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There are few programs available aimed at preventing short- and long-term negative consequences after preterm birth and covering the entire care continuum. The “Transition to Home (TtH)” model is such a program, offering structured, individual support for families with preterm infants before and after hospital discharge. This study gathers and examines the parents’ views of receiving support from an interprofessional team under the TtH model of care during hospitalization and after discharge. Using a qualitative explorative design, 39 semi-structured interviews with parents were analyzed thematically. From this analysis, three main themes were identified: (1) TtH and the relevance of continuity of care; (2) Enhancement of parents’ autonomy and self-confidence; (3) Perception of interprofessional collaboration. Within these themes, the most relevant aspects identified were continuity of care and the appointment of a designated health care professional to anchor the entire care continuum. Emotional support complemented by non-medical approaches, along with strength-based and family resource-oriented communication, also emerged as key aspects. Continuous, family-centered care and well-organized interprofessional collaboration promote the well-being of the family after a premature birth. If the aspects identified in this study are applied, the transition from hospital to home will be smoothened for the benefit of affected families.

There are few programs available aimed at preventing short- and long-term negative consequences after preterm birth and covering the entire care continuum. The "Transition to Home (TtH)" model is such a program, offering structured, individual support for families with preterm infants before and after hospital discharge. This study gathers and examines the parents' views of receiving support from an interprofessional team under the TtH model of care during hospitalization and after discharge. Using a qualitative explorative design, 39 semi-structured interviews with parents were analyzed thematically. From this analysis, three main themes were identified: (1) TtH and the relevance of continuity of care; (2) Enhancement of parents' autonomy and self-confidence; (3) Perception of interprofessional collaboration. Within these themes, the most relevant aspects identified were continuity of care and the appointment of a designated health care professional to anchor the entire care continuum. Emotional support complemented by non-medical approaches, along with strength-based and family resource-oriented communication, also emerged as key aspects. Continuous, family-centered care and well-organized interprofessional collaboration promote the well-being of the family after a premature birth. If the aspects identified in this study are applied, the transition from hospital to home will be smoothened for the benefit of affected families.

Summary Background Human milk analyzers are increasingly used to rapidly measure the macronutrient content in breast milk for individual target fortification, to reduce the risk of postnatal growth restriction. However, many milk analyzers are used without calibration, validation or quality assurance. Aims To investigate measurement quality between different human milk analyzers, to test whether accuracy and precision of devices can be improved by establishing individual calibration curves, and to assess long-term stability of measurements, following good clinical laboratory practice (GCLP). Methods Sets of identical breast milk samples were sent to 13 participating centres in North America and Europe, for a total of 15 devices. The study included 3 sets of samples: A) initial assessment of the device's performance consisting of 10 calibration samples with random replicates; B) long term stability and quality control consisting of 2 batches of samples to be measured every time before the device is used, over 6 months; C) ring trial consisting of 2 samples to be measured monthly. The devices tested were Unity SpectraStar (n = 5) and MIRIS Human Milk Analyzer (n = 10). Results There are significant variations in accuracy and precision between different milk analyzers' fat, protein and lactose measurements. However, the accuracy of measurements can be improved by establishing individual correction algorithms. Repeated measurements are more robust when coming from a larger batch volume. Long term stability also varies between devices. Conclusion The variations in measurements between devices are clinically significant and would impact both daily dietary prescriptions, and the outcomes of clinical studies assessing the effect of targeted adjustment of nutrient intake in preterm babies. This study shows that it is crucial to follow GCLP when using milk analyzers to ensure proper measurement of macronutrients, similar to what is required of other medical devices.

Although the complexity and length of treatment is connected to the newborn’s maturity and birth weight, most case-mix grouping schemes classify newborns by birth weight alone. The objective of this study was to determine whether the definition of thresholds based on a changepoint analysis of variability of birth weight and gestational age contributes to a more homogenous classification. This retrospective observational study was conducted at a Tertiary Care Center with Level III Neonatal Intensive Care and included neonate cases from 2016 through 2018. The institutional database of routinely collected health data was used. The design of this cohort study was explorative. The cases were categorized according to WHO gestational age classes and SwissDRG birth weight classes. A changepoint analysis was conducted. Cut-off values were determined. When grouping the cases according to the calculated changepoints, the variability within the groups with regard to case related costs could be reduced. A refined grouping was achieved especially with cases of >2500 g birth weight. An adjusted Grouping Grid for practical purposes was developed. A novel method of classification of newborn cases by changepoint analysis was developed, providing the possibility to assign costs or outcome indicators to grouping mechanisms by gestational age and birth weight combined.

Aim:The aim of the study was to determine the presence or absence of ear acupuncture points (EAP) in newborn children with or without neonatal abstinence syndrome (NAS) and to confirm the hypothesis that neonates with NAS have more EAP than healthy neonates.Methods:We conducted a prospective case control study with ethical consent at the University Children's Hospital, Division of Neonatology Bern and the Department of Gynecology and Obstetrics Inselspital Bern in Switzerland. We determined the EAP inn= 26 newborn children born to drug-dependent mothers compared withn= 50 healthy newborns. For the detection of EAP, we used an ear point detection pen. EAP are present only if weakness exists in the corresponding area.Results:Twenty-six neonates who were born to drug-dependent mothers and developed NAS were screened on the 5th day after delivery (range 1–22). The median Finnegan Score was 12 points (range 6–18) on the day of examination. Twenty-four active EAP were detected on the left earlobe and 25 were detected on the right earlobe. There was no significant difference between the right and left lobes (p= 0.9285, two tailed test) and the number of acupuncture points. The correlation between the Finnegan Score and the number of EAP was highly significant (p= 0.0001). The most common active points were the psycho-vegetative rim of the reflex zone of sympathicus and parasympathicus. Organic points were also commonly detected. The urinary bladder, kidney and hip points were detected with a frequency of 12–15%. The shen men pain point was found in three neonates, and the point of desire as a psychological point, was also detected. The correlation between sex and active EAP was highly significant (p= 0.0093, Mann-Whitney test for the left earlobe andp= 0.0025 for the right earlobe). Boys had a significantly higher number of EAP than girls. All NADA points were detected in the neonates born to drug-dependent mothers, and the most frequent point was the vegetative point. Healthy neonates showed only the vegetative point in the vegetative rim 1/3 among the NADA points. A comparison of newborns born to drug-dependent mothers and 50 healthy neonates showed that the former group had statistically significantly more active points. For the left earlobe, the difference between neonates born to drug-dependent mothers and controls was statistically significant (p= 0.0008, Mann-Whitney test). Highly similar results were found for the right earlobe (p= 0.0001, Mann-Whitney test).Discussion:Our current work confirms that neonates born to drug-dependent mothers with high Finnegan scores and NAS have more EAP than healthy neonates. The vegetative rim is the most common point as shown in our previous studies. Our observations showed that twins had similar but not identical points; each individual had unique points depending on health status. Newborn boys with NAS had a higher number of EAP than newborn girls in the neonatal intensive care unit. This findings may be attributed to the reserve of newborns with NAS. Newborn girls are considered more robust than boys in the neonatal care setting. EAP in neonates might potentially be used for diagnosis and therapeutic opinions in neonates in the future.

Objective To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). Study design Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. Results Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (−4.8 days less than reference, 95% CI –7.3 to −2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI –12.3 to −11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. Conclusions We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

Objective Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. Study Design Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight Results In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. Conclusion HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

Background: Individual contextual factors like gestational age (GA) or previous painful experiences have an influence on neonates’ pain responses and may lead to inaccurate pain assessment when not appropriately considered. Objectives: We set out to determine the influence of individual contextual factors on variability in pain response in neonates, measured with the modified Bernese Pain Scale for Neonates (BPSN), and, if necessary, to incorporate relevant individual fac- tors into a revised version of the BPSN. Methods: We videotaped 154 full-term and preterm neonates of different GAs dur- ing 1–5 capillary heel sticks in their first 14 days of life. For each heel stick, we produced three video sequences: baseline, heel stick, and recovery. The randomized sequences were rated on the BPSN by five blinded nurses. Individual contextual fac- tors were retrospectively extracted from patient charts and from the video recordings. We analysed the data in single and multiple linear mixed models. Results: Premature birth (b = −0.721), caffeine (b = −0.302), and the behavioural states quiet and awake (b = −0.283), active and asleep (b = −0.158), and quiet and asleep (b = −0.498) were associated with changes in behavioural pain scores. Premature birth (b = −0.232), mechanical ventilation (b = −0.196), and duration of the heel stick procedure (b = 0.0004) were associated with changes in physiological pain scores. Premature birth (b = −0.907), Caffeine (b = −0.402), the behavioural states quiet and awake (b = −0.274), and quiet and asleep (b = −0.459), and duration of the heel stick procedure (b = 0.001) were associated with changes in the modified BPSN total scores. Conclusions: Postmenstrual age, behavioural state, caffeine, and ventilation status have an influence on neonates’ pain response and should be incorporated in the re- vised BPSN to enhance clinical pain assessment in neonates with different GAs. Significance: We identified individual contextual factors associated with dampened pain response in neonates and will incorporate them into a revised version of the Bernese Pain Scale for Neonates to provide clinicians with a tool they can use to more accurately assess and manage pain in this vulnerable population.

