranium, quantified for the first time, was 100 times higher in all types of IF than in HM. Our results indicate that concentrations of most trace elements were within internationally accepted ranges for HM and IF. However, preterm infants are at increased risk of nutritional deficiencies and toxicity. IF manufacturers should reduce the content of toxic trace elements.

Metabolic Bone Disease of Prematurity: Risk Factors and Associated Short-Term Outcomes.

Despite the importance of early recognition of metabolic bone disease (MBD) of prematurity, there is still significant variability in screening practices across institutions. We conducted an observational study of infants born at ≤32 weeks of gestation with a birth weight of ≤1500 g (n = 218) to identify clinical factors associated with biochemical indicators of MBD. Bone mineral status was assessed by measuring alkaline phosphatase and phosphate levels between weeks 3 and 5 of life. Two comparisons were performed after classifying infants as either MBD (cases) or non-MBD (controls), and as either high or low risk for MBD, as determined based on the results of MBD screening. In total, 27 infants (12.3%) were classified as cases and 96 (44%) as high-risk. Compared with controls, MBD infants had a significantly lower gestational age and birth weight, and a longer duration of parenteral nutrition and hospital stay. Respiratory outcomes were significantly poorer in high- versus low-risk infants. Multivariate logistic regression showed that birth weight was the only independent risk factor for MBD (odds ratio [OR]/100 g, 0.811; confidence interval [CI95%], 0.656-0.992; p = 0.045) and that birth weight (OR/100 g, 0.853; CI95%, 0.731-0.991; p = 0.039) and red blood cell transfusion (OR, 2.661; CI95%, 1.308-5.467; p = 0.007) were independent risk factors for high risk of MBD. Our findings provide evidence of risk factors for MBD that could help clinicians to individualize perinatal management. The association of red blood cell transfusion with MBD is a novel finding that may be related to iron overload and that merits further study.

Retrospective study to identify risk factors for chronic kidney disease in children with congenital solitary functioning kidney detected by neonatal renal ultrasound screening.

To evaluate the prognostic significance of factors frequently associated with a reduction in renal mass, such as prematurity, low birth weight, and congenital anomalies of kidney and urinary tract (CAKUT), in patients with solitary functioning kidney (SFK) and investigate signs of early renal injury due to glomerular hyperfiltration damage or dysplasia in the remaining kidney.Retrospective observational study of congenital SFK diagnosed and followed at a tertiary care hospital over a period of 10 years in which 32,900 newborns underwent routine neonatal abdominal ultrasound screening. We analyzed age at diagnosis, sex, gestational age, anthropometric measurements at birth and prenatal and neonatal ultrasound findings, in addition to follow-up data corresponding to imaging findings (ultrasound, micturating cystourethrography, dimercaptosuccinic acid renal, and scintigraphy), ipsilateral CAKUT, compensatory hypertrophy, and renal injury in the form of albuminuria, blood pressure, and estimated glomerular filtration rate (eGFR).In total, 128 congenital SFK cases were detected (1 per 257 live births). Of these, 117 (91.4%) were diagnosed by neonatal ultrasound screening and 44.5% of these had been previously identified by prenatal ultrasound. Neonatal ultrasound had a specificity of 100% and a sensitivity of 92.1%. Forty-five patients (35.2%) had ipsilateral CAKUT and the most common type was urinary collecting system anomalies (75.5%). Over a median follow-up of 6.3 years (1-10 years), compensatory renal hypertrophy was observed in 81 patients (63.7%), most of whom had ipsilateral CAKUT (76.1% vs 56.6% of patients without ipsilateral CAKUT). Albuminuria and hypertension were observed in 3.12% and 5% of patients, respectively, and both were associated with ipsilateral CAKUT (P < .05). In addition, 75% of albuminuria cases (P = .031), 83.3% of hypertension cases (P = .004), and 100% of decreased eGFRcases (P = .031) were significantly associated with CAKUT (renal parenchymal anomaly category), being the strongest predictor of GFR the presence or absence of CAKUT.Neonatal ultrasound screening is useful for the early diagnosis of SFK. The presence of ipsilateral CAKUT should be evaluated in all patients with SFK as congenital anomalies of the renal parenchyma are associated with a poorer prognosis. Because morbidity from CAKUTs may not develop until adulthood, patients should be closely followed throughout life.

Congenital intestinal atresias with multiple episodes of sepsis: A case report and review of literature.

INTRODUCTION: Hereditary multiple intestinal atresia associated with severe combined immunodeficiency (MIA-SCID) is a very rare disease caused by deleterious mutations in the tetratricopeptide repeat domain-containing protein 7A gene TTC7A. It is characterized by intestinal obstruction, sepsis, and a poor prognosis. Insights into phenotype-genotype correlations could help to guide genetic counseling and increase our knowledge of the natural history of this disease. CASE PRESENTATION: We report the case of a newborn in which his fetal magnetic resonance imaging showed jejunal atresia and microcolon and an abdominal x-ray at birth confirmed intestinal obstruction. The clinical course was complicated by multiple episodes of sepsis, and laboratory investigations showed SCID. The genetic analysis identified a homozygous c.53344_53347 mutation in the TTC7A gene compatible with MIA-SCID syndrome. The patient required 3 operations because of new intestinal atresias in the first months of life. She underwent bone marrow transplantation at 8 months of age but died of liver failure secondary to graft-versus-host disease. CONCLUSION: Immunologic assessment and genetic screening for TTC7A mutations are important in patients with MIA. Greater knowledge of the functions of the TTC7A protein will have important therapeutic implications for patients with MIA-SCID syndrome.