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The measurement of quality indicators supports quality improvement initiatives. The German Interdisciplinary Society of Intensive Care Medicine (DIVI) has published quality indicators for intensive care medicine for the fourth time now. After a scheduled evaluation after three years, changes in several indicators were made. Other indicators were not changed or only minimally. The focus remained strongly on relevant treatment processes like management of analgesia and sedation, mechanical ventilation and weaning, and infections in the ICU. Another focus was communication inside the ICU. The number of 1ndicators remained the same. The development method was more structured and transparency was increased by adding new features like evidence levels or author contribution and potential conflicts of interest. These quality indicators should be used in the peer review in intensive care, a method endorsed by the DIVI. Other forms of measurement and evaluation are also reasonable, for example in quality management. This fourth edition of the quality indicators will be updated in the future to reflect the recently published recommendations on the structure of intensive care units by the DIVI.

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Background: Less invasive surfactant administration (LISA) has become the preferred method of surfactant administration for spontaneously breathing babies on continuous positive airway pressure (CPAP). Summary: The development of LISA followed the need to combine CPAP and surfactant replacement as mainstay treatment options for respiratory distress syndrome, thereby avoided exposure to positive pressure ventilation. Key Messages: This review summarises the current knowns and unknowns of LISA including the physiological concept, its relevance for short-term and long-term outcomes and the challenges for practical implementation of LISA as part of a less invasive respiratory care bundle. Further, we provide an update of the evidence on alternatives to LISA, for example, nebulised surfactant administration, pharyngeal deposition of surfactant and delivery via supraglottic airway. [ABSTRACT FROM AUTHOR]

Aim: The supine sleeping position in the prevention of sudden infant death syndrome in preterm infants is poorly understood. We aimed to investigate the effect of sleep posture on cardiorespiratory parameters and movement patterns in preterm infants close to discharge. Methods: This observational study included neonates born in 2022 at the University Hospital Schleswig‐Holstein, Lübeck, Germany. Motion sensor data, heart rate, respiratory rate and oxygen saturation were recorded for infants with postconceptional age 35–37 weeks during sleep in the prone and supine positions. Results: We recorded data from 50 infants, born at 31 (24–35) weeks of gestation (mean(range)), aged 5.2 ± 3.7 weeks (mean ± SD), of whom 48% were female. Five typical movement patterns were identified. In the prone position, the percentage of calm, regular breathing was higher and active movement was less frequent when compared to the supine position. The percentage of calm irregular breathing, number of apnoeas, bradycardias, desaturations and vital sign changes were not influenced by position. Conclusion: The prone position seems to be associated with a higher arousal threshold. The supine position appears advantageous for escape from life‐threatening situations such as sudden infant death syndrome. [ABSTRACT FROM AUTHOR]

Background: In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed. We tested whether mothers' immigrant status and language barriers are associated with perinatal health and short-term neonatal outcomes. Methods: The data are from the national multi-centre German Neonatal Network (GNN) cohort, including VP births from 2009 onwards. In total, 3606 (n = 1738 female) children were assessed, and 919 (n = 449 female) of these children had immigrant backgrounds. Immigrant status was operationalised as a binary variable based on the children's mothers' countries of birth (born in Germany vs. foreign-born). Self-reported home language (L1) was used to calculate the average linguistic distance to German as one continuous variable. Results: Mixed-effects models showed that two out of fourteen effects of interest survived the adjustment for known confounders and accounting for the nestedness of data within birth hospitals. Linguistic distance from mothers' L1s to German was independently associated with diagnoses of preeclampsia (OR = 1.01, 95% CI = [1.00, 1.01]). Infants of foreign-born mothers had higher odds for amniotic infection syndrome (AIS; OR = 1.45 [1.13, 1.86]) than infants of German mothers. Conclusions: Our findings from this large multi-centre longitudinal cohort of VP-born children indicate that maternal immigrant status and language barriers have limited impact on perinatal health and severe neonatal outcomes. This suggests that, regardless of background or language skills, there may be few inequalities in the perinatal health of pregnant women and their newborn preterm infants. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development. Methods: Retrospective cohort study of data from 68 tertiary level neonatal intensive care units in Germany. Preterm infants born at 22 + 0 to 28 + 6 weeks of gestation between January 2009 and December 2021 were enrolled. Results: We included n = 12 565 infants. Prevalence of any ROP was 49.2% with most infants being diagnosed with stage 1 (21.5%) and 2 disease (17.2%). ROP stage 3 was present in 10.2%, stage 4 in 0.3%, and ROP requiring treatment in 6.6%. Infants with ROP had significantly more frequently a history of RBC transfusions. Adjusting for confounders, RBC transfusions were associated with increased odds of ROP (OR 1.4, p < 0.001), ROP progression (OR 2.1, p < 0.01) and ROP requiring treatment (OR 3.6, p < 0.001). Restrictive transfusion approaches correlated with decreased (OR 0.7, p < 0.001), liberal regimes with increased odds (OR 1.2, p = 0.001). Conclusion: The present study confirmed an association of RBC transfusions and ROP. Our findings emphasise the need for anaemia prevention and critical re‐evaluation of transfusion practices in preterm infants. [ABSTRACT FROM AUTHOR]

Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects. Our explorative study aimed to determine age-dependent changes in the expression of C5aR1 and C5aR2 in neonatal immune cell subsets. Via flow cytometry, we analyzed the expression pattern of C5a receptors on immune cells isolated from peripheral blood of preterm infants (n = 32) compared to those of their mothers (n = 25). Term infants and healthy adults served as controls. Preterm infants had a higher intracellular expression of C5aR1 on neutrophils than control individuals. We also found a higher expression of C5aR1 on NK cells, particularly on the cytotoxic CD56dim subset and the CD56- subset. Immune phenotyping of other leukocyte subpopulations revealed no gestational-age-related differences for the expression of and C5aR2. Elevated expression of C5aR1 on neutrophils and NK cells in preterm infants may contribute to the phenomenon of "immunoparalysis" caused by complement activation or to sustained hyper-inflammatory states. Further functional analyses are needed to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Amniotic infection syndrome (AIS) with perinatal inflammation may increase the susceptibility to intraventricular hemorrhage (IVH) in preterm infants. Given its anti-inflammatory and ductus arteriosus constricting capacities, we hypothesized that prophylactic administration of indomethacin reduces the incidence, severity, and consequences of IVH in the context of perinatal inflammation. Methods: We evaluated data of infants born between 2009 and 2020 of 22 + 0–25+6 weeks of gestation from 68 German Neonatal Network centers. The effect of indomethacin prophylaxis on outcomes was analyzed in univariate analyses and multivariate regression models including a subgroup of infants with available data on 5-year follow-up. Results: 4760 infants were included with a median gestational age of 24.6 SSW [interquartile range (IQR) 24.1w–25.2w] and a birth weight of 640 g [IQR 550–750 g]. 1767/4760 (37.1%) preterm infants were born in the context of AIS and 527/4760 (11.1%) received indomethacin prophylaxis. AIS infants receiving prophylactic indomethacin had lower rates of IVH (32.7% vs. 36.9%, p = 0.04), IVH III/IV (9.7% vs. 16.0%, p = 0.02) and the combined outcome of severe IVH or death (15.9% vs. 23.2%, p = 0.01) as compared to infants without prophylaxis. Multivariate logistic regression analyses confirmed our observations. In a subgroup analysis of 730 preterm infants at 5 years of age, we did not find any correlation between prophylactic indomethacin and intelligence quotient <70 or cerebral palsy. Conclusions: Our observational data demonstrate that prophylactic indomethacin is associated with a reduced risk of IVH in the highly vulnerable subgroup of preterm infants <26 weeks of gestation born from AIS. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) in adults is a result of environmental risk factors and genetic factors. Polygenic COPD risk scores are highly predictive for lung function in adults. We hypothesized that a polygenic COPD risk score is also predictive for lung function in children who are born preterm. Methods: Infants with a birth weight of less than 1500 g (n=17,394) were enrolled in the German Neonatal Network. Among these children, we included those with chip genotyping and 5-year follow-up assessment (n=1957) in this analysis. A polygenic COPD risk score derived in adults with COPD was calculated on the basis of 1,637,882 single-nucleotide polymorphisms associated with forced expiratory volume within 1 second (FEV1) and 1,179,331 single-nucleotide polymorphisms associated with FEV1/FVC (forced vital capacity). This score was related to FEV1, FVC, and FEV1/FVC z scores by linear regression analysis. Results: At a mean age at follow-up of 5.8±0.4 years, the polygenic COPD risk score was strongly associated with FEV1 (-0.05 z score/decile, P=6.5×10-9) and FEV1/FVC (-0.07 z score/decile, P=4.4×10-11) but not FVC. Children in the 10th decile of the polygenic COPD risk score -- that is, those at the highest risk -- had a mean FEV1 z score of -1.74 (±1.1), indicating lower lung function by these measures and higher rates of obstructive bronchitis. Conclusions: The upper deciles of a polygenic COPD risk score derived in adults identified a subgroup of children who were born preterm and who are at high risk for obstructive pulmonary disease of prematurity. This finding supports the notion that COPD-associated genes strongly impact lung function in premature children. (Funded by the German Federal Ministry of Education and Research.) Polygenic risk score (PRS) for FEV1 and FVC was calculated in children born prematurely. COPD risk score was strongly associated with FEV1 (-0.05 z score/decile, P=6.5×10-9) and FEV1/FVC (-0.07 z score/decile, P=4.4×10-11) but not FVC. Children at highest risk had lower lung function by these measures and higher rates of obstructive bronchitis. [ABSTRACT FROM AUTHOR]

