Abstract Background Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing ...guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies. Objectives To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm. Methods This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9‐point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds. Results An initial list of 140 data items was generated. Ninety‐six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio‐economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life. Conclusions This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally.
Objective To investigate the association between body temperature at admission to neonatal intensive care and in-hospital mortality in very preterm infants, stratified by postnatal age of death. ...Moreover, we assessed the association between admission temperature and neonatal morbidity. Study design In this cohort study from 19 regions in 11 European countries, we measured body temperature at admission for infants admitted for neonatal care after very preterm birth (<32 weeks of gestation; n = 5697) who were followed to discharge or death. Associations between body temperature at admission and in-hospital mortality and neonatal morbidity were analyzed by the use of mixed effects generalized linear models. The final model adjusted for pregnancy complications, singleton or multiple pregnancy, antenatal corticosteroids, mode of delivery, gestational age, infant size and sex, and Apgar score <7 at 5 minutes. Results A total of 53.4% of the cohort had a body temperature at admission less than 36.5°C, and 12.9% below 35.5°C. In the adjusted model, an admission temperature <35.5°C was associated with increased mortality at postnatal ages 1-6 days, (risk ratio 2.41; 95% CI 1.45-4.00), and 7-28 days (risk ratio 1.79; 1.15-2.78) but not after 28 days of age. We found no associations between admission temperature and neonatal morbidity. Conclusion Admission hypothermia after very preterm birth is a significant problem in Europe, associated with an increased risk of early and late neonatal death.
Ventilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, ...inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing.
Within a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation. TA was collected from 43 premature infants randomly assigned to receive either iNO or placebo gas (birth weight 530-1230 g, median 800 g, gestational age 24 to 28 2/7 weeks, median 26 weeks). Interleukin (IL)-1β, IL-6, IL-8, transforming growth factor (TGF)-β1, interferon γ-induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, acid sphingomyelinase (ASM), neuropeptide Y and leukotriene B4 were measured in serial TA samples from postnatal day 2 to 14. Furthermore, TA levels of nitrotyrosine and nitrite were determined under iNO therapy.
The TA levels of IP-10, IL-6, IL-8, MIP-1α, IL-1β, ASM and albumin increased with advancing postnatal age in critically ill preterm infants, whereas nitrotyrosine TA levels declined in both, iNO-treated and placebo-treated infants. The iNO treatment generally increased nitrite TA levels, whereas nitrotyrosine TA levels were not affected by iNO treatment. Furthermore, iNO treatment transiently reduced early inflammatory and fibrotic markers associated with BPD development including TGF-β1, IP-10 and IL-8, but induced a delayed increase of ASM TA levels.
Treatment with iNO may have played a role in reducing several inflammatory and fibrotic mediators in TA of preterm infants compared to placebo-treated infants. However, survival without BPD was not affected in the main EUNO trial.
NCT00551642.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Innovation is important to improve patient care, but few studies have explored the factors that initiate change in healthcare organizations.
As part of the European project EPICE on evidence-based ...perinatal care, we carried out semi-structured interviews (N = 44) with medical and nursing staff from 11 randomly selected neonatal intensive care units in 6 countries. The interviews focused on the most recent clinical or organizational change in the unit relevant to the care of very preterm infants. Thematic analysis was performed using verbatim transcripts of recorded interviews.
Reported changes concerned ventilation, feeding and nutrition, neonatal sepsis, infant care, pain management and care of parents. Six categories of drivers to change were identified: availability of new knowledge or technology; guidelines or regulations from outside the unit; need to standardize practices; participation in research; occurrence of adverse events; and wish to improve care. Innovations originating within the unit, linked to the availability of new technology and seen to provide clear benefit for patients were more likely to achieve consensus and rapid implementation.
Innovation can be initiated by several drivers that can impact on the success and sustainability of change.
Abstract
Background
Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is ...well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts.
Methods
We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2–3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor’s/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2–3, 4–7 and 8–15 years.
Results
The study included 10 145 VPT children from 12 cohorts at 2–3 years, 8829 from 12 cohorts at 4–7 years and 1865 children from 6 cohorts at 8–15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures pooled unadjusted SMDs: 2–3 years = −0.32 (95% confidence intervals: −0.43 to −0.21); 4–7 years = −0.57 (−0.67; −0.47); 8–15 years = −0.54 (−0.72; −0.37). Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results.
Conclusions
Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.
Abstract
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.
Introduction: Bronchopulmonary dysplasia (BPD) represents a tremendous disease burden following preterm birth. The strong association between compromised gas exchange after birth and BPD demands ...particular focus on the perinatal period. The mode of delivery can impact on lung fluid clearance and microbial colonization, but its impact on BPD and potential trade-off effects between death and BPD are not established. Methods: A total of 7,435 live births (24+0 to 31+6 weeks postmenstrual age) in 19 regions of 11 European countries were included. Principal outcomes were death and BPD at 36 weeks. We estimated unadjusted and adjusted associations with mode of delivery using multilevel logistic regression to account for clustering within units and regions. Sensitivity analyses examined effects, taking into consideration regional variations in C-section rates. Results: Compared to vaginal delivery, delivery by C-section was not associated with the incidence of BPD (OR 0.92, 95% CI: 0.68–1.25) or the composite outcome of death or BPD (OR 0.94, 95% CI: 0.74–1.19) after adjustment for perinatal and neonatal risk factors in the total cohort and in pregnancies for whom a vaginal delivery could be considered. Sensitivity analyses among singletons, infants in cephalic presentation, and infants of ≥26+0 weeks of gestation did not alter the results for BPD, severe BPD, and death or BPD, even in regions with a high C-section rate. Conclusions: In our population-based cohort study, the mode of delivery was not associated with the incidence of BPD. The intention to reduce BPD does not justify a C-section in pregnancies where a vaginal delivery can be considered.
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.
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.
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.
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.
The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first ...manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis.