The first de novo non-mosaic 14q11.2q13.1 tetrasomy of paternal origin.

Tetrasomy 14q11q13 is a very rare chromosome aberration. So far, only five patients with such an imbalance were described. All these patients had a de novo marker chromosome idic(14)(q13) leading to a partial tetrasomy of chromosome 14. We report on the first case of a de novo non-mosaic partial tetrasomy 14q resulted not from a marker chromosome, but from an inverted triplication on paternal chromosome 14, characterized by using FISH and SNP array. Our patient showed some anomalies described in tetrasomy 14q11q13 with striking presence of paternal UPD(14) features (blepharophimosis, small thorax, and joint contractures, developmental delay). This unique patient supports the hypothesis that 14q11q13 may contain imprinted gene(s) that contribute to the paternal UPD(14) features of joint contractures and/or blepharophimosis. This patient demonstrates the utility of parent of origin testing in patients with de novo chromosome 14 aberrations. Overdosage of 14q11.1q13.1 may cause some features related to UPD(14) phenotype.

Evaluation of serum chemokine RANTES concentration as a biomarker in the diagnosis of early-onset severe infections in neonates.

OBJECTIVE: Only a few studies on improving the early diagnosis of severe neonatal infections have focused on the role of serum RANTES concentration (sRC). The aim of the study was to establish sRC in neonates with early-onset infections, according to their gestational age, sex, birth asphyxia, mode of delivery and value of some biochemical and hematological parameters. MATERIAL/METHODS: The analysis comprised 129 neonates, including 89 infected (52 preterm, 37 full-term; 43 with sepsis, 39 with congenital pneumonia, 7 with severe urinary tract infection) and 40 healthy (control group, 25 full-term, 15 preterm). The sRC in peripheral vein blood was measured by the ELISA method using Quantikine Set (R & D systems, USA). RESULTS: The sRC in infected neonates ranged from 10.83 to 122.55 µg/ml, in full-term neonates from 18.28 to 122.55 µg/ml, and in preterm from 10.83 to 118.24 µg/ml. The mean sRCs in full-term septic neonates (73.95±25.99 µg/ml) and with organ infections (58.43±29.24 µg/ml) were significantly higher than healthy ones (28.25±14.06 µg/ml). The mean sRCs in septic preterm neonates (59.17±28.29 µg/ml) and those with organ infections (50.86±28.16) were significantly higher than in healthy preterm neonates (25.61±8.29 µg/ml). Positive correlations between sRC and CRP value (r=0.3014, p=0.004) and between sRC and band cell count (r=0.2489, p=0.019) were found in all infected neonates. CONCLUSION: The significant increase of serum RANTES concentration in early-onset infections in neonates, regardless of their gestational age, sex and birth asphyxia, not only proves the presence of an active immunological process but also may be a useful biomarker for diagnosis of severe neonatal infections.

Spatial and temporal clustering of isolated cleft lip with or without cleft palate in Poland.

BACKGROUND: Geographic variation in the prevalence of isolated cleft lip with or without cleft palate may be due to exogenous environmental factors or genetic variation. In this study, we aim to evaluate the prevalence of isolated cleft lip with or without cleft palate in Polish urban and rural environments in order to identify geographic areas with high prevalence (defect clusters). METHODS: We use all cases of congenital malformations reported to the Polish Registry of Congenital Malformations in the years 1998-2008 from the total population of 2,362,502 births. RESULTS: We detect a strong signal of increased prevalence of isolated cleft lip with or without cleft palate in a single region of Poland, the Dolnoslaskie voivodeship. Furthermore, we demonstrate a statistically significant prevalence differences between the urban and rural areas within this region. Through our comprehensive spatiotemporal analysis, we precisely define the cluster of the highest risk that comprises the eastern part of this voivodeship.

Associations between endogenous dimethylarginines and renal function in healthy children and adolescents.