Introduction: Preterm infants have an immature epidermis barrier function that may lead to an increased permeability to pathogens. On the surface of the human skin, antimicrobial peptides (AMPs) are important molecules of the innate immune system, have broad antimicrobial properties, and provide an essential role in integrity of the microbiome. Given the marked susceptibility of preterm infants to infection, we hypothesize a decreased expression of AMPs on the skin of preterm infants. Materials and methods: In a prospective single-center study with 35 preterm and 20 term infants, we analyzed skin rinsing probes for the presence of the AMPs psoriasin (S100A7) and ribonuclease 7 (RNase 7) via enzyme-linked immunosorbent assay. Samples were taken from preterm infants < 34 0/7 weeks gestational age (mean ± SD gestational age, 28.8 ± 2.4 weeks) on days 0, 7, 14, and 28 after birth. Term infants (> 36 6/7 weeks) (controls) were washed on days 0 and 28. Results: Psoriasin and RNase 7 were both expressed on skin of preterm and term infants and increased in concentration significantly over time. RNase 7 was more expressed in term infants on day 0 [preterm = 1.1 (0.7-2.9) vs. term = 2.0 (1.1-3.4) ng/ml, p = 0.017]. On day 28, premature infants showed higher values of psoriasin [preterm = 10.9 (5.6-14.2) vs. term = 6.3 (3.4-9.0) ng/ml, p < 0.001]. Notably, preterm infants with infectious or inflammatory context driven by histological proof of chorioamnionitis and early-onset or late-onset sepsis had higher concentrations of psoriasin as compared with non-affected preterm infants. After exclusion of infants with inflammatory hit, median concentrations of RNase 7 and psoriasin did not differ between preterm and full-term infants on days 0 and 28. Discussion: Psoriasin and RNase 7 concentrations increase over time on the skin of newborn infants and seem to play a role in the first defense against infection. This is of particularly interest as the role of AMPs on a maturing skin microbiome and its possible new prevention strategies is unclear and needs to be determined. [ABSTRACT FROM AUTHOR]

