The sequence of prenatal growth restraint and postnatal catch-up growth: normal heart but thicker intima-media and more pre-peritoneal fat in late infancy.

BACKGROUND: The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES: To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS: Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS: Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2 years. CONCLUSIONS: From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.

Liver volume and hepatic adiposity in childhood: relations to body growth and visceral fat.

BACKGROUND AND OBJECTIVE: The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume. SUBJECTS/METHODS: The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.e.m.), 8.5±0.1 years), recruited into two prospective longitudinal studies. Anthropometry, endocrine-metabolic variables and inflammatory and hepatic markers were assessed, along with liver volume, hepatic adiposity and abdominal fat partitioning (by magnetic resonance imaging). RESULTS: AGA and SGA children differed in hepato-visceral adiposity, but had similar liver volumes. Boys had larger livers than girls, and higher sex hormone binding globulin and inflammation markers. Liver volume correlated with height Z-score, body mass index Z-score, HOMA-IR (homeostasis model assessment-insulin resistance) and with subcutaneous and visceral fat, but not with birth weight Z-score or with hepatic adiposity. Height, visceral fat, gender and HOMA-IR were major determinants of liver volume, together explaining 61% of its variance. CONCLUSIONS: The trajectory from prenatal restraint, via postnatal catch-up, to hepato-visceral adiposity and insulin resistance does not appear to be detectably influenced by prepubertal alterations of liver volume. Further follow-up will disclose the potential role of liver volume in the pubertal segment of this trajectory, and whether the augmented fat content and visceral adiposity in SGA subjects is followed by the development of metabolic syndrome and hepatic dysfunction in adulthood.

Perirenal fat is related to carotid intima-media thickness in children.

BACKGROUND/OBJECTIVES: It is well known that increased abdominal fat is associated with cardiovascular (CV) risk. Perirenal fat has been recently associated with CV risk in adults. However, studies with children are lacking. We investigated the relationship of perirenal fat and other abdominal fat depots (including preperitoneal, intra-abdominal and subcutaneous fat) with carotid intima-media thickness (cIMT-a surrogate marker of CV risk) in prepubertal children, so as to identify novel markers that can be easily assessed and used in the early prevention of cardiovascular disease. SUBJECTS/METHODS: Subjects were 702 asymptomatic prepubertal Caucasian children (418 lean, 142 overweight and 142 obese) who were recruited in a primary care setting. Ultrasound measurements (perirenal, preperitoneal, intra-abdominal and subcutaneous fat and cIMT), clinical (body mass index (BMI) and systolic blood pressure) and metabolic parameters (insulin resistance (HOMA-IR), high molecular weight (HMW) adiponectin and serum lipids) were assessed. RESULTS: Perirenal fat was associated with diverse metabolic and CV risk factors in all the studied subjects. However, in overweight and obese children, perirenal fat was mostly associated with cIMT (P<0.001) and was the only fat depot that showed independent associations with cIMT in multivariate analyses (overweight chidren: ß=0.250, P=0.003, r2=12.8%; obese children: ß=0.254, P=0.002, r2=15.5%) after adjusting for BMI, gender, age and metabolic parameters. Perirenal fat was also the only fat depot that showed independent associations with HMW-adiponectin in obese children (ß=-0.263, P=0.006, r2=22.8%). CONCLUSIONS: Perirenal fat is the main abdominal fat depot associated with cIMT, especially in overweight and obese children, and may thus represent a helpful parameter for assessing CV risk in the pediatric population.

GLP-1 and IGF-I levels are elevated in late infancy in low birth weight infants, independently of GLP-1 receptor polymorphisms and neonatal nutrition.

