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.

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.

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.

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.

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.

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.

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.

The role of FV 1691G>A, FII 20210G>A mutations and MTHFR 677C>T; 1298A>C and 103G>T FXIII gene polymorphisms in pathogenesis of intraventricular hemorrhage in infants born before 32 weeks of gestation.

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.

The significance of polymorphisms in genes encoding Il-1ß, Il-6, TNFα, and Il-1RN in the pathogenesis of intraventricular hemorrhage in preterm infants.

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-1ß 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.

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.

Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns.

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).

Intraventricular hemorrhage in neonates born before 32 weeks of gestation-retrospective analysis of risk factors.

INTRODUCTION: Intraventricular hemorrhage (IVH) affects 15-20 % of babies born before 32 weeks of pregnancy. A lot of risk factors of developing IVH are known. The making appropriate recommendations for dealing with infant born less than 32 weeks of gestation aimed at reducing the incidence of IVH is still needed. The study aim was to determine the incidence and analyze risk factors of IVH stage 3 and 4 in infants born before 32 + 0 weeks of pregnancy. METHODS: The retrospective analysis of 267 preterm babies (24 to 32 weeks of gestation) hospitalized in 2011-2013 at Department of Neonatology, Poznan University of Medical Sciences was performed. The diagnosis of IVH was confirmed by ultrasound scans according to Papille criteria. Stage 3 and 4 of IVH was confirmed in 14 (25 %) newborns from 23 to 24 weeks of gestation; 21 (37.5 %) from 25 to 26 weeks of gestation; 11 (19.6 %) from 27 to 28 weeks of gestation; 9 (16.1 %) from 29 to 30 weeks of gestation; and 1 (1.8 %) from 31 to 32 weeks of gestation. RESULT: The incidence of IVH stage 3 and 4 was higher in children: with less use of AST (OR 1.27; 0.62-2.61), born out of third-level hospitals (OR 2.25; 1.23-4.08), born with asphyxia (OR 3.46; 1.8-6.64), with acidosis treated with NaHCO3 (OR 6.67; 3.78-11.75), those who in the first days of life were treated for hypotension (OR 9.92; 5.12-19.21). CONCLUSION: No or uncompleted antenatal steroid therapy increased probability for development of severe intraventricular hemorrhage. Antenatal steroids therapy should be promoted among women at risk of a premature delivery. Hypotension therapy with catecholamines and acidosis with sodium hydrogen carbonate should be carefully considered. The use of appropriate prophylaxis of perinatal (antenatal steroids therapy women at risk of preterm birth, limiting the indications for the use of catecholamines for hypotension treatment and sodium hydrogen carbonate for acidosis therapy, limitation of preterm deliveries outside tertiary referral centeres) significantly reduces the incidence of intraventricular hemorrhage stage 3 and 4. The significance of intraventricular hemorrhage creates a need to carry out periodical analysis, at regional level, concerning its incidence, causes and effects to improve local treatment outcomes by identifying further courses of action.

The incidence of severe intraventricular hemorrhage based on retrospective analysis of 35939 full-term newborns-report of two cases and review of literature.

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 Poznan. 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.

Association of ACE and AGTR1 variants with retinopathy of prematurity: a case-control study and meta-analysis.

Retinopathy of prematurity (ROP) is a major cause of childhood blindness worldwide, linked to gene variants in the renin-angiotensin-aldosterone system, including angiotensin-converting enzyme (ACE) and angiotensin II receptor type 1 (AGTR1). This study aims to evaluate the association between ACE insertion/deletion (I/D) and AGTR1 rs5186A > C variants with the occurrence and progression of ROP in a Polish cohort. A total of 377 premature infants were enrolled in the study. The ACE variant was evaluated using PCR, and AGTR1 was assessed using TaqMan probes. Clinical characteristics, including risk factors and comorbidities, were documented. A meta-analysis of the effects of the studied variants on ROP was also conducted. The AGTR1 rs5186C allele was significantly associated with both the progression of ROP and treatment outcomes. Homozygotes exhibited a 2.47-fold increased risk of developing proliferative ROP and a 4.82-fold increased risk of treatment failure. The impact of this allele increased at low birth weight. A meta-analysis, including 191 cases and 1661 controls, indicated an overall risk of 1.7 (95%CI 1.02-2.84) for the recessive effect of the rs5186C allele. The ACE variant did not show a significant association with ROP in our population; however, a meta-analysis of 996 cases and 2787 controls suggested a recessive effect of the insertion allele (an odds ratio of 1.21 (95%CI 1.00-1.60)). These results indicate that gain-of-function AGTR1 variants may play a crucial role in the development of ROP, potentially by promoting angiogenesis and pro-inflammatory effects. Screening for these variants could facilitate the development of personalized risk assessment and treatment strategies for ROP.

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.

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.

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.