RISEinFAMILY project: the integration of families at neonatal intensive care units (NICUs) to empower them as primary caregivers: study protocol for a stepped wedge cluster controlled trial.

BACKGROUND: Family Integrated Care (FICare) has demonstrated positive outcomes for sick neonates and has alleviated the psychological burden faced by families. FICare involves structured training for professionals and caregivers along with the provision of resources to offer physical and psychological support to parents. However, FICare implementation has been primarily limited to developed countries. It remains crucial to assess the scalability of this model in overcoming social-cultural barriers and conduct a cost-effectiveness analysis. The RISEinFAMILY project aims to develop an adapted FICare model that can serve as the international standard for neonatal care, accommodating various cultural, architectural, and socio-economic contexts. METHODS: RISEinFAMILY is a pluri-cultural, stepped wedge cluster controlled trial conducted in Spain, Netherlands, the UK, Romania, Turkey, and Zambia. Eligible participants include infant-family dyads admitted to the Neonatal Intensive Care Unit (NICU) requiring specialised neonatal care for a minimum expected duration of 7 days, provided there are no comprehension barriers. Notably, this study will incorporate a value of implementation analysis on FICare, which can inform policy decisions regarding investment in implementation activities, even in situations with diverse data. DISCUSSION: This study aims to evaluate the scalability and adaptation of FICare across a broader range of geographical and sociocultural contexts and address its sustainability. Furthermore, it seeks to compare the RISEinFAMILY model with standard care, examining differences in short-term newborn outcomes, family mental health, and professional satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov NCT06087666. Registered on 17 October 2023. PROTOCOL VERSION: 19 December 2022; version 2.2.

Barriers to implementation of placental transfusion of babies at birth in Zambia.

Delayed cord clamping (DCC) and umbilical cord milking (CM) have many benefits. However, a previous study done in Zambia showed that it was not a common practice among midwives. This study investigated possible barriers to DCC and CM, at the University Teaching Hospital in Lusaka. This was a qualitative study. A convenience sample was chosen, and snowball sampling was used. The midwives were interviewed using semi-structured interviews. Burnard's method of thematic content analysis was used. Through 14 interviews it became clear that the midwives were aware of DCC and used it whenever possible. The participants reported that the main barriers were the high workload and a variation in knowledge. A lack of facilities, such as heaters and resuscitation equipment in the delivery room also led to earlier cord clamping. The midwives were motivated to continue improving the routines. They expressed a need for more training as well as equipment and resources to facilitate DCC.

Distinct patterns of naive, activated and memory T and B cells in blood of patients with ulcerative colitis or Crohn's disease.

Both major subcategories of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease are characterized by infiltration of the gut wall by inflammatory effector cells and elevated biomarkers of inflammation in blood and feces. We investigated the phenotypes of circulating lymphocytes in the two types of IBD in treatment-naive pediatric patients by analysis of blood samples by flow cytometry. Multivariate analysis was used to compare the phenotypes of the blood lymphocytes of children with ulcerative colitis (n = 17) or Crohn's disease (n = 8) and non-IBD control children with gastrointestinal symptoms, but no signs of gut inflammation (n = 23). The two IBD subcategories could be distinguished based on the results from the flow cytometry panel. Ulcerative colitis was characterized by activated T cells, primarily in the CD8+ population, as judged by increased expression of human leukocyte antigen D-related (HLA-DR) and the ß1-integrins [very late antigen (VLA)] and a reduced proportion of naive (CD62L+ ) T cells, compared with the non-IBD controls. This T cell activation correlated positively with fecal and blood biomarkers of inflammation. In contrast, the patients with Crohn's disease were characterized by a reduced proportion of B cells of the memory CD27+ phenotype compared to the non-IBD controls. Both the patients with ulcerative colitis and those with Crohn's disease showed increased percentages of CD23+ B cells, which we demonstrate here as being naive B cells. The results support the notion that the two major forms of IBD may partially have different pathogenic mechanisms.

Allergic disease in 8-year-old children is preceded by delayed B cell maturation.