The structural isomer of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), is eliminated almost entirely by urinary excretion and considered a sensitive index of glomerular filtration rate (GFR). However, reports on this relationship in healthy subjects younger than 18 years of age are rare. Therefore, our aim was to investigate relations between endogenous dimethylarginines and renal function indices in healthy children and adolescents. We studied 40 subjects aged 3­18 years free of coexistent diseases or subclinical carotid atherosclerosis. A serum creatinine-derived estimated GFR (eGFR) was calculated by the revised bedside Schwartz equation. L-arginine, ADMA and SDMA were measured by liquid chromatography-tandem mass spectrometry. Mean eGFR was 122 ± 22 (SD) mL/min per 1.73 m2. Creatinine and eGFR exhibited closer correlations with the SDMA/ADMA ratio (r = 0.64, p < 0.0001; r = −0.63, p < 0.0001, respectively) than with SDMA (r = 0.31, p = 0.05; r = −0.35, p = 0.03). Neither creatinine nor eGFR correlated with ADMA or L-arginine. Adjustment for age or height only slightly attenuated the associations between the SDMA/ADMA ratio and eGFR or creatinine. Our findings suggest the superiority of the SDMA/ADMA ratio over SDMA as a renal function index in healthy children. Thus, further studies are warranted to verify our preliminary results in a larger group of subjects below 18 years of age.

An analysis of factors determining serum leptin concentration in healthy and infected newborns.

OBJECTIVE: The effect leptin on fetal growth in healthy and infected newborns is not well known. This study is aimed at: 1) evaluating serum leptin concentration in full term and preterm, healthy and infected newborns, according to their gender, birth asphyxia, intrauterine and neonatal infections, and 2) assessing the correlation between serum leptin levels and anthropometric parameters among healthy and infected newborns. MATERIALS AND METHODS: The study involved 146 newborns: 73 full-term and 73 preterm, 86 male and 60 female, 56 healthy and 90 infected, aged from 2nd to 4th day of life. Anthropometric parameters, including: birth weight, length, head and chest circumference, and serum leptin concentration were measured in all the subjects. Intrauterine and neonatal infections were diagnosed by the standard criteria. RESULTS: In this study, it was found that both healthy and infected, but full-term newborns had significantly higher mean leptin concentration than the premature ones (p<0.05). Statistically significant (p<0.05), positive correlations were found between serum leptin level and gestational age, birth weight, head and chest circumference, both in healthy, and in infected newborns. CONCLUSIONS: Findings of this study suggest that the serum leptin concentration in full term newborns is higher than in the preterm ones, and in females it is higher than in males, 2) among both healthy and infected newborns, there is a positive, linear correlation between the serum leptin concentration and anthropometric parameters, 3) intrauterine and neonatal infections do not have a significant influence on serum leptin concentration. The role of leptin in fetal growth deserves further research.

Comparative study of clinical characteristics of amniotic rupture sequence with and without body wall defect: further evidence for separation.

BACKGROUND: Amniotic rupture sequence (ARS) is a disruption sequence presenting with fibrous bands, possibly emerging as a result of amniotic tear in the first trimester of gestation. Our comparative study aims to assess whether there is a difference in the clinical pattern of congenital limb and internal organ anomalies between ARS with body wall defect (ARS-BWD) and ARS without BWD (ARS-L). METHODS: Among 1,706,639 births recorded between 1998 and 2006, 50 infants with a diagnosis of ARS were reported to the Polish Registry of Congenital Malformations. The information on 3 infants was incomplete, thus only 47 cases were analyzed. These infants were classified into groups of ARS-L (38 infants) and ARS-BWD (9 infants). RESULTS: The ARS-BWD cases were more frequently affected by various congenital defects (overall p < 0.0001), and in particular by urogenital malformations (p = 0.003). In both groups, limb reduction defects occurred in approximately 80% of cases; however, minor and distal limb defects (phalangeal or digital amputation, pseudosyndactyly, constriction rings) predominated in the ARS-L group (p = 0.0008). The ARS-L group also had a higher frequency of hand and upper limb involvement. CONCLUSIONS: This observation suggests that amniotic band adhesion in ARS-L takes place at a later development stage. Although limited by a small sample size, our study contributes to the growing evidence that both ARS entities represent two nosologically distinct conditions.