Low birth weight followed by rapid postnatal weight gain is associated with increased risks for obesity and diabetes in adulthood. Modulation of glucagon-like-peptide 1 (GLP-1) secretion by (epi)genetic mechanisms or nutrition may, in part, influence this risk. Formula-fed infants born small-for-gestational-age (SGA) have higher circulating GLP-1 at age 4 months than breastfed SGA or appropriate-for-gestational-age (AGA) infants. Here we assessed GLP-1 concentrations in healthy AGA (n=149) and SGA (n=107) subjects at age 12 months and their association with endocrine-metabolic and body composition parameters and GLP-1 receptor (GLP-1R) rs6923761 and rs3765467 polymorphisms. At birth, cord GLP-1 concentrations were comparable in AGA and SGA infants. At age 12 months, insulin-like growth factor I (IGF-I) and GLP-1 levels were higher than at birth; SGA infants displayed higher IGF-I and GLP-1 concentrations than AGA infants (both P<0.001) that were unrelated to neonatal nutrition or GLP-1R genotype and that were paralleled by a significant increase in weight Z-score (P<0.001 vs AGA). In conclusion, SGA infants have augmented IGF-I and prefeeding GLP-1 concentrations in late infancy. Increased GLP-1 levels may impair hypothalamic and/or peripheral GLP-1R signaling, exert long-term negative effects on the hypothalamic nuclei regulating energy homeostasis and increase the risks for obesity and diabetes.

α-Defensins and bacterial/permeability-increasing protein as new markers of childhood obesity.

OBJECTIVES: The aim of this paper is to test whether α-defensins and bacterial/permeability-increasing protein were related to obesity and cardiovascular risk factors in prepubertal children. METHODS: Plasma α-defensins and bacterial/permeability-increasing protein, body mass index (BMI), waist circumference, systolic blood pressure (SBP), carotid intima media thickness (cIMT), HOMA-IR and HMW-adiponectin were assessed. RESULTS: In a cross-sectional study (N = 250), higher α-defensins concentrations were positively associated with BMI, waist, SBP, cIMT, HOMA-IR and negative correlated with HMW-adiponectin (all between r = 0.191 and r = 0.377, p ≤ 0.01 and p ≤ 0.0001). Conversely, plasma bacterial/permeability-increasing protein concentrations presented inversed associated with the same parameters (all between r = -0.124 and r = -0.329; p ≤ 0.05 and p ≤ 0.0001). In a longitudinal study (N = 91), α-defensins at age 7 were associated with BMI (ß = 0.189, p = 0.002; model R2 = 0.847) and waist (ß = 0.241, pthinsp;= 0.001; model R2 = 0.754) at age 10. CONCLUSIONS: α-Defensins and bacterial/permeability-increasing protein may be the markers of childhood obesity. Increased concentrations of α-defensins may predict BMI and abdominal fat deposition in children.

Recognition of a sequence: more growth before birth, longer telomeres at birth, more lean mass after birth.

BACKGROUND: Telomere length at birth is a major determinant of telomere length in late adulthood. However, the prenatal setting of telomere length is poorly understood. Individuals born large from non-diabetic mothers are at lower risk for later-life disorders than those born small, a feature of their longer health span being a higher lean mass that provides more muscle strength and that is already present in infancy. METHODS: At birth, we studied leukocyte telomere length (by quantitative polymerase chain reaction) in 103 small-for-gestational-age, appropriate-for-gestational-age or large-for-gestational-age (SGA, AGA or LGA) infants born after uncomplicated, term, singleton pregnancies. All infants were breastfed for ≥4 months. At 2 weeks and 12 months, body composition was assessed by dual X-ray absorptiometry. RESULTS: Telomere lengths were shorter in SGA newborns and longer in LGA newborns than in AGA newborns (P < 0.001), also after adjustment for maternal age, pre-gestational body mass index, gestational weight gain and gestational age. Telomere length at birth associated (all P ≤ 0.001) to birthweight (r = 0.50) and to both lean mass (r = 0.43) and fat mass (r = 0.48) at age 2 weeks, but only to lean mass at 12 months (r = 0.51). CONCLUSION: Higher weight and longer telomeres at birth are followed by more lean mass in late infancy. Relatively large, breastfed infants from non-diabetic mothers may become models of how to make a healthy start.

The macrophage activation product sCD163 is associated with a less favourable metabolic profile in prepubertal children.

