Meeting the need for effective and standardized neonatology training: a pan-European Master's Curriculum.

Neonatology is a pediatric sub-discipline focused on providing care for newborn infants, including healthy newborns, those born prematurely, and those who present with illnesses or malformations requiring medical care. The European Training Requirements (ETR) in Neonatology provide a framework for standardized quality and recognition of equality of training throughout Europe. The latest ETR version was approved by the Union of European Medical Specialists (UEMS) in April 2021. Here, we present the curriculum of the European School of Neonatology Master of Advanced Studies (ESN MAS), which is based on the ETR in Neonatology and aims to provide a model for effective and standardized training and education in neonatal medicine. We review the history and theory that form the foundation of contemporary medical education and training, provide a literature review on best practices for medical training, pediatric training, and neonatology training specifically, including educational frameworks and evidence-based systems of evaluation. The ESN MAS Curriculum is then evaluated in light of these best practices to define its role in meeting the need for a standardized empirically supported neonatology training curriculum for physicians, and in the future for nurses, to improve the quality of neonatal care for all infants. IMPACT STATEMENT: A review of the neonatology training literature was conducted, which concluded that there is a need for standardized neonatology training across international contexts to keep pace with growth in the field and rapidly advancing technology. This article presents the European School of Neonatology Master of Advanced Studies in Neonatology, which is intended to provide a standardized training curriculum for pediatricians and nurses seeking sub-specialization in neonatology. The curriculum is evaluated in light of best practices in medical education, neonatology training, and adult learning theory.

Reducing False Alarm Rates in Neonatal Intensive Care: A New Machine Learning Approach.

In neonatal intensive care units (NICUs), 87.5% of alarms by the monitoring system are false alarms, often caused by the movements of the neonates. Such false alarms are not only stressful for the neonates as well as for their parents and caregivers, but may also lead to longer response times in real critical situations. The aim of this project was to reduce the rates of false alarms by employing machine learning algorithms (MLA), which intelligently analyze data stemming from standard physiological monitoring in combination with cerebral oximetry data (in-house built, OxyPrem). MATERIALS & METHODS: Four popular MLAs were selected to categorize the alarms as false or real: (i) decision tree (DT), (ii) 5-nearest neighbors (5-NN), (iii) naïve Bayes (NB) and (iv) support vector machine (SVM). We acquired and processed monitoring data (median duration (SD): 54.6 (± 6.9) min) of 14 preterm infants (gestational age: 26 6/7 (± 2 5/7) weeks). A hybrid method of filter and wrapper feature selection generated the candidate subset for training these four MLAs. RESULTS: A high specificity of >99% was achieved by all four approaches. DT showed the highest sensitivity (87%). The cerebral oximetry data improved the classification accuracy. DISCUSSION & CONCLUSION: Despite a (as yet) low amount of data for training, the four MLAs achieved an excellent specificity and a promising sensitivity. Presently, the current sensitivity is insufficient since, in the NICU, it is crucial that no real alarms are missed. This will most likely be improved by including more subjects and data in the training of the MLAs, which makes pursuing this approach worthwhile.

Case report of neonatal ductus venosus atresia.

INTRODUCTION: In the fetus, the ductus venosus (DV) connects the umbilical vein and the portal veins to the inferior vena cava in order to bypass the high-resistance hepatic vascular network. Via the Eustachian valve, the DV directs umbilical venous blood with the highest oxygen content preferentially towards the myocardium and the brain. An absence (agenesis) or a secondary obliteration of an initially normally developed DV (atresia) is associated with various shunt types and may lead to severe hydrops. CASE REPORT: A routine check-up of a healthy 34-year-old woman at 27 5/7 wks GA revealed a severe hydrops fetalis with pleural effusions and ascites. After birth at 28 0/7 wks GA, the bilateral pleural effusions needed drainage via thoracic drains. Arterial hypotension was initially treated with volume replacement and dopamine, later on adrenaline and hydrocortisone were added. The initial echocardiography showed normal anatomic structures and normal bi-ventricular function. Despite maximal intensive care treatment, a global respiratory and cardiovascular insufficiency developed. The girl died on fourth day of life. At autopsy, a secondary atresia of the DV was identified, and moreover a pathogenic de novo heterozygous mutation in the KRAS gene was found in the chorion biopsy probe. DISCUSSION: For all cases of non-haemolytic hydrops fetalis, a prenatal or postnatal sonography with Doppler examination of the venous system and of the heart should be performed. Furthermore, testing for RASopathies should be recommended especially in presence of increased nuchal translucency thickness and polyhydramnios.