To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes.This cohort study included infants born at 24-28 weeks of gestation and birth weight1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio.From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis.Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Background Paediatric end-of-life care is challenging and requires a high level of professional expertise. It is important that healthcare teams have a thorough understanding of paediatric subspecialties and related knowledge of disease-specific aspects of paediatric end-of-life care. The aim of this study was to comprehensively describe, explore and compare current practices in paediatric end-of-life care in four distinct diagnostic groups across healthcare settings including all relevant levels of healthcare providers in Switzerland. Methods In this nationwide retrospective chart review study, data from paediatric patients who died in the years 2011 or 2012 due to a cardiac, neurological or oncological condition, or during the neonatal period were collected in 13 hospitals, two long-term institutions and 10 community-based healthcare service providers throughout Switzerland. Results Ninety-three (62%) of the 149 reviewed patients died in intensive care units, 78 (84%) of them following withdrawal of life-sustaining treatment. Reliance on invasive medical interventions was prevalent, and the use of medication was high, with a median count of 12 different drugs during the last week of life. Patients experienced an average number of 6.42 symptoms. The prevalence of various types of symptoms differed significantly among the four diagnostic groups. Overall, our study patients stayed in the hospital for a median of six days during their last four weeks of life. Seventy-two patients (48%) stayed at home for at least one day and only half of those received community-based healthcare. Conclusions The study provides a wide-ranging overview of current end-of-life care practices in a real-life setting of different healthcare providers. The inclusion of patients with all major diagnoses leading to disease- and prematurity-related childhood deaths, as well as comparisons across the diagnostic groups, provides additional insight and understanding for healthcare professionals. The provision of specialised palliative and end-of-life care services in Switzerland, including the capacity of community healthcare services, need to be expanded to meet the specific needs of seriously ill children and their families.

BACKGROUND The incidence of retinopathy of prematurity (ROP) and ROP screening criteria differ between countries. We assessed whether ROP screening could be reduced based on the local ROP incidence. METHODS Observational cohort study of infants born in Switzerland between 2006 and 2015

OBJECTIVE Late preterm infants (born between 34 0/7 and 36 6/7 weeks of gestation) have been shown to have a higher morbidity and mortality than term infants. Furthermore, twins, both term and preterm, have a higher neonatal morbidity than singletons. The aim of our study was to examine if late preterm twins consequently have twice the neonatal morbidity when both risk factors prematurity and multiple pregnancy are present. STUDY DESIGN A retrospective single-centre study was conducted to compare neonatal outcome of late preterm singletons and late preterm twins born between 34 0/7 and 36 6/7 weeks of gestation as well as term twins with a gestational age from 37 0/7 to 41 6/7 weeks. Primary outcome was length of hospitalisation. Secondary outcome was neonatal morbidity. RESULTS A total of 845 infants were included. Late preterm twins (n = 243) were hospitalised significantly longer than term twins (n = 107) (13.5 ± 8.0 vs 6.29 ± 2.0 days, p