OBJECTIVE: Macrophages are known to be involved in low-grade inflammatory processes such as obesity. soluble cluster of differentiation 163 (sCD163) is shed from the cell surface as specific macrophage activation marker. In prepubertal children, we studied if circulating sCD163 is associated with metabolic and cardiovascular risk markers. METHODS: A population of 236 school-aged Caucasian children (111 girls and 125 boys) aged 8 ± 1 year [81 normal weight (body mass index [BMI]-SDS < 1); 74 overweight (1 ≤ BMI-standard deviation score [SDS] < 2) and 81 with obesity (BMI-SDS ≥ 2)] were studied. BMI, waist circumference, fat mass and visceral fat were measured. Fasting serum sCD163, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, gamma-glutamyl transpeptidase and lipids were quantified. RESULTS: Circulating sCD163 concentrations were higher in children with obesity (p < 0.0001). Associations were observed between circulating sCD163 and a less favourable metabolic profile as judged by higher waist circumference, fat mass, visceral fat, epicardial fat, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, gamma-glutamyl transpeptidase and triglycerides (all between r = 0.173 and r = 0.363; p < 0.05 to p < 0.0001) and lower high-density lipoprotein-cholesterol (r = -0.285, p < 0.0001). In multiple regression analyses, circulating sCD163 was independently associated with HOMA-IR (ß = 0.162, p = 0.016; model R2 = 0.179) and high density lipoprotein-cholesterol/triglycerides ratio (ß = -0.167, p = 0.012; model R2 = 0.209). CONCLUSIONS: Childhood obesity may increase the risk of developing metabolic diseases later in life through chronic macrophage activation having deleterious effects on metabolism.

Uric acid, carotid intima-media thickness and body composition in prepubertal children.

BACKGROUND: Increased uric acid is an independent biomarker for cardiovascular disease in obese adolescents and adults. OBJECTIVE: We investigated whether uric acid relates to carotid intima-media thickness (cIMT) in prepubertal children, and whether body mass index (BMI) and preperitoneal fat modulate this association. METHODS: 359 asymptomatic prepubertal Caucasian children were stratified according to BMI categories (171 with BMI-SDS < 0; 188 with BMI-SDS ≥ 0) and according to preperitoneal fat levels (180 with preperitoneal fat <50th centile; 179 with preperitoneal fat >50th centile). Uric acid levels, insulin resistance (homeostasis model assessment insulin resistance; HOMA-IR), C-reactive protein (CRP), triacylglycerol (TG), systolic blood pressure (SBP), abdominal fat and cIMT (both by ultrasound) were assessed. RESULTS: Uric acid was associated with several cardiovascular risk factors, namely higher HOMA-IR, CRP, TG, BMI, waist, SBP, preperitoneal fat and cIMT (all P < 0.001 to P < 0.0001). Significant BMI and preperitoneal fat interactions were documented in the relationship between uric acid and cIMT (both P < 0.05), as uric acid was preferentially related to cIMT in heavier children (ß = 0.247, P < 0.001, r(2) = 9.1%) and in children with more preperitoneal fat (ß = 0.263, P < 0.0001, r(2) = 11.9%). CONCLUSIONS: Serum uric acid is associated with cIMT in asymptomatic prepubertal children. Both higher BMI and preperitoneal fat aggravate the potential risk of atherosclerotic disease imposed by higher concentrations of uric acid.

The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3-6 years.

BACKGROUND: Infants born small-for-gestational-age (SGA) who develop post-natal weight catch-up are at risk for insulin resistance, central adiposity and cardiovascular disease in later life, even in the absence of overweight. OBJECTIVE: In young (age 3-6 years) non-obese SGA children, we assessed arterial health (as judged by intima-media thickness [IMT]) and abdominal fat distribution (subcutaneous, visceral, preperitoneal and hepatic components by magnetic resonance imaging [MRI] and/or ultrasound [US]) besides a selection of endocrine markers. METHODS: Comparisons of measures in SGA (n = 27) vs. appropriate-for-GA (AGA) children (n = 19) of similar height, weight and body mass index. Longitudinal outcomes (age 3-6 years) were carotid IMT (cIMT); fasting glucose, circulating insulin, IGF-I and high-molecular-weight (HMW) adiponectin; abdominal fat partitioning by US. Cross-sectional outcomes (age 6 years) were aortic IMT (aIMT) and abdominal fat partitioning by MRI. RESULTS: At 3 and 6 years, cIMT and IGF-I results were higher and HMW adiponectin lower in SGA than AGA children; at 6 years, SGA subjects had also a thicker aIMT and more pre-peritoneal and hepatic fat, and were less insulin sensitive (all P values between <0.05 and <0.0001). cIMT correlated positively with pre-peritoneal fat, particularly at 6 years. Post-SGA status and weight gain in early childhood (between 3 and 6 years) were independent predictors of cIMT at 6 years, explaining 48 % of its variance. CONCLUSION: SGA children aged 3-6 years were found to have a thicker intima- media and more pre-peritoneal and hepatic fat than AGA children of comparable size.

Circulating GLP-1 in infants born small-for-gestational-age: breast-feeding versus formula-feeding.

Prenatal growth restraint associates with the risk for later diabetes, particularly if such restraint is followed by postnatal formula-feeding (FOF) rather than breast-feeding (BRF). Circulating incretins can influence the neonatal programming of hypothalamic setpoints for appetite and energy expenditure, and are thus candidate mediators of the long-term effects exerted by early nutrition. We have tested this concept by measuring (at birth and at age 4 months) the circulating concentrations of glucagon-like peptide-1 (GLP-1) in BRF infants born appropriate-for-gestational-age (AGA; n=63) and in small-for-gestational-age (SGA) infants receiving either BRF (n=28) or FOF (n=26). At birth, concentrations of GLP-1 were similar in AGA and SGA infants. At 4 months, pre-feeding GLP-1 concentrations were higher than at birth; SGA-BRF infants had GLP-1 concentrations similar to those in AGA-BRF infants but SGA-FOF infants had higher concentrations. In conclusion, nutrition appears to influence the circulating GLP-1 concentrations in SGA infants and may thereby modulate long-term diabetes risk.

Circulating FGF19 and FGF21 surge in early infancy from infra- to supra-adult concentrations.

BACKGROUND/OBJECTIVE: Fibroblast growth factor 19 (FGF19) and 21 (FGF21) have been linked to obesity and type 2 diabetes in adults. We assessed the circulating concentrations of these factors in human neonates and infants, and their association with the endocrine-metabolic changes associated to prenatal growth restraint. SUBJECTS/METHODS: Circulating FGF19 and FGF21, selected hormones (insulin, insulin-like growth factor I and high- molecular-weight (HMW) adiponectin) and body composition (absorptiometry) were assessed longitudinally in 44 infants born appropriate- (AGA) or small-for-gestational-age (SGA). Measurements were performed at 0, 4 and 12 months in AGA infants; at 0 and 4 months in SGA infants; and cross-sectionally in 11 first-week AGA newborns. RESULTS: Circulating FGF19 and FGF21 surged >10-fold in early infancy from infra- to supra-adult concentrations, the FGF19 surge appearing slower and more pronounced than the FGF21 surge. Whereas the FGF21 surge was of similar magnitude in AGA and SGA infants, FGF19 induction was significantly reduced in SGA infants. In AGA and SGA infants, cord-blood FGF21 and serum FGF19 at 4 months showed a positive correlation with HMW adiponectin (r=0.49, P=0.013; r=0.43, P=0.019, respectively). CONCLUSIONS: Our results suggest that these early FGF19 and FGF21 surges are of a physiological relevance that warrants further delineation and that may extend beyond infancy.

Newborns with lower levels of circulating polyunsaturated fatty acids (PUFA) are abdominally more adipose.

