[Early and late complications of hyperglycemic extremely low birth-weight infants]. / Az extrém alacsony születési súlyú koraszülöttek hyperglykaemiájának korai és késoi szövodményei.

Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270-1278.

Birth by cesarean section is associated with elevated neonatal plasma levels of dimethylarginines.

BACKGROUND: This study was undertaken to compare the effects of vaginal delivery and cesarean section on the L-arginine-nitric oxide system by measuring levels of L-arginine, an endogenous nitric oxide synthase antagonist asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in the cord blood and postnatally. METHODS: Plasma samples were obtained from the umbilical vein and artery at birth and from peripheral venous blood on the second postnatal day in 30 full-term newborn infants: 10 born vaginally and 20 born by cesarean section. RESULTS: After vaginal delivery, ADMA concentration was higher in the umbilical vein than in the umbilical artery (mean 1.06 vs 0.90 µmol/L [P = 0.027]); and ADMA level fell after birth to 0.66 µmol/L on the second postnatal day (P = 0.007 vs umbilical artery). Newborns born by cesarean section had similar ADMA levels in umbilical arterial and venous blood, 1.19 and 1.18 µmol/L, and the ADMA level fell to 0.84 µmol/L by the second postnatal day (P < 0.001). Vaginal birth induced neither significant umbilical venoarterial difference nor a postnatal fall in SDMA. After cesarean section, SDMA was essentially the same in umbilical vein, umbilical artery and postnatal peripheral vein samples. At 2 days of age, both ADMA and SDMA levels stayed higher in infants born by cesarean section than in vaginally born infants. CONCLUSIONS: ADMA level falls after both vaginal and cesarean birth, whereas SDMA level does not. The higher ADMA level after cesarean birth compared with vaginal birth may contribute to decreased nitric oxide production and bioavailability in neonatal vascular beds.

Male reproductive tract abnormalities: more common after assisted reproduction?

BACKGROUND: In this era of increased use of assisted reproduction (AR) techniques, the prevalence rates of hypospadias, cryptorchidism, poor semen quality have been increasing in parallel with a rising incidence of testicular cancer. It is suggested that these problems result from the disruption of gonadal development during fetal life causing the testicular dysgenesis syndrome (TDS). AIM: The aim of our study was to evaluate the influence of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), on the development of male genital tract abnormalities. STUDY DESIGN AND SUBJECTS: We analyzed a cohort of 15,206 neonates born from January 1, 1999 through December 31, 2008 at the Department of Obstetrics and Gynecology, Medical School, University of Pécs, including 890 children (5.9%) born after IVF or ICSI. We examined the association between these AR methods and developmental abnormalities of the genital tract (hypospadias, cryptorchidism), after controlling for potential confounding factors, such as prematurity, low birthweight and twinning. RESULTS: Preterm birth and low birthweight are risk factors for hypospadias and cryptorchidism (p<0.001), twinning increases the risk of hypospadias (p<0.001). ICSI was revealed as a risk factor for hypospadias in singletons (OR: 3.190, 95%CI: 1.266-8.042) and in normal birthweight (>2500 g) infants (OR: 3.966, 95%CI: 1.193-13.181, respectively). Similar but not nonsignificant trends were seen for cryptorchidism. CONCLUSION: IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias.

Plasma levels of asymmetric dimethylarginine in premature neonates: its possible involvement in developmental programming of chronic diseases.

AIM: The endothel dysfunction in early life may play a role in developmental programming of cardiovascular morbidity. The changes of dimethylarginines' plasma levels during the first month among preterm infants and their determinants had been investigated in our study. METHODS: Twenty preterm infants of healthy mothers were studied. Mean (+/-SD) birth weight and gestational age were 919.5 +/- 235.5 g and 26.7 +/- 1.6 weeks, respectively. Blood samples were taken by venipuncture at the 3rd, 7th, 14th, 21st and 28th days. Plasma concentrations of L-arginine, asymmetric and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-mass spectrometry method, evaluated by multivariate linear regression analysis. RESULTS: L-arginine (p < 0.001) and asymmetric dimethylarginine (ADMA) levels (p < 0.001) were positively associated with postnatal age. ADMA levels were negatively correlated with gestational age (p = 0.007), dopamine-need on the 3rd day of life (p = 0.015) and late infection (p = 0.038). The higher birth weight was associated with higher L-arginine (p = 0.052) and ADMA (p = 0.002) concentrations. The dopamine-need on the 7th day of life had a significant effect on postnatal elevation of SDMA levels (p = 0.035). CONCLUSION: The progressive increase of ADMA levels described by our study among preterm infants suggests that early endothel dysfunction may take part in developmental programming of chronic adult diseases.

Fructosamine levels and hyperglycemia in preterm neonates.

BACKGROUND: Hyperglycemia is a common complication of prematurity, which requires attention because of its high prevalence and multiple consequences. Serum fructosamine used in diabetic patients provides information about the average glucose concentration in the preceding period of 2-3 weeks. OBJECTIVE: We investigated the physiologic characteristics of a glycemic marker, fructosamine, in preterm and term neonates. We also studied its association with hyperglycemia and related morbidities of preterm infants. METHOD: Fructosamine levels of 22 extremely premature (gestational age, GA: 25.8 +/- 1.0 weeks), 36 moderately premature (GA: 29.8 +/- 1.3 weeks) and 26 term infants (GA: 39.1 +/- 1.3 weeks) were determined in the 1st week of life. Fructosamine assay was repeated in all preterm neonates in the 4th and 7th postnatal weeks. Hyperglycemic episodes and main morbidities of preterm infants were recorded and analyzed in association with fructosamine levels. RESULTS: Preterm infants had higher fructosamine levels after birth compared to term infants and a postnatal fall was observed. Serum fructosamine did not show association with the occurrence of hyperglycemia or its main morbidities in preterm infants. CONCLUSION: In the framework of our study, we could not confirm the usefulness of fructosamine determination in the glycemic control of preterm neonates during the perinatal period.

[Life expectancy of extremely preterm infants]. / Extrém alacsony gesztációs korú koraszülöttek életkilátásai.

Extremely preterm infants [gestational age (GA) between 24-28 weeks] should be delivered optimally in an institute where neonatal intensive care unit (NICU) is available and their short- and long-term care is ensured. At the Department of Obstetrics and Gynecology, Medical School, University of Pécs, 7499 infants were born between 1st of January, 2000 and 31st of December, 2004. During this period the rate of preterm deliveries was 20% (1499/7499). Among preterm infants the incidence of extremely preterm babies (GA 28 weeks or less) was 18% (272/1499), the rate of profoundly preterm infants (GA less than 25 weeks) was 3.2% (48/1499). Advancing with gestational age the survival rate is increasing. At the department, the rate of handicapped infants among extremely premature babies was 15.3%. The majority of the handicapped infants were profoundly preterm, meanwhile, more than 50% of infants born at the 26 gestational weeks were free of symptoms influencing social activities. It is important to stress the prognostic value of the screening for hearing loss (otoacoustic emission), visual problems, and intracranial bleeding for the early detection and cure of the possible complications of prematurity.

[Metabolic bone disease in premature infants and genetic polymorphisms]. / Koraszülöttek csontanyagcsere-betegsége és genetikai polimorfizmusok.

UNLABELLED: Metabolic bone disease is an important complication among infants very-low-birth-weight (< 1500 g). In adults, osteoporosis has been shown to be associated with polymorphisms of vitamin D receptor, estrogen receptor, and collagen Ialpha1 receptor genes. AIM: The primary goal of the study was to investigate the possible association between metabolic bone disease and the allelic polymorphisms of these three genes. METHOD: 104 infants very-low-birth-weight were enrolled to the study. Bone formation (serum alkaline phosphatase, osteocalcin) and bone resorption (urinary excretion of calcium and pyridinium crosslink) markers were determined and x-rays of the chest and wrist (together with the distal portions of associated long bones) were obtained. RESULTS: Thirty infants (28,8%) were diagnosed with metabolic bone disease based on high activity of bone formation, bone resorption markers, and positive radiologic signs. Statistically significant correlation between thymine-adenine repeat [(TA) n ] allelic variant of estrogen receptor gene and bone disease was observed. Infants with metabolic bone disease more often carried low number of repeats [(TA) n < 19] [odds ratio (OR): 5.82, 95% confidence interval (CI): 2.26-14.98]. Significantly higher number of repeats [(TA)n > 18] was found more frequently in the control group (OR: 0.20, 95% CI: 0.05-0.82). Furthermore significant interaction between vitamin D receptor and collagen Ialpha1 receptor genotypes ( p = 0.023) was observed. In a forward stepwise logistic regression model, bone disorder of preterms correlated with male gender ( p = 0.001), duration of hospitalization ( p = 0.007), homozygous allelic variants of high number of (TA) n repeats ( p = 0.025) and interaction between vitamin D receptor (Tt) and estrogen receptor (homozygous allelic variants of low number of repeats) genotype ( p = 0.037). CONCLUSION: The results suggest that the development of metabolic bone disease in infants very-low-birth-weight may be associated with genetic polymorphisms.

[Cutis marmorata telangiectatica congenita--case report]. / Cutis marmorata teleangiectatica congenita egy eset kapcsán.

Cutis marmorata telangiectatica congenita is a rare, usually congenital, localized or generalized cutaneous vascular abnormality characterized by a persistent cutis marmorata pattern, spider naevus-like telangiectasia and ulceration or atrophy of the involved skin, which frequently improves with age. Approximately 300 cases have been reported worldwide. The authors present a case of cutis marmorata telangiectatica congenita with typical clinical findings: phlebectasia of the scalp with ulceration, almost generalized persistent cutis marmorata, telangiectasia. No associated anomalies were detected. The relevant literature is also reviewed.

Plasma asymmetric dimethylarginine concentration during the perinatal period.

Experimental and clinical evidence has been accumulated to indicate that elevated plasma asymmetric dimethylarginine (ADMA) levels can be regarded as a marker of endothelial dysfunction that mediates cardiovascular morbidity by impairing NO-dependent vascular reactions; therefore, it may have a role in the cardiopulmonary adaptation of the neonate. The present study was undertaken to investigate the perinatal NO metabolism by measuring L-arginine, the NO synthase substrate, ADMA, the endogenous inhibitor of NO synthase, and symmetrical dimethylarginine (SDMA), the biologically inactive L-arginine metabolite in umbilical venous and arterial plasma and in peripheral plasma of the neonate. Measurements were done in ten healthy pregnant women at term delivery and in their newborn infants on the second day of life by using liquid chromatography-mass spectrometry method. It was demonstrated that cord blood L-arginine, ADMA, and SDMA levels were markedly elevated with a moderate, but consistent veno-arterial difference suggesting that they are mainly generated by the placental endothelium. L-Arginine and ADMA levels were found to fall significantly (p < 0.001) by the second postnatal day, whereas SDMA remained unaltered. This finding indicates accelerated enzymatic ADMA elimination and reduction in the inhibition of NO-synthase activity. It is concluded that ADMA may play a role in the control of feto-placental circulation and the circulatory adaptation of the neonate.

Influence of genetic polymorphisms on bone disease of preterm infants.

Bone disease is an important complication among very low birth weight (VLBW, <1500 g) infants. In adults, osteoporosis is associated with polymorphisms of vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIA1) genes. However, limited information is available regarding the role of these polymorphisms in bone disease in premature infants. We have investigated the possible association between bone disease and the allelic polymorphisms of these three genes in 65 VLBW infants. Twenty infants (30.8%) were diagnosed with bone disease based on high activity of bone formation (serum alkaline phosphatase and osteocalcin), bone resorption (urinary excretion of calcium and pyridinium crosslink) markers, and positive radiologic signs. Statistically significant correlation between thymine-adenine repeat [(TA)(n)] allelic variant of ER gene and bone disease was observed. Infants without bone disorder more often carried a high number of repeats [(TA)(n) >18] [odds ratio (OR): 0.17, 95% confidence interval (CI): 0.05-0.55]. A low number of repeats [(TA)(n) <19] was found more frequently in infants suffering from bone disease (OR: 6.00, 95% CI: 1.77-20.31). Significant interaction (p = 0.009) between VDR and COLIA1 genotypes was observed. In a logistic regression model, bone disorder of preterms significantly correlated with male gender (p = 0.002), lower gestational age (p = 0.015), homozygous allelic variants of high number of (TA)(n) repeats (p = 0.006), and interaction between VDR and COLIA1 genotype (p = 0.009).