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Purpose The aim of this study was to evaluate the possible relationship between four single nucleotide polymorphisms of hemangioma-linked genes encoding for anthrax toxin receptor 1 (ANTXR1 G976A), R kinase insert domain receptor (KDR T1444C), adrenoceptor beta 2 (ADRB C79CG), and insulin-like growth factor 1 receptor (IGF-1R G3174A) and the occurrence of IVH in a population of preterm infants. Methods The study includes a population of 105 infants born from 24 + 0 to 32 + 0 weeks of gestation and hospitalized at the Department of Neonatology (III level hospital) of Poznan University of Medical Science. Intraventricular hemorrhage was diagnosed with the use of cranial ultrasound. The classification of intraventricular bleeding was based on the Papile IVH classification. Results The incidence of IVH was higher in infants with lower birth weight, lower APGAR scores, and low birth weight. The study revealed that IVH was approximately two times less likely to occur in infants with the allele G of IGF-1R 3174G > A. Conclusion Identifying susceptible premature infants through genetic analysis could be a potential way to alleviate severe IVH and its subsequent consequences. Further research examining a wider range of relevant gene polymorphisms could help highlight any genetic patterns in this deleterious bleeding complication.

Excessive oxidative stress resulting from hyperoxia or hypoxia is a recognized risk factor for diseases of prematurity. However, the role of the hypoxia-related pathway in the development of these diseases has not been well studied. Therefore, this study aimed to investigate the association between four functional single nucleotide polymorphisms (SNPs) in the hypoxia-related pathway, and the development of complications of prematurity in relation to perinatal hypoxia. A total of 334 newborns born before or on the 32nd week of gestation were included in the study. The SNPs studied were HIF1A rs11549465 and rs11549467, VEGFA rs2010963, and rs833061. The findings suggest that the HIF1A rs11549465T allele is an independent protective factor against necrotizing enterocolitis (NEC), but may increase the risk of diffuse white matter injury (DWMI) in newborns exposed to hypoxia at birth and long-term oxygen supplementation. In addition, the rs11549467A allele was found to be an independent protective factor against respiratory distress syndrome (RDS). No significant associations with VEGFA SNPs were observed. These findings indicate the potential involvement of the hypoxia-inducible pathway in the pathogenesis of complications of prematurity. Studies with larger sample sizes are needed to confirm these results and explore their clinical implications.

Therapeutic hypothermia acts as the standard of care for infants with moderate to severe hypoxic ischemic encephalopathy (HIE). A proportion of neonates who undergo hypothermia due to HIE have shown to develop various degrees of hearing impairment. Analyzing and identifying infants at high risk of developing hearing difficulties is fundamental for early intervention of such auditory complications. The aim was to assess clinical factors in the development of hearing impairment following therapeutic hypothermia in HIE infants. A retrospective analysis was performed on infants hospitalized in our neonatology department in Poznan University of Medical Sciences, Poland. All infants experienced moderate to severe HIE, and were treated with therapeutic hypothermia. Risk factors for hearing impairment were identified in all infants included in the study. Clinical data during hospital stay and follow-up hearing status were analyzed. A total of 87 HIE infants were included in the study. Seventy-six infants (40 male and 36 female) had otoacoustic emission (OAE) examination following birth, of which 14 (18.4%) demonstrated abnormal (positive) results. Infants with abnormal OAE results had significantly lower blood pH (6.86 ± 0.16

BackgroundBronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved in the pathogenesis of BPD. Fibronectin is a multi-domain glycoprotein present in nearly all vertebrate tissues and organs. Material and methodsThe study included 108 infants born between 24 and 32 weeks of gestation. BPD was diagnosed based on the National Institutes of Health Consensus definition. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655. ResultsBPD developed in 30 (38.5%) out of the 108 preterm infants. Incidence of BPD was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Investigation did not confirm any significant prevelance for BPD development in any genotypes and alleles of FN1. Conclusion Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of BPD.

There are no established premedication schemes for less invasive surfactant administration (LISA) in neonatal RDS. The aim was to describe "real-world" practices and to assess the safety of premedication and its impact on the technical ease of the LISA procedure.Data from the prospective LISA cohort study conducted in 31 tertiary neonatal units were evaluated for premedication practices. Infants who received analgesics and/or sedatives before LISA and those receiving non-pharmacological sedation with sublingual 30% glucose were compared versus nonpremedicated neonates, acting as a reference. Safety of premedication was assessed with the rate of adverse events during LISA, changes in oxygenation status, the need for rescue intubation, and mechanical ventilation in the first 24 h of life. Ease of conducting LISA was an efficacy endpoint.Of 500 enrolled newborns, 102 (20.4%) received premedication for LISA; 88 infants were given analgesics/sedatives and 14 sublingual glucose. Pharmacological sedation was most often performed with ketamine (51/88; 57.9%), midazolam (16/88; 18.2%) and propofol (8/88; 1.6%). Compared to non-premedication, the use of analgesics/sedatives was associated with a significant increase in the rate of apnea (9.1 vs 2.6%;Analgesics/sedatives prior to LISA increased the rate of apnea and decreased blood oxygenation but did not lead to tracheal intubation and early mechanical ventilation. Trials addressing the impact on LISA-related stress are necessary to determine the ultimate usefulness of premedication.