Parents' mental health after the birth of an extremely preterm child: a comparison between bereaved and non-bereaved parents.

OBJECTIVE: To assess the impact of extremely preterm birth (24-26 weeks of gestation) on the mental health of parents two to six years after delivery, and to examine potential differences in post-traumatic growth between parents whose newborn infant died and those whose child survived. METHOD: A total of 54 parents who had lost their newborn and 38 parents whose preterm child survived were assessed by questionnaires with regard to depression and anxiety (HADS) and post-traumatic growth (PTGI). RESULTS: Neither group of parents had clinically relevant levels of depression and anxiety. Mothers showed higher levels of anxiety than fathers. Bereaved parents with no other, living child reported higher levels of depression than bereaved parents with one or more children. Mothers reported higher post-traumatic growth compared to fathers. In particular, bereaved mothers experienced the value and quality of their close social relationships more positively compared to the non-bereaved parents. CONCLUSION: In the long term, bereaved and non-bereaved parents cope reasonably well with an extremely preterm birth of a child. Post-traumatic growth appears to be positively related to bereavement, particularly in mothers.

Retrospective cohort study of all deaths among infants born between 22 and 27 completed weeks of gestation in Switzerland over a 3-year period.

OBJECTIVES: The aim of this research is to assess causes and circumstances of deaths in extremely low gestational age neonates (ELGANs) born in Switzerland over a 3-year period. DESIGN: Population-based, retrospective cohort study. SETTING: All nine level III perinatal centres (neonatal intensive care units (NICUs) and affiliated obstetrical services) in Switzerland. PATIENTS: ELGANs with a gestational age (GA) <28 weeks who died between 1 July 2012 and 30 June 2015. RESULTS: A total of 594 deaths were recorded with 280 (47%) stillbirths and 314 (53%) deaths after live birth. Of the latter, 185 (59%) occurred in the delivery room and 129 (41%) following admission to an NICU. Most liveborn infants dying in the delivery room had a GA ≤24 weeks and died following primary non-intervention. In contrast, NICU deaths occurred following unrestricted life support regardless of GA. End-of-life decision-making and redirection of care were based on medical futility and anticipated poor quality of life in 69% and 28% of patients, respectively. Most infants were extubated before death (87%). CONCLUSIONS: In Switzerland, most deaths among infants born at less than 24 weeks of gestation occurred in the delivery room. In contrast, most deaths of ELGANs with a GA ≥24 weeks were observed following unrestricted provisional intensive care, end-of-life decision-making and redirection of care in the NICU regardless of the degree of immaturity.

Hypoplastic thymus and T-cell reduction in EECUT syndrome.

We report on a patient with EEC/EECUT syndrome and concomitant hypoplasia of the thymus and reduction of T cells in secondary lymphatic organs. The patient was born prematurely at 35 weeks of gestational age and exhibited ectodermal dysplasia, ectrodactyly, cleft palate and urinary tract abnormalities. On the left side, a large ureterocele was present. On the right side, an atretic ureter was found. Both conditions had led to intrauterine hydronephrosis, renal dysplasia, oligohydramnios, pulmonary hypoplasia, and death of the child. Ureteral malformations are thought to be of epithelial origin. Autopsy showed only small rudiments of thymic tissue containing single epithelial cells, but were completely devoid of Hassall corpuscules. Again, this clearly points to an ectodermal defect. Although there was severe reduction of T cells in secondary lymphatic organs, the thymic defect would not have necessarily led to immunological deficiency; perhaps this is the reason that an epithelial defect in the thymus of patients with EEC syndrome has not yet been reported. With regard to an updating of the diagnosis of the EEC/EECUT syndrome, an "EEC/EECUT plus" syndrome is suggested.

Interactions between the right ventricle and pulmonary vasculature in the fetus.