Introduction: Evidence concerning delivery room management in extremely low birth weight infants (ELBW) has grown substantially within the last 20 years, leading to several guidelines and recommendations. However, it is unknown in which extent local treatment strategies have changed and if they reflect current recommendations. Methods: A detailed questionnaire about treatment strategies for ELBW infants was sent to all German neonatal intensive care units (NICUs) treating ELBW infants in 1997. A follow-up survey was conducted in 2011 and sent to all NICUs in Germany, Austria and Switzerland. Results on delivery room management were compared to the first survey. Results: In 1997 and 2011, 63.6 and 66.2% of the approached hospitals responded. In 2011 similar results were observed between university and non-university hospitals as well as NICUs of different size. Differences between Germany, Austria and Switzerland were minimal. Changes over time were a lower initially applied fraction of inspired oxygen (FiO2) and peak inspiratory pressure (PiP) in 2011 compared to 1997. A longer time of apnea was tolerated before tracheal intubation is performed; the time of apnea was less frequently a sole criterion for intubation and surfactant was applied at lower FiO2 in 2011. The time of no thorax excursions and transport of the infant were considered an indication for intubation in 30.2 and 22.5%, and did not change in the observation period. Conclusion: Treatment strategies for delivery room management in ELBW infants changed significantly between 1997 and 2011 and largely reflect current recommendations.

BACKGROUND Therapeutic hypothermia following hypoxic ischaemic encephalopathy in term infants was introduced into Switzerland in 2005. Initial documentation of perinatal and resuscitation details was poor and neuromonitoring insufficient. In 2011, a National Asphyxia and Cooling Register was introduced. AIMS To compare management of cooled infants before and after introduction of the register concerning documentation, neuromonitoring, cooling methods and evaluation of temperature variability between cooling methods. STUDY DESIGN Data of cooled infants before the register was in place (first time period: 2005-2010) and afterwards (second time period: 2011-2012) was collected with a case report form. RESULTS 150 infants were cooled during the first time period and 97 during the second time period. Most infants were cooled passively or passively with gel packs during both time periods (82% in 2005-2010 vs 70% in 2011-2012), however more infants were cooled actively during the second time period (18% versus 30%). Overall there was a significant reduction in temperature variability (p < 0.001) comparing the two time periods. A significantly higher proportion of temperature measurements within target temperature range (72% versus 77%, p < 0.001), fewer temperature measurements above (24% versus 7%, p < 0.001) and more temperatures below target range (4% versus 16%, p < 0.001) were recorded during the second time period. Neuromonitoring improved after introduction of the cooling register. CONCLUSION Management of infants with HIE improved since introducing the register. Temperature variability was reduced, more temperature measurements in the target range and fewer temperature measurements above target range were observed. Neuromonitoring has improved, however imaging should be performed more often.

Background Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. Methods We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. Findings Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p

Background The Bernese Pain Scale for Neonates (BPSN) is a multidimensional pain assessment tool that is already widely used in clinical settings in the German speaking areas of Europe. Recent findings indicate that pain responses in preterm neonates are influenced by individual contextual factors, such as gestational age (GA), gender and the number of painful procedures experienced. Currently, the BPSN does not consider individual contextual factors. Therefore, the aim of this study is the validation of the BPSN using a large sample of neonates with different GAs. Furthermore, the influence of individual contextual factors on the variability in pain reactions across GA groups will be explored. The results will be used for a modification of the BPSN to account for individual contextual factors in future clinical pain assessment in neonates. Methods and design This prospective multisite validation study with a repeated measures design will take place in three university hospital neonatal intensive care units (NICUs) in Switzerland (Bern, Basel and Zurich). To examine the impact of GA on pain responses and their variability, the infants will be stratified into six GA groups ranging from 24 0/7 to 42 0/7. Among preterm infants, 2–5 routine capillary heel sticks within the first 14 days of life, and among full-term infants, two heel sticks during the first days of life will be documented. For each heel stick, measurements will be video recorded for each of three phases: baseline, heel stick, and recovery. The infants’ pain responses will be rated according to the BPSN by five nurses who are blinded as to the number of each heel stick and as to the measurement phases. Individual contextual factors of interest will be extracted from patient charts. Discussion Understanding and considering the influence of individual contextual factors on pain responses in a revised version of the BPSN will help the clinical staff to more appropriately assess pain in neonates, particularly preterm neonates hospitalized in NICUs. Pain assessment is a first step toward appropriate and efficient pain management, which itself is an important factor in later motor and cognitive development in this vulnerable patient population. Trial registration The study is registered in the database of Clinical Trial gov. Study ID-number: NCT 02749461 . Registration date: 12 April 2016.

