Metabolic syndrome and endothelial dysfunction in a population born small for gestational age relationship to growth and Gh therapy.

UNLABELLED: Being born small for gestational age (SGA) and a rapid increase in weight during early childhood and infancy have been strongly linked to metabolic syndrome. A transversal study was conducted on 167 pre-pubertal and 102 pubertal subjects; auxological parameters, systolic and diastolic blood pressure, laboratory data, and carotid-wall thickness (CA-IMT) were measured. RESULTS: Patients born SGA with spontaneous catch-up growth have higher values of BMI, blood pressure, HOMA index, and CA-IMT than those treated with GH and the appropriate-for-gestational age (AGA) group. In conclusion, subjects born SGA are at high risk of developing chronic diseases, including obesity, hypertension, insulin resistant, and endothelial dysfunction, at an early age, mainly those with good catch-up growth compared with the receiving GH because of negative catch-up growth. Our data is compared with published results.

Familial short stature and intrauterine growth retardation associated with a novel mutation in the IGF-I receptor (IGF1R) gene.

CONTEXT: IGF-I is essential for normal human growth and mediates its effects through the IGF1R. IGF1R mutations have been associated with varying degrees of intrauterine and postnatal growth retardation. OBJECTIVE: To identify IGF1R gene mutations in a short-statured family with intrauterine growth retardation and microcephaly. METHODS: Direct DNA sequencing was used to identify IGF1R mutations. Multiplex ligation-dependent probe amplification analyses were performed for deletions and duplications of all IGF1R exons. Functional studies were conducted to assess mutation pathogenicity. RESULTS: A novel heterozygous IGF1R missense mutation in exon 7 (c.A1549T, p.Y487F) was identified in a short-statured girl with severe prenatal growth retardation and microcephaly. The same mutation was also identified in her mother, who presented prenatal and postnatal growth failure, and her short-statured maternal grandmother, both of whom exhibited microcephaly. The index case showed a partial response to rhGH. Functional studies performed in dermal fibroblasts from the index case and her mother showed normal IGF-I binding; however, IGF-I activation of intracellular signalling measured as AKT and extracellular signal-regulated kinase phosphorylation was markedly reduced, with patients' values being lower than those of her mother. IGF-I stimulation of DNA synthesis was significantly reduced compared with controls. CONCLUSION: Our results show a novel missense mutation in the IGF1R gene (c.A1549T, p.Y487F) associated with prenatal and postnatal growth failure and microcephaly in the context of familial short stature. The functional studies are in line with the inactivation of one copy of the IGF1R gene with variable expression within the same family.

Neurocognitive development of children born small for gestational age (SGA). An update.

The aim of the present study is to confirm that being born SGA is a serious risk for a negative neurocognitive development. 233 cases have been controlled yearly and longitudinally by the same investigator, some of them 11 times, showing 25,8 % an IQ less than 2 SD, being less affected the catch-up + group (15 %), compared to the catch-up - group (31,4 %). The GH therapy (n 64) started before the age of 6 (n 38) or after 6 (n 26), doesn't improve the negative outcome.

Psychomotor and intellectual development (Neurocognitive Function) of children born small for gestational age (SGA). Transversal and longitudinal study.

Although much is now known about the effects of intrauterine growth retardation (IUGR) on children born SGA with regard to anthropometric and biochemical parameters and their treatment, there are still many gaps associated with its impact on neurocognitive functions. In our experience published several years ago, IUGR has a negative effect on neurocognitive development, regardless of whether these children showed evidence of catch-up growth or not or of the socio-economic conditions that might contribute to the situation. We have now accumulated a large number of cases, many of whom have been followed longitudinally, some for up to 7 years, many having been treated with GH from the time when this therapy was first approved by the EMA. Apart from the cases mentioned, other confounding factors such as gestational age, Apgar score, neonatal comorbidity and the possible effects of GH treatment have also been included. In addition and using our own reference standards, we now present our experience, which confirms what we had already noted in the past, that IUGR is in itself a condition that often causes psychomotorintellectual impairment, may be extremely severe and tends to worsen. This negative impact of IUGR on neurocognitive development does not depend on how the child grows,spontaneous growth is better and when growth is not altered by GH therapy. Later studies will be able to confirm whether early treatment with GH throughout the 2nd year of life, or an early specific stimulation programme, or the sum of both, can improve the neurocognitive development of these children. IUGR prevention, acting on causal factors that are partly avoidable such as smoking, working conditions and stress during pregnancy (see the corresponding article in this supplement) proves once again to be the best way to stop this negative impact on the IQ of many children born SGA.