A midsystolic plateau differentiates the pattern of fetal pulmonary trunk blood flow from aortic flow. To determine whether this plateau arises from interactions between the left (LV) and right ventricle (RV) via the ductus arteriosus or from interactions between the RV and the lung vasculature, we measured blood flows and pressures in the pulmonary trunk and aorta of eight anesthetized (ketamine and alpha-chloralose) fetal lambs. Wave-intensity analysis revealed waves of energy traveling forward, away from the LV and the RV early in systole. During midsystole, a wave of energy traveling back toward the RV decreased blood flow velocity from the RV and produced the plateau in blood flow. Calculations revealed that this backward-traveling wave originated as a forward-traveling wave generated by the RV that was reflected from the lung vasculature back toward the heart and not as a forward-traveling wave generated by the LV that crossed the ductus arteriosus. Elimination of this backward-traveling wave and its associated effect on RV flow may be an important component of the increase in RV output that accompanies birth.

Artificial sweetener reduces nociceptive reaction in term newborn infants.

BACKGROUND: Sucrose has been shown to have an analgesic effect in preterm and term neonates. Sucrose, however, has a high osmolarity and may have deleterious effects in infants with fructose intolerance. Furthermore, it may favour caries. We therefore investigated the effects of a commercially available artificial sweetener (10 parts cyclamate and 1 part saccharin), glycine (sweet amino acid) or breast milk in reducing reaction to pain as compared with a placebo. SUBJECTS: Eighty healthy term infants, four days old, with normal birth weight. INTERVENTIONS: The infants were randomly assigned to one of four groups: 2 ml sweetener, glycine, expressed breast milk or water were given 2 min before a heel prick for the Guthrie test. The procedure was filmed with a video camera and analysed by two observers who did not know which medication the infant had received. RESULTS: Using a multivariate regression analysis, the following variables had significant correlation with relative crying time and recovery time: behavioural state before the intervention, the pricking nurse, and the type of medication. Relative crying time and recovery time were significantly less in the sweetener group but not in the glycine and the breast milk group. CONCLUSIONS: The artificial sweetener used in our study reduces pain reaction to a heel prick in term neonates, and thus provides an alternative to sucrose. In contrast, glycine tends to increase pain reaction whereas breast milk has no effect.

Two years outcome of very pre-term and very low birthweight infants in Switzerland.

BACKGROUND: There are only few reports worldwide on the outcome of very pre-term infants and very low birthweight infants for a whole country. In Switzerland official population statistics are based on birthweight only, gestational age not yet being documented. AIM: The aim of the present study was to assess the outcome at two years of age for a geographically defined high-risk neonatal population based on both birthweight and gestational age. METHODS: All infants born in 1996 included in the Swiss Neonatal Network (a national anonymous registry established by the Swiss Society of Neonatology for liveborn infants before 32 completed gestational weeks or weighing less than 1500 g) were divided into three groups according to gestational age and birth weight: Group 1: born <32 completed gestational weeks and weighing =1500 g; group 2: born after 32 completed gestational weeks and weighing <1500 g; group 3: born <32 gestational weeks and weighing <1500 g. Information at 24 months corrected age about growth, neurological outcome, frequency of respiratory infections, prescription of antibiotics and medical consultations during this period was obtained from the paediatricians caring for the infants. Fair outcome was defined as survival without serious neonatal complications or abnormal neurological findings at 24 months corrected for prematurity. RESULTS: 723 infants were born alive in Switzerland between 1.1. and 31.12.1996 before 32 completed weeks or weighing less than 1500 g at birth. Mortality was 4.3% for a total of 163 infants in group 1 (<32 weeks, =1500 g), 4.6% for 108 infants in group 2 (>32 weeks, <1500 g) and 18.6% for 452 infants in group 3 (<32 weeks, <1500 g). 6.5% of group 1 survivors followed up to 24 months corrected age had a poor neurological outcome as compared to 9.3% in group 2 and 10.9% in group 3. Infants in group 1 needed antibiotics less often after hospital discharge (interquartile range IQR: 0-2 courses) than infants in group 2 (0-3 courses) and 3 (0-3 courses). Infants in group 2 suffered from fewer airway infections (interquartile range 2-5 times) than in group 1 (2-6 times) and 3 (1-7 times). Infants in group 3 needed more medical consultations (IQR 12-21) than those in group 1 (10-16) and 2 (11-16). The overall fair outcome at 24 months corrected age was 85.3% in group 1, 80.7% in group 2 and 59.6% in group 3. A close correlation between overall fair outcome and gestational age at birth on the one hand and with birthweight on the other can be observed. CONCLUSIONS: This study gives estimates for mortality, poor and fair outcome at 24 months corrected age for very low birth weight infants (<1500 g) and for very pre-term infants (<32 completed gestational weeks). Gestational age is as important for predicting outcome as birthweight and should therefore be integrated into national statistics.

Coagulation abnormalities in low birth weight infants with peri-intraventricular hemorrhage.

Fifty-four appropriate for gestational age preterm infants (less than 35 weeks gestation) were followed prospectively from birth with coagulation and real-time ultrasound studies. Coagulation analyses included fibrinogen, prothrombin time, thrombin time and platelet count. The occurrence of peri-intraventricular hemorrhage (PIVH) was documented by portable 5 MHz Echo Scanner. Definite PIVH was present in 21 babies (38%). Coagulation studies showed especially lower values of fibrinogen levels in babies of less than 30 weeks gestation compared to a control group without PIVH (p less than 0.03). Furthermore, significant correlation was observed in these patients between platelet count and degree of PIVH. Infants with Grade 3 and 4 PIVH had lower platelet count than infants with less severe bleeding (Grade 1 and 2) (p less than 0.02). These data suggest that hemostatic abnormalities play a major role as co-factor in the incidence and severity of neonatal PIVH in very low birth weight infants of less than 30 weeks gestation.

Relationship between peri-intraventricular hemorrhage and neonatal hyperbilirubinemia in very low-birthweight infants.

The incidence of hyperbilirubinemia (serum bilirubin values greater than 205 mumol/l) in two groups of preterm infants (birthweight less than 1500 gm) with and without peri-intraventricular hemorrhage (PIVH) was studied. In the first 10 days of life, 16 (39%) of the 41 infants with PIVH vs. 22 (46.8%) of those without PIVH (n = 47) had high bilirubin levels. No difference in peak serum bilirubin concentrations nor a need for phototherapy was noted between the two groups (P greater than 0.07). Forty-one infants had PIVH: 30 had PIVH grade I or II and 11 had grade III or IV. No statistically significant correlation was found between degree of PIVH and hyperbilirubinemia. Moreover, at 12 months corrected age, major and minor handicaps were equally distributed between the two groups. The neurologic outcome appeared to relate, in largest part, to the severity of the PIVH, and to not be influenced by the hyperbilirubinemia. We conclude that there is no positive relationship between incidence and extension of PIVH, plasma bilirubin levels, and outcome in very low-birth weight infants.

[Neonatal alloimmune thrombocytopenia due to a rare anti-HPA-1b antibody]. / Neonatale Alloimmunthrombozytopenie durch einen Antikörper gegen das selten immunogene HPA-1b.

Foetal and neonatal alloimmune thrombocytopenia is caused by transplacental transfer of antibodies directed against platelet antigens and affects approximately 1 in 1000-2500 neonates. Clinically relevant complications are the intracranial haemorrhages that occur in 10-20% of cases. 20 platelet antigen systems are currently known. However, immunisation is most frequently seen against two of these (HPA-1a and HPA-5b). Treatment options include transfusion of compatible or, if these are not available while urgently needed, random donor platelets, intravenous immunoglobulin, and steroids. We report on a case of neonatal alloimmune thrombocytopenia due to an anti-HPA-1b antibody in the third pregnancy of a 31-year-old Caucasoid woman. The infant was treated with repeated maternal and random donor platelet transfusions and with a single dose of intravenous immunoglobulin.

Agreement between capillary and arterial lactate in the newborn.

UNLABELLED: Arterial blood lactate is a reliable indicator of tissue oxygen debt and is of value in expressing the degree and prognosis of circulatory failure as a result of various diseases. Therefore, the practical issue of whether capillary lactate measurements might be of equal value was investigated in newborns. In total, 193 simultaneous measurements of capillary and arterial blood lactate concentrations were performed in 25 newborn babies with an indwelling umbilical arterial catheter. A strong linear correlation was found between capillary and arterial lactate concentration (Lcap = 1.02 Lart + 0.04; r = 0.98; p < 0.001). The mean difference was -0.08 mmol/l and the limits of agreement (+/- 2 SD) were +/- 0.69 mmol/l (-0.77 to 0.61 mmol/l). CONCLUSION: Our data show that capillary blood lactate measurements in newborn babies yield lactate concentrations equivalent to arterial measurements over a large concentration range.

[Value of the RPM safety index in retinopathy of prematurity]. / Aussagekraft des RPM-Sicherheitsindex bei der Retinopathia praematurorum.

The safety-index (S-index): S = log birth weight (kg) + gestational age (weeks)/oxygen therapy (days) combines the three main risk factors for a development of ROP. Only in very immature children which had a long time oxygen therapy (and therefore a low S-index) one finds severe stages of ROP. In our study, we correlated retrospectively ROP stages versus S-index in 261 children. The results confirm that children with S-index greater than 1 never had a severe ROP (that means, stage 3 and more, which need treatment). Therefore, the 2/3 of all newborn infants at risk with an S-index greater than 1 need only minimal ophthalmological controls.

Retinopathy of prematurity and bilirubin--no clinical evidence for a beneficial role of bilirubin as a physiological anti-oxidant.

The prevention of retinopathy of prematurity (ROP) remains a persistent problem. A previous report has focused on the possible protective effect of bilirubin on the development of ROP. These results still await clinical confirmation by other research groups. Therefore, we undertook a retrospective clinical study trying to confirm this attractive hypothesis. Twelve premature newborns under 32 weeks of gestation with ROP stage 3-4 were matched for gestational age with 12 infants without ROP. Data were collected about the infant's characteristics, medical illnesses, ventilatory settings and treatments. The total serum bilirubin concentrations between the 1st and 8th postnatal day were also gathered. The two matched groups were comparable as to their basic data, clinical characteristics and treatment, except for a slight, but significant longer duration of phototherapy for group ROP 0 (mean, 50.2 h; SD 48,6 vs 31.6 h; SD 42.7 in ROP 3-4; P = 0.02). No statistical difference relative to bilirubin was found between the two groups, neither when expressed as daily mean concentrations, nor as area under the curve (AUC) (mean, ROP 0: 17876.7; SD 6077.3 vs 18888.4; SD 55552.7 in ROP 3-4; P = 0.404) or AUC/h (mean, ROP 0: 135.1; SD 36.3 vs 144.1; SD 23.2 in ROP 3-4; P = 0.515). Our findings do not confirm the hypothesis of a clinically measurable, beneficial role of bilirubin on the development of ROP.

Assessment of jaundice in preterm neonates: comparison between clinical assessment, two transcutaneous bilirubinometers and serum bilirubin values.

AIM: 1) To compare the clinical assessment of craniocaudal progression of jaundice and two transcutaneous bilirubinometers with serum bilirubin values in preterm neonates; 2) to identify factors affecting the difference between non-invasive bilirubin estimation and serum bilirubin. METHODS: Serum bilirubin was clinically estimated in healthy preterm newborn infants (34 to 36.9 gestational weeks) independently by a primary investigator and by nurses, and subsequently compared with separate measures of two transcutaneous bilirubinometers. RESULTS: A total of 107 measurements were performed on 69 infants. Minolta JM-102 showed the best performance, with ROC area under the curve of 0.96, followed by BiliCheck over the sternum (0.89) and over the forehead (0.88), clinical assessment by nurses (0.73) and by a physician (0.70). Serum bilirubin >190 micromol/l can be detected with 95% sensitivity with Minolta JM-102 > or =19 units, with BiliCheck > or =145 micromol/l over the sternum and > or =165 micromol/l over the forehead and with jaundice progression to the trunk or further (Kramer zone > or =2). Gestational age affects all non-invasive methods in the estimation of serum bilirubin, whereas skin colour affects both BiliCheck and clinical assessment. Ambient light affects only clinical assessment. CONCLUSION: Minolta JM-102 showed the best performance, closely followed by BiliCheck, with clinical assessment performing far worse than either transcutaneous method. None of the three methods are recommended as complete substitutes for serum bilirubin values in jaundiced preterm infants.

Right atrial pressure as measure of ventricular constraint in newborn lambs.

Although the lungs and pericardium constrain the heart and limit cardiac output, no method exists to assess this constraint in sick newborns. We hypothesize that a useful estimate of ventricular constraint may be obtained by measuring right atrial pressure (P(RA)) in the newborn. To test this hypothesis, we measured P(RA), thoracic inferior vena caval pressure (P(IVC); saline-filled catheters), and ventricular constraint (pericardial pressure, P(PER); liquid-containing balloon) in 4-wk-old (neonatal, n = 12) and 3-day-old (newborn, n = 6) anesthetized lambs. The measurements were made while LV filling pressure was altered (0-20 mmHg) and while positive end-expiratory pressure (PEEP) was maintained at 2.5 or 15 cmH2O. In all of the lambs, a strong linear relationship (r) existed between P(RA) and P(PER) (P(RA) = 1.19 P(PER) + 0.0, r = 0.99) and between P(IVC) and P(PER) (P(IVC) = 1.24 P(PER) + 0.1, r = 0.99; PEEP of 2.5 cmH2O). Similar relationships were also observed with increased PEEP (P(RA) = 1.29 P(PER)-1.2, r = 0.98 and P(IVC) = 1.32 P(PER)-1.2, r = 0.97). Because P(RA) provides an accurate measure of ventricular constraint in the normal lamb, it may be a useful measure of ventricular constraint in the sick newborn.

Wolf-Hirschhorn syndrome due to a 3:1 segregation of a maternal balanced t(4;15)(p16.3;q11) translocation.

The Wolf-Hirschhorn syndrome (WHS) is characterized by severe pre- and postnatal growth retardation, specific pattern of dysmorphisms, and severe developmental delay. These clinical findings are the result of a deletion within the short arm of chromosome 4. Most cases occur de novo and are of paternal origin. Cases due to a balanced translocation are mostly of maternal origin and the deletion of distal 4p, including the WHS critical region, is often combined with a duplication of the other chromosomal segment involved in the rearrangement. Here, we report on a newborn female infant with WHS and pure tertiary monosomy due to a 3:1 segregation of a balanced maternal 4;15 translocation. In this context, importance of fluorescence in situ hybridization (FISH) with specific probes to determine the exact breakpoints in unbalanced chromosomal rearrangements with breakpoints localized around known microdeletion syndromes is emphasized.

Left ventricular stroke volume in the fetal sheep is limited by extracardiac constraint and arterial pressure.

1. Extracardiac constraint and sensitivity to arterial pressure may be critical factors that limit the functional reserves of the developing fetal heart in utero. We hypothesise that extracardiac constraint is the predominant factor that limits fetal stroke volume (SV). To test this hypothesis we studied six chronically instrumented fetal sheep to determine the relative roles that extracardiac constraint and arterial pressure play in determining left ventricular (LV) function. 2. Pregnant ewes (128-131 days gestation, term = 147 days) were anaesthetised (5 mg kg(-1) Propofol I.V., then 1.5 % halothane, 50 % O(2), balance N(2)O by inhalation) and instrumented using sterile surgical techniques to record LV end-diastolic pressure (P(lved)), aortic pressure (P(ao)), pericardial pressure (P(per)), and LV SV. 3. After a minimum of 72 h recovery, LV function was assessed by altering fetal blood volume to vary P(lved). Ventricular function curves were generated using two measures of ventricular function, SV and stroke work index (SWI = SV x P(ao)), and two measures of ventricular filling, P(lved) and LV end-diastolic transmural pressure (P(lved,tm) = P(lved) - P(per)). 4. Although decreasing P(lved) from the resting level decreased SV, increasing P(lved) from the resting level did not increase SV because the ventricular function curve plateaued. This plateau was not explained solely by an increase in aortic pressure, as the plateau remained present in the SWI versus P(lved) curve. When extracardiac constraint was accounted for (SV against P(lved,tm)), the plateau was largely eliminated (approximately 80 %). The remaining portion of the plateau (approximately 20 %) was eliminated when both extracardiac constraint and arterial pressure were accounted for (SWI versus P(lved,tm)). 5. Thus, the major limitation upon LV function in the near-term fetus results from extracardiac constraint limiting ventricular filling while, at the same time, a much smaller limitation arises from increasing arterial pressure.