TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro-BNP performance.

AIM: Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants. METHODS: Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development. RESULTS: Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28). CONCLUSION: The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.

Decreased neonatal pain response after vaginal-operative delivery with Kiwi OmniCup versus metal ventouse.

BACKGROUND: Vaginal delivery, especially operative assisted vaginal delivery, seems to be a major stressor for the neonate. The objective of this study was to evaluate the stress response after metal cup versus Kiwi Omnicup® ventouse delivery. METHODS: The study was a secondary observational analysis of data from a former prospective randomised placebo controlled multicentre study on the analgesic effect of acetaminophen in neonates after operative vaginal delivery and took place at three Swiss tertiary hospitals. Healthy pregnant women ≥35 weeks of gestation with an estimated fetal birth weight above 2000 g were recruited after admission to the labour ward. Pain reaction was analysed by pain expression score EDIN scale (Échelle Douleur Inconfort Nouveau-Né, neonatal pain and discomfort scale) directly after delivery. For measurement of the biochemical stress response, salivary cortisol as well as the Bernese Pain Scale of Newborns (BPSN) were evaluated before and after an acute pain stimulus (the standard heel prick for metabolic testing (Guthrie test)) at 48-72 h. RESULTS: Infants born by vaginal operative delivery displayed a lower pain response after plastic cup than metal cup ventouse delivery (p < 0.001), but the pain response was generally lower than expected and they recovered fully within 72 h. CONCLUSIONS: Neonatal pain response is slightly reduced after use of Kiwi OmniCup® versus metal cup ventouse. TRIAL REGISTRATION: Trial was registered under under NCT00488540 on 19th June 2007.

Neonatal Abstinence Syndrome: Twelve Years of Experience at a Regional Referral Center.

Infants exposed to opiates antenatally display withdrawal symptoms after birth referred to as neonatal abstinence syndrome (NAS).A total of 366 newborns (166 females, 10 twins) from 361 mothers were diagnosed with NAS from 2000 to 2011 at a single large metropolitan referral center.Retrospective chart review of all newborn infants exposed to opiates in utero.20% were premature (gestational age<37 weeks), 32% were small-for-gestational-age (<10th percentile). 70% of infants (195/278) antenatally exposed to methadone (racemic methadone or levomethadone) required pharmacological treatment for 11 (1-55) days (median; range); however, 45% of infants (28/62) exposed to buprenorphine required pharmacological treatment for a median of only 5 (1-20) days (p=0.014). Pharmacological treatment of infants with phenobarbital (n=189) took a median of 9 (1-53) days, but treatment with morphine (n=39) took 19 (3-55) days (p<0.001). The median duration of hospitalization increased from 11 days in 2000-2004 to 19 days in 2008-2011 (p<0.001). The increased durations of neonatal hospitalization were associated with similar increases in the average dosages of maternal methadone.Use of buprenorphine, rather than methadone, for treatment of opiate-addicted pregnant women is associated with fewer and shorter neonatal withdrawal symptoms. The duration of hospitalization and treatment for NAS has increased over time.

[Survival, Medical Care and Quality of Life in Children with Trisomy 13 and 18]. / Überleben, medizinische Betreuung und Lebensqualität von Kindern mit Trisomie 13 und 18.

BACKGROUND: While infants with trisomy 13 (T13) and trisomy 18 (T18) are known to die early, parents want to know more about life expectancy and quality of life. METHODS: 30-year single-center retrospective chart analysis (1980-2010) of cytogenetically confirmed T13 and T18 cases. Mothers of infants who had lived 3 months or longer were approached to judge their infant's quality of life and talk about their experiences with medical staff. RESULTS: Data of 18/20 T13 infants and 18/21 T18 infants could be retrieved. Median survival times were 5 d for T13 and 19 d for T18. One T13 and 2T18 children survived past 1 year. Out of 5 mothers whose infants had survived at least 3 months, 4 described their infant as friendly, happy and peaceful. They observed some degree of psychomotor development and were in favour of the numerous medical and surgical interventions performed. They wished to have had a doctor coordinating these interventions and missed an active offer for psychological help. CONCLUSION: While most infants with T13 or T18 die as neonates, mothers of infants surviving longer periods of time have positive memories about their infants' quality of life.

Electrocortical Activity at 7 Days of Life is Affected in Extremely Premature Infants with Patent Ductus Arteriosus.

BACKGROUND: The aim of this study was to determine whether the aEEG at 7 days of life is influenced by the presence of a PDA in non-sedated extremely low gestational age preterm infants. PATIENTS: We prospectively recruited infants born at less than 28 weeks of gestation between 11/2007 and 12/2009. METHOD: aEEGs were recorded at seven days of life and assessed by using the Burdjalov score and the electronically assessed lower border (eLBA). Kruskal-Wallis-Test and linear regression analysis were performed to determine how GA and a PDA affect the aEEG score and the eLBA. Using linear regression analysis we tested which components of the score are affected by a PDA. RESULTS: We recruited 44 infants with a GA of 26.5/7 (23.4/7-27.6/7) weeks and a birth weight of 837 (461-1230) g. The total sum of score points increased from 4 (1-6) to 8 (5-9) points in infants born at 23/24 weeks and 27 weeks of gestation, respectively. In infants with relevant PDA the aEEG scored lower with 8 (3-10) points compared to those with PDA: 5 (1-8) points. Linear regression analysis showed a positive influence of GA and a negative influence of a PDA on the total score. GA had a positive influence on SWC and the visually assessed LBA. A PDA had a negative influence on continuity. The eLBA increased from 4.61 (3.18-5.53) µV to 5.27 (3.38-6.51) µV in infants of 23/24 vs. 27 gestational weeks, but was not significantly influenced by a PDA. CONCLUSION: A PDA has a negative influence on the total Burdjalov score and continuity at 7 days of age in infants born at less than 28 weeks of gestation. The electrocortical disturbances may be the consequence of a diminished cerebral perfusion in the presence of a PDA.

[Age-related characteristics of the efficacy of different glucocorticosteroids in the therapy of acute lymphoblastic leukemia].

AIM: To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL). SUBJECTS AND METHODS: The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525). RESULTS: The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (p=0.046); therapy-induced mortality was 6.4% (DEXA) andl 1.1% (MePRED) (p=0.01 4); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) (p=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (p=0.087); OS, 72±6 and 61±6%, respectively; (p=0.l 7). CONCLUSION: The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient's age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.

Postnatal maturation of skin barrier function in premature infants.

BACKGROUND: In preterm infants, skin barrier maturation entails regional variability. OBJECTIVES: To characterize postnatal skin barrier development in covered, uncovered and diapered regions in healthy premature infants over a longitudinal observation period. METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), pH and sebum were measured at postnatal ages of 1-7 days and 2-7 weeks on the forehead, abdomen, thigh and buttock of preterm infants (gestational age 30-37 weeks; n = 48) under monitored ambient conditions. A standard minimal skin care regimen was practised. RESULTS: TEWL increased significantly on the buttock (p = 0.007), while remaining stable on the forehead, abdomen and thigh. SCH and sebum remained stable in all studied body regions with increasing age. On the buttock, pH increased (p = 0.049), while other body regions exhibited a significant decrease (p ≤ 0.019). TEWL (p < 0.001) and SCH (p ≤ 0.002) revealed significantly higher values on the buttock, compared to other body regions. CONCLUSIONS: Stable TEWL, SCH and sebum values may indicate a lack of skin barrier maturation. Postnatal decrease in skin pH suggests an adaptation process with acid mantle formation. Differences in skin barrier development were observed between anatomical regions. SCH, TEWL and pH values demonstrated a distinct course in the diaper area, indicating an impaired skin barrier function in this region.

Predictive and concurrent validity of standardized neurodevelopmental examinations by the Griffiths scales and Bayley scales of infant development II.

Standardized examinations of preterm infants are used to identify candidates for early intervention. We aimed to assess the predictive power and concurrent validity of the mental development index of the Bayley scales of infant development II (Bayley MDI) and the Griffiths scales developmental quotient (Griffiths DQ) in healthy term and preterm infants <1500 g birth weight without major perinatal complications.137 Infants (89 term, 48 preterm) were examined by both tests at a corrected age of 6, 12, and 22 months, and 114 went on to undergo Bayley assessments at 39 months.There were significant correlations between Bayley and Griffiths results at 6, 12, and 22 months (r=0.530, 0.714, and 0.833, respectively, p<0.001) but Bland Altman plots revealed major systematic bias at 6 months (Griffiths>Bayley, mean differences 14.3±9.8) and 22 months (Bayley>Griffiths, mean difference 5.2±13.9) and wide 95% limits of agreement at 6, 12 and 22 months (35.9%, 40.0%, and 52.4%, respectively). The agreement for a presumptive diagnosis of developmental impairment in the group of preterm infants between Bayley examinations obtained at 39 months corrected age (reference) and previous examinations was poor at 6, 12, and 22 months for both Bayley and Griffiths (Cohen's kappa for Griffiths: 0.225, 0.192, 0.369; for Bayley: 0.121, 0.316, 0.369, respectively).Caution should be exercised when interpreting results from standardized neurodevelopmental examinations obtained during the first 2 years of life in comparatively well preterm infants.

