Variation in follow-up for children born very preterm in Europe.

BACKGROUND: Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. METHODS: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N = 3635). RESULTS: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks' gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. CONCLUSIONS: Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age.

High Healthcare Use at Age 5 Years in a European Cohort of Children Born Very Preterm.

OBJECTIVES: To describe parent-reported healthcare service use at age 5 years in children born very preterm and investigate whether perinatal and social factors and the use of very preterm follow-up services are associated with high service use. STUDY DESIGN: We used data from an area-based cohort of births at <32 weeks of gestation from 11 European countries, collected from birth records and parental questionnaires at 5 years of age. Using the published literature, we defined high use of outpatient/inpatient care (≥4 sick visits to general practitioners, pediatricians, or nurses, ≥3 emergency room visits, or ≥1 overnight hospitalization) and specialist care (≥2 different specialists or ≥3 visits). We also categorized countries as having either a high or a low rate of children using very preterm follow-up services at age 5 years. RESULTS: Overall, 43% of children had high outpatient/inpatient care use and 48% had high specialist care use during the previous year. Perinatal factors were associated with high outpatient/inpatient and specialist care use, with a more significant association with specialist services. Associations with intermediate parental educational level and unemployment were stronger for outpatient/inpatient services. Living in a country with higher rates of very preterm follow-up service use was associated with lower use of outpatient/inpatient services. CONCLUSIONS: Children born very preterm had high healthcare service use at age 5 years, with different patterns for outpatient/inpatient and specialist care by perinatal and social factors. Longer follow-up of children born very preterm may improve care coordination and help avoid undesirable health service use.

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.

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.

Specialist health care services use in a European cohort of infants born very preterm.

AIM: Children born very preterm require additional specialist care because of the health and developmental risks associated with preterm birth, but information on their health service use is sparse. We sought to describe the use of specialist services by children born very preterm in Europe. METHOD: We analysed data from the multi-regional, population-based Effective Perinatal Intensive Care in Europe (EPICE) cohort of births before 32 weeks' gestation in 11 European countries. Perinatal data were abstracted from medical records and parents completed a questionnaire at 2 years corrected age (4322 children; 2026 females, 2296 males; median gestational age 29wks, interquartile range [IQR] 27-31wks; median birthweight 1230g, IQR 970-1511g). We compared parent-reported use of specialist services by country, perinatal risk (based on gestational age, small for gestational age, and neonatal morbidities), maternal education, and birthplace. RESULTS: Seventy-six per cent of the children had consulted at least one specialist, ranging across countries from 53.7% to 100%. Ophthalmologists (53.4%) and physiotherapists (48.0%) were most frequently consulted, but individual specialists varied greatly by country. Perinatal risk was associated with specialist use, but the gradient differed across countries. Children with more educated mothers had higher proportions of specialist use in three countries. INTERPRETATION: Large variations in the use of specialist services across Europe were not explained by perinatal risk and raise questions about the strengths and limits of existing models of care. WHAT THIS PAPER ADDS: Use of specialist services by children born very preterm varied across Europe. This variation was observed for types and number of specialists consulted. Perinatal risk was associated with specialist care, but did not explain country-level differences. In some countries, mothers' educational level affected use of specialist services.

UTILIZACIÓN DE SERVICIOS DE SALUD ESPECIALIZADOS EN UN ESTUDIO DE COHORTE EUROPEO DE NIÑOS NACIDOS MUY PREMATUROS: OBJETIVO: Niños nacidos muy prematuramente requieren cuidados especializados adicionales debido a su salud y a los riesgos asociados con la prematuros, sin embargo la información sobre el uso de servicios de salud es escasa. Buscamos describir la utilización de servicios especializados por niños nacidos muy prematuramente, en Europa. MÉTODO: Analizamos datos de una cohorte de nacimientos ocurridos antes de las 32 semanas de gestación tomados del Effective Perinatal Intensive Care in Europe (EPICE), basado en la población y multirregional, en 11 países europeos. Los datos perinatales fueron extraídos de las historias clínicas y los padres completaron un cuestionario a los 2 años de edad corregida (4.322 niños; 2026 sexo femenino, 2.296 masculino; edad gestacional mediana 29 semanas, rango intercuartílico (IQR) 27-31 semanas; mediana de peso de nacimiento 1.230 gr, IQR 970-1.511 gr). Comparamos el uso de servicios especializados (según informe de los padres) por país, riesgo perinatal (basado en edad gestacional, bajo peso para edad gestacional y morbilidades neonatales), educación materna y lugar de nacimiento. RESULTADOS: En total 65% de los niños habían consultado por lo menos a un especialista, con un rango entre países de 53,7% a 100%. Los especialistas más frecuentemente consultados fueron Oftalmólogos (53,4%) y Fisioterapeutas (48%) pero los especialistas consultados por cada individuo variaron mucho según el país. El riesgo perinatal se asoció al uso de especialista, pero el gradiente varió entre los países. Niños de madres con mayor nivel educativo tuvieron mayor proporción de uso de especialistas en tres países. INTERPRETACIÓN: Las grandes variaciones en el uso de servicios especializados en Europa no fueron explicadas por el riesgo perinatal y arrojan cuestionamientos sobre las fortalezas y limitaciones de los modelos de cuidados existentes.

USO DE SERVIÇOS DE SAÚDE ESPECIALIZADOS EM UMA COORTE EUROPÉIA DE LACTENTES NASCIDOS MUITO PREMATUROS: OBJETIVO: Crianças nascidas muito prematuras requerem cuidado especializado adicional por causa dos riscos à saúde e ao desenvolvimento associados ao nascimento premature, mas informações sobreo uso de serviços de saúde são escassas. Procuramos descrever o uso de serviços especializados por crianças nascidas muito prematuras na Europa. MÉTODO: Analisamos dados de uma coorte populacional multi-regional, do Cuidado Intensivo Neonatal Efetivo na Europa (EPICE), com lactentes nascidos antes de 32 semanas de gestação em 11 países europeus. Dados perinatais foram extraídos dos registros médicos, e os pais completaram um questionário com 2 anos de idade corrigida (4.322 crianças; 2.026 do sexo feminino, 2.296 do sexo masculino; idade gestacional mediana 29semanas, intervalo interquartile [IIQ] 27-31sem; peso ao nascimento mediano 1,230g, IIQ 970-1511g). Comparamos o uso de serviços especializados reportados pelos pais por país, risco perinatal (com base na idade gestacional, pequeno para a idade gestacional e morbidades neonatais), educação materna e local de nascimento. RESULTADOS: Setenta e seis por cento das crianças consultou pelo menos um especialista, variando entre países de 53,7 a 100%. Oftalmologistas (53,4%) e fisioterapeutas (48,0%) foram os mais frequentemente consultados, mas os especialistas individuais variaram bastante por país. O risco perinatal se associou com uso de serviços especializados, mas o gradient diferiu entre países. Crianças com mães mais educadas tinham maior proporção de uso de especialistas em três países. INTERPRETAÇÃO: Grandes variações no uso de serviços especializados na Europa não foram explicadas pelo risco perinatal, e levantam questões sobre as forças e limitações dos modelos de cuidado existentes.

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.

Duration and Time Trends in Hospital Stay for Very Preterm Infants Differ Across European Regions.

OBJECTIVES: To compare duration and changes over time in length of hospital stay for very preterm and extremely preterm infants in 10 European regions. DESIGN: Two area-based cohort studies from the same regions in 2003 and 2011/2012. SETTING: Ten regions from nine European countries. PATIENTS: Infants born between 22 + 0 and 31 + 6 weeks of gestational age and surviving to discharge (Models of Organising Access to Intensive Care for Very Preterm Births cohort in 2003, n = 4,011 and Effective Perinatal Intensive Care in Europe cohort in 2011/2012, n = 4,336). INTERVENTIONS: Observational study, no intervention. MEASUREMENTS AND MAIN RESULTS: Maternal and infant characteristics were abstracted from medical records using a common protocol and length of stay until discharge was adjusted for case-mix using negative binomial regression. Mean length of stay was 63.6 days in 2003 and varied from 52.4 to 76.5 days across regions. In 2011/2012, mean length of stay was 63.1 days, with a narrower regional range (54.0-70.1). Low gestational age, small for gestational age, low 5-minute Apgar score, surfactant administration, any surgery, and severe neonatal morbidities increased length of stay. Infant characteristics explained some of the differences between regions and over time, but large variations remained after adjustment. In 2011/2012, mean adjusted length of stay ranged from less than 54 days in the Northern region of the United Kingdom and Wielkopolska, Poland to over 67 days in the Ile-de-France region of France and the Eastern region of the Netherlands. No systematic decrease in very preterm length of stay was observed over time after adjustment for patient case-mix. CONCLUSIONS: A better understanding of the discharge criteria and care practices that contribute to the wide differences in very preterm length of stay across European regions could inform policies to optimize discharge decisions in terms of infant outcomes and health system costs.