BACKGROUND The ICD-10 categories of the diagnosis "perinatal asphyxia" are defined by clinical signs and a 1-minute Apgar score value. However, the modern conception is more complex and considers metabolic values related to the clinical state. A lack of consistency between the former clinical and the latter encoded diagnosis poses questions over the validity of the data. Our aim was to establish a refined classification which is able to distinctly separate cases according to clinical criteria and financial resource consumption. The hypothesis of the study is that outdated ICD-10 definitions result in differences between the encoded diagnosis asphyxia and the medical diagnosis referring to the clinical context. METHODS Routinely collected health data (encoding and financial data) of the University Hospital of Bern were used. The study population was chosen by selected ICD codes, the encoded and the clinical diagnosis were analyzed and each case was reevaluated. The new method categorizes the diagnoses of perinatal asphyxia into the following groups: mild, moderate and severe asphyxia, metabolic acidosis and normal clinical findings. The differences of total costs per case were determined by using one-way analysis of variance. RESULTS The study population included 622 cases (P20 "intrauterine hypoxia" 399, P21 "birth asphyxia" 233). By applying the new method, the diagnosis asphyxia could be ruled out with a high probability in 47% of cases and the variance of case related costs (one-way ANOVA: F (5, 616) = 55.84, p < 0.001, multiple R-squared = 0.312, p < 0.001) could be best explained. The classification of the severity of asphyxia could clearly be linked to the complexity of cases. CONCLUSION The refined coding method provides clearly defined diagnoses groups and has the strongest effect on the distribution of costs. It improves the diagnosis accuracy of perinatal asphyxia concerning clinical practice, research and reimbursement.

Objective: Cortical gray matter thinning takes place during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Alterations in brain structure occur in very preterm born children with prolonged maturation of the frontal lobes and smaller cortical and white matter volume. These findings give rise to the question if age affects cortical thinning differently in very preterm born children compared to controls. The aim of the present study was to investigate the relationship between age and cortical thickness in very preterm born children when compared to controls. Participants and Methods: Forty-one very preterm born children (

OBJECTIVES: Premature babies require supplementation with calcium and phosphorus to prevent metabolic bone disease of prematurity. To guide mineral supplementation, two methods of monitoring urinary excretion of calcium and phosphorus are used: urinary calcium or phosphorus concentration and calcium/creatinine or phosphorus/creatinine ratios. We compare these two methods in regards to their agreement on the need for mineral supplementation. METHODS: Retrospective chart review of 230 premature babies with birthweight

BACKGROUND Nebulized surfactant therapy has been proposed as an alternative method of surfactant administration. The use of a perforated vibrating membrane nebulizer provides a variety of advantages over conventional nebulizers. We investigated the molecular structure and integrity of poractant alfa pre- and post-nebulization. METHOD Curosurf® was nebulized using an Investigational eFlow® Nebulizer System. Non-nebulized surfactant ("NN"), recollected surfactant droplets from nebulization through an endotracheal tube ("NT") and nebulization of surfactant directly onto a surface ("ND") were investigated by transmission electron microscopy. Biophysical characteristics were assessed by the Langmuir-Wilhelmy balance and the Captive Bubble Surfactometer. RESULTS Volume densities of lamellar body-like forms (LBL) and multi-lamellar forms (ML) were high for "NN" and "NT" samples (38.8% vs. 47.7% for LBL and 58.2% vs. 47.8% for ML). In the "ND" sample, we found virtually no LBL's, ML's (72.6%) as well as uni-lamellar forms (16.4%) and a new structure, the "garland-like" forms (9.4%). Surface tension for "NN" and "NT" was 23.33 ± 0.29 and 25.77 ± 1.12 mN/m, respectively. Dynamic compression-expansion cycling minimum surface tensions were between 0.91 and 1.77 mN/m. CONCLUSION The similarity of surfactant characteristics of nebulized surfactant via a tube and the non-nebulized surfactant suggests that vibrating membrane nebulizers are suitable for surfactant nebulization. Alterations in surfactant morphology and characteristics after nebulization were transient. A new structural subtype of surfactant was identified. Pediatr Pulmonol. 2014; 49:348-356. © 2013 Wiley Periodicals, Inc.