Aim: We explored whether subnormal forced expiratory volume within 1 s (FEV1) at 5–9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. Methods: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23–26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. Results: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%–113%) of predicted values in the LISA group and 86% (interquartile range 77–102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval −3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. Conclusion: The proportion of children aged 5–9 years with subnormal FEV1 was not significantly different between the groups. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is regarded as a risk factor for brain injury in preterm infants. We herein hypothesize that extremely low birth weight infants (ELBWI, birth weight <1,000 g) having survived recurrent blood culture-proven late-onset sepsis (LOS) episodes are more likely to have an adverse long-term neurologic outcome. Methods: In a large multicenter observational study of ELBWI ≤28 6/7 weeks, we evaluated the impact of recurrent LOS (blood culture-proven, after day 7 of life) on development at 5–6 years. Neurodevelopment, behavior, and motor qualities were tested by blinded investigators. Univariate and logistic regression analyses were performed. Results: The cohort consisted of 1343 ELBWI including 1,080 infants without LOS, 186 infants with one LOS, and 77 with recurrent LOS, i.e., 55 infants with two and 22 infants with three LOS episodes. After Bonferroni-Holm correction, multiple logistic regression analysis revealed recurrent sepsis to be significantly associated with adverse motor development (critical MABC-2 testing: 3.3 [1.5–7.3], p = 0.003, pB = 0.012), whereas no significant impact of recurrent LOS was found on intelligence quotient and behavioral difficulties. Odds of having critical motor testing results for infants with recurrent LOS were 1.7 times (95% confidence interval 1.4–2.3) that of infants with one LOS. Conclusion: Recurrent sepsis in preterm infants is associated with adverse long-term motor development. However, infants with recurrent infections are also more likely to have preterm-related complications, and reasons for a worse neurodevelopmental outcome remain to be elucidated. [ABSTRACT FROM AUTHOR]

This document is a response to a letter to the editor regarding a study on the association between red blood cell transfusions and retinopathy of prematurity (ROP) in premature infants. The authors of the response express gratitude for the comment on the post-conceptional age-related effect of transfusions on retinal morbidity. They discuss the mechanism of HbF reduction and the potential impact on ROP development. The authors acknowledge the limitations of their study and emphasize the need for future research to explore the causal associations between transfusions and ROP. They also highlight the importance of promoting anemia and transfusion-preventing practices in neonatal intensive care. [Extracted from the article]

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BACKGROUND. Recent investigations have reported an influence of thrombophilic mutations and antithrombotic risk factors with development of intraventricular hemorrhage. It was our objective for this study to investigate the impact of genetic polymorphisms of hemostasis genes on the primary outcome measures of sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and periventricular leukomalacia in a large cohort of very low birth weight infants. METHODS. There were 586 very low birth weight infants enrolled prospectively in a multicenter trial between September 2003 and July 2005, and an additional 595 very low birth weight infants, who had been recruited in a previous prospective trial, were studied. DNA samples were taken by buccal swab, and genotypes of factor V Leiden mutation, prothrombin G20210A mutation, the factor VII-323 del/ins polymorphism, and the factor XIII-Val34Leu polymorphisms were determined by polymerase chain reaction and restriction enzyme digestion. RESULTS. In contrast to data published previously, the frequency of intraventricular hemorrhage or periventricular leukomalacia was not significantly influenced by any of the genetic variants tested. Carriers of the factor XIII-Val34Leu polymorphism, however, had a higher sepsis rate and a longer period of hospital care compared with noncarriers. The factor VII-323 del/ins polymorphism was found to be a potential protective factor against bronchopulmonary dysplasia. CONCLUSIONS. We could not confirm previously reported associations of hemostasis gene variants and development of intraventricular hemorrhage in very low birth weight infants. To better understand gene-disease associations in very low birth weight infants, the prospective development of large-scale cohorts with well-defined phenotypes and corresponding DNA samples is essential. Key Words VLBW, outcome, hemostasis genes, polymorphism Abbreviations VLBW--very low birth weight IVH--intraventricular hemorrhage PVL--periventricular leukomalacia BPD--bronchopulmonary dysplasia ROP--retinopathy of prematurity, GENETIC ASSOCIATION STUDIES have been applied to a wide range of complex diseases to identify populations who are at an increased risk. For example, substantial progress has been made in [...]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)