Pain responses in preterm infants and parental stress over repeated painful procedures: a randomized pilot trial.

OBJECTIVES: In this pilot study, the aims were to determine the feasibility of whether pain behavior in extremely and very preterm infants and perceived parental stress change when parents are involved in pain reducing measures, either actively, performing facilitated tucking or passively, observing the intervention, in comparison to the involvement of nurses only. In addition, the infant's pain reactivity and parental stress over three time points of measurement was of interest. METHODS: Extremely and very preterm infants in need of subcutaneous erythropoietin were randomly assigned to the two intervention groups. The intervention encompassed that one parent of each infant was involved during the painful procedure: Either parents executed facilitated tucking themselves or stood by, observing the procedure. Usual care involved that nurse executed facilitated tucking. All infants received 0.5 ml of 30% oral glucose solution via cotton swab before the painful procedure. Infant pain was observed with the Bernese Pain Scale for Neonates (BPSN) and measured with the MedStorm skin conductance algesimeter (SCA) before, during, and after the procedure. Parents' stress levels were measured before and after the painful procedure on the infant, using the Current Strain Short Questionnaire (CSSQ). Feasibility of a subsequent trial was determined by assessing recruitment, measurement and active parental involvement. Quantitative data collection methods (i.e. questionnaires, algesimeter) were employed to determine the number of participants for a larger trial and measurement adequacy. Qualitative data (interviews) was employed to determine parents' perspectives of their involvement. RESULTS: A total of 13 infants (98% participation rate) were included along with their mothers. Median gestational age was 27 weeks (IQR 26-28 weeks), 62% were female. Two infants (12.5%) dropped out of the study as they were transferred to another hospital. Facilitated tucking turned out to be a good method to actively involve parents in pain reducing measures. No significant differences between the two intervention and control groups were found concerning parental stress and infant pain (p = .927). Power analysis indicated that at least N = 741 infants (power of 81%, α = .05) would be needed to obtain statistically significant results in a larger trial, as effect sizes were smaller than expected. Two of the three measurement tools - i.e. the BPSN and CSSQ) - proved easy to implement and were well accepted. owever, the SCA was challenging in this context. Measurements were also found to be time-consuming and resource-intense (i.e. health professionals as assistants). CONCLUSIONS: Although the intervention was feasible and was readily accepted by parents, the study design was found to be challenging along with the SCA. In preparation of the larger trial, the study design needs to be revisited and adjusted. Thus, issues of time and resources may be resolved. In addition, national and international collaboration with similar neonatal intensive care units (NICU) needs to be considered. Thus, it will be possible to conduct an appropriately powered larger trial, which will yield important results to improve pain management in extremely and preterm infants in NICU.

Enhancing Parents' Well-Being after Preterm Birth-A Qualitative Evaluation of the "Transition to Home" Model of Care.

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.

Ear Acupuncture Points in Neonates From Drug-Dependent Mothers: A Prospective Study.

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 in n = 26 newborn children born to drug-dependent mothers compared with n = 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 and p = 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.

High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity.

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 <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. 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.

Euphrasia Eye Drops in Preterm Neonates With Ocular Discharge: A Randomized Double-Blind Placebo-Controlled Trial.

Aim: To investigate whether the early administration of Euphrasia eye drops® in preterm neonates presenting with ocular discharge fosters the resolution of the ocular discharge and reduces the need for topical antibiotic therapy, as compared to placebo. Methods: We conducted a randomized double-blind placebo-controlled trial at the University Children's Hospital Bern, Switzerland. Preterm neonates with white, yellow, or green ocular discharge were included. Infants were randomly assigned (1:1) to the Euphrasia arm (Euphrasia eye drops®, Weleda AG, Arlesheim) or the placebo arm (NaCl 0.9%). Euphrasia or placebo was administrated at a dose of one drop in each eye four times a day over a period of 96 h. The primary outcome was the treatment success, defined as no ocular discharge at 96 h and no use of topical antibiotic therapy during the 96-h intervention. Results: A total of 114 neonates were screened and 84 were randomized. Among neonates in the Euphrasia arm, 22 (55.0%) achieved our primary outcome compared to 21 (51.2%) in the placebo arm (p = 0.85). In the Euphrasia arm, time to resolution of reddening tended to fall within the shorter bracket of 24 to 48 h (24 (92.3%) vs. 12 (80.0%) in the placebo arm, p = 0.34) and relapse or first signs of reddening during the 96-h intervention tended to be lower [3 (7.9%) eyes vs. 8 (18.2%) eyes in the placebo arm, p = 0.17]. Tearing at 96 h tended to be lower in the Euphrasia arm [5 (12.8%) eyes in the Euphrasia arm vs. 12 (27.3%) eyes in the placebo arm, p = 0.10]. Discussion: Euphrasia did not significantly improve treatment success, defined as no ocular discharge at 96 h and no use of topical antibiotic therapy during the 96-h intervention. However, results suggest that Euphrasia may be of benefit for symptoms such as reddening and tearing, and thus improve the comfort of patients. Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04122300 and at the portal for human research in Switzerland SNCTP000003490.

Acute pain measured with the modified Bernese Pain Scale for Neonates is influenced by individual contextual factors.

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 factors into a revised version of the BPSN. METHODS: We videotaped 154 full-term and preterm neonates of different GAs during 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 factors 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 revised 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.

Changepoint analysis of gestational age and birth weight: proposing a refinement of Diagnosis Related Groups.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The influence of gestational age in the psychometric testing of the Bernese Pain Scale for Neonates.

BACKGROUND: Assessing pain in neonates is challenging because full-term and preterm neonates of different gestational ages (GAs) have widely varied reactions to pain. We validated the Bernese Pain Scale for Neonates (BPSN) by testing its use among a large sample of neonates that represented all GAs. METHODS: In this prospective multisite validation study, we assessed 154 neonates between 24 2/7 and 41 4/7 weeks GA, based on the results of 1-5 capillary heel sticks in their first 14 days of life. From each heel stick, we produced three video sequences: baseline; heel stick; and, recovery. Five blinded nurses rated neonates' pain responses according to the BPSN. The underlying factor structure of the BPSN, interrater reliability, concurrent validity with the Premature Infant Pain Profile-Revised (PIPP-R), construct validity, sensitivity and specificity, and the relationship between behavioural and physiological indicators were explored. We considered GA and gender as individual contextual factors. RESULTS: The factor analyses resulted in a model where the following behaviours best fit the data: crying; facial expression; and, posture. Pain scores for these behavioural items increased on average more than 1 point during the heel stick phases compared to the baseline and recovery phases (p < 0.001). Among physiological items, heart rate was more sensitive to pain than oxygen saturation. Heart rate averaged 0.646 points higher during the heel stick than the recovery phases (p < 0.001). GA increased along with pain scores: for every additional week of gestation, the average increase of behavioural pain score was 0.063 points (SE = 0.01, t = 5.49); average heart rate increased 0.042 points (SE = 0.01, t = 6.15). Sensitivity and specificity analyses indicated that the cut-off should increase with GA. Modified BPSN showed good concurrent validity with the PIPP-R (r = 0.600-0.758, p < 0.001). Correlations between the modified behavioural subscale and the item heart rate were low (r = 0.102-0.379). CONCLUSIONS: The modified BPSN that includes facial expression, crying, posture, and heart rate is a reliable and valid tool for assessing acute pain in full-term and preterm neonates, but our results suggest that adding different cut-off points for different GA-groups will improve the BPSN's clinical usefulness. TRIAL REGISTRATION: The study was retrospectively registered in the database of Clinical Trial gov. Study ID-number: NCT 02749461 . Registration date: 12 April 2016.

Congenital Heart Disease Increases Mortality in Neonates With Necrotizing Enterocolitis.

Background: Studies on the influence of congenital heart disease (CHD) on neonates with necrotizing enterocolitis (NEC) have produced varied results. We therefore examined the influence of CHD on NEC outcomes. Methods: We carried out a retrospective single-center study including infants with confirmed NEC, treated between 2004 and 2017. We excluded patients with isolated patent ductus arteriosus or pulmonary hypertension (n = 45) and compared outcomes of patients with hemodynamically relevant CHD (n = 38) and those without CHD (n = 91). Results: Patients with CHD were more mature than those without CHD [gestational age, median, 95% confidence interval (CI95), 37.1, 34.5-37.2w, vs. 32.6, 31.9-33.3w; P < 0.01]. The presence of CHD did not influence the frequencies of severe disease (overall 21% Bell stage III), nor surgical interventions (overall 30%), the occurrence of intestinal complications (overall 13%), nor the duration of hospitalization (overall 38 days in survivors). The overall mortality as well as NEC-related mortality was increased with the presence of CHD, being 50% (19 out of 38) and 13% (5 out of 38), respectively, when compared to patients without CHD, being 8% (7 out of 91) and 3% (3 out of 91). The presence of CHD and of advanced NEC stage III were independent predictors of NEC-associated fatalities with multivariable odds ratios (CI95) of 7.0, 1.3-39.5 for CHD, and of 3.4, 1.6-7.5 for stage III disease. Conclusions: While some outcome parameters in neonates with NEC remained unaffected by the presence of CHD, the mortality risk for patients with CHD was seven times higher than without CHD.