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.

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.

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).

PRACTICAL ASPECTS OF THERAPEUTIC HYPOTHERMIA IN NEONATES WITH HYPOXIC ISCHEMIC ENCEPHALOPATHY--QUESTIONS AND ANSWERS. PART I. PROVIDING NEWBORN CARE BEFORE AND DURING TRANSFER TO THE REFERENCE CENTER.

The first decade of the 21st century saw the worldwide spread of therapeutic hypothermia as a beneficial therapeutic procedure in neonates with hypoxic-ischemic encephalopathy. New guidelines for the resuscitation of newborns confirm that therapeutic hypothermia should be the standard method of treatment offered to neonates with acute perinatal hypoxia. The quality of care which an asphyxiated newborn receives during and immediately after resuscitation, as well as the mode of preparation for transport, can have a significant impact on improving the outcome, but it can also result in the deterioration of neonates treated with hypothermia. Since to a considerable degree the therapeutic effect depends on the time of beginning the cooling procedure, there is no reason to unnecessarily delay treatment. For this purpose, neonatologists or pediatricians from referring hospitals who do not have the equipment for hypothermia can and even should begin the cooling process while waiting for the arrival of the neonatal transport team. In that short period a number of concerns arise regarding the optimal methods of child care and preparation for transport to the hypothermia center. The authors discuss the possibility of initiating cooling before transportation using simple, so called low-tech cooling methods, the possible risks associated with the incidence of hyperthermia, difficulties in the interpretation of the eligibility criteria, supportive therapy, and the problems connected with the communication process between the medical team and the parents. The aspects that have been analyzed should be helpful for professionals in neonatal wards, outside hypothermia centers.

Late-onset bloodstream infections of Very-Low-Birth-Weight infants: data from the Polish Neonatology Surveillance Network in 2009-2011.

BACKGROUND: Late-Onset Bloodstream Infections (LO-BSI) continue to be one of the most important complications associated with hospitalization of infants born with very low birth weight (VLBW). The aims of this study were to assess the epidemiology of LO-BSI together with the risk factors and the distribution of causative pathogens at six Polish neonatal intensive care units that participated in the Polish Neonatology Surveillance Network from January 1, 2009 to December 31, 2011. METHODS: The surveillance covered 1,695 infants whose birth weights were <1501 grams (VLBW) in whom LO-BSI was diagnosed >72 hours after delivery. Case LO-BSI patients were defined according to NeoKISS. RESULTS: Four hundred twenty seven episodes of LO-BSI were diagnosed with a frequency of 25.3% and an incidence density of 6.7/1000 patient-days (pds). Results of our multivariate analysis demonstrated that surgical procedures and lower gestational age were significantly associated with the risk of LO-BSI. Intravascular catheters were used in infants with LO-BSI significantly more frequently and/or for longer duration: Central venous cathters (CVC) (OR 1.29) and Peripheral venous catheters (PVC) (OR 2.8), as well as, the total duration of total parenteral nutrition (13 vs. 29 days; OR 1.81). Occurrence of LO-BSI was significantly associated with increased the length of mechanical ventilation (MV) (OR 2.65) or the continuous positive airway pressure (CPAP) (OR 2.51), as well as, the duration of antibiotic use (OR 2.98). The occurrence of more than one infection was observed frequently (OR 9.2) with VLBW with LO-BSI. Microorganisms isolated in infants with LO-BSI were dominated by Gram-positive cocci, and predominantly by coagulase-negative staphylococci (62.5%). CONCLUSIONS: Independent risk factor for LO-BSI in VLBV infants are: low gestational age and requirement for surgery. The incidence rates of LO-BSI especially CVC-BSI were higher in the Polish NICUs surveillance than those of other national networks, similar to the central- and peripheral utilization ratio.

[Heliox augmented mechanical ventilation in the treatment of premature infants with respiratory distress syndrome]. / Wentylacja mechaniczna z zastosowaniem helioxu w leczeniu wczesniaków z zespolem zaburzen oddychania.

