Case report: Intrapulmonary tidal volumes in a preterm infant with chest wall rigidity

BACKGROUND Chest wall rigidity is a known side effect of fentanyl use, which is why fentanyl is usually combined with a muscle relaxant such as mivacurium. Verifying endotracheal intubation is difficult in case of a rigid chest wall. CASE PRESENTATION We present the case of a preterm infant (29 completed weeks gestation, birth weight 1,150 g) with a prolonged chest wall rigidity after fentanyl administration for intubation despite adequate doses of mivacurium. This resulted in a pronounced desaturation without any effect on heart rate. Clinically, the infant showed no chest wall movement despite intubation and common tools to verify intubation (including end-tidal carbon dioxide measurement and auscultation) were inconclusive. However, using electrical impedance tomography (EIT), we were able to demonstrate minimal tidal volumes at lung level and thereby, EIT was able to accurately show correct placement of the endotracheal tube. CONCLUSIONS This case may increase vigilance for fentanyl-induced chest wall rigidity in the neonatal population even when simultaneously administering mivacurium. Higher airway pressures exceeding 30 mmHg and the use of μ-receptor antagonists such as naloxone should be considered to reverse opioid-induced chest wall rigidity. Most importantly, our data may imply a relevant clinical benefit of using EIT during neonatal intubation as it may accurately show correct endotracheal tube placement

Detection of hyperbilirubinaemia in jaundiced full-term neonates by eye or by bilirubinometer?

The aim of this study was to compare predictions of hyperbilirubinaemia by eye, performed by trained physicians and nurses, with predictions obtained using two commercial bilirubinometers. Jaundice was assessed in 92 white and 48 non-white healthy full-term neonates using three non-invasive methods and by total serum bilirubin as the reference method. Clinical assessment of cephalocaudal progression of jaundice was carried out independently by a physician and by nurses. Simultaneously, the Minolta Airshields JM-102 was applied on the sternum, the BiliCheck on both the forehead and the sternum, and finally, serum bilirubin concentrations were determined. The Minolta JM-102 showed the best performance with r2=0.90, an intraclass correlation coefficient (ICC) of 0.93, and a 95% confidence interval (CI) of ±4units (approx. 56µmol/l). The BiliCheck performed slightly better on the forehead than over the sternum with r2=0.90, an ICC of 0.88, and a CI of ±62µmol/l. Assessment of jaundice by eye was least accurate with r2=0.74, an ICC of 0.67, and a CI of ±1.5 zones (corresponding to ±75µmol/l). Skin pigmentation and ambient light both adversely affected non-invasive bilirubin estimation. Conclusion:All three non-invasive methods are well suited for estimation of serum bilirubin but show large confidence intervals. In healthy term newborns, hyperbilirubinaemia (>250µmol/l) can be safely ruled out by eye if jaundice does not reach the abdomen or the extremities (Kramer zones 1 and 2), with <22 units (<230µmol/l) for the Minolta JM-102, or with a cut-off of 190µmol/l for the BiliCheck. If these respective thresholds are exceeded, serum bilirubin concentrations should be measure

Exploring societal solidarity in the context of extreme prematurity

QUESTION: Extreme prematurity can result in long-term disabilities. Its impact on society is often not taken into account and deemed controversial. Our study examined attitudes of the Swiss population regarding extreme prematurity and people’s perspectives regarding the question of solidarity with disabled people. METHODS: We conducted a nationwide representative anonymous telephone survey with 1210 Swiss residents aged 18 years or older. We asked how people estimate their own personal solidarity, the solidarity of their social environment and the solidarity across the country with disabled persons. Spearman’s correlation calculations were used to assess if a correlation exists between solidarity and setting financial limits to intensive care and between solidarity and withholding neonatal intensive care. RESULTS: According to 36.0% of the respondents intensive medical care should not be withheld from extremely preterm infants, even if their chances for an acceptable quality of life were poor. For 28.8%, intensive care should be withheld from these infants, and 26.9% held an intermediate position depending on the situation. A total of 31.5% were against setting a financial limit to treatment of extremely preterm newborns with an uncertain future quality of life, 34.2% were in favour and 26.9% were deliberating. A majority (88.8%) considered their solidarity toward disabled people as substantial; the solidarity of their personal environment and of the society at large was estimated as high by 79.1% and 48.6%, respectively. CONCLUSIONS: The Swiss population expressed a high level of solidarity which may alleviate some pressure on parents and health care providers in the decision-making process in neonatal intensive care units. In addition, there was no relationship between solidarity and people’s willingness to pay for the care or withholding treatment of extremely preterm babies