[Google translate is not sufficient to overcome language barriers in neonatal medicine]. / Erste Erfahrungen mit Google Translate in der Neonatologie.

Language barriers hinder the interaction with patients and relatives. The use of language services increases knowledge, satisfaction and the use of medical care and thus improves patient's clinical outcome. The recommended use of professional interpreters (PI) is not always feasible. We tested an online translation tool as an alternative for PI for the transla-tion of standardized sentences from a neonatal doctor-/nurse-relative-interview.Translation of 20 sentences from a German neonatal intensive care unit parent information brochure to English, Portuguese and Arabic, using Google Translate (GT). Assessment of accuracy concerning grammar and content, in a second step simplification of all incorrect sentences, translation by GT and critical re-assessment and evaluation.An average of 42% of the sentences was correctly translated concerning grammar and content. The proportion of incorrectly translated sentences varied between 45-70%. By simpli-fication another 23% were translated correctly.Translations by GT were often incorrect in content and grammar. We suppose that the design of GT, which is a statistical translation engine, might be an explanation for this phenomenon. Presently, GT cannot guarantee unambiguous translations and cannot substitute PIs, only in particular circumstances, the use of GT or similar engines may be justified. For future use of electronic translation services, we suggest to compile a catalogue of sentences containing central information, which can be translated into defined foreign languages without misinterpretation or loss of information.

[Individual neonatal end-of-life care and family-centred bereavement support]. / Familienzentrierte Sterbe- und individuelle Trauerbegleitung an einem Perinatalzentrum.

Neonatal end-of-life care and family-centred bereavement support in perinatal medicine are a multiprofessional challenge directed to the dying newborn and the parents as well as to the care-givers. Clinical experience shows that many aspects of individual neonatal end-of-life care and family-centred bereavement support are not well known to the health-care providers. This is especially true for a standardised quality management and the components of bereavement support offered to parents. An interdisciplinary concept for an individual neonatal end-of-life care and famlily-centred bereavement support has been developed at the Center of Perinatal Medicine at the Charité, Berlin. The concept aims for two main aspects: (1) meeting the individual medical, psychological, emotional and spiritual needs of the dying newborn, the parents and family, and (2) facilitating standardised and process-orientated preparation, evaluation and reflexion of every case of end-of-life care. In this article some recommendations for implementing a basic care concept for families and their dying newborns are presented.

[Postnatal therapy for congenital toxoplasmosis: a comparison of 2 different treatment approaches]. / Postnatale Therapie der konnatalen Toxoplasmose: Ein Vergleich zweier unterschiedlicher Vorgehensweisen.

Protocols recommended in the USA and Germany for the postnatal treatment of congenital toxoplasmosis are mainly based on the National Collaborative Chicago-based Congenital Toxoplasmosis Study that calls for daily administration of pyrimethamine in combination with sulfadiazine for several months, then 3 times a week. The recommended total duration of treatment is 12 months. This scheme necessitates frequent white blood cell counts that often result in the discontinuation of treatment because of severe neutropenia even with the concomitant administration of folinic acid. In contrast, the administration of pyrimethamine with sulfadoxine every 2 weeks for 2 years, as used by a referral centre in Toulouse, France, is associated with less toxicity. The efficacy may even be improved, as judged by the rate of new chorioretinal lesions. In the absence of larger randomised studies the Toulouse protocol appears to have several advantages when a decision has to be made to treat infants with congenital toxoplasmosis.

[Treating Neonates with Levetiracetam: a survey among German University Hospitals]. / Übersicht über den Einsatz von Levetiracetam bei Neugeborenen an deutschen Universitätskliniken.

In contrast to drugs established to treat neonatal seizures, levetiracetam shows little neurotoxicity in experimental animal models and has good safety records in adults and children. Here, we present results from a survey on the off-label use of levetiracetam in newborn infants among neonatologists and pediatric neurologists in German university hospitals.

The 2010 Guidelines on Neonatal Resuscitation (AHA, ERC, ILCOR): similarities and differences--what progress has been made since 2005?

In 2010, the American Heart Association (AHA), the European Resuscitation Council (ERC) and the International Liaison Committee on Resuscitation (ILCOR) issued new guidelines on newborn resuscitation. The new recommendations include: (1) pulse-oximetry for patient assessment during newborn resuscitation; (2) to start resuscitation of term infants with an FiO (2) of 0.21; (3) cardio-respiratory resuscitation with a 3:1 chest compression/inflation ratio for a heart rate <60 beats/min; (4) regarding infants born from meconium stained amniotic fluid: no recommendation is given to suction the upper airways at the perineum (when the head is born), but it is recommended to inspect the oropharynx and trachea for obstruction and suction the lower airway before inflations are given when the infant is depressed; (5) for birth asphyxia in term or near term infants, to induce hypothermia (33.5-34.5°C) within 6 h after birth. AHA, ERC and ILCOR used nearly identical literature for their evidence evaluation process. While the AHA and ILCOR guidelines are almost identical, the ERC guidelines differ slightly from the latter with regards to (i) promoting sustained inflations at birth, (ii) promoting a wider range in applied inflations during resuscitation, and (iii) to suction the airways in infants born from meconium stained amniotic fluid, before inflations are given.

Predicting neurodevelopmental impairment in preterm infants by standardized neurological assessments at 6 and 12 months corrected age.

AIM: Neurodevelopmental impairment in very preterm infants can be reasonably diagnosed by 18-24 months corrected age, whereas the predictive value of earlier assessments is debated. We hypothesized that neurological findings at 6 and 12 months indicative of subsequent cerebral palsy predict 18-24 months' neurodevelopmental impairment. METHODS: Neurodevelopmental examinations (Griffiths scales) at 20 months of age in 561 preterm infants (birth weight <1 500 g) were compared with results of standardized neurological examinations (Early Motor Pattern Profile; EMPP) and Griffiths scales at 6 (n = 451) and 12 months (n = 496) corrected age. RESULTS: Griffiths developmental quotients at 20 months were weakly but significantly related to EMPP scores at 6 (R(s) = 0.328) and 12 months (R(s) = 0.493). Areas under receiver operator characteristic curves for the EMPP to predict neurodevelopmental impairment (Griffiths scores

Probiotics for prevention of necrotising enterocolitis: an updated meta-analysis.

Several randomized controlled trials (RCTs) have investigated the prophylactic use of probiotics in preterm infants aimed at reducing the rate of necrotising enterocolitis (NEC). There are 4 meta-analyses on this subject. 2 more RCTs have been published since these meta-analyses were completed. Each meta-analysis, as well as the 2 recent RCTs, document reduced rates of NEC and mortality with the use of prophylactic probiotics. We calculated meta-analyses based on 3 approaches: A - RCTs common to all meta-analyses, B - RCTs ever accounted for in a meta-analysis but not common to all, and C - the 2 recent RCTs. The 3 subgroups yield similar results, with an overall reduction in the relative risk (RR) of NEC (Bell > or =2) to 0.35 (95% CI 0.23-0.55) and of mortality to 0.41 (0.28-0.60). NEC rates and mortalities in the dominant RCTs are in the range reported from North American and European networks. Best results appear to be achieved with probiotics based on 2 or more probiotic species and/or with a combination of Bifidusbacterium spp. and Lactobacillus acidophilus. No unwanted side effects have been reported among 1 117 infants randomized to receive probiotics. We conclude that probiotics are safe and beneficial in preterm infants at risk for NEC.

Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study.

AIM: To explore the variability in pain response in preterm infants across time who received sucrose during routine heel stick. METHOD: Single group, exploratory repeated measures design. SETTING: Two tertiary level neonatal intensive care units (NICU) in Switzerland. SUBJECTS: Nine preterm infants born between 28 2/7 and 31 4/7 weeks of gestation during their first 14 days of life. MEASUREMENTS: Pain was assessed by the Bernese Pain Scale for Neonates (BPSN), the Premature Infant Pain Profile (PIPP) and the Visual Analogue Scale (VAS). Salivary cortisol was analysed. RESULTS: 72-94% of the variability was within-subject variability, indicating inconsistency of pain responses across the 5 heel sticks. Interrater agreement was highest during heel sticks 1-3 and decreased during heel stick 4 and 5, indicating a possible alteration of pain patterns. No significant differences in the amount of cortisol could be detected before and after the heel sticks (p = 0.55), indicating no stress-induced peak after the painful intervention. However, a general gradual decrease of cortisol levels across time could be detected. CONCLUSION: A high variability in pain response among preterm neonates across time could be described. Consistency of cortisol levels before and after the heel sticks could indicate the effectiveness of sucrose across time.

Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group.

PURPOSE: In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. PATIENTS AND METHODS: Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. RESULTS: At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC. CONCLUSION: The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.

A highly sensitive quantitative bioassay for human granulocyte-macrophage colony-stimulating factor.

Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM-CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin-stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml.