András Nobilis

Angiotensin II type 1 receptor A1166C polymorphism and prophylactic indomethacin treatment induced ductus arteriosus closure in very low birth weight neonates

Altered pulmonary vascular resistance might be a factor for delayed closure of the ductus arteriosus (DA) in preterm infants. Angiotensin II plays a central role in the elevation of pulmonary vascular resistance. Angiotensin II exerts its vasoconstrictor effect on the angiotensin II type 1 receptor (AT1R). Homozygous carriers of the AT1R A1166C genetic variant present an exaggerated vasoconstrictor response to angiotensin II. We have investigated whether the presence of AT1R CC1166 influences the effect of prophylactic indomethacin treatment on the closure of DA until the fifth postnatal day in preterm infants. In this retrospective study detailed medical history of the first postnatal week was obtained in 159 infants born before the 33rd gestational week. All were treated by prophylactic indomethacin to induce permanent closure of the DA. On the sixth postnatal day the DA was still open in 56, whereas it was permanently closed in 103. The AT1R A1166C genotype of the infants was determined from Guthrie spots. Stepwise binary logistic regression analysis was used to assess the effect of medical conditions and genotype on the risk of patent DA (PDA). Birth weight, infantile respiratory distress, and severe hypotension were independent risk factors for PDA (p < 0.01, p < 0.05, p < 0.05, respectively). The carrier state of AT1R CC1166 was protective against PDA (p < 0.05; odds ratio, 0.067). AT1R AC1166 genotype was not associated with PDA. Our results indicate that the risk of PDA might be lower in infants of AT1R CC1166 than in those with AC or AA genotypes.

Variance of ACE and AT1 receptor gene does not influence the risk of neonatal acute renal failure

Abstract. High neonatal activity of the renin-angiotensin system (RAS) is crucial for the maintenance of glomerular filtration of the newborn. The aim of the present study was to investigate whether genetic polymorphisms leading to lower angiotensin converting enzyme activity (ACE) or impaired functionality of angiotensin II (AII) type 1 receptor (AT1R) might predispose very low birth weight newborns (VLBWs) to the development of acute renal failure (ARF). The medical records of 110 VLBW infants were analyzed. ARF developed in 42 of them during the first postnatal week, while 68 neonates exhibited normal renal function. The ACE I/D polymorphism and the A1166C variants of AT1R were determined from dried blood samples. The frequency of the ACE I allele did not differ in ARF and non-ARF groups (0.307 and 0.284); the frequency of the AT1R C1166 variant was also the same in ARF and non-ARF groups (0.250 and 0.227). Although low activity of RAS has been implicated in the development of neonatal ARF and data indicated that the functionality of RAS is influenced by the I/D variants of the ACE gene and the A1166C variant of the AT1R gene, we could not demonstrate any effect of these polymorphisms on the development of ARF in VLBW infants.

Selectin polymorphisms and perinatal morbidity in low-birthweight infants

Background: Studies have shown an association between altered expression of selectins and premature birth, early sepsis and bronchopulmonary dysplasia. Aim: To investigate the possible link between functional polymorphisms of the E‐, P‐ and L‐selectin genes and perinatal morbidity. Methods: We compared the genotype distribution of the E‐selectin Ser128Arg, P‐selectin Thr715Pro and L‐selectin Pro213Ser polymorphisms in 125 low‐birthweight singleton infants with those of 156 healthy term neonates. We also analysed the association of genotype with risk of sepsis and bronchopulmonary dysplasia. Results: We found no association between E‐selectin or P‐selectin polymorphisms and premature birth, nor did we find any association between E‐selectin or P‐selectin and early postnatal sepsis or bronchopulmonary dysplasia. Carriers of the 213Ser L‐selectin allele were found to be more prevalent in low‐birthweight infants, particularly in those with bronchopulmonary dysplasia. We found no association between the L‐selectin polymorphism and early postnatal sepsis.

Emergence of VIM-4- and SHV-12-producing Enterobacter cloacae in a neonatal intensive care unit

In order to reveal colonization with multidrug-resistant bacteria early, routine screening is done on samples of all patients of the neonatal intensive care units at Semmelweis University, Hungary. Due to the extended-spectrum β-lactamase (ESBL) screening examinations, emergence of multidrug-resistant Enterobacter cloacae isolates was found with suspicion of clonal transmission, therefore active microbiological surveillance was initiated. The aim of our study was to characterize 60 E. cloacae isolates recovered in a 7-month period in 2010. MIC values of antibiotics were determined and ESBL and carbapenemase production was tested. Metallo-β-lactamase (MBL) genes, ESBL genes, and class-1 integrons were characterized, and the possible clonal relationship between isolates was investigated. The isolates showed increased MIC values for carbapenems and cephalosporins. All 60 E. cloacae strains recovered from 16 neonates proved to be VIM-4 MBL producers. Fifty-three strains were SHV-12 ESBL producers also. In all cases, the bla(VIM-4) gene was a part of class-1 integron, In238a. XbaI-macrorestriction analysis by pulsed-field gel electrophoresis (PFGE) revealed identical patterns for the isolates. Our study supports the importance of active microbiological surveillance as well as molecular epidemiology at the NICUs as a part of infection control.

Functional and structural properties of Na+/K+-ATPase enzyme in neonatal erythrocytes

The Na+/K+‐pump is the main regulator enzyme of intracellular monovalent cation concentration. There are only limited data available concerning its structure and function in healthy neonates, in comparison with data available regarding its structure and function in children.

Angiotensin-converting enzyme DD genotype is preventive against circulatory failure in very-low-birthweight neonates

UNLABELLED We studied the association between genetic polymorphisms of the renin-angiotensin system and the risk for circulatory failure (CF) during the first three postnatal days in 104 very-low-birthweight preterm infants. CONCLUSION Infants with angiotensin-converting enzyme DD genotype were protected against CF (adjusted OR 0.41, 95% CI 0.19-0.89).

Clinical microbiology of neonatal candidiasis in Hungary

The occurrence of Candida spp. was investigated during a three-year period in two neonatal intensive care units, Budapest, Hungary. The species distribution among the 41 analysed cases was the following: C. albicans (30/41, 73%), C. parapsilosis (10/41, 24%) and C. glabrata (1/41, 3%). All of the isolates were susceptible to the tested drugs. There was a significant difference in the birth weight, the gestational age <30 weeks and the occurrence of caesarean section between the C. albicans and the C. parapsilosis groups of the cases. Respiratory tract colonization was the same (76-77%) in the extremely low birth weight (ELBW) and the very low birth weight (VLBW) groups. Comparing the ELBW, VLBW, and >1500 g birth weight groups, significant difference was found in the parenteral nutrition, the gestation weeks <36 or <30, the polymicrobial infection and the transfusion. The ratio of C. albicans, C. parapsilosis and C. glabrata was 9:7:1 in ELBW group; 6:3:0 in VLBW group and 15:1:0 in >1500 g group. The mortality rate for C. parapsilosis was higher than for C. albicans.

Na + /K + -ATPase isoforms in neonatal erythrocytes: a possible explanation for higher digoxin tolerance of the newborn

The aim of our study was to test, whether the different digoxin sensitivity of the neonates and children can be explained by the different functional properties of the Na+/K+ -ATPase enzyme. The activity, ouabain sensitivity and isoform composition of erythrocyte Na+/K+-ATPase of 53 healthy full term neonates (1-5 postnatal days) and that of 61 healthy children (6-38 months) were compared. The enzyme activity was elevated in neonates (mean±SEM: 429.2±17.1 vs 295.5±10.2 nmol ATP/mg prot*h-1, p<0.001). 150 value for ouabain inhibition was also higher (1.5±0.1*10.6 vs 0.96±0.1*10.6 mol/1, p<0.05). In neonates the expression of enzyme alpha subunits(1.16±0.1 vs 75±0.03, p<0.001) and the alpha1/alpha2 subtypes-ratio (4.14±0.21 vs 2.02±0.16, p<0.01) was higher than in children.