Hormone levels in preterm and donor human milk before and after Holder pasteurization.

BACKGROUND: After birth, breastfeeding is the exclusive source of hormonal signaling between mother and infant. Hospitalized infants often receive donor milk when their own mother's milk is unavailable. METHODS: The presence of insulin, leptin, cortisol, progesterone, and testosterone was examined in samples from milk bank donors and mothers of preterm infants. We further investigated the effect of Holder pasteurization (HoP) on hormone levels. RESULTS: Comparing nonpasteurized samples, leptin levels were nearly threefold higher in milk from mothers of preterm infants versus donated milk, and regardless of milk source, leptin levels were significantly decreased by HoP. Insulin concentrations were also decreased by HoP, and among mothers of preterm infants, obesity was associated with significantly higher content of leptin and insulin. While combined use of donor milk and HoP was associated with cortisol levels nearly threefold higher than those in nonpasteurized own mother's milk, progesterone and testosterone content did not differ by source or pasteurization. CONCLUSIONS: The hormonal composition of breast milk is impacted by HoP and maternal obesity. Compared to nonpasteurized maternal milk, use of pasteurized donor milk dramatically decreases the intake of leptin while increasing the intake of cortisol. Further research is necessary to define optimal breast milk processing practices.

Disparities and relative risk ratio of preterm birth in six Central and Eastern European centers.

AIM: To identify characteristic risk factors of preterm birth in Central and Eastern Europe and explore the differences from other developed countries. METHOD: Data on 33,794 term and 3867 preterm births (<37 wks.) were extracted in a retrospective study between January 1, 2007 and December 31, 2009. The study took place in 6 centers in 5 countries: Czech Republic, Hungary (two centers), Romania, Slovakia, and Ukraine. Data on historical risk factors, pregnancy complications, and special testing were gathered. Preterm birth frequencies and relevant risk factors were analyzed using Statistical Analysis System (SAS) software. RESULTS: All the factors selected for study (history of smoking, diabetes, chronic hypertension, current diabetes, preeclampsia, progesterone use, current smoking, body mass index, iron use and anemia during pregnancy), except the history of diabetes were predictive of preterm birth across all participating European centers. Preterm birth was at least 2.4 times more likely with smoking (history or current), three times more likely with preeclampsia, 2.9 times more likely with hypertension after adjusting for other covariates. It had inverse relationship with the significant predictor body mass index, with adjusted risk ratio of 0.8 to 1.0 in three sites. Iron use and anemia, though significant predictors of preterm birth, indicated mixed patterns for relative risk ratio. CONCLUSION: Smoking, preeclampsia, hypertension and body mass index seem to be the foremost risk factors of preterm birth. Implications of these factors could be beneficial for design and implementation of interventions and improve the birth outcome.

Dietary nutrients during gestation cause obesity and related metabolic changes by altering DNA methylation in the offspring.

Growing evidence shows that maternal nutrition from preconception until lactation has an important effect on the development of non-communicable diseases in the offspring. Biological responses to environmental stress during pregnancy, including undernutrition or overnutrition of various nutrients, are transmitted in part by DNA methylation. The aim of the present narrative review is to summarize literature data on altered DNA methylation patterns caused by maternal macronutrient or vitamin intake and its association with offspring's phenotype (obesity and related metabolic changes). With our literature search, we found evidence for the association between alterations in DNA methylation pattern of different genes caused by maternal under- or overnutrition of several nutrients (protein, fructose, fat, vitamin D, methyl-group donor nutrients) during 3 critical periods of programming (preconception, pregnancy, lactation) and the development of obesity or related metabolic changes (glucose, insulin, lipid, leptin, adiponectin levels, blood pressure, non-alcoholic fatty liver disease) in offspring. The review highlights that maternal consumption of several nutrients could individually affect the development of offspring's obesity and related metabolic changes via alterations in DNA methylation.

Effect of Holder Pasteurization, Mode of Delivery, and Infant's Gender on Fatty Acid Composition of Donor Breast Milk.