BACKGROUND: Maternal nutrition is the main source of Poly-Unsaturated Fatty Acids (PUFA) for the fetus. PUFA may influence the accumulation of fat in early life. OBJECTIVES & METHODS: In 33 breastfed infants born appropriate-for-gestational-age, we studied whether body composition (judged by absorptiometry at 2 wk and 4 mo) relates to PUFA levels (assessed by gas chromatography) in the maternal or fetal circulation at birth. RESULTS: Abdominal fat at 2 wk associated negatively to umbilical-cord levels of separate PUFA (linoleic, arachidonic, eicosapentanoic and docosahexaenoic acid; all P between 0.001 and 0.015). Collectively, the assessed n-6 PUFA on one hand and the n-3 PUFA on the other hand associated negatively to the absolute amount of abdominal fat (in grams; P = 0.001 and P = 0.002, respectively) and to the relative amount of abdominal fat (fraction of total fat; P = 0.001 and P = 0.006, respectively). No other significant associations were observed. CONCLUSION: In conclusion, newborns with lower levels of circulating PUFA were found to be abdominally more adipose. The mechanisms underpinning these associations remain to be determined.

Increased serum IgG and IgA in overweight children relate to a less favourable metabolic phenotype.

BACKGROUND: The adaptive immune system has emerged as an unexpected modulator of insulin resistance. B lymphocytes accumulate in adipose tissue and produce pathogenic antibodies that cause insulin resistance. OBJECTIVE: We studied whether circulating immunoglobulins (IgG, IgA and IgM) were related to metabolic risk markers in pre-pubertal children with and without overweight. DESIGN AND METHODS: Subjects were 270 asymptomatic pre-pubertal Caucasian children (145 lean, 125 overweight) recruited in a primary care setting. Assessments included serum IgG, IgA and IgM concentrations (nephelometry), insulin resistance (HOMA-IR) and fasting lipids (triacylglycerol and high-density lipoprotein [HDL]-cholesterol). RESULTS: Overweight children had higher IgG and IgA serum levels than lean children (P ≤ 0.01). Increasing serum IgG and IgA, but not IgM, were associated with a less favourable metabolic phenotype, consisting of higher HOMA-IR and triacylglycerol and lower HDL-cholesterol, particularly in obese children, in whom serum IgG and IgA were both independently associated with HOMA-IR (ß = 0.308, P = 0.017, r2 = 9.5% and ß = 0.361, P = 0.005, r2 = 13.0%, respectively) and triacylglycerol (ß = 0.343, P = 0.006, r2 = 11.1% and ß = 0.354, P = 0.003, r2 = 12.2%, respectively). CONCLUSIONS: Increased circulating IgG and IgA in overweight children are associated with a less favourable metabolic phenotype, particularly in obese children. These results suggest a relationship between adaptive immunity and insulin resistance in childhood obesity.

Decreased placental expression of pre-adipocyte factor-1 in children born small-for-gestational-age: association to early postnatal weight gain.

BACKGROUND: Preadipocyte factor-1 (Pref-1) is a key regulator of adipocyte differentiation acting as an inhibitor of adipogenesis; Pref-1 is highly expressed in embryonic tissues and placenta supporting a role in embryonic and fetal growth. The potential impact of placental Pref-1 expression in human pre- and postnatal development is unclear. OBJECTIVE AND HYPOTHESES: To assess the contribution of placental Pref-1 to fetal and postnatal growth. POPULATION AND METHODS: Placentas (N = 99) were collected at term delivery from singleton infants, who were born either appropriate (AGA; n = 59) or small-for-gestational-age (SGA; n = 40). Auxological data of all subjects were obtained at birth. In a subset of subjects (n = 31) we also obtained weight data at 4 mo and at 1 yr, together with body composition assessment (by DXA) at the age of 1 yr. Placental expression of Pref-1 was quantified by real-time PCR; the housekeeping gene GAPDH was used for comparisons. RESULTS: Pref-1 was significantly downregulated in the placentas from SGA babies as compared to AGA controls (P = 0.005). In SGA infants placental Pref-1 expression associated positively to body weight at 4 and 12 mo (r = 0.44, P = 0.05; r = 0.66, P = 0.001 respectively); at age 12 mo, placental Pref-1 expression was inversely related to total fat mass and positively correlated with total lean mass (r = -0.59, P = 0.01; and r = -0.59, P = 0.01,respectively). CONCLUSION: Placental Pref-1 expression in SGA fetuses was decreased and associated with postnatal body weight, suggesting a role of Pref-1 in the regulation of postnatal development.

Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration.

OBJECTIVE: Shorter sleep duration predisposes to obesity, but the mechanisms whereby sleep deprivation affects body weight are poorly understood. We tested whether this association is modulated by the obesity genes FTO, TMEM18 and NRXN3. SUBJECTS: Body mass index (BMI), waist circumference, visceral fat (abdominal ultrasound), homeostasis model assessment for insulin resistance (HOMA-IR), systolic blood pressure (SBP) and sleep time per 24 h were assessed in 297 asymptomatic children (151 boys, 146 girls; age range 5-9 years; BMI s.d. score range -2.0-4.0). Associations between sleep duration and the abovementioned outcomes were tested for three common single-nucleotide polymorphisms (SNPs), namely FTO (rs9939609), TMEM 18 (rs4854344) and NRXN3 (rs10146997), as well as for their combination. RESULTS: TT homozygotes (but not A(*) carriers) for the FTO SNP, exhibited nominal associations between decreasing sleep duration and increasing BMI, waist circumference, visceral fat and HOMA-IR (all P<0.05). Similar associations were observed in children with risk alleles (but not in those without risk alleles) for the TMEM18 and NRXN3 SNPs (P<0.05 to P<0.0001). The three SNPs had additive effects on the negative associations between sleep and, respectively, BMI (P<0.001), waist (P<0.005), visceral fat (P<0.001), HOMA-IR (P=0.010) and SBP (P<0.0005). The combined effects on obesity measures and SBP remained significant after correction for multiple testing. On average, 2 h of sleep less per night was associated with an increase in BMI of 1.0 s.d. (95% confidence interval 0.5-1.6 s.d.) and with 8.0 cm (95% confidence interval 3.6-12.2 cm) more waist circumference in genetically susceptible children. CONCLUSION: By age 7, common variations in FTO, TMEM18 and NRXN3 influence the vulnerability to metabolic complications of sleep deprivation. Further genetic studies are warranted to replicate these findings in other populations.

Circulating follistatin in the human foetus at term birth.

BACKGROUND: Prenatal weight partitioning is gender specific, and infants born small for gestational age (SGA) have a lower fat mass and a lower fat-free mass than infants born appropriate for gestational age (AGA). Follistatin is an adipokine with adipogenic properties. OBJECTIVES: We examined whether follistatin circulates in the human foetus at term birth and, if so, whether cord blood follistatin relates to birthweight and neonatal body composition. METHODS: The study population was comprised of 248 term newborns (128 girls, 120 boys; 133 AGA, 115 SGA). The main outcome measures used for the study were birthweight, follistatin and insulin in umbilical cord serum, and neonatal body composition by absorptiometry. RESULTS: Follistatin was detectable in all cord serum samples. Cord follistatin concentrations were similar in girls and boys, being about 25% higher (P < 0.001) in SGA than AGA infants. In SGA infants, higher follistatin concentrations related to lower fat mass. CONCLUSION: [corrected] Follistatin is detectable in the circulation of the human foetus at term birth. The circulating levels of follistatin, an adipogenic adipokine, are higher in SGA than AGA infants, particularly so in SGA infants with a lower fat mass.

Soluble fatty acid synthase relates to bone biomarkers in prepubertal children.