To compare the influence of three different nonpharmacological interventions on cortical activation, heart rate and peripheral oxygen saturation (SaO2 ) after heelstick in preterm infants.Twenty five preterm infants between 24 0/7 and 32 0/7 weeks of gestational age were randomized to either oral sucrose (S), facilitated tucking (FT) or a combination of the two interventions (SFT) prior to five heelsticks each within the first 14 days of life. SaO2 , heart rate and oxygenation of the somatosensory cortex, measured by near infrared spectroscopy (NIRS), were analysed.Hundred and twenty five heelsticks were performed. The heart rate increased significantly after heelstick in all three intervention groups (p 0.004 in all groups). The increase was higher in the FT group compared with the other groups (S: p = 0.007; SFT: p = 0.004). There was no difference among the two groups receiving sucrose (S and SFT; p = 0.87). SaO2 did not change significantly after heelstick in all intervention groups. Near infrared spectroscopy measurements did not show a significant change in the curve but patients in the FT group showed a trend towards higher average oxygenation of the contralateral somatosensory cortex.Oral sucrose seems to be more effective in reducing reaction to pain than FT. Application of both interventions did not show an additive effect.

To assess the efficacy of paracetamol (acetaminophen) for neonatal pain relief.Randomized, double-blind placebo-controlled trial in 3 Swiss university hospitals. Term and near-term infants (n = 123) delivered by forceps or vacuum were randomized to receive 2 suppositories with paracetamol (60/80/100 mg in infants3000 g/3000-4000 g/4000 g birth weight) or placebo at 2 and 8 hours of life. Pain and discomfort during the first 24 hours was assessed by the échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] score. The response to the subsequent heel prick for metabolic screening at days 2-3 of life was investigated by the Bernese Pain Scale for Neonates (BPSN).The échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] pain scale ratings after assisted vaginal delivery were low and declined within 4 hours of life (P.01) irrespective of paracetamol administration. At 2-3 days of life, BPSN scores after heel prick were significantly higher in infants who had received paracetamol, compared with controls, both when BPSN were scored by nurses at the bedside (median [IQR] 4 [2-7] vs 2 [0-5], P = .017) or off-site from videos (4 [2-8] vs 2 [1-7], P = .04). Thirty-five of 62 (57%) infants treated with paracetamol cried after heel prick, compared with 25 of 61 (41%) controls (P = .086).Infants born by assisted vaginal delivery have low pain scores in the immediate period after birth. Paracetamol given to newborns soon after birth may aggravate a subsequent stress response.

This cross-sectional study examined the performance of children born very preterm and/or at very low birth weight (VPT/VLBW) and same-aged term-born controls in three core executive functions: inhibition, working memory, and shifting. Children were divided into two age groups according to the median (young, 8.00–9.86 years; old, 9.87–12.99 years). The aims of the study were to investigate whether (a) VPT/VLBW children of both age groups performed poorer than controls (deficit hypothesis) or caught up with increasing age (delay hypothesis) and (b) whether VPT/VLBW children displayed a similar pattern of performance increase in executive functions with advancing age compared with the controls. Fifty-six VPT/VLBW children born in the cohort of 1998–2003 and 41 healthy-term-born controls were recruited. All children completed tests of inhibition (Color-Word Interference Task, Delis–Kaplan Executive Function System (D-KEFS)), working memory (Digit Span Backwards, HAWIK-IV), and shifting (Trail Making Test, Number–Letter Sequencing, D-KEFS). Results revealed that young VPT/VLBW children performed significantly poorer than the young controls in inhibition, working memory, and shifting, whereas old VPT/VLBW children performed similar to the old controls across all three executive functions. Furthermore, the frequencies of impairment in inhibition, working memory and shifting were higher in the young VPT/VLBW group compared with the young control group, whereas frequencies of impairment were equal in the old groups. In both VPT/VLBW children and controls, the highest increase in executive performance across the ages of 8 to 12 years was observed in shifting, followed by working memory, and inhibition. Conclusions: This study provides evidence that (a) poor performance in inhibition, working memory, and shifting of young VPT/VLBW children might reflect a delay rather than a deficit and (b) that VPT/VLBW children are likely to display a similar pattern of performance increase in these three executive functions compared with that of controls.

