Elena Spada

Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr)

The aim of this study is to extend to pre-school ages the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP)-2002 growth charts for height, weight and body mass index (BMI), to obtain charts (SIEDP-2006) that apply to the Italian population from 2 to 20 yr of age, taken as a whole, or separately in two geographical areas (Central-North Italy and South Italy). The charts are based on a sample of about 70,000 subjects attending infant, primary and secondary schools, between 1994 and 2004. The distribution of the sample by gender, age and geographic area was roughly similar to that of Italian school population in the last decade of the 20th century. Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP-2006 references are presented both as centiles and as LMS curves for the calculation of SD scores, and include the extra-centiles for overweight and obesity. Large differences in BMI growth pattern emerged between the SIEDP-2006, 2000 CDC and UK90 references: in Italy, BMI is higher and its distribution is more skewed during childhood and adolescence. At the end of growth, median values of the three references are similar, but the 97th centile of 2000 CDC charts is much higher and increases more steeply than that of SIEDP-2006 charts, which on the contrary reach a plateau. SIEDP-2006 references intend to supply pediatricians with a tool that avoids the use of charts that are outdated or that refer to other populations, and thus should be suitable for adequately monitoring the growth of their patients.

Neonatal Anthropometric Charts: The Italian Neonatal Study Compared With Other European Studies

Background and Objective: This was a nationwide prospective study carried out in Italy between 2005 and 2007, involving 34 centers with a neonatal intensive care unit. The study reports the Italian Neonatal Study charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, comparing them with previous Italian data and with the most recent data from European countries. Patients and Methods: Single live born babies with ultrasound assessment of gestational age within the first trimester, and with both parents of Italian origin. Only fetal hydrops and major congenital anomalies diagnosed at birth were excluded. The reference set consists of 22,087 girls and 23,375 boys. Results: At each gestational age, boys are heavier than girls by about 4%. Later-born neonates are heavier than firstborn neonates by about 3%. The effects of sex and birth order on length and head circumference are milder. No differences were observed between babies born in central-north Italy and southern Italy. A large variability emerged among European neonatal charts, resulting in huge differences in the percentage of Italian Neonatal Study neonates below the 10th centile, which is traditionally used to define small-for-gestational-age babies. In the last 2 decades prominent changes in the distribution of birth weight emerged in Italy and in the rest of Europe, in both term and preterm neonates. Conclusions: The existing European neonatal charts, based on more or less recent data, were found to be inappropriate for Italy. Until an international standard is developed, the use of national updated reference charts is recommended.

Postnatal weight increase and growth velocity of very low birthweight infants

Background: Only a few studies have dealt with postnatal growth velocity of very low birthweight (VLBW) infants. Objective: To analyse weight growth kinetics of VLBW infants from birth to over 2 years of age. Patients: A total of 262 VLBW infants were selected; inaccurate estimate of gestational age, major congenital anomalies, necrotising enterocolitis, death, and loss to follow up within the first year were the exclusion criteria. Methods: Body weight was recorded daily up to 28 days or up to discontinuation of parenteral nutrition, weekly up to discharge, then at 1, 3, 6, 9, 12, 18, and 24 months of corrected age. Individual growth profiles were fitted with a seven constant, exponential-logistic function suitable for modelling weight loss and weight recovery, two peaks, and the subsequent slow decrease in growth velocity. Results: After a postnatal weight loss, all infants showed a late neonatal peak of growth velocity between the 7th and 21st weeks; most also experienced an early neonatal peak between the 2nd and 6th week. VLBW infants who were small for gestational age and those with major morbidities grew less than reference VLBW infants who were the appropriate size for gestational age without major morbidities: at 2 years of age, the difference in weight was about 860 g. The more severe growth impairment seen in VLBW infants with major morbidities is almost entirely due to the reduced height of the late neonatal peak of velocity. Conclusions: The growth model presented here should be a useful tool for evaluating to what extent different pathological conditions or nutritional and medical care protocols affect growth kinetics.

Mouse genome-wide association mapping needs linkage analysis to avoid false-positive loci

We carried out genome-wide association (GWA) studies in inbred mouse strains characterized for their lung tumor susceptibility phenotypes (spontaneous or urethane-induced) with panels of 12,959 (13K) or 138,793 (140K) single-nucleotide polymorphisms (SNPs). Above the statistical thresholds, we detected only SNP rs3681853 on Chromosome 5, two SNPs in the pulmonary adenoma susceptibility 1 (Pas1) locus, and SNP rs4174648 on Chromosome 16 for spontaneous tumor incidence, urethane-induced tumor incidence, and urethane-induced tumor multiplicity, respectively, with the 13K SNP panel, but only the Pas1 locus with the 140K SNP panel. Haplotype analysis carried out in the latter panel detected four additional loci. Loci reported in previous GWA studies failed to replicate. Genome-wide genetic linkage analysis in urethane-treated (BALB/c×C3H/He)F2, (BALB/c×SWR/J)F2, and (A/J×C3H/He)F2 mice showed that Pas1, but none of the other loci detected previously or herein by GWA, had a significant effect. The Lasc1 gene, identified by GWA as a functional element (Nat. Genet., 38:888–95, 2006), showed no genetic effects in the two independent intercross mouse populations containing both alleles, nor was it expressed in mouse normal lung or lung tumors. Our results indicate that GWA studies in mouse inbred strains can suffer a high rate of false-positive results and that such an approach should be used in conjunction with classical linkage mapping in genetic crosses.

Age-specific nomogram for the decline in antral follicle count throughout the reproductive period

OBJECTIVE To investigate the relationship between antral follicle count (AFC) and chronological age and to establish normal values for AFC in women with regular menstrual cycles. DESIGN Cross-sectional study. SETTING University hospital. PATIENT(S) Four hundred fifteen premenopausal women were recruited for the study. Data from 362 patients were available for the statistical analysis. INTERVENTION(S) AFC was measured by transvaginal ultrasound examination. MAIN OUTCOME MEASURE(S) Estimating the relationship between AFC and age and developing the AFC nomogram. RESULT(S) The analysis showed a linear decline in AFC with age; for every year increase in age, the median AFC decreases by 0.4. The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each age have been calculated. CONCLUSION(S) A linear relationship of AFC to age was found. For the first time, a nomogram reporting normal and interquartile values for AFC, age by age, throughout the reproductive period has been provided. Until now, the interpretation of the measurement was mainly based on the individual experience of the operator, because no normative data were present. Therefore, the establishment of a nomogram of AFC values is the first step to counsel patients on a scientific basis.

Weight growth velocity of very low birth weight infants: role of gender, gestational age and major morbidities

Its well known that VLBWI fail to thrive, however its still unclear how gender, GA and morbidities affect growth pattern: aim of this study is to assess the influence of these factors on weight growth. 262 VLBWI were selected. Weight was recorded daily up to 28 days, weekly up to discharge and during 7 scheduled follow-up visits up to 2 years of corrected age. Individual profiles were fitted with a mathematical function suitable to model selected growth milestones and mean distance and velocity curves were drawn. Effects of gender, GA, major-morbidities, nutritional and respiratory support on individual weight growth milestones were estimated using a multivariate linear model. Each of these variables acts differently on weight growth pattern mainly modifying velocity curves characteristics. In particular, infants with major morbidities weight growth impairment-seen on distance curves at 2 years of corrected age-depends on poor weight velocity during a critical period ending within 4th month of postnatal age, for SGA or BPD infants, starting from 5th month of postnatal for severely neurologically impaired infants. These critical periods could be the most appropriate to identify risk factors for weight growth impairment in VLBWI.

Häävikko's method to assess dental age in Italian children

The aim of this study was to determine if Häävikkos maturation standards are applicable to Italian children. The sample included 500 healthy Caucasian children 3.9-15.4 years of age: 267 girls [mean age 9.6 years, standard deviation (SD) 2.1] and 233 boys (mean age 9.9 years, SD 2.1), living in Italy. All dental ages were assessed from panoramic films by one examiner using Häävikkos method. A second examiner independently scored 48 panoramic films to evaluate the reproducibility of the dental age measurements. A good correlation (0.95) was found, as shown by Cohens kappa. To evaluate the relationship between dental age estimated by Häävikkos standards and the chronological age of the Italian sample, Bland and Altmans graphical method was employed. Moreover, centiles of dental age were constructed both for girls and boys using the LMS (L=skewness, M=median, S=coefficient of variation) method of Cole and Green. It was found that Häävikkos standards tended to underestimate chronological age in this Italian sample. Dental maturation standards as described by Häävikko do not appear suitable for Italian children; instead, centile curves constructed for girls and boys using the LMS method could be used for the estimation of dental age in the Italian population.

Growth of fetal lean mass and fetal fat mass in gestational diabetes

This study was carried out to investigate growth indicators of fetal lean mass and fat mass in the second half of the gestational period in pregnancies complicated by gestational diabetes mellitus (GDM) in comparison to normal control pregnancies.

A polygenic model with common variants may predict lung adenocarcinoma risk in humans.

Genome‐wide screening for genetic loci associated with risk of lung adenocarcinoma (ADCA) was carried out in pooled DNA using the Illumina 300K single‐nucleotide polymorphism (SNP) array, in a joint analysis of 2 Italian case–control series matched by age, gender and smoking habit. The rare allele carrier status of 8 SNPs was associated with a decreased lung ADCA risk [odds ratios (OR): 0.6–0.8]. In a polygenic model characterized by additive and interchangeable effects, individuals carrying 2 to 6 rare alleles at these 8 SNPs showed a significant trend toward a decreased risk of lung ADCA (up to OR of 0.3). These results suggest the relevance of a polygenic model in the modulation of individual risk of lung ADCA in the general population.

Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus.

The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis‐susceptible C3H/He strain. Genome‐wide linkage analysis using a 1536–single‐nucleotide polymorphism array in a (C3H/He × BALB/c)F2 intercross population treated with urethane to induce hepatocellular tumor development revealed a locus with a major role in the resistance to hepatocarcinogenesis. This locus, designated hepatocarcinogen resistance 3 (Hpcr3) and mapping to central chromosome 15, showed a linkage at LOD score = 16.52 and accounted for 40% of the phenotypical variance. The BALB/c‐derived allele at Hpcr3 reduced tumor‐occupied area of the liver up to 25‐fold, in a semidominant way. Additional minor loci were mapped to chromosomes 1, 10, and 18. A gene expression profile of normal adult mouse liver showed a significant association with susceptibility of BALB/c, C3H/He, and F1 mice to hepatocarcinogenesis and identified the genes expressed in the Hpcr3 locus region; moreover, this analysis implicated the E2F1 pathway in the modulation of the phenotype susceptibility to hepatocarcinogenesis. Conclusion: These findings, indicating the complex genetics of dominant resistance to hepatocarcinogenesis, represent a step toward the identification of the genes underlying this phenotype. (HEPATOLOGY 2008;48:617–623.)