SUMMARY: Circulating soluble fatty acid synthase (FASN, a key enzyme in de novo biosynthesis of fatty acids, expressed in both adipocytes and osteoblasts) is clinically related to a less favorable bone profile in healthy prepubertal children. Soluble FASN may participate in the reciprocal regulation between fat and bone metabolism. INTRODUCTION: Fatty acid synthase (FASN), a key enzyme in de novo biosynthesis of fatty acids, is expressed in adipocytes and osteoblasts. We hypothesized that FASN may participate in the crosstalk between fat and bone. To this aim, we studied the relation between circulating soluble FASN (an extracellular FASN that reflects previously intracellular enzymatic activity) and adipose tissue and bone biomarkers in prepubertal children. METHODS: Circulating soluble FASN, total and high molecular weight (HMW) adiponectin, bone biomarkers [osteocalcin (OC), uncarboxylated osteocalcin (ucOC), C-terminal cross-linked telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP)], and a profile of energy metabolism [body fat, insulin resistance and secretion (HOMA), serum lipids] were assessed in 84 asymptomatic prepubertal children (44 girls, 40 boys, age 6.8 ± 0.1 year). Serum 25-OH Vitamin D (Vit D) was additionally measured. RESULTS: Circulating soluble FASN increased with increasing HMW adiponectin (r = 0.29, p = 0.01) and decreasing serum Vit D (r = -0.21, p < 0.05), and was related to a less favorable bone profile, showing negative associations with bone-derived metabolic parameters [total OC (r = -0.33, p = 0.002) and ucOC (r = -0.37, p < 0.0001)] and a positive association with the CTX-to-BSAP ratio (r = 0.31, p < 0.01). These correlations were not explained by age, gender, body fat, insulin resistance or secretion or serum lipids; however, they were predominant in those subjects with Vit D levels below the population median. CONCLUSIONS: Circulating soluble FASN relates to both adipose tissue and bone biomarkers in prepubertal children, with associations that are dependent on Vit D concentrations. These findings suggest that FASN may participate in the crosstalk between fat and bone metabolism.

El papel de la antibioterapia en la sinusitis aguda: revisión sistemática y metaanálisis / The role of antibiotics in acute sinusitis: a systematic review and metaanalysis

Introducción: El objetivo fue determinar si los antibióticos son más eficaces que el placebo o ninguna intervención en el tratamiento de la sinusitis aguda. Pacientes y métodos: Se revisaron las bases de datos y buscadores: PubMed, EMBASE, Cochrane Central Register of Controlled Trials y Google Académico para identificar ensayos clínicos aleatorizados (ECA) realizados en niños que compararan antibiótico frente a placebo. Se consideró sinusitis, la persistencia de sintomatología clínica compatible durante al menos 10 días. La calidad metodológica se evaluó mediante la escala de Jadad. Fueron seleccionados 4 ECA. Se evaluaron las siguientes variables: curación-mejoría clínica (a día 10-14), recaídas-recurrencias (a día 14-60) y presencia de efectos adversos. Los resultados se combinaron mediante metaanálisis. Se adoptó un análisis según modelo de efectos fijos o aleatorios en función de si existía o no heterogeneidad. El parámetro combinado que se estimó fue el riesgo relativo (RR) y su intervalo de confianza del 95% (IC 95%). Resultados: Dos ECA tenían una puntuación en la escala de Jadad ≥ 3. Variable curación-mejoría (4 ECA): RR: 1,11 (IC 95%: 0,9 a 1,3). Variable recaída-recurrencia (3 ECA): RR: 0,9 (IC 95%: 0,6 a 1,5); efectos adversos (4 ECA): 2,01 (IC 95%: 1,1 a 3,8). Conclusiones: En niños con sinusitis aguda, el tratamiento antibiótico a las dosis estudiadas no parece aportar beneficio alguno en cuanto a la curación-mejoría evaluada al 10-14 día de seguimiento. El porcentaje de recaídas-recurrencias no fue inferior entre los niños que recibieron antibiótico. Los antibióticos se asocian con mayor probabilidad a efectos adversos (AU)

Introduction: The aim of this systematic review is to assess whether antibacterial agents are more effective than either placebo or no intervention at all in the treatment of acute bacterial sinusitis. Patients and methods: We reviewed the databases and search engines: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Google Scholar to identify randomized clinical trials (RCTs) in children comparing antibiotics versus placebo. Sinusitis was considered as the persistence of clinically compatible symptoms for at least 10 days. The methodological quality was assessed using the Jadad scale. Four RCTs were selected. We studied the following variables: cure, clinical improvement (on days 10 to 14), relapse-recurrence (from day 14 to day 60) and presence of adverse effects. The results were combined using meta-analysis. We used the fixed effects model or random model depending on whether or not there was heterogeneity. We estimated the combined relative risk (RR) and 95% confidence interval. Results: Only two RCTs had a Jadad scale score ≥3. Variable cure-improvement (4 RCTs): RR 1.11 (95% CI: 0.9 to 1.3). Variable relapse-recurrence (3 RCTs): RR 0.9 (95% CI: 0.6 to 1.5). Adverse effects (4 RCTs): 2.01 (95% CI 1.1 to 3.8). Conclusions: In children with acute sinusitis, antibacterial agents at the studied doses did not appear to provide benefit in terms of cure and improvement, assessed at 10 to 14 days of follow up. Similarly, the percentage of relapse-recurrence was not lower among children who received antibiotics. Antibiotics are associated more frequently with adverse effects( AU)

[The role of antibiotics in acute sinusitis: a systematic review and meta-analysis]. / El papel de la antibioterapia en la sinusitis aguda: revisión sistemática y metaanálisis.

INTRODUCTION: The aim of this systematic review is to assess whether antibacterial agents are more effective than either placebo or no intervention at all in the treatment of acute bacterial sinusitis. PATIENTS AND METHODS: We reviewed the databases and search engines: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Google Scholar to identify randomized clinical trials (RCTs) in children comparing antibiotics versus placebo. Sinusitis was considered as the persistence of clinically compatible symptoms for at least 10 days. The methodological quality was assessed using the Jadad scale. Four RCTs were selected. We studied the following variables: cure, clinical improvement (on days 10 to 14), relapse-recurrence (from day 14 to day 60) and presence of adverse effects. The results were combined using meta-analysis. We used the fixed effects model or random model depending on whether or not there was heterogeneity. We estimated the combined relative risk (RR) and 95% confidence interval. RESULTS: Only two RCTs had a Jadad scale score ≥3. Variable cure-improvement (4 RCTs): RR 1.11 (95% CI: 0.9 to 1.3). Variable relapse-recurrence (3 RCTs): RR 0.9 (95% CI: 0.6 to 1.5). Adverse effects (4 RCTs): 2.01 (95% CI 1.1 to 3.8). CONCLUSIONS: In children with acute sinusitis, antibacterial agents at the studied doses did not appear to provide benefit in terms of cure and improvement, assessed at 10 to 14 days of follow up. Similarly, the percentage of relapse-recurrence was not lower among children who received antibiotics. Antibiotics are associated more frequently with adverse effects.

Placental FTO expression relates to fetal growth.

OBJECTIVE: The fat mass and obesity-associated gene (FTO) participates in the control of postnatal weight gain. We assessed whether FTO is expressed in human placenta and whether such expression relates to prenatal weight gain and to the rs9939609 single nucleotide polymorphism (SNP) in FTO. DESIGN AND SUBJECTS: In a birth cohort study, placentas from women (n = 147) with an uncomplicated, singleton, term pregnancy were weighed at delivery. Real-time PCR was used to study, in placental tissue, the expression of FTO and of housekeeping genes (TATA box binding protein and succinate dehydrogenase complex, subunit A) and to genotype the rs9939609 SNP in FTO. Weights and lengths of the newborns were measured; circulating insulin and insulin-like growth factor-I (IGF-I) were quantified in cord blood. RESULTS: FTO was highly expressed in placenta and was associated with increased fetal weight and length (P<0.001 to P<0.0001). Maternal parity showed an interaction (P<0.001) in the association between placental FTO expression and placental weight. Placental FTO mRNA expression was associated with increased fetal-to-placental weight ratio (P<0.005) in infants from primiparous women, and was associated with increased fetal weight and length and placental weight (P<0.001 to P<0.0001) in infants from nonprimiparous women. These associations were not explained by either cord insulin or IGF-I. Placental FTO expression was unrelated to placental FTO rs9939609 SNP. CONCLUSION: FTO is expressed in the human placenta. In a maternal parity-dependent manner, placental FTO may participate either in the control of fetal weight gain or in the partitioning between placental and fetal growth.