Background Circulating natriuretic and endothelial pro-peptides have been shown to be associated with respiratory distress in infants. Their role as potential biomarkers for prediction of BPD is unclear. Aims and Objectives To assess the value of plasma CT-pro-Endothelin-1 (CT-proET1) and mid-regional atrial natriuretic peptide (MR-proANP) for prediction of BPD in very preterm infants and to examine the association with the duration of supplemental oxygen requirement. Methods In a two-center prospective cohort study including very preterm infants (gestational age (GA) 23 -32 weeks) (Clinical Trials Identifier: NCT02083562) plasma levels of CT-proET1 and MR-proANP were measured on day 7 of life. BPD was defined as supplemental oxygen requirement at 36 weeks corrected age. Results Blood samples of 158 preterm infants (mean (SD) GA 28.8 weeks (±2.4), mean (SD) birthweight 1130 g (±400g)) were analysed. Levels of CT-proET1 were significantly higher in infants with BPD (267 vs 179 pmol/L, p Conclusions CT-proET-1 and MR-proANP measured on day 7 of life are markedly elevated in infants with BPD. Both biomarkers are associated with the duration of supplemental oxygen requirement. They appear to be useful as early biomarkers for the prediction of BPD.

OBJECTIVE To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN We included 58 004 infants born weighing

BACKGROUND There is no agreement of the influence of patent ductus arteriosus (PDA) on outcomes in patients with necrotizing enterocolitis (NEC). In this study, we assessed the influence of PDA on NEC outcomes. METHODS A retrospective study of 131 infants with established NEC was performed. Outcomes (death, disease severity, need for surgery, hospitalization duration), as well as multiple clinical parameters were compared between NEC patients with no congenital heart disease (n=102) and those with isolated PDA (n=29). Univariate, multivariate and stepwise logistic regression analyses were performed. RESULTS Birth weight and gestational age were significantly lower in patients with PDA [median (95% CI): 1120 g (1009-1562 g), 28.4 wk (27.8-30.5 wk)] than in those without PDA [median (95% CI): 1580 g (1593-1905 g), 32.4 wk (31.8-33.5 wk); P

The pattern-recognition molecule M-ficolin is synthesized by monocytes and neutrophils. M-ficolin activates the complement system in a manner similar to mannan-binding lectin (MBL), but little is known about its role in host defense. Neonates are highly vulnerable to bacterial sepsis, in particular, due to their decreased phagocytic function.M-ficolin cord blood concentration was positively correlated with the absolute phagocyte count (ρ 0.51, P0.001) and with immature/total neutrophil ratio (ρ 0.34, P0.001). When comparing infants with sepsis and controls, a high M-ficolin cord blood concentration (1,000 ng/ml) was associated with early-onset sepsis (EOS) (multivariate odds ratio 10.92, 95% confidence interval 2.21-54.02, P = 0.003). Experimental exposure of phagocytes isolated from adult donors to Escherichia coli resulted in a significant time- and dose-dependent release of M-ficolin.In conclusion, M-ficolin concentrations were related to circulating phagocytes and EOS. Our results indicate that bacterial sepsis can trigger M-ficolin release by phagocytes. Future studies should investigate whether M-ficolin may be used as a marker of neutrophil activation during invasive infections.We investigated M-ficolin in 47 infants with culture-positive sepsis during the first 30 days of life (13 with EOS and in 94 matched controls. M-ficolin was measured in cord blood using time-resolved immunofluorometric assay (TRIFMA). Multivariate logistic regression was performed.

OBJECTIVES: To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants. METHODS: A multicenter randomized controlled trial in 3 NICUs in Switzerland compared the effectiveness of oral sucrose, facilitated tucking (FT), and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation. Data were collected during the first 14 days of their NICU stay. Three phases (baseline, heel stick, recovery) of 5 heel stick procedures were videotaped for each infant. Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in random order by using the Bernese Pain Scale for Neonates, a validated pain tool. RESULTS: Seventy-one infants were included in the study. Interrater reliability was high for the total Bernese Pain Scale for Neonates score (Cronbach’s α: 0.90–0.95). FT alone was significantly less effective in relieving repeated procedural pain (P < .002) than sucrose (0.2 mL/kg). FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores (P = .003) compared with both the single-treatment groups. There were no significant differences in pain responses across gestational ages. CONCLUSIONS: Sucrose with and without FT had pain-relieving effects even in preterm infants of

The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome.PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases.Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of30% of total body surface area. Stevens-Johnson syndrome affects10%, whereas involvement of 10%-30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%-50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved.Profound knowledge of exfoliative skin diseases is needed to improve therapy and outcome of these life-threatening illnesses.

