Based on our observations and previously published data, the association of the VEGF gene promoter polymorphisms and the risk of advanced ROP is weak. VEGF serum concentration assessment as early as on the 20th day of life appears to be a promising approach to recognize newborns at risk of the development of advanced ROP.

ABSTRACT:The aim of the study was to assess the association between bronchopulmonary dysplasia (BPD) and polymorphisms of genes coding for vascular endothelial growth factor (VEGF), transforming growth factor (TGF-␤1), insulin-like growth factor (IGF-1), and 5,10-methylenetetrahydrofolate reductase (MTHFR). A sample of 181 newborns with mean gestational age of 28 wk was prospectively evaluated. Molecular analysis of TGF-␤1 Ϫ800GϾA, Ϫ509CϾT, 10TϾC, 25GϾC, VEGF Ϫ460TϾC and 405GϾC and MTHFR 677CϾT polymorphisms were performed and the number of CA repeats in the promoter region of IGF-1 gene was assessed. The frequency of all TGF-␤1, IGF-1, and MTHFR polymorphisms, as well as the frequency of VEGF 405GϾC polymorphism was similar in all groups. The newborns with Ϫ460TT and Ϫ460CT genotypes were significantly overrepresented in the BPD groups compared with the no BPD group. Multivariate analysis revealed that carrying T allele increased the risk of BPD by 9% (95%CI: 2-14%) above the baseline risk established for given gestational age, length of oxygen therapy, and sex. Based on our data from a single center, we propose that VEGF Ϫ460TϾC polymorphism may influence the risk of BPD. A n increase in survival of extremely preterm infants has been associated with an increased incidence of bronchopulmonary dysplasia (BPD) (1), which has become a major clinical challenge because of its serious health consequences. Surviving infants with BPD are at higher risk for recurrent respiratory infections, bronchial hyperreactivity, repeated hospitalizations, and neurodevelopmental abnormalities (1,2).The current consensus is that BPD is a complex disease: the interaction of a susceptible host with a multitude of external risk factors underlies its pathogenesis. It is still unclear why BPD progresses to severe disease in one group of very low birth weight (VLBW) infants but regresses spontaneously in other infants with similar clinical characteristics. This difference in BPD development may result from differences in reactions to inflammatory stimuli and varied ability to tolerate oxidative stress and inflammation. Genetic foundations for the development of BPD are implicated in twin studies, which reveal highly significant concordance rates for BPD: 3.69-fold in monozygotic and 1.4-fold in dizygotic twins (3).The criteria for selection of BPD candidate genes in the present study were their potential involvement in angiogenesis and alveolarization regulating mechanisms, as well as their involvement in free radical elimination.The first factor worth examining is vascular endothelial growth factor (VEGF). VEGF is a relatively specific endothelial cell mitogen that regulates endothelial cell differentiation and angiogenesis, and plays a central role in vascular repair. VEGF has multiple roles in vascular development and maintenance and is essential for the formation of embryonic vasculature (4,5). The absence of VEGF results in impaired fetal lung microvascular development. The VEGF gene is also a good candidate because there are a consid...

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition in which immaturity of the gonadal axis is accepted as the cause. Based on our case and 8 cases from the literature, we made an attempt to specify the mechanisms underlying the syndrome and its pathognomonic signs. All POHS newborns were born between 24 and 31 weeks postconception age (WPCA) and developed vulvar, hypogastric and upper leg swelling, and ovarian follicular cyst/cysts (10–40 mm in diameter) with mildly or considerably elevated E₂ concentrations (80–5,300 pmol/l) between 35 and 39 WPCA. The GnRH test, performed in 5 cases, confirmed gonadal axis activation. In our case the observed normalization of elevated gonadotropin values by 43 WPCA, accompanied by a simultaneously increasing E₂ value (approximately 800 pmol/l), could correspond with the maturation of the gonadal steroid-dependent negative-feedback mechanism. The continuously increasing E₂ levels after this period (maximum 1,300 pmol/l) suggest its autonomous secretion. In all the cases, including 3 neonates treated with medroxyprogesterone and surgery, the swelling resolved by 6 months. Conclusions: A pathognomonic sign of POHS is swelling which develops around 37 ± 3 WPCA, and the syndrome is only infrequently diagnosed when the swelling is profound. The direct etiologic factor here is not E₂. POHS does not require therapy as long as there is no danger of cyst torsion.

Background: Retinopathy of prematurity (ROP) is one of the most common preventable causes of blindness and impaired vision among children in developed countries. The aim of the study was to compare whole-genome expression in the first month of life in groups of infants with and without ROP. Methods: Blood samples were drawn from 111 newborns with a mean gestational age of 27.8 wk on the 5th, 14th, and 28th day of life (DOL). The mRNa samples were evaluated for gene expression with the use of human whole-genome microarrays. The infants were divided into two groups: no ROP (n = 61) and ROP (n = 50). results: Overall, 794 genes were differentially expressed on the 5th DOL, 1,077 on the 14th DOL, and 3,223 on the 28th DOL. In each of the three time points during the first month of life, more genes were underexpressed than overexpressed in the ROP group. Fold change (Fc), which was used in analysis of gene expression data, ranged between 1.0 and 1.5 in the majority of genes differentially expressed. conclusion: Pathway enrichment analysis revealed that genes in four pathways related to inflammatory response were consistently downregulated due to the following variables: ROP and gestational age.

A simplified urinary marker analysis for diagnosis of congenital adrenal hyperplasia (CAH) and 5α-reductase deficiency in infancy by GC/MS-SIM is introduced. The analysis was performed in 161 patients aged 3-90 days, 99 females and 62 males. CAH due to 21-hydroxylase deficiency was diagnosed in 61 patients (42 females and 19 males; in 10 cases simple virilizing form and in 51 patients salt-wasting form) and CAH induced by 3β-hydroxysteroid dehydrogenase deficiency without salt loss in 1 female patient. In 2 full-term newborns and 6 preterm infants, a false-positive diagnosis of CAH, which had been based on serum steroid evaluation, was made. In these cases, increased excretion of fetal adrenal zone steroids was confirmed as a possible source of false-positive serum 11-deoxycortisol and 17α-hydroxyprogesterone values. Lack of fetal adrenal zone steroid metabolites in 2 male newborns with salt loss symptoms led to the diagnosis of adrenal insufficiency due to X-linked adrenal hypoplasia and adrenal hemorrhage. A single analysis of urinary CAH markers by the very sensitive and selective GC/MS-SIM method can replace numerous assays of various steroids that must be carried out for positive diagnosis of abnormal steroidogenesis in infancy.