BACKGROUND: We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5+ B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age. OBJECTIVE: To examine if B and T cell maturation are associated with allergic disease and farming environment over the first 8 years in life. METHODS: In the prospective FARMFLORA study, including both farming and non-farming families, 48 of 65 children took part in the 8-year follow-up study. Various B and T cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment. RESULTS: We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-year follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5+ B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions. CONCLUSION AND CLINICAL RELEVANCE: High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment.

Placental transfusion: a review.

Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution.

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

UNLABELLED: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. CONCLUSION: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

Measuring parents' experiences and satisfaction with care during very preterm birth: a questionnaire development study.

OBJECTIVE: To develop a questionnaire to assess parents' experiences and satisfaction with care during very preterm birth. DESIGN: Questionnaire development. SETTING: Parents whose babies had been cared for at five tertiary neonatal units in England. POPULATION: A total of 145 women who gave birth before 32 weeks of gestation, and 85 of their partners. METHODS: A 30-item questionnaire was developed on the basis of qualitative interviews with parents of very preterm babies, a literature review and discussion with relevant experts. The questionnaire was posted to a second group of parents, and its reliability and validity were explored. MAIN OUTCOME MEASURES: The Preterm Birth Experience and Satisfaction Scale (P-BESS) was correlated with two global questions measuring satisfaction with care during the birth. Internal consistency was measured using Cronbach's α. RESULTS: Parents of 458 babies were invited to take part and 147 (32%) responded. Two women and 22 partners were excluded or ineligible, leaving 145 women and 85 partners. Factor analysis produced three clear dimensions: Staff professionalism and empathy, Information and explanations, and Confidence in staff. The total scale and three subscales showed high reliability. Strong positive correlations were found between the questionnaire scales and the two global questions, indicating convergent validity. For women whose partners were present at the birth, a fourth factor was identified 'Partner Involvement'. CONCLUSIONS: The P-BESS appears to be a valid measure of satisfaction with care during very preterm birth.

High proportions of FOXP3(+) CD25(high) T cells in neonates are positively associated with allergic sensitization later in childhood.

BACKGROUND: The role of FOXP3(+) regulatory T cells in the prevention against sensitization and allergy development is controversial. OBJECTIVE: We followed 65 newborn Swedish children from farming and non-farming families from birth to 3 years of age and investigated the relation between CD4(+) T cell subsets in blood samples and development of sensitization and allergic disease. METHODS: The proportions of FOXP3(+) CD25(high) , CTLA-4(+) CD25(+) , CD45RO(+) , HLA-DR(+) , CCR4(+) or α4ß7(+) within the CD4(+) T cell population were examined by flow cytometry of blood samples at several time-points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL-1ß, IL-6, TNF, IFN-γ, IL-5 and IL-13 were measured. A clinical evaluation regarding the presence of allergen-specific IgE and allergy was performed at 18 and 36 months of age. RESULTS: Multivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3(+) CD25(high) T cells at birth and at 3 days of life than children who remained non-sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA-4(+) CD25(+) T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3(+) CD25(high) T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3(+) CD25(high) T cells in early infancy and to a more prominent T cell memory conversion and cytokine production. CONCLUSION & CLINICAL RELEVANCE: Our results indicate that high proportions of FOXP3(+) CD25(high) T cells in neonates are not protective against later sensitization or development of allergy.

Parents' experiences and satisfaction with care during the birth of their very preterm baby: a qualitative study.

OBJECTIVE: To assess parents' experiences and satisfaction with care during very preterm birth and to identify domains associated with positive and negative experiences of care. DESIGN: Qualitative study using semi-structured interviews. SETTING: Three neonatal units in tertiary care hospitals in South-East England. POPULATION: Thirty-two mothers and seven fathers who had a baby born before 32 weeks of gestation and spoke English well. METHODS: Semi-structured interviews were conducted. Results were analysed using thematic analysis. MAIN OUTCOME MEASURES: Participants' experiences and satisfaction with care during the birth of their preterm baby. RESULTS: Overall, 80% of participants were extremely satisfied with the care during the birth of their preterm baby, seven were generally satisfied but felt some things could be improved and one was dissatisfied. Four key determinants of experiences of care were identified: staff professionalism, which included information and explanation, being calm in a crisis, appearing confident and in control, and conversely not listening to the woman; staff empathy, which included caring and emotional support, and encouragement and reassurance; involvement of the father; and birth environment. CONCLUSIONS: Although the determinants of experiences of care are generally consistent with previous research on term births, unique factors to preterm birth were identified. These were the importance of the staff appearing calm during the birth, and the staff portraying confidence and taking control during the birth. Women valued being listened to, and both they and their partners valued staff helping fathers to feel involved during the birth.

[Significance of scores in intensive care medicine]. / Stellenwert von Scores in der Intensivpflege.

For nurses in intensive care units (ICUs), the use of scoring instruments is a familiar and important part of their work. Frequently, condition-referred instruments are used to assess various conditions, e.g., pain intensity or degree of alertness. Furthermore, ICU nurses use instruments to assess the risk, e.g., of developing pressure ulcers or to fall. A third important group of instruments are those used to document resource utilization by nurses. However, the estimation of the overall benefit of such scores in the intensive care setting is problematic. In Germany, assessment instruments are mainly required for use within the range of the SGB XI. With regard to intensive care settings, the majority of publications address the presentation of scores or the development of new instruments. From the nursing perspective, no clear conceptual distinction can be made between scores and scales; many instruments lack scientific proof of their benefit for nursing care. Discrepancies with the physicians' viewpoint may exist in some cases.

[Reference ranges for biochemical parameters in guinea pigs for the Vettest®8008 blood analyzer]. / Referenzwerte blutchemischer Parameter bei Meerschweinchen bestimmt mit dem Vettest® 8008.

OBJECTIVE: Studies to establish reference ranges for blood chemistry in guinea pigs are scarce and always apply to bench chemistry. Most veterinary surgeries, however, use dry chemistry methods for in-house blood analysis, for which no reference ranges are available in guinea pigs. In this study, reference ranges for guinea pigs were established by the use of a common dry chemistry blood analyzer (Vettest®8008). MATERIAL AND METHODS: The animals were pets from clients of the Potsdam Veterinary Hospital (24 males, 34 females). The age ranged from 8 weeks to 5 years. Plasma samples were prepared for routine blood chemistry analysis. The investigation comprised 20 parameters (see below). Reference ranges were established via SPSS Statistics 17.0 from 2.5%- and 97.5%-percentiles. RESULTS: Enzymes: alkaline phosphatase: 50.80-328.10 U/l; alanine aminotransferase: 41.45-165.35 U/l; amylase: 726.93-1831.55 U/l; aspartate aminotransferase: 25.25 to 349.23 U/l; creatine kinase: 66.13-1255.40 U/l; γ-glutamyl transferase: 0.45-90.75 U/l; lactate dehydrogenase: 5.61-1503.00 U/l, lipase: no measurable activity. Substrates: albumin: 17.45-31.65 g/l; ammonia: 4.80-225.30 mmol/l; cholesterol: 0.00-2.06 mmol/l; creatinine: 23.90 to 73.45 µmol/l; total bilirubin: 2.00-17.60 µmol/l; total protein: 50.00-70.85 g/l; glucose: 4.62-19.55 mmol/l; blood urea nitrogen: 2.04-11.28 mmol/l; triglycerides: 0.46-4.23 mmol/l. Globulins results by calculation: 30.43-42.00 g/l. Electrolytes: anorganic phosphate: 0.72-2.12 mmol/l, calcium: 2.58-3.16 mmol/l; magnesium: 0.72 to 1.60 mmol/l. CONCLUSIONS: Some major differences were found between the results of three recent studies and the present study, respectively. This leads to the conclusion that reference ranges obtained by differing methods are not necessarily useful for the veterinary in-house laboratory. Instead, in-house analyzers require their own specific reference ranges. Possible reasons for the differences in reference ranges of the compared studies may be due to undetected subclinical diseases and the use of differing chemical or statistical methods.

