Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia.

BACKGROUND: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. METHODS: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(-) groups, according to the development of BPD. RESULTS: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. CONCLUSIONS: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.

The prevalence and risk factors of allergic and respiratory symptoms in a regional cohort of extremely low birth weight children (<1000 g).

BACKGROUND: Children who were <1000 g (ELBW extremely low birth weight) at birth more frequently present with wheezing which is the most common reason that pediatric consultation is sought. Therefore asthma is diagnosed very often. However is the asthma that is diagnosed in ELBW subjects atopic in origin, or is there a different etiology? AIM: To determine if ELBW infants are at higher risk for the development of allergic and respiratory symptoms and to establish if there were any specific risk factors for these symptoms. METHODS: 81 children born with a mean birthweight of 845 g (91% of available cohort) were evaluated at the mean age 6.7 years. The control group included 40 full-term children. The children were examined for clinical signs of allergy, and were subjected to the following tests: serum total IgE, skin prick tests (SPT), exhaled nitric oxide measurement (FeNO) and spirometry. RESULTS: ELBW children had wheezing episodes more often (64% vs. 25%; OR (odds ratio): 5.38; 95% CI (confidence interval): 2.14-13.8) and were diagnosed more frequently with asthma (32% vs. 7.5%; OR: 5.83, 95% CI: 1.52-26) than their term born peers. The most important risk factors for wheezing persistence were hospitalization and wheezing episodes in first 24 months of life. Mean serum tIgE level (geometric mean: 32+/-4 vs. 56+/-4 kU/L; p=0.002) was higher and the number of children with positive results of tIgE level (12% vs. 32%; p=0.02) were more frequent in the control group. Children from the control group also more frequently had SPT, however this data was not statistically significant (11% vs. 24%; p=0.09). All of the ELBW had normal FeNO level (<=20 ppb), but 5 children from the control group had abnormal results (p=0.02). There was no difference between the groups in the occurrence of allergic symptoms. CONCLUSION: ELBW children have more frequent respiratory, but not allergic problems at the age of 6-7 years compared to children born at term. The need for rehospitalization in the first 2 years of life, was a more important risk factor of future respiratory problems at the age of 7 than perinatal factors, the diagnosis of bronchopulmonary dysplasia or allergy.

Impact of antenatal glucocorticosteroids on whole-genome expression in preterm babies.

AIM: To study the impact that using antenatal steroid to treat threatened preterm delivery has on whole-genome expression. METHODS: A prospective whole-genome expression study was carried out on 50 newborn infants, delivered before 32 weeks gestation, who had been exposed to antenatal steroids, including 40 who had received a full antenatal steroid course. Seventy infants not exposed to antenatal steroids formed the control group. Microarray analyses were performed five and 28 days after delivery, and the results were validated by real-time PCR. The study was conducted between September 2008 and November 2010. RESULTS: Twenty thousand six hundred and ninety-three genes were studied in the infants' leucocytes. Thirteen were differentially expressed 5 days after delivery, but there were no differences at day 28. Four genes related to cancer or inflammation were up-regulated. Nine genes were down-regulated: six were Y-linked and associated with malignancies, graft-versus-host disease, male infertility and cell differentiation and three were associated with pre-eclampsia, oxidative stress and chloride/bicarbonate exchange. Seven gene pathways were up-regulated at day five and only one at day 28. These were associated with cell growth, cell cycle regulation, metabolism and apoptosis. CONCLUSION: Antenatal steroid therapy affects a limited number of genes and gene pathways in leucocytes in preterm babies at day five of life. The effect is short-lived, but long-term effects cannot be ruled out.

Assessment of long-term renal complications in extremely low birth weight children.

We assessed the long-term renal complications in a regional cohort of extremely low birth weight (ELBW) children born in 2002-2004. The study group, comprising 78 children born as ELBW infants (88% of the available cohort), was evaluated with measurement of serum cystatin C, urinary albumin excretion, renal ultrasound, and 24-h ambulatory blood pressure measurements. The control group included 38 children born full-term selected from one general practice in the district. Study patients were evaluated at a mean age of 6.7 years, and had a median birthweight of 890 g (25th-75th percentile: 760-950 g) and a median gestational age of 27 weeks (25th-75th percentile: 26-29 weeks). Mean serum cystatin C levels were significantly higher (0.64 vs. 0.59 mg/l; p = 0.01) in the ELBW group. Hypertension was diagnosed in 8/78 ELBW and 2/38 of the control children (p = 0.5). Microalbuminuria (>20 mg/g of creatinine) was detected only in five ELBW children (p = 0.17). The mean renal volume was significantly lower in the ELBW group (absolute kidney volume 81 ml vs. 113 ml; p < 0.001, relative kidney volume 85 vs. 97%; p < 0.001). Abnormally small kidneys (<2/3 of predicted size) were detected in 19 ELBW and four control children (p = 0.08). Multivariate logistic regression revealed that the only independent risk factor for renal complications was weight gained during neonatal hospitalization (odds ratio: 0.67; 95% confidence interval: 0.39-0.94). Serum cystatin C and kidney volume are significantly lower in school-age ELBW children. It is important to include systematic renal evaluation in the follow-up programs of ELBW infants.

Preterm birth and respiratory disease in later life.

Chronic respiratory diseases are a common complication of preterm birth, particularly among very immature infants or those suffering from bronchopulmonary dysplasia. Major progress in the treatment of preterm newborns has changed the pattern of late respiratory complications. The major respiratory problem in infancy and early childhood is respiratory exacerbations caused by infections (particularly viral ones), which need hospitalization. The symptoms become mild in school-age children; however, a group of children still present with chronic airway obstruction defined by recurrent episodes of wheezing and decreased lung function tests (decreased forced expiratory volume). For some preterm infants, particularly those with bronchopulmonary dysplasia, obstructive lung disease persists into adulthood. They are very likely to develop chronic obstructive pulmonary disease or similar disease later in life. In these patients, a program of lung function monitoring and pulmonary prophylaxis by means of elimination of specific risk factors in adulthood is advisable.

[Difficulties in diagnosing febrile states in 3-month-old infant]. / Trudnosci diagnostyczne stanów goraczkowych u 3-miesiecznego niemowlecia.

Wide spectrum of infectious causes should be considered while diagnosing febrile states in infants.The aim of study is to present the case of 3-month-old infant with febrile states. Boy was admitted to Department of Pediatrics to Infant Unit because of the febrile states lasting for 4 weeks. Perinatal history: first pregnancy, cesarean section in 39 weeks of gestation due to mother's pointed condyloma, birth weight 3140 g, Apgar score 10 in first minute. There was no information about the course of pregnancy, mother's diseases, father was unknown. The child was ambulatory cured with several antibiotics because of the respiratory tract infections. On admission to hospital the general status of the infant was quite good, there was respiratory tract infection, hepatomegaly, and aphthae found in physical examination. Increased levels of inflammation markers and elevated activity of liver enzymes were observed in laboratory tests. Perihilar inflammatory density was found in chest radiogram. After finishing pharmacological treatment there were no pathological changes on auscultation of the lungs. The hospital course was complicated with Rotaviral infection. As the febrile states and hyperactivity of liver enzymes persisted, the diagnostics was extended. There was sepsis, neuroinfection, number of bacterial and viral infections excluded. There was also urine collected for the levels of catecholamines, the result was normal. Due to reverse proportion of the CD4 and CD8 lymphocytes, persistent active CMV infection and clinical status of the child, HIV test was performed. There was confirmed presence of p24 antigen of HIV in immunological test. The child was transfered to Child's Infectious Diseases Unit of Stefan Zeromski Hospital in Cracow to verify the result of laboratory test and start therapy.

Genetic risk factors of bronchopulmonary dysplasia.

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-[beta]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-[beta]1 -800G>A, -509C>T, 10T>C, 25G>C, VEGF -460T>C and 405G>C and MTHFR 677C>T polymorphisms were performed and the number of CA repeats in the promoter region of IGF-1 gene was assessed. The frequency of all TGF-[beta]1, IGF-1, and MTHFR polymorphisms, as well as the frequency of VEGF 405G>C polymorphism was similar in all groups. The newborns with -460TT and -460CT 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 -460T>C polymorphism may influence the risk of BPD.