Purpose The aim of the presented study was to evaluate the differences between selected biochemical markers in infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) and their impact on patient prognosis. Methods A total of 57 cooled newborns were divided into groups according to Sarnat staging of HIE (A, moderate vs. B, severe). The differences between groups were evaluated depending on the mode of delivery, pregnancy and labor complications, gestational age at birth, birth weight, and Apgar score at 1.3 and 5 min. The differences in biochemical biomarkers of HIE (pH, base excess, serum lactate) as well as biomarkers of hepatic injury (aspartate transaminase, (AST), alanine transaminase (ALT), prothrombin time (PT), and activated partial thromboplastin time (APTT)), kidney failure (creatinine, urea), myocardial injury (troponin T (TnT)), levels of fibrinogen, and platelet counts were also examined. Univariate Kaplan-Meier method was used for survival analyses. Results The biomarker levels in severe HIE newborns compared with moderate were as follows: pH (7.10 vs. 6.99), serum lactate (22.50 vs. 17.00 mg/dL), AST (109.50 vs. 270.55 IU/L), ALT (27.30 vs. 108.05 IU/L), PT (17.00 vs. 44.20 s), APTT (47.75 vs. 47.90 s), TnT (0.22 vs. 0.85 ng/mL), creatinine (0.68 vs. 1.15 mg/dL), urea (44.55 vs. 73.30 mg/dL), and fibrinogen (1.65 vs. 1.90 mg/dL). Survival analyses showed significantly reduced survival for severe HIE infants (75%) vs. moderate HIE (100%). Conclusion In conclusion, the severity of HIE can be evaluated based on selected markers; however, their levels do not correspond with future prognosis of newborns.

Background/introduction Intraventricular hemorrhage (IVH) is a dangerous complication facing a significant proportion of preterm infants. It is multifactorial in nature, and an observed fibronectin deficiency in the germinal matrix basal lamina is among the most prominent factors that influence such rupture. Better understanding of the FN1 gene polymorphisms and their role in IVH may further clarify the presence of a genetic susceptibility of certain babies to this complication. The aim of this study was to assess if 5 single nucleotide polymorphisms of the fibronectin gene may be linked to an increased incidence of IVH. Material and methods The study included 108 infants born between 24 and 32 weeks of gestation. IVH was diagnosed using cranial ultrasound performed on the 1st,3rd, and 7th day after birth and classified according to Papile et al. IVH classification. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655. Results IVH developed in 51 (47.2%) out of the 108 preterm infants. This includes, 18 (35.3%) with stage I IVH, 19 (37.3%) with stage II, 11 (21.6%) with stage III, and 3 (5.9%) with stage IV IVH. Incidence of IVH was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Analysis showed that IVH stage II to IV was approximately seven times more likely to occur in infants with the genotype TT FN1 rs10202709 (OR 7237 (1046–79.59; p = 0,044)). No other significant association was found with the rest of the polymorphisms. Conclusion The results of our study indicate a sevenfold increased genetic susceptibility to IVH in preterm infants with the TT FN1 rs10202709 gene polymorphism. The fibronectin gene polymorphism may therefore be of crucial importance as a genetic risk factor for IVH in preterm infants. Further studies are warranted.

Introduction A growing body of evidence shows that genetics plays a vital role in the development and progression of retinopathy of prematurity (ROP). Perinatal inflammation is also considered an important risk factor of ROP. Therefore, understanding the interplay of genetics and susceptibility to inflammation might shed light on the pathogenesis of ROP and make its screening and treatment more effective in preventing visual impairment in premature infants. Material and methods This study investigated the correlation of inflammation-associated gene polymorphisms: IL-1β +3953 C>T, IL-1RN VNTR 86 bp, IL-6 -174 G>C, IL-6 -596 G>A, and TNF-α -308 G>A as well as demographic and clinical characteristics of ROP in preterm infants (n = 90). Results Our results demonstrate that IL-1RN rs2234663 1/1 genotype prevails in infants with ROP that regresses without intervention, when compared to those requiring laser photocoagulation/anti-VEGF injection (p = 0.031). Genotype 2/2 of IL-1RN occurs more frequently in children with severe ROP (28.6%) than in the group in which ROP regressed spontaneously (4.0%). The analysis revealed also differences between the genotypes of IL-1RN in ROP patients with intrauterine infection and in patients who had ROP without intrauterine infection; however, this was not statistically significant. Other studied polymorphisms were not associated with ROP development or its progression. Conclusions These results suggest that different genotypes of IL-1RN might have an impact on the course of ROP. Genotype 2/2 of IL-1RN gene may predispose to ROP progression.

Purpose SARS-CoV-2 vaccines are a key step in fighting the pandemic. Nevertheless, their rapid development did not allow for testing among specific population subgroups such as pregnant and breastfeeding women, or elaborating specific guidelines for healthcare personnel working in high infection risk specialties, such as otolaryngology (ORL). This clinical consensus statement (CCS) aims to offer guidance for SARS-CoV-2 vaccination to this high-risk population based on the best evidence available. Methods A multidisciplinary international panel of 33 specialists judged statements through a two-round modified Delphi method survey. Statements were designed to encompass the following topics: risk of SARS-Cov-2 infection and use of protective equipment in ORL; SARS-Cov-2 infection and vaccines and respective risks for the mother/child dyad; and counseling for SARS-CoV-2 vaccination in pregnant, breastfeeding, or fertile healthcare workers (PBFHW). All ORL PBFHW were considered as the target audience. Results Of the 13 statements, 7 reached consensus or strong consensus, 2 reached no consensus, and 2 reached near-consensus. According to the statements with strong consensus otorhinolaryngologists—head and neck surgeons who are pregnant, breastfeeding, or with childbearing potential should have the opportunity to receive SARS-Cov-2 vaccination. Moreover, personal protective equipment (PPE) should still be used even after the vaccination. Conclusion Until prospective evaluations on these topics are available, ORL-HNS must be considered a high infection risk specialty. While the use of PPE remains pivotal, ORL PBFHW should be allowed access to SARS-CoV-2 vaccination provided they receive up-to-date information., info:eu-repo/semantics/published

Background Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature newborns. Many different factors, increasingly genetic, are involved in the pathogenesis of BPD. Fibronectin is a multi-domain glycoprotein present in nearly all vertebrate tissues and organs. Material and methods The study included 108 infants born between 24 and 32 weeks of gestation. BPD was diagnosed based on the National Institutes of Health Consensus definition. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655.Results BPD developed in 30 (38.5%) out of the 108 preterm infants. Incidence of BPD was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Investigation did not confirm any significant prevelance for BPD development in any genotypes and alleles of FN1. Conclusion Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of BPD.

Retinopathy of prematurity (ROP) is potentially blinding, but screening and timely treatment can stop its progression. The data on treatment outcomes of ROP from Central and Eastern Europe are scarce. Therefore, we aimed to analyze the latest results of ROP management in Poznan medical center to update the data from this world region. In the years 2016–2019, 178 patients (350 eyes) received treatment for ROP (6.1% of the screened population). The mean gestational age was 26 weeks (range 22–31 weeks), the mean birth weight was 868 g (range 410–1890 g). The most frequent ROP stage at treatment was zone II, stage 3 + (34.9%). As the first line of treatment, 115 infants (226 eyes, 64.6%) underwent laser photocoagulation (LP); 61 infants (120 eyes, 34.3%) received intravitreal ranibizumab injections (IVR); and 2 infants (4 eyes, 0.6%) were treated simultaneously with LP and IVR. One hundred twenty-six eyes (36%) of 63 patients required retreatment: 20.4% treated with LP and 66.7% treated with IVR. Retinal detachment occurred in 14 eyes (4%). The incidence of ROP, ROP requiring treatment, and reoccurrence rates are higher in the Polish population than in Western Europe and the USA. The identified treatment patterns find increasing use of anti-VEGF agents.

Hypoxic ischemic encephalopathy (HIE) is a serious neurological complication that may develop in asphyxiated infants. Severity of encephalopathy may vary, and concurrent multiorgan dysfunctions are commonly observed. Analyzing the incidence of such complications according to severity of HIE, and how they correlate with each other, may shape clinical judgment and allow for early intervention. The study included a total of 57 HIE infants, in which 27/57 (47.37%) met Sarnat inclusion criteria for moderate stage II HIE (Group A) and 30/57 (52.63%) for severe stage III HIE (Group B). Both groups were assessed and compared for incidence of kidney dysfunction, liver dysfunction, coagulopathy, qualitative cardiac abnormalities, respiratory-related dysfunction, and bone marrow insufficiency/thrombocytopenia. All assessments were performed before initiation of therapeutic hypothermia. The complications were further assessed for the presence of correlations. Group B experienced significantly higher incidence of kidney dysfunction (A: 2/27 [7.4%] vs. B: 21/30 [70%]

Introduction: Recent medical literature has drawn attention to the possible influence of COVID-19 on the course of pregnancies. As the coherence of results seems to vary, especially in relation to first and second trimester pregnancies, a concise qualitative systematic review can shed light on the most recent data. Material and methods: A structured systematic search was performed to collect all COVID-19 pregnancy-related articles published between January 1 and September 16, 2020. Two independent reviewers evaluated studies using the STROBE statement in combination with the CERQual quality assessment of findings. Results: In total 1387 articles were screened and finally 22 studies were evaluated (179 1st/2nd trimesters of pregnant women with COVID-19). The majority of reported mothers who contracted COVID-19 during 1st/2nd trimesters are yet to complete their pregnancy. Conclusions: Evidently a limited amount of data is available. Usually, mothers and newborns are discharged from the hospital without any serious complications. Further observations are imperative. [ FROM AUTHOR] Copyright of Archives of Medical Science is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Neonatal congenital leukemia (CL) constitutes less than 1% of all childhood leukemia cases and is diagnosed in 1 to 5 per million live births. In the neonatal period acute myeloid leukemia (AML) is described in 56-64% of cases, acute lymphoblastic leukemia (ALL) in 21-38% of cases and mixed-phenotype acute leukemia (MPAL) in less than 5% of cases. Rearrangements of the mixed-lineage leukemia (KMT2A alias MLL) gene are found in > 70% of infant leukemia cases. The incidence of the most frequent KMT2A rearrangements in newborns with congenital MPAL is unknown. We report a male term newborn with “blueberry muffin” syndrome, which had been noted at birth, as a presenting sign of acute leukemia. Eight-color multiparameter flow cytometry showed a blast population corresponding to a myeloid lineage with monocytic differentiation positive for CD33+/CD15+/CD11c+/CD64+/HLA-DR+/CD4+, negative for MPO–/CD34–/CD19–/CD79a–/CD117–/CD13–/CD14–/CD36–/cCD3–/CD2–/CD7–, and additionally positive for sCD3 (40%). Mixed-phenotype acute leukemia according to the World Health Organization (WHO) classification was diagnosed with complex translocation t(10;11)(p12;q23) with KMT2A/MLLT10 rearrangement. The patient had an unfavorable response to chemotherapy and died on the 5th day of life.

Introduction : Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects primarily preterm infants. Genetic factors are also taken into consideration in the pathogenesis of BPD. Genetic predispositions to higher production of inflammation mediators seem to be crucial. Material and methods: The aim of this study was to evaluate the possible relationship between polymorphisms: interleukin-1β +3953 C>T, interleukin-6 -174 G>C and -596 G>A, tumour necrosis factor -308 G>A and interleukin-1RN VNTR 86bp and the occurrence of BPD in a population of 100 preterm infants born from singleton pregnancy, before 32+0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. Results : In the study population BPD was diagnosed in 36 (36%) newborns. Among the studied polymorphisms we found the higher prevalence for BPD developing of the following genotypes: 1/2 (OR 1.842 [0.673-5.025] and 2/2 IL-1RN (OR 1.75 [0.418-6.908] 86bpVNTR; GC (2.222 [0.658-8.706]) and CC IL-6 -174G>C (1.6 [0.315-8.314]) and GA (2.753 [0.828-10.64]) and AA (1.5 [0.275-8.067] IL-6 -596G>A), GA 1.509 (0.515-4.301) TNF-α -308G>A. However, these finding were not statistically significant. Conclusions : Genetic factors are undeniably involved in the pathogenesis of BPD. In the times of individualised therapy finding genes responsible for BPD might allow the development of new treatment strategies. A new way of specific therapy could ensure the reduction of complications connected with BPD and treatment costs.

Introduction Periventricular leukomalacia (PVL) is one of the most common hypoxic-ischemic pathologies among preterm newborns. The bracket most vulnerable to PVL are newborns born before 34 weeks’ gestation, especially those with very low and extremely low birth weights. In a population of very low birth weight newborns, the frequency of periventricular white matter injury (PWMI) including PVL is 5–15%. The aim of our study was to verify the potential risk factors of the occurrence of PVL among infants born between 23 and 26 weeks’ gestation. Methods The retrospective study included a group of 115 unrelated infants born between 23 and 26 week's gestation, hospitalized in the Neonatal Intensive Care in the Department of Neonatology, Poznan University of Medical Sciences in 2010–2014, born in the clinic or transported to it after birth in the hospital of lower references. The diagnosis of PVL was based on transcranial ultrasound. Results PVL was diagnosed in 17 (14.8%), including 5 (29.4%) infants born from 23 to 24 weeks’ gestation and 12 (70.6%) born from 25 to 26 weeks gestation. Higher incidence of PVL was found among infants born outside tertiary hospital (OR 7.933 (2.206–35.19); p = 0.0005) and newborns diagnosed with III and IV intraventricular hemorrhage (IVH) (OR 3.273 (1.042–10.28); p = 0.036). Conclusions Delivery in the third-level hospital as well as IVH prevention significantly reduces the risk of PVL. Well-developed prenatal care, fetus transport in utero and delivery in the third-level hospital seem to be crucial in the prevention of this pathology.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is defined as a platelet count

Background The study aim was to determine the incidence and analyze risk factors of IVH stage 3 and 4 in infants born before 26 weeks of gestation. Objectives A retrospective analysis of 110 preterm babies (23-26 weeks of gestation) hospitalized from 2009 to 2014 at the Department of Neonatology of Poznan University of Medical Sciences was performed. Material and methods In the study group there were 29 (26.4%) children in the 23rd-24th weeks of pregnancy and 81 (73.6%) in the 25th-26th weeks of gestation. Results Among IVH stage 3 and 4 in neonates without prenatal steroids therapy, OR was 1.616 (1.059- 2.456; p = 0.022) for children born in the 23rd-24th week of gestation and 1.677 (1.001-2.809; p = 0.047) for children born in the 25th-26th week of pregnancy. An analysis of various risk factors revealed the chance of the appearance IVH stage 3 and 4 among neonates born in the 23th-24th and 25th-26th week of gestation rising only among those children who were treated for hypotension with catecholamines (OR 2.031 (0.269-24.21), p = 0.033 and OR 1.989 (0.224-16.55), p = 0.024). Conclusions The lower the gestational age, the more frequent the risk of IVH stage 3 and 4. The use of appropriate prophylaxis of perinatal patients (steroids in all pregnant women at risk of preterm birth, limiting the indications for the use of catecholamines for hypotension treatment) reduces the incidence of severe IVH.

Background Central diabetes insipidus is a condition associated with the dysfunction of hypothalamic-pituitary axis and, consequently impaired synthesis and secretion of vasopressin. This condition is rarely found in preterm neonates which is why we decided to report it. Also, there are no guidelines on how to treat this condition in neonates, so it is important to share our experience and provide information on the therapies we used therapies and their results. Case presentation In our paper we describe a case of a male infant born at 24 weeks of gestation, who suffered an intraventricular hemorrhage of grade IV severity. The hemorrhage caused damage to the posterior pituitary lobe which in turn resulted in central diabetes insipidus. Oral desmopressin therapy was administered. Conclusion In our case we achieved positive clinical results – normalization of diuresis and natremia. It shows that oral desmopressin can be taken into consideration for treatment of diabetes insipidus in preterm neonates. This case report can be useful for both neonatologists and endocrinologists. It is also important to compare our case with similar cases to expand our knowledge about this rare disease in neonates and to find possible therapies.

Introduction Intraventricular hemorrhage (IVH) is mostly documented in premature infants, and the younger the gestational age, the more often it occurs. IVH is very rarely reported in full-term neonates. Case report Retrospective analysis was performed in 35939 full-term neonates, who were born in the Clinical Hospital of Gynecology and Obstetrics at the University of Medical Sciences in Poznań. Clinical data were retrieved from their medical records. We report a case series of 2 term newborns, who developed severe IVH grade 3 and 4 with no evidence of asphyxia, neuroinfection, TORCH infections, coagulation disorders and trombocytopenia, metabolic disorders, arteriovenous malformations, and selected genetic abnormalities (factor V Leiden 1601G > A polymorphism and MTHFR 677C > T; 1298A > C polymorphisms). IVH in both cases was complicated by posthemorrhagic hydrocephalus treated with decompressive lumbar punctures and next ventriculoperitoneal shunt placement. Conclusions In conclusion, several factors influence the predisposition for severe IVH in term neonates. Perinatal period complicated by fetal distress, birth trauma, and severe asphyxia should be taken into account. However, it is possible that etiopathogenesis cannot be defined clearly as in our cases. Cranial ultrasounds in a specific group of term newborns (taking into account risk factors for IVH) should be widely recommended.

IntroductionThrombocytes may regulate the activity of vascular endothelial growth factor (VEGF), limiting neovascularization in retinopathy of prematurity (ROP). The aim of this study was to examine the role of platelet counts, thrombocytopenia, and infections in the pathogenesis of ROP.Material and methodsThe study included 163 preterm infants diagnosed with ROP, comparing 76 patients who required treatment with 87 patients in whom ROP resolved spontaneously (control group). Further analysis concerned 52 patients in whom a first line treatment was sufficient to stop ROP progression, and 24 patients who required re-treatment.ResultsA statistically significant difference was found in the occurrence of thrombocytopenia (p = 0.015), platelet counts before the diagnosis of ROP (p = 0.008), and the presence of late-onset infection (p = 0.007). The ROC curve analysis showed that the value of platelets above 232 × 109/l may stimulate spontaneous resolution of ROP. A significant difference between patients once treated and patients that required re-treatment was found in platelet count before the diagnosis of ROP (p = 0.017), platelet count before the first intervention (p = 0.013), and the number of transfusions (p = 0.042).ConclusionsThe results of the study confirm the association between ROP development and its severity with thrombocytopenia. While there were no differences in the occurrence of thrombocytopenia right after the birth, its episode before the diagnosis of ROP seems to be significant for ROP development. The deficiency of platelets prior to a treatment intervention may be associated with necessity of re-treatment.

The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC–UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1–1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1–0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1–0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

Pro-drug treosulfan (TREO) is currently evaluated in randomized phase III clinical trials as a conditioning agent prior to HSCT. In the present paper pharmacokinetics of both TREO and its biologically active monoepoxide (S,S-EBDM) was investigated in pediatric patients for the first time. The studies were carried out in 16 children (median age 7.5 years) undergoing TREO-based preparative regimen prior to HSCT, who received 10, 12 or 14 g/m(2) of the drug as a 1h or 2h intravenous infusion. Plasma concentrations of TREO as well as S,S-EBDM were determined using the validated HPLC-MS/MS method. The changes in S,S-EBDM concentration over time followed TREO levels. The area under the curve (AUC) of TREO was 100-fold higher than AUC of S,S-EBDM. No statistically significant dependency of the dose-normalized AUC of either TREO or S,S-EBDM on the patients' age and body surface area was stated. Moreover, plasma C(max) as well as AUC of S,S-EBDM demonstrated linear correlation with the C(max) and AUC of TREO, respectively. The biological half-lives of TREO and S,S-EBDM were similar. This indicates that S,S-EBDM was completely eliminated from the patients' blood within relatively short time, comparable to TREO.

Subcutaneous fat necrosis (SCFN) is a rare, transient and self-limiting complication of birth asphyxia [1]. It is characterized by painless nodules developing on the back, limbs and buttocks, which move freely over muscle and bone. The overlying skin may be of normal color or with erythematous discoloration. These lesions disappear spontaneously without scarring, but there may be systemic complications associated with SCFN. The most serious potential complication is hypercalcemia, which carries with it serious risks to the child's health and life [1].

Background The birthweight of multiples is naturally lower than that of singletons. Given that the incidence of twin pregnancy has risen in recent years, it seems reasonable to create standards of birthweight separately for twins. This could help in the objective assessment of small and large for gestational age twin newborns. The main goal of this study was therefore to construct and present up-to-date birthweight references. Methods The present percentile charts for twins are based on a cohort retrospective study of 757 pairs of twins (767 boys and 709 girls) born between weeks 25 and 39 of gestation. Mean and standard deviation were calculated for the subsequent weeks of gestation. Percentiles were read for the subsequent gestational age. The obtained curves were smoothed with a fifth-degree polynomial function. The significance of differences between the 50th percentile values for twins and singletons was estimated using median test. Results In both sexes, a continuous observable trend occurs of a significantly lower average birthweight for twins. Differences increase with increasing gestational age and are greater in girls. The estimated 50th percentile for twins was greater than the estimated 10th percentile for singletons. This supports the notion of discordant growth as a physiological adaptation that promotes maturity. Conclusions Percentile charts for singletons are not applicable for twins. This indicates the importance of applying separate percentile charts for twins, enabling objective evaluation of their health status and identifying deviations from normality.

Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1β 3953C>T, Il-6 −174G>C and −596G>A, TNFα −308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and −786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71–208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33–21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care. Electronic supplementary material The online version of this article (doi:10.1007/s11010-017-3135-5) contains supplementary material, which is available to authorized users.

Background Congenital thrombophilia is associated with an increased intraventricular hemorrhage (IVH) risk among newborns, but it may also play a protective role. The role of genetic polymorphisms involved in the coagulation pathway of IVH pathogenesis is probably a consequence of an increased risk of thrombosis in the fine blood vessels in the germinal matrix region. Material and methods The aim of this study was to evaluate the possible relationship between Factor V (FV) 1691G>A, Factor II (FII) 20210G>A mutations and methylenetetrahydrofolate reductase (MTHFR) 677C>T; 1298A>C and Factor XIII (FXIII) 103G>T gene polymorphisms and the occurrence of IVH in 100 infants born from 24 + 0 to 32 + 0 weeks of gestation, born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities. Results IVH developed 45 (45%) infants, including 15 (33.33%) diagnosed with IVH stage I, 20 (42.22%) with stage II, 8 (17.77%) with stage III, and 3 (6.66%) with stage IV. Analysis showed a prevalence 4.5 times higher of IVH stages II to IV in infants with the genotype CC (OR 4511 (1147–17.75); p = 0.026) of MTHFR 1298A>C gene polymorphism. Our investigation did not confirm any significant prevalence of IVH development in other studied mutations/polymorphisms. Conclusions This study confirmed that the MTHFR 1298A>C polymorphism is associated with the risk of IVH. IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that is focused on understanding the etiology, mechanism, and risk factors for IVH is imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies. Electronic supplementary material The online version of this article (doi:10.1007/s00381-017-3460-8) contains supplementary material, which is available to authorized users.

Introduction Intraventricular hemorrhage (IVH) is a significant morbidity seen in very low birth weight infants. Genes related to inflammation may be risk factors for IVH. Material and methods We examined five polymorphisms for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroid therapy, and without congenital abnormalities. These polymorphisms include interleukin-1β 3953 C>T, interleukin-6 −174G>C and −596G>A, tumor necrosis factor −308 G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il -1RN 86 bp VNTR). Results In our study population, 45 (45%) infants developed IVH, including 15 (33.33%) with stage 1, 19 (42.22%) with stage 2, 8 (17.77%) with stage 3, and 3 (6.66%) with stage 4. In contrast to the previously published data, the prevalence of IVH did not vary between infants with different IL-6 and TNFα alleles and genotypes. Our novel investigations in Il-1 +3953 C>T and Il-1RN 86 bp VNTR polymorphism did not show any significant link between those alleles or genotypes and IVH. Conclusions IVH is a significant problem for preterm infants. In addition to little progress in preventing IVH in preterm babies, substantial research that are focused on understanding the etiology, mechanism and risk factors for IVH are imperative. In the era of personalized medicine, identification of genetic risk factors creates opportunities to generate preventative strategies. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of IVH. Electronic supplementary material The online version of this article (doi:10.1007/s00381-017-3458-2) contains supplementary material, which is available to authorized users.

In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows. It has been shown that the ability of autoregulation of cerebral flows in response to variations in arterial blood pressure in preterm infants is impaired. This impaired autoregulation causes an increased risk of germinal matrix rupture and IVH occurrence. We examined three polymorphisms of genes, related to regulation of blood flow, for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. These polymorphisms include: eNOS (894G > T and −786T > C) and EDN1 (5665G > T ) gene. We found that infants with genotype GT eNOS 894G > T have 3.4-fold higher risk developing of IVH born before 28 + 6 weeks of gestation. Our investigation did not confirm any significant prevalence for IVH development according to eNOS −786T > C genes polymorphism. Our novel investigations in EDN1 5665G > T polymorphism did not show any link between alleles or genotypes and IVH. Future investigations of polymorphisms in blood-flow associated genes may provide valuable insight into the pathogenetic mechanisms underlying the development of IVH.

Proinflammatory cytokines are essential mediators and indicators of an inflammatory process occurring in the body. Their physiological role is to stimulate the immune response, yet their excessive propagation and interaction with cells outside the immune system may be linked to the risk of organ damage. This is specifically important in the case of immature tissues of fetuses and prematurely born infants. Analysis of the concentrations of specific cytokines in different compartments makes it possible to assess the risk of premature birth, preterm rupture of the membranes, and to determine an existing intrauterine infection. The purpose of this paper is to summarize the existing research concerning the relationships between the concentrations of specific proinflammatory cytokines in different compartments (maternal blood serum, amniotic fluid, umbilical cord blood, arterial and venous blood, and cerebrospinal fluid of the newborn) and the risk of intraventricular hemorrhage (IVH) and the degree of its severity. The paper takes also into account the assessment of the usefulness of cytokines as biomarkers for IVH and its complications (posthemorrhagic hydrocephalus, white matter injury).

In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996–2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

We report a case of a 4-year-old girl with diagnosed proB acute lymphoblastic leukaemia with co-expression CD33 antigen, treated according to Acute Lymphoblastic Leukaemia Intercontinental - Berlin Frankfurt Münster 2002 (ALL-IC BFM 2002) protocol for standard risk group. Haematological remission was obtained on day 33 of induction treatment (on time). During induction and consolidation therapy there were no early serious adverse effects. The late isolated bone marrow relapse of acute myeloid leukaemia, type 7 was noted in our patient. We recognized this case as a lineage switch acute lymphoblastic leukaemia to acute myeloid leukaemia. In spite of Ida Flag regimen and following Acute Myeloid Leukaemia - Berlin Frankfurt Münster 2004 (AML-BFM 2004) protocol were administered, the clinical and haematological remission was not achieved and the patient died because of disease progression (circulatory and respiratory insufficiency).

Introduction Acquired aplastic anemia is very rare disease characterized by and pancytopenia and hypoplastic bone marrow. In 70% of cases the etiology is idiopathic but some cases can be caused by drugs, chemical substances and viruses. One of the main pathophysiological mechanism of aplastic anemia is immune-mediated destruction of hematopoietic cells. As a result of that the immunosuppressive therapy (IST) persists the treatment of choice in patients with severe acquired aplastic anemia (SAA), who don’t have matched sibling donor. Since few last years there is a discussion if it is still the best way of treatment. We wanted to show the side effects of IST during the therapy of SAA using the rabbit antithymocyte globulin(r-ATG) Methods The group of 55 children ( 32 boys, 23 girls) with SAA and vSAA (very severe aplastic anemia) treated with r-ATG , steroids, CSA, and/or GSF-CS was retrospectively analyzed. The median age of the children was 10 years (range 6mth-17,5 years). Response rate was assessed on days 84, 112,180, 360. Kaplan–Meier estimator, univariate analysis and multivariate Cox regression models were used to estimate the influence of side effects for PFS (progression free survival) and EFS( event free survival). Results Infectious complications (fever of unknown origin-FUO-26,92%, stomatitis -19,23% and sepsis -17,03% ) were the most common side effects of IST. The most common etiology were : E. coli, P. aureginosa, S. aureus, Kl. pneumonie, E. fecium, E. cloace. There was a significant association between EFS and infectious side effects (p=0,00093- log rank). Among side effects of r-ATG fever (30,30%) and dyspnoe (24,24%) were the most common.After CSA mainly gingival hyperplasia, hirsutysm and hypertension were observed. The most common hemorrhagic side effects of IST were skin petechiae. The other were central nervous system bleeding, gastrointestinal tract bleeding. There was significant correlation between the hemorrhagic side effects and PFS(p= 0,0144 log rank).After the G-CSF therapy muscular pains, and capillary leak syndrome, was observed but it didn’t influence survival. Among all patients 15 deaths was observed (27,27%)-5 early and 10 late deaths. Infections were the main causes of death. The relapse rate was 1,81%. The 2-year probability of not having relapse was 87,68%. Relapse free survival was 75,16% at 5 and 10 years. There was one transformation to paroxysmal nocturnal hemoglobinuria (PNH). There were no transformation to MDS or AML.Discussion. Infections are the most common side effects during the IST with r- ATG. Hemorrhagic side effects and infectious complications are very important factors which can affect the survival rate in children with SAA. Disclosures: Szczepanski: Octapharma AG: Investigator Other.

Abstract 3435 Objective: One of the main patophysiological mechanism of aplastic anemia (AA) is immune-mediated destruction of hematopoietic cells. In children with severe acquired aplastic anemia (SAA) allogenic bone marrow transplantation is the first choice. If there is no matched sibling donor the first line of treatment is immunosuppressive therapy (IST) which consists of ATG combined with cyclosporine A. Aim. The aim of this study was to analyze the results of IST containing rabbit anti-thymocyte globulin (r-ATG) performed on children with SAA and vSAA treated between 1996–2009 yr. We wanted to assess the influence of such factors as response to treatment, etiology, sex, age, type of AA, for: event free survival (EFS), and progression free survival (PFS) We analyzed deaths rate, relapses rate, clonality and side effects of IST. Materials and methods. We retrospectively analyzed group of 55 children with SAA and vSAA. The group consisted of 23 girls and 32 boys, the median age was 10 years (range 6mth-17,5 years). IST contained antithymocyte globulin,given intravenous at a dose of 3,75 mg/kg/day for 5 days, and cyclosporine A(CSA) at 5 mg/kg/day by mouth in divided doses started on day 1 and continued for at least 6 months(till 24 months). Response rate was assessed on 112, 180 and 360 day and defined as CR, PR, NR. Kaplan–Meier estimator, univariate analysis and multivariate Cox regression models were used to estimate the influence of such factors as response to treatment, etiology, sex, age for EFS, PFS, toxicity and other side effects. Results. The 2- year probability of event free survival (EFS) was 71,52%. The 5 and 10 –year EFS was 57,7%. Progression free survival (PFS) was 66,53%, at 2 years and 59,13% at 5- and 10 year Patients with CR and PR had significantly longer EFS than children with no response(NR) (p 0,05 Log rank). In all group we observed 15 deaths (27,27%), 5 early and 10 late deaths. Infections were the main causes of death. The relapse rate was 1,81%. The 2-year probability of not having relapse was 87,68%. Relapse free survival was 75,16% at 5 and 10 years. There was one transformation to paroxysmal nocturnal hemoglobinuria (PNH).Non responders (4 patients) received second IST and 11 children underwent MUD-BMT. Infections were the most often side effects of IST (FUO-26,92% of infectious side effects). There was significant association found between EFS and infectious side effects. (p=0,00093 log rank) The most common adverse effects after rabbit immunoglobulin were fever (30,30%) and dyspnoe (24,24%). After CSA treatment we observed mainly gingival hyperplasia (29,16% of side effects of CSA). Most common hemorrhagic side effects were skin petechie. There was significant correlation between hemorrhagic side effects and PFS (p= 0,0144 log rank) Conclusions. 1. Rabbit-ATG is an effective frontline therapy for children with SAA without familiar bone marrow donor.2.Remission achieved on day 112 seems to be constant. 3.5-year EFS seems to be stable within next 5 years.4.5-year relapse free survival seems to be constant during the next 5 years.5.Etiology, type of SAA, age and sex have no influence on the survival.)6.Infectious and hemorrhagic side effects are a very important factors affecting the survival rate in children with SAA. Disclosures: No relevant conflicts of interest to declare.

Intraventricular hemorrhage (IVH) affects 15-20% of babies born before 32 weeks of pregnancy. Besides gestational age (below 32 weeks) there are a number of IVH risk factors. Increasing attention is being paid to genetic factors in the development of IVH. The authors discuss genetic factors (mutations of coagulation factors, gene polymorphisms in pro-inflammatory cytokines, mutation of type IV collagen gene, polymorphisms of genes responsible for the regulation of systemic blood pressure and cerebral blood flows) whose involvement in IVH pathogenesis has been confirmed in the highest number of reports and for which being a carrier plays an important role in their pathophysiology. The role of genetic factors in IVH remains unclear. Further analysis of the role of genetic factors in the pathophysiology of IVH will make it possible to determine the group of newborns who are specifically at risk of developing IVH in the perinatal period.