Prediction of ROP Treatment and Evaluation of Screening Criteria in VLBW Infants-a Population Based Analysis.

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 <32 0/7 weeks. Chronological and postmenstrual ages at ROP treatment were analyzed. A model to identify ROP treatment on patients born between 2006 and 2012 (training set) was developed and tested on patients born between 2013 and 2015 (validation set). RESULTS: Of 7817 live-born infants, 1098 died within the first 5 weeks of life. The remaining 6719 infants were included into analysis. All patients requiring ROP treatment would have been identified if screening had been performed before reaching 60 days of life or 37 3/7 weeks postmenstrual age, whichever came first. The training and validation sets included 4522 and 2197 preterm infants encompassing 56 and 20 patients receiving ROP treatment, respectively. All patients would have required screening to reach 100% sensitivity. To reach a sensitivity of 95.0% and a specificity of 87.6%, we predicted a reduction in 13.2% of patients requiring screening (c-statistic = 0.916). CONCLUSIONS: A substantial reduction of infants requiring screening seems possible, but necessitates prospective testing of new screening criteria.

Patterns of paediatric end-of-life care: a chart review across different care settings in Switzerland.

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.

Do late preterm twins face an increased neonatal morbidity compared with singletons?

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 <0.001) and late preterm singletons (n = 495) (13.5 ± 8.0 vs 12.6 ± 8.6 days, p = 0.011). Hyperbilirubinaemia occurred significantly more often in late preterm singletons than in late preterm twins (49.7 vs 29.2%; p<0.001). Otherwise, no significant differences were detected regarding neonatal morbidities or mortality of late preterm singletons and late preterm twins. Late preterm twins had a significantly higher incidence of most morbidities than term twins. CONCLUSION: Late preterm twins are hospitalised significantly longer than similar-aged singletons, but have otherwise similar neonatal morbidities. Hyperbilirubinaemia is less frequent in late preterm twins than late preterm singletons.

Incidence of retinopathy of prematurity (ROP) and ROP treatment in Switzerland 2006-2015: a population-based analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a severe complication of preterm birth and can lead to severe visual impairment or even blindness if untreated. The incidence of ROP requiring treatment is increasing in some developed countries in conjunction with higher survival rates at the lower end of gestational age (GA). MATERIAL AND METHODS: The incidence of ROP and severe ROP (sROP) requiring treatment in Switzerland was analysed using the SwissNeoNet registry. We conducted a retrospective cohort analysis of very preterm infants with a GA below 32 weeks who were born between 2006 and 2015 in Switzerland. Patient characteristics were stratified according to GA. RESULTS: 9.3% and 1.8% of very preterm infants in Switzerland developed ROP of any stage and sROP, respectively. The incidence of ROP treatment was 1.2%. Patients with 24 and 25 weeks GA had the highest proportion of ROP treatment at 14.5% and 7.3%, respectively, whereas the proportion of treated infants at or above a GA of 29 weeks was 0.06%. Similarly, the risk of sROP declined strongly with increasing GA. During the observation period of 10 years, the incidence of ROP treatment ranged between 0.8% and 2.0%. Incidences of sROP or ROP treatment did not increase over time. CONCLUSION: The incidence of ROP treatment in Switzerland is low and was stable over the analysed period. The low incidence of sROP in patients with a GA of 29 weeks or more leaves room for a redefinition of ROP screening criteria.

Individual contextual factors in the validation of the Bernese pain scale for neonates: protocol for a prospective observational study.

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.

Asphyxia in the Newborn: Evaluating the Accuracy of ICD Coding, Clinical Diagnosis and Reimbursement: Observational Study at a Swiss Tertiary Care Center on Routinely Collected Health Data from 2012-2015.

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.

Length Normalized Indices for Fat Mass and Fat-Free Mass in Preterm and Term Infants during the First Six Months of Life.

OBJECTIVE: Postnatal tissue accretion in preterm infants differs from those in utero, affecting body composition (BC) and lifelong morbidity. Length normalized BC data allows infants with different body lengths to be compared and followed longitudinally. This study aims to analyze BC of preterm and term infants during the first six months of life. METHODS: The BC data, measured using dual energy X-ray absorptiometry, of 389 preterm and 132 term infants from four longitudinal studies were combined. Fat-mass/length² (FMI) and fat-free mass/length² (FFMI) for postmenstrual age were calculated after reaching full enteral feeding, at term and two further time points up to six months corrected age. RESULTS: Median FMI (preterm) increased from 0.4 kg/m² at 30 weeks to 2.5, 4.3, and 4.8 kg/m² compared to 1.7, 4.7, and 6 kg/m² in term infants at 40, 52, and 64 weeks, respectively. Median FFMI (preterm) increased from 8.5 kg/m² (30 weeks) to 11.4 kg/m² (45 weeks) and remained constant thereafter, whereas term FFMI remained constant at 11 kg/m² throughout the tested time points. CONCLUSION: The study provides a large dataset of length normalized BC indices. Followed longitudinally, term and preterm infants differ considerably during early infancy in the pattern of change in FMI and FFMI for age.

Outcome in neonates with necrotizing enterocolitis and patent ductus arteriosus.

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<0.05]. The risk of NEC-attributable fatality was higher in NEC patients with PDA (35%) than in NEC patients without PDA (14%)[univariate odds ratio (OR)=3.3, 95% CI: 1.8-8.6, P<0.05; multivariate OR=2.4, 95% CI: 0.82-2.39, P=0.111]. Significant independent predictors for non-survival within the entire cohort were advanced disease severity stage III (OR=27.9, 95% CI: 7.4-105, P<0.001) and birth weight below 1100 g (OR=5.7, 95% CI: 1.7-19.4, P<0.01). CONCLUSIONS: In patients with NEC, the presence of PDA is associated with an increased risk of death. However, when important differences between the two study groups are controlled, only birth weight and disease severity may independently predict mortality.

Less invasive ventilation in extremely low birth weight infants from 1997 to 2011: survey versus evidence.

Evidence for target values of arterial oxygen saturation (SaO2), CO2, and pH has changed substantially over the last 20 years. A representative survey concerning treatment strategies in extremely low-birth-weight infants (ELBW) 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. During the observation period, NICUs targeting SaO2 of 80, 85, and 90 % have increased, while units aiming for 94 and 96 % decreased (all p < 0.001). Similarly, NICUs aiming for pH 7.25 or lower increased, while 7.35 or higher decreased (both p < 0.001). Furthermore, more units targeted a CO2 of 50 mmHg (7.3 kPa) or higher (p < 0.001), while fewer targeted 40 or 35 mmHg (p < 0.001). Non-invasive ventilation (NIV) was used in 80.2 % of NICUs in 2011. The most frequently used ventilation modes were synchronized intermittent mandatory ventilation (SIMV) (67.5 %) and intermittent positive pressure ventilation (IPPV) (59.7 %) in 1997 and SIMV (77.2 %) and synchronized intermittent positive pressure ventilation (SIPPV) (26.8 %) in 2011. NICUs reporting frequent or always use of IPPV decreased to 11.0 % (p < 0.001). SIMV (77.2 %) and SIPPV (26.8 %) did not change from 1997 to 2011, while high-frequency oscillation (HFO) increased from 9.1 to 19.7 % (p = 0.018). Differences between countries, level of care, and size of the NICU were minimal. CONCLUSIONS: Target values for SaO2 decreased, while CO2 and pH increased significantly during the observation period. Current values largely reflect available evidence at time of the surveys. WHAT IS KNOWN: • Evidence concerning target values of oxygen saturation, CO 2 , and pH in extremely low-birth-weight infants has grown substantially. • It is not known to which extent this knowledge is transferred into clinical practice and if treatment strategies have changed. WHAT IS NEW: • Target values for oxygen saturation in ELBW infants decreased between 1997 and 2011 while target values for CO 2 and pH increased. • Similar treatment strategies existed in different countries, hospitals of different size, or university versus nonuniversity hospitals in 2011.

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease.

BACKGROUND: Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS: Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS: The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS: Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER: NCT02164604; Date of registration: 13.06.2014.