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Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Despite improvements in viability, the long-term neurodevelopmental outcomes of preterm babies remain serious concern as a significant percentage of these infants develop neurological and/or intellectual impairment, and they are also at increased risk of psychiatric illnesses later in life. The current challenge is to develop neuroprotective approaches to improve adverse outcomes in preterm survivors. The purpose of this review was to provide an overview of the current evidence on pharmacological agents targeting the neuroprotection of the preterm brain. Among them, magnesium sulfate, given antenatally to pregnant women with imminent preterm birth before 30 to 34 weeks of gestation, as well as caffeine administered to preterm infants after birth, exhibited neuroprotective effects for human preterm brain. Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions. Further studies are also required to assess whether melatonin, neurosteroids, inhaled nitric oxide, allopurinol, or dietary supplements (omega-3 fatty acids, choline, curcumin, etc.) could be implemented as neuroprotectants in clinical practice. Furthermore, other pharmacological agents showing promising signs of neuroprotective efficacy in preclinical studies (growth factors, hyaluronidase inhibitors or treatment, antidiabetic drugs, cannabidiol, histamine-H3 receptor antagonists, etc.), as well as stem cell- or exosomal-based therapies and nanomedicine, may prove useful in the future as potential neuroprotective approaches for human preterm brain. Key Points Magnesium and caffeine have neuroprotective effects for the preterm brain. Follow-up of infants treated with erythropoietin is needed. Neuroprotective efficacy of several drugs in animals needs to be shown in humans. [ABSTRACT FROM AUTHOR]

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life. [ABSTRACT FROM AUTHOR]

Background. Only a few studies have been conducted with the objective of creating norms of the Alberta Infant Motor Scale (AIMS) for the assessment of gross motor development of preterm infants. The AIMS performance of preterm infants has been compared with that of the Canadian norms of full-term infants, but not with that of full-term infants of the same nationality. Moreover, the possible impact of prematurity-related morbidity factors on AIMS performance is unknown. Objectives. The aims of this study were: (1) to evaluate AIMS trajectory in a large population of Greek preterm infants and create norms, (2) to compare it with the AIMS trajectory of Greek full-term infants, and (3) to examine the possible influence of neonatal morbidity on AIMS scores in the preterm sample. Design. This was a cross-sectional study. Methods. Mean AIMS scores were compared, per month (1-19), between 403 preterm infants (≤32 weeks of age, corrected for prematurity) and 1,038 full-term infants. In preterm infants, the association of AIMS scores with respirator)' distress syndrome (RDS), intraventricular hemorrhage (IVH) of grade ≤III, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and sepsis was assessed by hierarchical regression analysis. Results. Alberta Infant Motor Scale scores were significantly lower in preterm infants than in full-term infants. Mean AIMS scores in preterm infants were significantly associated with RDS (b= -1.93; 95% CI= -2.70, -1.16), IVH (b=-0.97; 95% CI=-1.69, -0.25), and ROP (b= -1.12; 95% CI= -1.99, -0.24) but not with BPD or sepsis in hierarchical regression analysis. Conclusions. Alberta Infant Motor Scale norms were created for Greek preterm infants. This study confirms that AIMS trajectories of preterm infants are below those of full-term infants of the same nationality. The influence of morbidity factors, including RDS, IVH, and ROP, should be taken into account when administering the AIMS in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Obesity and cardiovascular disease (CVD) often co-exist, but the pathophysiologic mechanisms that link the two are not fully understood. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to be predictive of thromboembolic episodes in adults, independently of a variety of other potential risk factors, including markers of inflammation, renal function, and hemodynamic stress. However, the function of this lipase and its importance as a biomarker in childhood obesity is much less studied. The aim of the study was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children. Methods: Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z-score -0.2±0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4±1.2) age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was calculated based on the Greek BMI growth curves, and children were categorized as obese according to the Cole criteria. All children underwent physical examination and a fasting morning blood sample was obtained for glucose, insulin, lipid profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC Test), while other measurements were performed using standard methods. Results: Plasma Lp-PLA2 levels were significantly higher in obese children (322.5±77.8 ng/mL) compared with normal-weight ones (278.0±64.4 ng/mL, p<0.001). Lp-PLA2 concentrations were significantly correlated with the BMI z-score (p=0.004). Receiver operating characteristic analysis on Lp-PLA2 values resulted in significant areas under the curve (AUC) for distinguishing between obese and normal-weight groups of children (AUC, 0.726; p<0.001). Conclusions: We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels >200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents. [ABSTRACT FROM AUTHOR]

Early-term birth (37+0 to 38+6 gestational weeks) may have a negative impact on infants' neurodevelopment compared to delivery at 39 weeks or beyond. The purpose of this study was to evaluate the gross motor development of early-term infants using the Alberta Infant Motor Scale (AIMS). A total of 1087 healthy infants (559 early-term and 528 full-term infants born at 39+0 to 41+6 weeks of gestation) were studied. Mean AIMS scores were compared between the two groups at monthly intervals. The impact of gestational age on total AIMS scores was assessed by linear regression, after adjustment for chronological age, sex and SGA. Mean total AIMS scores, albeit within normal range, were significantly lower in early-term than full-term infants at the 2nd, 6th, 7th, 8th and 12th month of age; differences between groups were within three points. In multivariate regression analysis, a longer gestation by one week had a positive impact on total AIMS score during the first year of life (β = 0.90; 95% CI 0.45, 1.35). In conclusion, early-term infants exhibit worse gross motor performance during the first year of life in comparison with their full-term peers; however, the differences between the two groups are small. [ABSTRACT FROM AUTHOR]