Objective: Fetuses are exposed to high concentrations of estradiol due to placental production. Experimental data suggest that estradiol is an important modulator of the immune response. However, the role of estradiol in the pathogenesis of early-onset neonatal sepsis (EOS) is unknown. The purpose of this pilot study was to determine estradiol levels in umbilical venous blood of newborns with EOS or chorioamnionitis exposure. Methods: Estradiol concentrations were measured by enzyme immunoassay in 37 newborns with EOS, 37 newborns with chorioamnionitis and 37 controls matched for gestational age and gender. Results: Estradiol levels correlated with gestational age, birth weight, gender and mode of delivery (p < 0.05). Multivariate analysis revealed higher estradiol levels in the EOS than in the chorioamnionitis group (odds ratio 8.43, 95% CI 1.63-43.45, p = 0.01) with the highest levels in patients with proven bacteraemia (p = 0.02). No difference was found between the EOS and the control group. Exploratory analysis showed an association between lower estradiol levels and a longer duration of mechanical ventilation (n = 28, p = 0.02). Conclusion: Umbilical venous estradiol levels were similar in EOS compared to controls. Further investigation is needed to evaluate whether high estradiol levels in infants with chorioamnionitis increases the risk of developing EOS.

Color light therapy is a therapeutic method in complementary medicine. In color therapy, light of two contrasting colors is often applied in a sequential order. The aim of this study was to investigate possible physiological effects, i.e., changes in the blood volume and oxygenation in the brain and calf muscle of healthy subjects who were exposed to red and blue light in sequential order. The hypothesis was that if a subject is first exposed to blue and then red light, the effect of the red light will be enhanced due to the contrastingly different characteristics of the two colors. The same was expected for blue light, if first exposing a subject to red and then to blue light. Twelve healthy volunteers (six male, six female) were measured twice on two different days by near-infrared spectroscopy during exposure to colored light. Two sequences of colored light were applied in a controlled, randomized, crossover design: first blue, then red, and vice versa. For the brain and muscle, the results showed no significant differences in blood volume and oxygenation between the two sequences, and a high interindividual physiological variability. Thus, the hypothesis had to be rejected. Comparing these data to results from a previous study, where subjects were exposed to blue and red light without sequential color changes, shows that the results of the current study appear to be similar to those of red light exposure. This may indicate that the exposure to red light was preponderant and thus effects of blue light were outweighed.

Clinical trials have reported statistically significant and clinically relevant effects of homeopathic preparations. We applied ultraviolet (UV) spectroscopy to investigate the physical properties of homeopathic preparations and to contribute to an understanding of the not-yet-identified mode of action. In previous investigations, homeopathic preparations had significantly lower UV light transmissions than controls. The aim of this study was to explore the possible effects of external factors (UV light and temperature) on the homeopathic preparations. Homeopathic centesimal (c) dilutions, 1c to 30c, of copper sulfate (CuSO4), decimal dilutions of sulfur (S8), 1x to 30x, and controls (succussed potentization medium) were prepared, randomized, and blinded. UV transmission was measured at six different time points after preparation (from 4 to 256 days). In addition, one series of samples was exposed to UV light of a sterilization lamp for 12 h, one was incubated at 37°C for 24 h, and one was heated to 90°C for 15 min. UV light transmission values from 190 or 220 nm to 340 nm were measured several times and averaged. After each exposure, UV transmission of the homeopathic preparations of CuSO4was significantly reduced compared to the controls, particularly after heating to 37°C. Overall, the nonexposed CuSO4preparations did not show significantly lower UV transmission compared to controls; however, the pooled subgroup of measurements at days 26, 33, and 110 yielded significant differences. UV light transmission for S8preparations did not show any differences compared to controls. Our conclusion is that exposure to external factors, incubation at 37°C in particular, increases the difference in light transmission of homeopathic CuSO4 preparations compared to controls.