Opinion Paper: Rationale for Supra-National Training in Neonatology

Introduction: Clinical training in neonatology takes place where neonates are cared for, at the cot-side, in neonatal units. Neonatal units vary widely in size, specialization, resources, staffing and academic level. Among them, small units make up a large proportion which have more difficulties to offer structured training courses on site, local expertise on all relevant neonatal topics, and appropriate exposition of the trainee to high-risk cases. Although evidence-based medicine is widely accepted, training of physicians, including neonatologists, often follows ineffective learning methods, or even less favorable, learning by doing. When looking at the national training requirements and standards within Europe, there are large differences between countries. Some countries have training requirements, standards and national training courses in place other countries have none of this. Therefore, it is worthwhile to create a supra-regional or even supra-national training program that complements local clinical work on an individual basis to provide structured training and evidence-based education anywhere and anytime. The European Society for Paediatric Research (ESPR) has long been committed to the education and training of medical doctors specializing in neonatology. Together with the European Board of Neonatology (EBN), which is a substructure of ESPR devoted to the design and implementation of a syllabus that comprises the theoretical and practical needs for the European Training in Neonatology, the European Training Requirements (ETR) in Neonatology has been developed. The 2021 updated syllabus, the current ETR in Neonatology, is based on the previous 2007 syllabus version and has been approved by the Union of European Medicine Specialist (EAMS) in April 2021. Interestingly, the 2021 syllabus content was updated by the EBN members, but also critically incorporated and comments suggestions of national representatives of 30 European countries following two sequential surveys and face to face meetings. Each country pertaining to the EBN has a different national training curriculum to achieve the training standards required to exert as neonatologists. The aim of the ETR in Neonatology has been to harmonize training requirements within Europe to achieving a basic and reliable standard of quality in theoretical knowledge and practical skills alongside the European countries. We present an online training concept that meets the needs of neonatal training situations and implements the latest effective didactic elements

The effect of high-dose erythropoietin perinatally on retinal function in school-aged children born extremely or very preterm

PURPOSE: To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm. DESIGN: Randomized, double-blind clinical trial follow-up plus cohort study. METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. Study population: extremely or very preterm-born children aged 7-15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period. Inclusion criteria: participation in an ongoing neuropediatric study (EpoKids), written informed consent (IC). Exclusion criteria: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited. Inclusion criteria: term birth, IC. Exclusion criteria: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses. Observation procedures: Electroretinography (ERG) was performed with the RETeval device (LKC Technologies, Inc., Gaithersburg MD). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group. Main outcome measures: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only). RESULTS: No differences in ERG parameters between EPO (n=52; 104 eyes) and placebo (n=35; 70 eyes) subgroups were observed (all corrected p>0.05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n=52; 104 eyes) subgroup (coefficient/95% confidence interval (CI) = 0.53/0.21 to 0.85 and 0.36/0.13 to 0.60; p = 0.012 and 0.022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% CI = -4.33/-6.88 to -1.78; p = 0.011). Secondary outcomes were comparable across subgroups. CONCLUSIONS: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period

Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial.

IMPORTANCE Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date. OBJECTIVE To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH. DESIGN, SETTING, AND PARTICIPANTS Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022. INTERVENTIONS Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life. MAIN OUTCOMES AND MEASURES Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023). RESULTS Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores. CONCLUSIONS AND RELEVANCE This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02076373

Opinion paper: rationale for supra-national training in neonatology

Clinical training in neonatology takes place where neonates are cared for, at the cot-side, in neonatal units. Neonatal units vary widely in size, specialization, resources, staffing and academic level. Among them, small units make up a large proportion which have more difficulties to offer structured training courses on site, local expertise on all relevant neonatal topics, and appropriate exposition of the trainee to high-risk cases. Although evidence-based medicine is widely accepted, training of physicians, including neonatologists, often follows ineffective learning methods, or even less favorable, learning by doing. When looking at the national training requirements and standards within Europe, there are large differences between countries. Some countries have training requirements, standards and national training courses in place other countries have none of this. Therefore, it is worthwhile to create a supra-regional or even supra-national training program that complements local clinical work on an individual basis to provide structured training and evidence-based education anywhere and anytime. The European Society for Paediatric Research (ESPR) has long been committed to the education and training of medical doctors specializing in neonatology. Together with the European Board of Neonatology (EBN), which is a substructure of ESPR devoted to the design and implementation of a syllabus that comprises the theoretical and practical needs for the European Training in Neonatology, the European Training Requirements (ETR) in Neonatology has been developed. The 2021 updated syllabus, the current ETR in Neonatology, is based on the previous 2007 syllabus version and has been approved by the Union of European Medicine Specialist (EAMS) in April 2021. Interestingly, the 2021 syllabus content was updated by the EBN members, but also critically incorporated and comments suggestions of national representatives of 30 European countries following two sequential surveys and face to face meetings. Each country pertaining to the EBN has a different national training curriculum to achieve the training standards required to exert as neonatologists. The aim of the ETR in Neonatology has been to harmonize training requirements within Europe to achieving a basic and reliable standard of quality in theoretical knowledge and practical skills alongside the European countries. We present an online training concept that meets the needs of neonatal training situations and implements the latest effective didactic elements

Comparison of a new transcutaneous bilirubinometer (Bilimed®) with serum bilirubin measurements in preterm and full-term infants

<p>Abstract</p> <p>Background</p> <p>The gold standard to assess hyperbilirubinemia in neonates remains the serum bilirubin measurement. Unfortunately, this is invasive, painful, and costly. Bilimed^®, a new transcutaneous bilirubinometer, suggests more accuracy compared to the existing non-invasive bilirubinometers because of its new technology. It furthermore takes into account different skin colours. No contact with the skin is needed during measurement, no additional material costs occur. Our aim was to assess the agreement between the Bilimed^®and serum bilirubin in preterm and term infants of different skin colours.</p> <p>Methods</p> <p>The transcutaneous bilirubin measurements were performed on the infant's sternum and serum bilirubin was determined simultaneously. The agreement between both methods was assessed by Pearson's correlation and by Bland-Altman analysis.</p> <p>Results</p> <p>A total of 117 measurement cycles were performed in 99 term infants (group1), further 47 measurements in 38 preterm infants born between 34 - 36 6/7 gestational weeks (group 2), and finally 21 measurements in 13 preterm infants born between 28 - 33 6/7 gestational weeks (group 3). The mean deviation and variability (+/- 2SD) of the transcutaneous from serum bilirubin were: -14 (+/- 144) μmol/l; -0.82 (+/- 8.4) mg/dl in group 1, +16 (+/- 91) μmol/l;+0.93(+/- 5.3) mg/dl in group 2 and -8 (+/- 76) μmol/l; -0.47 (+/- 4.4) mg/dl in group 3. These limits of agreement are too wide to be acceptable in a clinical setting. Moreover, there was to be a trend towards less good agreement with increasing bilirubin values.</p> <p>Conclusion</p> <p>Despite its new technology the Bilimed^®has no advantages, and more specifically no better agreement not only in term and near-term Caucasian infants, but also in non-Caucasian and more premature infants.</p

MicroRNA-96 Directly Inhibits γ-Globin Expression in Human Erythropoiesis

Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ∼22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (<1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased γ-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased γ-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of γ-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of γ-globin. Based on these results we conclude that microRNA-96 directly suppresses γ-globin expression and thus contributes to HbF regulation

Overlapping borders: limit of viability and late terminations of pregnancy - a retrospective multicentre observational study

AIMS OF THE STUDY Based on an incidental observation made in the context of the Swiss National Science Foundation (SNSF) Project 67 &ldquo;End-of-life decision-making in extremely low birth weight infants in Switzerland&rdquo;, this retrospective multicentre observational study aimed to analyse circumstances of delivery room deaths after late termination of pregnancy (LTOP) in Switzerland over a 3-year period. METHODS All delivery room deaths (including live and stillbirths) following LTOP among infants with a gestational age between 22 0/7 and 27 6/7 weeks at the nine Swiss level III perinatal centres between 1 July 2012 and 30 June 2015 were analysed. Indications for LTOP were classified as either (a) maternal emergencies or (b) fetal anomalies severe enough to cause significant maternal psychological distress. Whenever possible, specific diagnoses were recorded. Spontaneous intrapartum death and fetal death caused by injection of a cardioplegic drug were distinguished for stillborn infants. RESULTS A total of 465 delivery room deaths among extremely low gestational age newborns (ELGANs) were identified over the 3-year study period of the SNSF project. Of these, 195 (42%) occurred in the context of LTOP. Central nervous system malformations, chromosomal anomalies, severe congenital heart disease, multiple malformations and maternal emergencies accounted for 70% of all LTOPs. LTOPs resulted in live births in 76 (39%) cases. No correlation between gestational age and rate of live births was observed. Fetal death caused by injection of a cardioplegic drug was documented in only three cases. All infants born alive after LTOP died in the delivery room without resuscitation attempts. The use of drugs for palliative care in these patients was either rare or, alternatively, incompletely documented. CONCLUSION LTOPs contribute significantly to mortality rates among ELGANs and should therefore be included in perinatal registries. Uniform reporting of LTOPs should be established. Infants born alive after LTOP are entitled to comprehensive palliative care like any other infant born under different circumstances. Development of national guidelines for LTOPs (including the role of fetal death caused by injection of a cardioplegic drug and palliative birth as an alternative to induced abortion) would be highly desirable to guarantee acceptable standards of care