Spectroscopic noninvasive measurement of hemoglobin compared with capillary and venous values in neonates.

BACKGROUND: Venepuncture-related blood loss is a common cause of neonatal anemia. Currently, this is the only way to obtain hemoglobin levels. This causes distress for the infant but can also lead to the need for blood transfusions. Recently, a new technique for measuring hemoglobin levels non-invasively has been developed to reduce iatrogenic blood loss and pain. OBJECTIVE: To compare hemoglobin levels obtained using a transcutaneous spectroscopic device (Mediscan 2000, MBR Optical Systems, Wuppertal, Germany) with venous or capillary blood samples in neonates. METHODS: Single-center prospective cohort study of term and preterm infants. The white light spectroscopic device was placed on the forearm for 60 s to measure hemoglobin content within 4 h of venous or capillary blood sampling. Pain reactions of the infants were assessed by using a neonatal pain assessment tool. Results were analyzed by Bland-Altman comparison and Wilcoxon signed-rank test. RESULTS: 80 infants (mean gestational age 29.8 +/- 3.8 weeks, mean birth weight 1,300 +/- 690 g) were enrolled into the study. A total of 313 spectroscopic recordings within 2 h of a clinically indicated blood sample (181 capillary, 142 venous) were taken. The correlation coefficient R(2) was 0.96 for capillary/spectroscopic and 0.99 for venous/spectroscopic pairs. Pain scores were significantly less for the spectroscopic measurements (p < 0.01). CONCLUSION: The results show good correlation between the hemoglobin blood levels and spectroscopic measurements. The slightly lower correlation coefficient for the capillary samples demonstrates a naturally higher variance in these values due to the laboratory method.

Management of congenital cytomegalovirus infection: an evidence-based approach.

UNLABELLED: Abstract Despite cytomegalovirus being the most common congenital infection leading to psychomotor impairment and sensori-neural hearing loss, little is known about early identification and management of congenitally infected neonates. This article reviews the literature and devises an algorithm for identification and management of these neonates. CONCLUSION: Application of the current knowledge in the management of congenital cytomegalovirus infected neonates could be beneficial, until further evidence is available.

Diagnostic value of subependymal pseudocysts and choroid plexus cysts on neonatal cerebral ultrasound: a meta-analysis.

BACKGROUND AND OBJECTIVE: Subependymal pseudocysts and choroid plexus cysts are seen in newborns on cerebral ultrasound. Clinicians are unsure whether these findings are related to an underlying disease which affects long-term outcome and requires medical intervention. In an attempt to establish the diagnostic value of cystic lesions on cerebral ultrasound and guide clinical management we searched the medical literature and performed a meta-analysis. METHODS: We performed a systematic literature review and summarised the data on the value of subependymal pseudocysts or choroid plexus cysts for the diagnosis of chromosomal anomalies or congenital infections. Sensitivity, specificity, predictive values and likelihood ratios were calculated for single, multiple, unilateral and bilateral cysts. RESULTS: 305 patients with cystic lesions were retrieved. Bilateral cysts, irrespective of their number, had a sensitivity of 88% and negative predictive value of 94% for a congenital infection or genetic disorder. Unilateral single cysts had a specificity of 92% for normal microbiological and genetic results. Bilateral multiple subependymal pseudocysts or choroid plexus cysts had a positive likelihood ratio of 9.1 for a chromosomal anomaly or congenital infection. Unilateral cysts had a negative likelihood ratio of 0.2 for a congenital infection or chromosomal anomaly. There was a chance of 1 in 4-5 for a congenital infection or chromosomal anomaly if bilateral multiple subependymal pseudocysts or choroid plexus cysts were found. CONCLUSIONS: Bilateral multiple subependymal pseudocysts or choroid plexus cysts suggest an underlying disease. Further investigations should be undertaken even if the patient is otherwise normal. Parents of well newborns with a single cyst should be reassured.

Early prediction of neurological outcome by term neurological examination and cranial ultrasound in very preterm infants.

AIM: To assess the value of term neurological examination and cranial ultrasound in the early prediction of neurological outcome at 12 months corrected age in a cohort of very preterm infants. METHODS: A cohort of 102 preterm infants born at <32 weeks gestation or with a birth weight of <1500 g were assessed using the Hammersmith Term Neurological Examination. They underwent cranial ultrasound examinations according to local guidelines. The Hammersmith Infant Neurological Examination was performed at 12 months corrected age. Scores for the term examinations were compared with scores derived from healthy infants born at term and with scores from low-risk preterm infants at term equivalent age. Term neurological scores and cranial ultrasound findings were compared in the prediction of 12-month neurological outcome. RESULTS: Seventy-eight (76.5%) preterm infants had suboptimal total neurological scores at term when compared to healthy infants born at term. However, most went on to have optimal neurological scores at 12 months corrected age. When our cohort was compared with low-risk preterm infants at term equivalent age only 14 (13.7%) scored outside the normal range. Neither system of scoring predicted neurological outcome at 12 months corrected age as reliably as cranial ultrasound (sensitivity 0.83, specificity 0.87). CONCLUSION: Neurological examination of preterm babies at term may be unreliable in the prediction of neurological outcome at 12 months corrected age. For early prediction of neurological outcome cranial ultrasound examination was found to be more reliable.

[Pitfalls in the diagnosis of congenital hyperinsulinism: a case report and review of the literature]. / Pitfalls bei der Diagnose des kongenitalen Hyperinsulinismus: Ein Fallbericht und Ubersicht der Literatur.

BACKGROUND: Congenital hyperinsulinism is the most common cause for recurrent hypoglycaemia in neonates and infants. Uncontrolled hypoglycaemia leads to seizures and long-term cerebral damage. Often, the diagnosis is delayed because of nonspecific symptoms and confusing laboratory results. PATIENT: We report a patient with hyperinsulinism who was initially wrongly diagnosed as having idiopathic cerebral convulsions and treated accordingly. CONCLUSIONS: Diagnosis of congenital hyperinsulinism is based on a strong suspicion and a thorough family history. Normal random blood glucose or random insulin levels are not helpful in excluding this disease.

Early versus delayed umbilical cord clamping in preterm infants.

BACKGROUND: Optimal timing for clamping of the umbilical cord at birth is unclear. Early clamping allows for immediate resuscitation of the newborn. Delaying clamping may facilitate transfusion of blood between the placenta and the baby. OBJECTIVES: To delineate the short- and long-term effects for infants born at less than 37 completed weeks' gestation, and their mothers, of early compared to delayed clamping of the umbilical cord at birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (2 February 2004), the Cochrane Neonatal Group trials register (2 February 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), PubMed (1966 to 2 February 2004) and EMBASE (1974 to 2 February 2004). SELECTION CRITERIA: Randomized controlled trials comparing early with delayed (30 seconds or more) clamping of the umbilical cord for infants born before 37 completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Three reviewers assessed eligibility and trial quality. MAIN RESULTS: Seven studies (297 infants) were eligible for inclusion. The maximum delay in cord clamping was 120 seconds. Delayed cord clamping was associated with a higher hematocrit four hours after birth (four trials, 134 infants; weighted mean difference 5.31, 95% confidence interval (CI) 3.42 to 7.19), fewer transfusions for anaemia (three trials, 111 infants; relative risk (RR) 2.01, 95% CI 1.24 to 3.27) or low blood pressure (two trials, 58 infants; RR 2.58, 95% CI 1.17 to 5.67) and less intraventricular haemorrhage (five trials, 225 infants; RR 1.74, 95% CI 1.08 to 2.81) than early clamping. REVIEWERS' CONCLUSIONS: Delaying cord clamping by 30 to 120 seconds, rather than early clamping, seems to be associated with less need for transfusion and less intraventricular haemorrhage. There are no clear differences in other outcomes.