Parental age as a risk factor for isolated congenital malformations in a Polish population.

Currently available data on the relationship between the prevalence of isolated congenital malformations and parental age are inconsistent and frequently divergent. We utilised the data from the Polish Registry of Congenital Malformations (PRCM) to accurately assess the interplay between maternal and paternal age in the risk of isolated non-syndromic congenital malformations. Out of 902 452 livebirths we studied 8683 children aged 0-2 years registered in the PRCM. Logistic regression was used to simultaneously adjust the risk estimates for maternal and paternal age. Our data indicated that paternal and maternal age were independently associated with several congenital malformations. Based on our data, young maternal and paternal ages were independently associated with gastroschisis. In addition, young maternal age, but not young paternal age, carried a higher risk of neural tube defects. Advanced maternal and paternal ages were both independently associated with congenital heart defects. Moreover, there was a positive association between advanced paternal age and hypospadias, cleft palate, and cleft lip (with or without cleft palate). No significant relationships between parental age and the following congenital malformations were detected: microcephaly, hydrocephaly, oesophageal atresia, atresia or stenosis of small and/or large intestine, ano-rectal atresia or stenosis, renal agenesis or hypoplasia, cystic kidney disease, congenital hydronephrosis, diaphragmatic hernia and omphalocele.

Effect of intrauterine infection and perinatal risk factors on serum concentrations of insulin like growth factor (IGF-I) in full-term and preterm newborns.

OBJECTIVES: IGF-I is believed to be a key factor in fetal growth dynamics It is widely known, that serious early-onset infection in the newborn is a risk factor for further developmental disturbances in a child. However, effect of congenital infection as well as an influence of infectious and non-infectious perinatal risk factors on circulating IGF-I concentrations in newborns has not been examined, yet. DESIGN: Thus, the aim of this study was: 1) evaluation of IGF-I venous blood serum concentration in full-term and premature infants considering their sex, occurrence of intrauterine infection and perinatal risk factors; 2) establishing the relationship between IGF-I serum concentrations and chosen anthropometric parameters values in infected and healthy newborns. SETTING: The study involved 112 newborns appropriate for gestational age. Taking into consideration occurrence of early onset infection and gestational age we divided examined children into 4 groups: I group--infected, full-term newborns; II group--infected premature newborns; III group--healthy full-term newborns; IV group--healthy premature newborns. In all infants immediately after birth anthropometric measurements were performed (birth weight, body length, circumference of head and circumference of chest) and serum IGF-I concentration was determined. RESULTS: We demonstrated that full-term infants with intrauterine infection have statistically significantly higher concentration of IGF-I in blood serum than infected premature infants and healthy full-term infants. Analysis of correlation revealed a significant positive linear correlations between IGF-I serum concentration and gestational age and anthropometric parameters values. CONCLUSIONS: We conclude that intrauterine infection increases serum IGF-I concentration in full-term infants, but not in preterm infants, that may be a result of immaturity. We suggest serum IGF-I concentration may be considered an additional element of developmental and nutritional state assessment in infected newborn.

[Assessment of retrocochlear hearing pathway activity in infants with central nervous system impairment occurring as an effect of perinatal asphyxia]. / Ocena funkcji pozaslimakowej czesci drogi sluchowej u niemowlat ze zmianami w obrebie osrodkowego ukladu nerwowego powstalymi na skutek asfiksji okoloporodowej.

INTRODUCTION: The most often changes in the central nervous system (CNS) occurring as an effect of perinatal asphyxia are found to be hypoxic-ischemic encephalopathy (HIE) in term newborns, peri- (PVH) or intraventricular hemorrhages (IVH) and periventricular leukomalacia (PVL) in preterm neonates. Chronic hypoxia is considered to affect the brainstem in infants, especially nuclei of the hearing pathway are vulnerable to low oxygen level. The aim of the study was to carry out the objective assessment of the retrocochlear hearing pathway activity using ABR in infants with CNS impairment occurring as an effect of perinatal asphyxia, imaged during trans-fontanel ultrasonography. MATERIAL AND METHODS: To the investigation 36 infants with HIE, IVH or PVL were included, the control group encompassed 32 born at term, health children. ABR recordings were performed in 3 months old children using Nicolet Spirit System for clicks of 85 and 80 dB nHL. RESULTS: No differences were found between latencies of waves I and II. ABR latencies of waves III, IV, V and interpeak latencies I-III, III-V, I-V were significantly delayed in InvG when compared to control patients. In conclusion, the brainstem activity in infants with CNS involvement as an effect of perinatal asphyxia is lower comparing to health children. Subclinical abnormalities as prolonged synaptic transmission of electric signal in retrocochlear auditory pathway were revealed.

Geospatial clustering of gastroschisis in Poland: Data from the Polish Registry of Congenital Malformations (PRCM).

OBJECTIVES: The aims of this study were: to evaluate the prevalence of abdominal wall defects in the Polish population, to analyze temporal trends in the prevalence, to identify areas (clusters) of high risk of abdominal wall defects, and to characterize, with respect to epidemiology, children with abdominal wall defects and their mothers in the area defined as a cluster. MATERIAL AND METHODS: We used isolated congenital malformations (gastroschisis Q79.3 and omphalocele Q79.2 according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10, the extended version)) data reported to the Polish Registry of Congenital Malformations (PRCM) over the years 1998- 2008 based on the population of 2 362 502 live births. We analyzed 11 administrative regions of Poland with complete epidemiologic data. RESULTS: Of 11 regions, 2 had a significantly higher standardized prevalence of isolated gastroschisis: Dolnoslaskie (1.7/10 000 live births, p = 0.0052) and Slaskie (1.9/10 000 live births, p < 0.0001). Furthermore, within the region of Dolnoslaskie, we defined a clear prevalence of the isolated gastroschisis cluster (p = 0.023). We comprehensively examined demographic and socio-economic risk factors for abdominal wall defects in this area, and we found that these factors failed to account for the cluster. CONCLUSIONS: We identified a distinct prevalence cluster for isolated gastroschisis, although a precise reason for the disease clustering in this region remains unknown. Cluster identification enables more focused research aimed at identification of specific factors with teratogenic effects.

[Assessment of cochlea activity in a group of newborns with central nervous system impairment as an effect of perinatal asphyxia using click-evoked otoacoustic emissions (CEOAEs)]. / Ocena funkcji slimaka za pomocq emisji otoakustycznej wywolanej trzaskiem (CEOAEs) u noworodków z niedotlenienienem oklporodowym i nastepowymi zmianami w obrebie osrodkowego ukladu nerwowego.

During adaptation of newborn to extra-uterine environment dramatic changes in functioning in the inner organs and the entire human body is observed. Complicated or premature birth as well as complicated course of a perinatal period may cause reversible or irreversible damage of various tissues, organs or systems, and, consequently, their dysfunction. The most often changes in the central nervous system (CNS) in newborns occurring as an effect of perinatal asphyxia are found to be ischemic-hypoxic encephalopathy (IHE), periventricular leucomalacia (PVL) and intraventricular hemorrhages (IVH). Chronic hypoxia is considered to affect the hearing organ in newborns. Reversible or irreversible changes within the cochlea, brainstem or cortex may result in perceptive hearing losses. The aim of the study was to carry out the objective assessment of the cochlea activity using CEOAEs in neonates with CNS impairment occurring following perinatal asphyxia. To the investigation 16 newborns with IHE, PVL or IVH were included. The control group encompassed the health newborns matched as to the age. Perinatal anamnesis, general pediatric status, results of trans-fontanel ultrasonography and biochemical test results were taken into account in statistical analyses. In all newborns otoscopic examination and CEOAEs after birth and 3 months later were performed. CEOAEs in session 1 were significantly reduced in the investigated group comparing to control babies but 3 months later no differences between groups were observed. The outer hair cells activity in first days of life is reduced in newborns with asphyxia in anamnesis but with time no differences in cochlea development are observed.

[Quantitative changes of CD3+, CD4+, CD8+, HLA-DR+, T lymphocytes and CD25+ cells in eutrophic full-term neonates with staphylococcal septicemia]. / Zmiany ilosciowe limfocytów CD3+, CD4+, CD8+ i HLA-DR+ oraz komórek CD25+ u eutroficznych noworodków donoszonych z posocznica gronkowcowa.

OBJECTIVE: Influence of staphylococcal septicemia on changes of share and changes of amount of CD3+ lymphocytes and their subpopulation as well as CD25+ cells in eutrophic full-term neonates. MATERIALS AND METHODS: In 52 full-term neonates, with birthweight ranged from 2900 to 4500 g, including 30 infants with staphylococcal septicemia caused by Staphylococcus epidermidis (19 cases), S. sciuri (2 cases) S. varneri, S. hominis, S. haemolyticus and S. aureus (6 cases) and 22 healthy neonates (control group) the subpopulation of CD3+, CD4+, CD8+, HLA-DR+ lymphocytes in venous blood was estimated using flow cytometer FACScan with monoclonal antibodies of Becton Dickinson. RESULTS: Average percentage of CD3+ (69.2 +/- 5.9%), CD4+ (48.9 +/- 10.7%) and HLA-DR+ (1.8 +/- 0.9%) lymphocytes and average CD4+/CD8+ ratio (2.97 +/- 1.33) in neonates with septicemia did not significantly differ from average values of these parameters in healthy neonates that were: CD3+ (69.1 +/- 9.0%), CD4+ (47.4 +/- 10.6%), HLA-DR+ (1.5 +/- 0.5%) and CD4+/CD8+ (2.29 +/- 1.29). Likewise the average numbers of these lymphocytes were close to the values found in the control group. Whereas the average subpopulation of CD8+ (19.2 +/- 4.6%) lymphocytes in ill neonates was significantly lower (p = 0.007) than in healthy ones (23.6 +/- 6.6%), and the average number of CD25+ cells was essentially (p = 0.01) higher in septicemia neonates (8.5 +/- 2.5) compared to the control group (6.6 +/- 1.3%). Average numbers of these cells in ill neonates did not substantially differ from their average values in control group. CONCLUSIONS: 1. Staphylococcal septicemia significantly decreases the values of subpopulation of CD8+ lymphocytes and increases the number of CD25+ cells in eutrophic full-term neonates. 2. Estimation of lymphocytes, and their subpopulation and CD25+ cells in neonates with staphylococcal septicemia may be useful in assessment of immunological changes in severe infections.

[Spirometric tests in school-age children with past bronchopulmonary dysplasia]. / Ocena wybranych parametrów spirometrycznych u dzieci szkolnych z przebyta dysplazja oskrzelowo-plucna.

The aim of the paper was to estimate 9 spirometric parameters in 38 children aged 8-12, among them in16 with past bronchopulmonary dysplasia and in 22 healthy ones. Mean values of VC, FEV1, FVC Ex, PEF, MEF 75, MEF 50 and MEF 25 in children with past bronchopulmonary dysplasia were significantly lower than in healthy children. In children with past bronchopulmonary dysplasia VC was decreased comparing to normal values in 94% of cases, FVC Ex and MEF 50 in 75% and FEV1 in 63% of subjects. Tiffeneau coefficient and value of FEV1% FVC Ex were normal. Inhaled salbutamol increased significantly the mean values of VC and MEF 25 in children with dysplasia. The increase of FEV1 > 15% in 56% and VC > 15% only in 25% of these children was observed. It was found, that past bronchopulmonary dysplasia induces ventilatory disorders, mainly restriction changes with obstruction component in airways of school-age children.