OBJECTIVE: The aim of the study was to assess the influence of mechanical ventilation with helium-oxygen mixture (heliox) on basic vital signs, oxygenation, acid-base balance and respiratory mechanics in newborns with respiratory distress syndrome (RDS), previously treated with surfactant. MATERIAL AND METHODS: The study was carried out in preterm newborns with respiratory failure requiring mechanical ventilation due to RDS, requiring Fi02>0.4 after a single dose of surfactant. Patients were ventilated using PC-SIMV Parameters of mechanical ventilation, respiratory function, oxygenation, acid-base balance and vital signs were recorded at baseline, one hour during and one hour after heliox ventilation. RESULTS: Ten newborns with RDS were enrolled in the study Mechanical ventilation with heliox did not affect vital signs and patient general condition remained stable during and after ventilation with heliox. Mechanical ventilation with heliox was associated with a statistically significant increase in tidal volume (mean 5.48 vs. 6.55 ml/kg). There were no significant changes in minute ventilation and peak expiratory flow rate. Mechanical ventilation with heliox allowed the use of significantly lower fractions of inspired oxygen (mean 0.55 vs. 0.35), with a significant decrease in the oxygenation index (mean 8.77 vs. 5.02) and alveolar-arterial oxygen tension difference (mean 263.81 vs. 113.28 mm Hg). After ventilation with this gas mixture was stopped, the patients required higher Fi02, 01 and AaD02 levels increased. CONCLUSIONS: Mechanical ventilation with heliox was safe, improved oxygenation and caused an increase in tidai, volume in newborns with RDS previously treated with surfactant.

[Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy]. / Hipotermia lecznicza w encefalopatii niedokrwienno-niedotlenieniowej u noworodka.

Hypoxia-ischemia in the perinatal period is a serious condition affecting infants, which can result in death and cerebral palsy and associated disabilities. There has been significant research progress in hypoxic-ischemic encephalopathy over the last 2 decades. Many new molecular mechanisms of asphyxia have been identified. Despite all these advances, therapeutic interventions in HIE remain to be limited. Recently it has been revealed that mild therapeutic hypothermia is the only modality shown to improve neurologic outcome. The authors present a summary of pathogenesis of HIE, animal studies of cooling for hypoxic and ischemic models, and first publications on human therapeutic hypothermia trials. The diagnosis of encephalopathy in full-term neonates and enrollment criteria for hypothermia are also discussed. The current data from randomized control trials of hypothermia as neuroprotection for full and near-term infants are presented along with the results of meta-analyses of these trials. Finally the status of ongoing neonatal hypothermia trials as well as status of therapeutic hypothermia in Poland is summarized.

[The use of therapeutic whole body cooling in treating hypoxic-ischemic encephalopathy in the newborn--the first case in Poland]. / Pierwszy przypadek w Polsce zastosowania hipotermii leczniczej calego ciala w leczeniu encefalopatii niedotlenieniowo--niedokrwiennei u noworodka.

Hypoxic-ischemic encephalopathy (ENN) concerns neonates born after 35 completed weeks of gestation. The incidence rate has been shown to be 1-6/1000 births and can lead to significant permanent neurological damage, cerebral palsy and even death. Until the whole body cooling and selective brain cooling methods have been accepted, the treatment of children with ENN was only symptomatic. The article describes the first case of ENN neonatal treatment with the whole body hypothermia in Poland, which took place at the Department of Neonatology Poznan University of Medical Sciences. Currently both methods--whole body hypothermia and selective brain cooling--offer a chance for a normal neurological development and a better life for children born with ENN. Both methods are accessible in a few centers in Poland.

[The first application of therapeutic hypothermia in Poland--selective head cooling (Cool-Cap) with whole-body moderate hypothermia in a newborn with features of hypoxic ischemic encephalopathy]. / Pierwsze zastosowanie hipotermii leczniczej w Polsce--selektywne chlodzenie glowy (Cool-Cap) z umiarkowana hipotermia ciala u noworodka z cechami encefalopatii niedokrwienno-niedotlenieniowej.

The authors present the first application of therapeutic hypothermia in a newborn in Poland. The female newborn, born with severe asphyxia, was transported to a referral perinatal center where the method of brain cooling was possible. Severe hypoxic ischemic encephalopathy was confirmed by an integrated EEG. During the cooling procedure (which lasted 72 hours), no important side effects were noticed. The neurodevelopmental outcome of the baby assessed during the first 2 years of her life is normal.