Breast milk (BM) plays a crucial role in providing essential fatty acids (FA) and energy for the growing infant. When the mother's own BM is not available, nutritional recommendations suggest donor milk (DM) in clinical and home practices. BM was collected from a variety of donor mothers in different lactation stages. Holder pasteurization (HoP) eliminates potential contaminants to ensure safety. FA content of BM samples from the Breast Milk Collection Center of Pécs, Hungary, were analyzed before and after HoP. HoP decreases the level of C6:0, C8:0, C14:1n-5c, C18:1n-9c, C18:3n-6c, C18:3n-3c, and C20:4n-6c in BM, while C14:0, C16:0, C18:1n-9t, C22:0, C22:1n-9c, C24:0, C24:1n-9c, and C22:6n-3c were found in elevated concentration after HoP. We did not detect time-dependent concentration changes in FAs in the first year of lactation. BM produced for girl infants contains higher C20:2n-6c levels. In the BM of mothers who delivered via cesarean section, C12:0, C15:0, C16:0, C17:0, C18:0, C18:1n-9t, C22:1n-9c levels were higher, while C18:2n-6c, C22:0, C24:0, and C22:6n-3c concentrations were lower compared to mothers who gave birth spontaneously. FAs in BM are constant during the first year of lactation. Although HoP modifies the concentration of different FAs, pasteurized DM provides essential FAs to the developing infant. Current data providing information about the FA profile of BM gives origination to supplementation guidelines.

Infantile hemangiomas and retinopathy of prematurity: clues to the regulation of vasculogenesis.

UNLABELLED: Retinopathy of prematurity (ROP) and infantile hemangiomas are vascular disorders that may share common mechanisms. This study examined a potential clinical association between these disorders in populations of preterm infants at two hospitals in the USA and Hungary. Clinically collected data from infants with gestational ages less than 32 weeks born between May 1, 2007 and December 31, 2010 seen in the University of Iowa Children's Hospital or the Department of Obstetrics and Gynecology, University of Pécs, were abstracted from electronic medical records and entered into a study database. Demographic and clinical variables were examined as potential covariates to the disorders of interest. Data were initially analyzed by center and then combined through meta-analysis. Six hundred eighty-four subjects were studied: 236 from Pécs and 448 from Iowa. There were no significant demographic differences between populations. Univariate analysis on each study population yielded covariates to ROP in each population, including infantile hemangioma, which were entered into a logistic regression model. These models were combined through random-effects meta-analysis and demonstrated a significant relationship between infantile hemangioma and ROP (odds ratio = 1.84, 95 % confidence interval 1.08-3.12). CONCLUSION: Infantile hemangioma and ROP co-occur in premature infant populations. Further studies are needed to investigate the pathogenesis of both disorders.

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies.

Less invasive surfactant administration techniques, together with nasal continuous airway pressure (LISA-nCPAP) ventilation, an emerging noninvasive ventilation (NIV) technique in neonatology, are gaining more significance, even in extremely premature newborns (ELBW), under 27 weeks of gestational age. In this review, studies on LISA-nCPAP are compiled with an emphasis on short- and long-term morbidities associated with prematurity. Several perinatal preventative and therapeutic investigations are also discussed in order to start integrated therapies as numerous organ-saving techniques in addition to lung-protective ventilations. Two thirds of immature newborns can start their lives on NIV, and one third of them never need mechanical ventilation. With adjuvant intervention, these ratios are expected to be increased, resulting in better outcomes. Optimized cardiopulmonary transition, especially physiologic cord clamping, could have an additively beneficial effect on patient outcomes gained from NIV. Organ development and angiogenesis are strictly linked not only in the immature lung and retina, but also possibly in the kidney, and optimized interventions using angiogenic growth factors could lead to better morbidity-free survival. Corticosteroids, caffeine, insulin, thyroid hormones, antioxidants, N-acetylcysteine, and, moreover, the immunomodulatory components of mother's milk are also discussed as adjuvant treatments, since immature newborns deserve more complex neonatal interventions.

The Effect of Holder Pasteurization and Different Variants on Breast Milk Antioxidants.

BACKGROUND: After birth, breast milk (BM) is a known essential source of antioxidants for infants. We analyzed the non-enzymatic total antioxidant capacity (TAC), oxygen radical absorbance capacity (ORAC), and glutathione, calcium, transferrin, and total protein levels of human breast milk before and after Holder pasteurization (HoP). METHODS: The collected donor BM samples were pasteurized with HoP. RESULTS: HoP decreased TAC (-12.6%), ORAC (-12.1%), transferrin (-98.3%), and total protein (-21.4%) levels; HoP did not influence the glutathione concentration, and it increased the total calcium (+25.5%) concentration. Mothers who gave birth via Cesarean section had significantly lower TAC in their BM. TAC and glutathione levels were elevated in the BM of mothers over the age of 30. BM produced in the summer had higher glutathione and calcium levels compared to BM produced in the winter. The glutathione concentration in term milk samples was significantly higher in the first two months of lactation compared to the period between the third and sixth months. The transferrin level of BM for female infants was significantly higher than the BM for boys, and mothers with a BMI above 30 had increased transferrin in their samples. CONCLUSIONS: Antioxidant levels in human milk are influenced by numerous factors. Environmental and maternal factors, the postpartum age at breast milk collection, and Holder pasteurization of the milk influence the antioxidant intake of the infant.

Insulin, Testosterone, and Albumin in Term and Preterm Breast Milk, Donor Milk, and Infant Formula.

BACKGROUND: Infants have three options for feeding: their own mother's breast milk, donor milk, or infant formula. Insulin, testosterone, total protein, and albumin levels were measured in breast milk samples from the first 6 months of lactation, in donor milk samples, and in different infant formulas. METHODS: Mothers who gave birth to term (n = 19) or preterm (n = 19) infants were recruited to collect breast milk samples during the first 6 months of lactation. The Breast Milk Collection Center (Unified Health Institution, Pécs, Hungary) provided 96 donor milk (DM) samples for analysis in our study. Insulin, testosterone, total protein, and albumin levels were measured in breast milk, donor milk, and infant formulas. RESULTS: During the first 2 months of lactation, the concentration of insulin was lower (-27.4%) while the testosterone concentration was higher (+20.8%) compared to the period between the 3rd and 6th months only in the preterm breast milk samples. The infant formulas examined did not contain insulin or testosterone. Holder pasteurization (HoP) did not influence the level of testosterone in human milk, although HoP decreased the insulin (-53.6%) and albumin (-38.6%) concentrations. CONCLUSIONS: Diet impacts the hormone intake of infants, underlining the importance of breastfeeding and the possible supplementation of formula-fed infants.

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.

Epigenetic Effect of Maternal Methyl-Group Donor Intake on Offspring's Health and Disease.

Maternal exposure to some dietary and environmental factors during embryonic development can affect offspring's phenotype and, furthermore, the risk of developing diseases later in life. One potential mechanism responsible for this early programming may be the modification of the epigenome, such as DNA methylation. Methyl-group donors are essential for DNA methylation and are shown to have an important role in fetal development and later health. The main goal of the present review is to summarize the available literature data on the epigenetic effect (DNA methylation) of maternal methyl-group donor availability on reproductivity, perinatal outcome, and later health of the offspring. In our literature search, we found evidence for the association between alterations in DNA methylation patterns caused by different maternal methyl-group donor (folate, choline, methionine, betaine) intake and reproductivity, birth weight, neural tube defect, congenital heart defect, cleft lip and palate, brain development, and the development of obesity and associated non-communicable diseases in later life. We can conclude that maternal methyl-group donor availability could affect offspring's health via alterations in DNA methylation and may be a major link between early environmental exposure and the development of diseases in the offspring. However, still, further studies are necessary to confirm the associations and causal relationships.

Thyroxine and Thyroid-Stimulating Hormone in Own Mother's Milk, Donor Milk, and Infant Formula.

