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Background: Fetal Growth Retardation (FGR) is considered a risk factor for atherosclerosis and coronary artery disease in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is reported to be elevated in atherosclerosis. Objectives: In this case-control study, we investigated whether FGR affects postnatal OPG serum concentrations and the possible association between OPG levels and aortic intima–media thickness (aIMT), an index of preclinical atherosclerosis. Methods: We studied 30 infants with FGR and 30 appropriate for gestational age (AGA) infants matched for gestational age and sex. Quantitative determination of plasma OPG was performed via enzyme immunoassay on the second (DOL2) and fifth (DOL5) day of life. aIMT was measured in the distal abdominal aorta and adjusted for aortic lumen diameter. Results: Infants with FGR had significantly higher OPG levels on both DOL2 and DOL5 as compared to controls (DOL2: 5.4 ± 1.0 pmol/L vs. 4.6 ± 1.0 pmol/L, p = 0.002 and DOL5: 5.1 ± 0.8 pmol/L vs. 3.9 ± 0.7 pmol/L, p < 0.001). Between DOL2 and DOL5, OPG concentrations did not change significantly in infants with FGR (difference 0.3 ± 0.2 pmol/L, p = 0.087) but decreased slightly in controls (difference 0.7 ± 0.3 pmol/L, p = 0.003). FGR was also associated with increased aIMT (0.11 ± 0.03 vs. 0.06 ± 0.02, p < 0.001). There was a positive correlation between OPG and aIMT on DOL2 (r = 0.494, p < 0.001), which became stronger on DOL5 (r = 0.791, p < 0.001). Conclusions: We report significantly increased concentrations of OPG in infants with FGR and a positive correlation with aIMT. Follow-up studies with repeat OPG and aIMT measurements may be indicated to evaluate whether these findings represent a permanent effect of FGR on the offspring.

Zonulin so far is the only known endogenous modulator of intercellular tight junctions which regulate the intestinal permeability. Breastfeeding is considered to enhance the integrity of the gastrointestinal tract; however, limited data are available about the effect of feeding patterns on intestinal permeability. We aimed to investigate the potential association between the mode of feeding (breast versus formula milk) and the serum zonulin levels as a marker of intestinal permeability. One hundred fifty-seven full-term, healthy infants, born after an uncomplicated pregnancy, were enrolled within 72–96 h of life. Blood samples from 105 infants were obtained at 3 to 4 months of life. Serum zonulin levels were measured by ELISA. Out of 105 infants, 52.4% (55) were female, and 58.1% (61) were delivered by caesarian section at a mean gestational age of 38.9 (SD ± 1.0) weeks. At the time of blood sampling, median age was 3.4 (IQR 3.20–3.50) months, and mean weight was 6332 (SD ± 692) gr. Infants were divided in three groups according to the feeding patterns: exclusive breastfeeding (n = 42), mixed feeding (n = 41), and cow’s milk formula (n = 22). The feeding pattern had no impact on infants’ serum zonulin levels. Moreover, zonulin levels were not affected by infant’s clinical and epidemiological characteristics such as body weight or family history of autoimmune disease.Conclusion: In our study, different feeding patterns were not associated with serum zonulin levels in healthy infants at 3–4 months of age. What is Known:• Serum zonulin is upregulated in conditions with increased intestinal permeability• Breast milk favors the physiological decline of the intestinal permeability after birth in the neonatesWhat is New:• Serum zonulin levels were not affected by the feeding pattern (breast milk versus formula) in infants at 3–4 months of age• Clinical and epidemiological characteristics of infants had no impact on zonulin levels

Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein with anti-atherogenic and vasoprotective effects that has never been studied in newborns exposed to preeclampsia. Our aim was to examine TRAIL serum concentrations in such neonates after birth and during the transitional period. Methods Serum TRAIL levels were measured on the first and fifth day of life (DOL1 and DOL5, respectively) in 38 newborns exposed to early-onset preeclampsia and 38 controls born of normotensive mothers. Results TRAIL values on DOL1 and DOL5 did not differ between cases and controls. However, from DOL1 to DOL5 TRAIL levels increased in controls (from 20.54 ± 7.35 to 23.93 ± 11.02 pg/ml, p  = 0.044) but decreased in those exposed to preeclampsia (from 25.58 ± 15.74 to 20.53 ± 10.72 pg/ml, p  = 0.035). Overall, the relative change of TRAIL values from DOL1 to DOL5 was positively related to birth weight (beta coefficient 0.234, p  = 0.042) and inversely related to preeclampsia (beta coefficient –0.241, p  = 0.036). Conclusion Newborns exposed to early-onset preeclampsia present a decrease in serum TRAIL levels during the transitional period. This pattern is exactly the opposite from what is observed in neonates born to normotensive mothers, and most likely points towards a defective mechanism of extrauterine adaptation related to preeclampsia exposure in utero. Impact Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels during the transitional period do not differ between infants exposed to early-onset preeclampsia and controls The pattern of change of TRAIL levels after birth is different; TRAIL decreases in newborns exposed to preeclampsia but increases in controls The decrease of TRAIL levels during the transitional period points towards a defective mechanism of extrauterine adaptation and an altered cardiometabolic profile in newborns exposed to early-onset preeclampsia.

Introduction The diagnosis of Growth Hormone Deficiency (GHD) during childhood has been the subject of much controversy over the last few years. Aiming to accurate medical treatment, there is a need for biomarker discovery. Objective To characterize the metabolic profile of GHD children, examine the effect of GH administration on the metabolic signature, and investigate the correlations between metabolites and IGF-1. Methods Nuclear Magnetic Resonance (NMR)-based untargeted and targeted metabolomic approach applied to study the metabolic profiles of children with GHD. Plasma, serum, and urine samples were collected from twenty-two children diagnosed with GHD and forty-eight age matched controls from the Pediatric Endocrinology Unit of the University Hospital of Patras. Experimental data were examined by both multivariate and univariate statistical analysis. Results The results of this pilot study revealed a different metabolic fingerprint of children with GHD in comparison to age-matched healthy individuals. However, the detected alterations in the metabolite patterns before and after GH treatment were subtle and of minor discriminative statistical power. Conclusions This study provides evidence that metabolome plays a pivotal role in GHD, but large-scale multicenter studies are warranted to validate the results.

IntroductionPremature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial.ObjectiveTo investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA.MethodsNuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled.ResultsMetabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine 1H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively.ConclusionThis study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI–driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint.