Comprehensive Analysis of the Role of Gene Variants in Matrix Metalloproteinases and Their Tissue Inhibitors in Retinopathy of Prematurity: A Study in the Polish Population.

This study was designed to investigate the relationship between variants of matrix metalloproteinases (MMP-1 rs179975, MMP-9 rs17576 and rs17577), their tissue inhibitors (TIMP-1 rs4898, TIMP-2 rs2277698 and rs55743137) and the development of retinopathy of prematurity (ROP) in infants from the Polish population. A cohort of 100 premature infants (47% female) was enrolled, including 50 ROP cases and 50 no-ROP controls. Patients with ROP were divided into those with spontaneous remission and those requiring treatment. A positive association between MMP-1 rs179975 1G deletion allele and ROP was observed in the log-additive model (OR = 5.01; p = 0.048). Furthermore, female neonates were observed to have a negative association between the TIMP-1 rs4898C allele and the occurrence of ROP and ROP requiring treatment (codominant models with respective p-values < 0.05 and 0.043). Two and three loci interactions between MMP-1 rs1799750 and TIMP1rs4989 (p = 0.015), as well as MMP-1 rs1799750, MMP-9 rs17576 and TIMP-1 rs4989 (p = 0.0003) variants influencing the ROP risk were also observed. In conclusion, these findings suggest a potential role of MMPs and TIMPs genetic variations in the development of ROP in the Polish population. Further studies using a larger group of premature infants will be required for validation.

Hypoxia-Inducible Pathway Polymorphisms and Their Role in the Complications of Prematurity.

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.

Potential role of eNOS and EDN-1 gene polymorphisms in the development and progression of retinopathy of prematurity.

The aim of this study was to investigate the association between selected polymorphisms of nitric oxide synthetase (eNOS) and endothelin-1 (EDN-1) with the occurrence and progression of retinopathy of prematurity (ROP). A prospective study was conducted on 90 preterm infants (44 female), comparing 39 cases with ROP and 51 controls without ROP. Patients who developed ROP were further divided into two subgroups-those with spontaneous regression of the disease and those with ROP requiring treatment. We found that preterm infants with TT genotype eNOS 894G > T had a 12.8-fold higher risk of developing ROP requiring treatment (p = 0.02). Our results showed that allele T of eNOS894G > T polymorphism was significantly more prevalent in ROP patients requiring treatment (p = 0.029). We also investigated preterm infants with TC genotype eNOS - 786 T > C and found an 8.8-fold higher risk developing of ROP requiring treatment (p = 0.021). Our results didn't show any association between EDN-1 5665G > T polymorphism and ROP development. The eNOS polymorphisms appears to influence incidence of ROP requiring treatment in preterm infants. Future research on single nucleotide polymorphisms may provide important information about the pathogenetic mechanisms underlying the development of ROP.

Hemangioma-related gene polymorphisms in the pathogenesis of intraventricular hemorrhage in preterm infants.

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.

Catheter-related bloodstream infections in infants hospitalized in neonatal intensive care units: a single center study.

Sepsis in neonates carries a high morbidity and mortality rate and is among the most feared complications in the neonatal intensive care unit (NICU). Catheter-related bloodstream infections (CRBSI) are a common etiology of late-onset sepsis. The aim of this study was to compare risk factors and characteristics between patients according to the type of catheter that was utilized and according to birth weight classification. The study included 51 newborns with confirmed CRBSI, which were hospitalized in our level 3 NICU between January 2017 and December 2018. The study population was stratified according to the type of venous catheter utilized (peripherally inserted central catheter, central venous catheter (CVC), and peripheral venous catheter). Infants with low birth weight and those who required prolonged parenteral nutrition were most likely to develop CRBSI in our study group. The type of venous catheter was not associated with blood culture results. Also, infants with a birth weight of < 1500 g and > 1500 g did not differ in sepsis etiology. Further research is required to assess venous catheters relative risk of causing sepsis and if the outcome can be traced back specifically to catheter type or patient characteristics.

The association of platelet counts with development and treatment for retinopathy of prematurity - is thrombocytopenia a risk factor?

Introduction: Thrombocytes 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 methods: The 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. Results: A 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). Conclusions: The 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.

Polymorphisms of fibronectin-1 (rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655) are not associated with bronchopulmonary dysplasia in preterm infants.

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. The aim of the study is to investigate the possible influence of fibronectin SNP on the occurrence of BPD. 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. BPD developed in 30 (27.8%) out of the 108 preterm infants. Incidence of BPD was higher in infants with lower APGAR scores and low birthweight. Investigation did not confirm any significant prevalence for BPD development in any genotypes and alleles of FN1. Further studies should be performed to confirm the role of genetic factors in etiology and pathogenesis of BPD.

Premedication practices for less invasive surfactant administration - results from a nationwide cohort study.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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%; p = 0.009) and a significantly higher decrease in SpO2/FiO2 (-55 ± 62 vs -32 ± 50; p < 0.001). However, the rates of rescue intubation and the need for early mechanical ventilation were not significantly different. Sedation with glucose did not affect the frequency of adverse events. LISA procedures had a similar level of ease regardless of the premedication used and were rated as easy or very easy in 69% of non-premedicated infants, 65.9% of the analgesics/sedatives group and 78.5% of the glucose group (p = ns). CONCLUSION: 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.

Hearing Impairment in Infants with Hypoxic Ischemic Encephalopathy Treated with Hypothermia.

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, p = 0.001) and base excess (BE) (-22.46 ± 2.59, p = 0.006). Of the 49 infants who returned for follow-up assessment, 4 (8.2%) were diagnosed with sensorineural bilateral hearing impairment (1 infant, mild [<40 dB], 2 moderate [41-70 dB], and 1 profound [>90 dB]). The biochemical analysis following birth revealed significantly lower umbilical BE levels (-23.90 ± 4.99, p = 0.041) and higher lactate levels (160.67 ± 4.93, p = 0.019) in the infants with eventual sensorineural hearing deficit. Infants with moderate or severe HIE are at risk of delayed onset hearing loss. Diligent efforts to monitor auditory status are required, even if early screening results for hearing are insignificant. Exploring biochemical parameters, such as lactate, BE, and blood pH, can prove beneficial in identifying HIE infants at risk of developing a hearing impairment.

Contracting COVID-19 in the first and second trimester of pregnancy: what we know - a concise qualitative systematic review.

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.

Appropriateness for SARS-CoV-2 vaccination for otolaryngologist and head and neck surgeons in case of pregnancy, breastfeeding, or childbearing potential: Yo-IFOS and CEORL-HNS joint clinical consensus statement.

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.

Management of retinopathy of prematurity (ROP) in a Polish cohort of infants.

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.

Organ Complications of Infants with Hypoxic Ischemic Encephalopathy Before Therapeutic Hypothermia.

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%], p < 0.001), liver dysfunction (A: 14/27 [51.8%] vs. B: 28/30 [93.3%], p < 0.001), and thrombocytopenia (A: 8/27 [29.6%] vs. B 21/30 [70%], p = 0.002) in our study group. Kidney dysfunction and bone marrow insufficiency showed the highest affiliation with other organ systems in both groups, correlating positively with each other as well as HIE severity, cardiac abnormalities, liver dysfunction, and infant death. A total of 8/57 (14%) infant deaths were observed, all originating from grade III severe HIE group (p = 0.003). Multiorgan dysfunction showed a significant difference between HIE severity (A: 12/27 [44.4%] vs. B: 28/30 [93.3%], p < 0.001). A positive correlation was obtained between multiorgan dysfunction, HIE severity, and infant death. Stage III HIE infants are more likely to experience abnormalities in the kidneys, liver, bone marrow as compared with stage II HIE infants. Correlations between organ complications are present, and should be taken into account during clinical assessment of HIE infants. The probability of mortality is higher in stage III HIE infants with observed multiorgan dysfunctions.

Single nucleotide vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) in the pathogenesis of prematurity complications.

The vitamin D receptor (VDR), coded by the VDR gene, plays a pivotal role in executing cellular functions when bound by the active form of vitamin D. Gene polymorphisms in this receptor have been increasingly associated with a heightened state of vulnerability to certain diseases. However, limited data is available concerning the role of VDR gene polymorphisms in preterm infant complications. In 114 premature infants (< 32 weeks gestation) we analyze four single nucleotide VDR polymorphisms (rs2228570 (FokI), rs1544410 (BsmI), rs797532 (ApaI), rs731236 (TaqI)) for their association with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The results show that BPD was almost four times more likely in infants with the genotype CC of ApaI (rs7975232) (OR 3.845; p = 0.038). While both BPD and NEC were 2.1 times more likely to occur in preterm infants with the allele C of ApaI (rs7975232) (respectively: OR 2.111 and OR 2.129, p < 0.05). The ApaI VDR polymorphism appears to influence incidence of BPD and NEC in preterm infants. Considering VDR polymorphisms in future genetic investigations, in preterm complications, may prove clinically relevant.

Biomarkers in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

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.

Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants.

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.

Inflammation-associated gene polymorphisms and clinical variables in the incidence and progression of retinopathy of prematurity.

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-1ß +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.

Percentile charts of twin birthweight.

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.

Candidate gene analysis in pathogenesis of surgically and non-surgically treated necrotizing enterocolitis in preterm infants.

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-1ß 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.

The significance of IL-1ß +3953C>T, IL-6 -174G>C and -596G>A, TNF-α -308G>A gene polymorphisms and 86 bp variable number tandem repeat polymorphism of IL-1RN in bronchopulmonary dysplasia in infants born before 32 weeks of gestation.

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-1ß +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.