Breastfeeding is widely supported in clinical and home practices, and it is known that different forms of infant feeding differ in hormone content. Thyroid hormones have essential physiological roles. In our study, we examined thyroid-stimulating hormone (TSH), thyroxine, and albumin levels in breast milk produced for term (n = 16) or preterm (n = 15) infants throughout the first 6 months of lactation. Moreover, we analyzed these components in donor human milk and in three different infant formulas. Term and preterm breast milk samples were collected monthly. The two groups had similar levels of TSH (18.4 ± 1.4 vs. 24.7 ± 2.9 nU/L), but term milk contained higher amounts of thyroxine (11,245.5 ± 73.8 vs. 671.6 ± 61.2 nmol/L) during the examination period. The albumin level was significantly higher in preterm breast milk than in term breast milk (328.6 ± 17.1 vs. 264.2 ± 6.8 mg/L). In preterm breast milk we detected downward trends in the levels of TSH (-30.2%) and thyroxine (-29.2%) in the 3rd through 6th month compared to the first 2 months of lactation. Microbiological safety of donor milk was ensured by Holder pasteurization (HoP). From the Breast Milk Collection Center of Pécs, Hungary, we enrolled 44 donor mothers into the study. HoP decreased TSH (-73.8%), thyroxine (-22.4%), and albumin (-20.9%) concentrations. Infant formulas used by the Neonatal Intensive Care Unit of the University of Pécs were found to not contain the investigated hormones, but their albumin levels were similar to the breast milk samples. The present study shows the lack of thyroid hormones in infant formulas compared to human milk and raises the question of whether formula-fed infants should be supplemented with thyroid hormones.

Breast Milk for Term and Preterm Infants-Own Mother's Milk or Donor Milk?

Hormones are important biological regulators, controlling development and physiological processes throughout life. We investigated pituitary hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and total protein levels during the first 6 months of lactation. Breast milk samples were collected every fourth week of lactation from mothers who gave birth to preterm (n = 14) or term (n = 16) infants. Donor milk is suggested when own mother's milk is not available; therefore, we collected breast milk samples before and after Holder pasteurization (HoP) from the Breast Milk Collection Center of Pécs, Hungary. Three infant formulas prepared in the Neonatal Intensive Care Unit of the University of Pécs were tested at three different time points. Our aim was to examine the hormone content of own mother's milk and donor milk. There were no significant changes over time in the concentrations of any hormone. Preterm milk had higher PRL (28.2 ± 2.5 vs 19.3 ± 2.3 ng/mL) and LH (36.3 ± 8.8 vs 15.9 ± 4.1 mIU/L) concentrations than term milk during the first 6 months of lactation. Total protein and FSH concentrations did not differ between preterm and term breast milk. Holder pasteurization decreased the PRL concentration (30.4 ± 1.8 vs 14.4 ± 0.6 ng/mL) and did not affect gonadotropin levels of donor milk. Infant formulas have higher total protein content than breast milk but do not contain detectable levels of pituitary hormones. Differences were detected in the content of pituitary hormones produced for preterm and term infants. Divergence between feeding options offers opportunities for improvement of nutritional guidelines for both hospital and home feeding practices.

The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide having trophic and protective functions in neural tissues, including the retina. Previously, we have shown that intravitreal PACAP administration can maintain retinal structure in the animal model of retinopathy of prematurity (ROP). The purpose of this study is to examine the development of ROP in PACAP-deficient and wild-type mice to reveal the function of endogenous PACAP. Wild-type and PACAP-knockout (KO) mouse pups at postnatal day (PD) 7 were maintained at 75% oxygen for 5 consecutive days then returned to room air on PD12 to develop oxygen-induced retinopathy (OIR). On PD15, animals underwent electroretinography (ERG) to assess visual function. On PD16, eyes were harvested for either immunohistochemistry to determine the percentage of the central avascular retinal area or molecular analysis to assess angiogenesis proteins by array kit and anti-apoptotic protein kinase B (Akt) change by western blot. Retinas of PACAP-deficient OIR mice showed a greater central avascular area than that of the wild types. ERG revealed significantly decreased b-wave amplitude in PACAP KO compared to their controls. Several angiogenic proteins were upregulated due to OIR, and 11 different proteins markedly increased in PACAP-deficient mice, whereas western blot analysis revealed a reduction in Akt phosphorylation, suggesting an advanced cell death in the lack of PACAP. This is the first study to examine the endogenous effect of PACAP in the OIR model. Previously, we have shown the beneficial effect of exogenous local PACAP treatment in the rat OIR model. Together with the present findings, we suggest that PACAP could be a novel retinoprotective agent in ROP.

Pituitary Glycoprotein Hormones in Human Milk before and after Pasteurization or Refrigeration.

Our aims were to investigate the presence of pituitary glycoprotein hormones in preterm and donor milk, and to examine the effects of Holder pasteurization and refrigeration on the levels of these hormones. We measured follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) in milk samples from mothers who delivered prematurely (n = 27) and in samples of mothers who delivered at term and donated milk to the Mother's Milk Bank of Iowa (n = 30). The gonadotropins and TSH were present in similar amounts within human milk produced for preterm and term infants. FSH increased 21% after refrigeration (p < 0.05), while LH declined by 39% (p < 0.05). Holder pasteurization decreased LH by 24% (p < 0.05) and increased TSH by 17% (p < 0.05). Holder pasteurization followed by refrigeration resulted in a 21% increase in FSH and a 41% decrease in LH (both p < 0.05), resulting in more than a 3-fold increase in donor milk FSH:LH ratios (p < 0.05 versus fresh donor milk). Despite structural similarities, the gonadotropins are differentially impacted by Holder pasteurization and refrigeration, and this results in marked alterations in the relative amount of FSH and LH that may be administered to preterm infants, potentially swinging hormonal balance towards ovarian hyperstimulation in females and hypogonadism in males.

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.

Distribution of bioactive factors in human milk samples.

Background: Breast milk provides nutrition for infants and also contains a variety of bioactive factors that influence the development of the newborn. Human milk is a complex biological fluid that can be separated into different layers (water phase and lipid phase with its component water and lipid fractions). It can affect the developing human body along the whole length of the gastrointestinal tract, and through the circulation, its factors may reach every organ. Methods: In the present study, we analyzed milk samples collected monthly for 6 months from 16 mothers from the 4th week postpartum between 2014 and 2016 in Baranya County, Hungary. The 96 samples provided us information about the fluctuation of certain bioactive factors during the first 6 months of lactation. We investigated with Luminex technology the concentrations of several cytokines (CD40, Flt-3L), chemokines (MCP-1, RANTES, GRO, MIP-1ß, MDC, eotaxin, fractalkine), and epidermal growth factor (EGF). Paired t-tests and one-way ANOVA followed by Bonferroni post-hoc tests were used to compare the data. Results: We detected the presence of each bioactive factor in every layer of the milk samples during the first 6 months of breastfeeding in widespread concentration ranges. In the case of GRO, MIP-1ß, MDC, Flt-3L, fractalkine, and eotaxin, the concentrations were constant during the first 6 months of lactation. The water phase of human milk contained higher factor concentrations compared to both fractions of the lipid phase for most factors (except eotaxin and MIP-1ß). The concentrations of CD40, EGF, MCP-1, and RANTES in the first 3 months were significantly different compared to the values detected between 4th and 6th months. In the water phase, the level of MCP-1 was significantly decreased, while all of the other factors increased during the 4th through 6th months. We found significantly higher EGF, GRO, and RANTES levels in the water fraction compared to the lipid fraction of the lipid phase. Conclusions: The novel findings of this investigation were the presence of Flt-3L and MDC in all layers of breast milk, and nearly all bioactive factors in the lipid phase. Due to their widespread physiological effects these factors may have an essential role in organogenesis.

[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.

[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.