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Background: A significant number of critically ill neonates face potentially adverse prognoses and outcomes, with some of them fulfilling the criteria for perinatal palliative care. When counselling parents about the critical health condition of their child, neonatal healthcare professionals require extensive skills and competencies in palliative care and communication. Thus, this study aimed to investigate the communication patterns and contents between neonatal healthcare professionals and parents of neonates with life-limiting or life-threatening conditions regarding options such as life-sustaining treatment and palliative care in the decision-making process. Methods: A qualitative approach to analysing audio-recorded conversations between neonatal team and parents. Eight critically ill neonates and a total of 16 conversations from two Swiss level III neonatal intensive care units were included. Results: Three main themes were identified: the weight of uncertainty in diagnosis and prognosis, the decision-making process, and palliative care. Uncertainty was observed to impede the discussion about all options of care, including palliative care. Regarding decision-making, neonatologists oftentimes conveyed to parents that this was a shared endeavour. However, parental preferences were not ascertained in the conversations analysed. In most cases, healthcare professionals were leading the discussion and parents expressed their opinion reactively to the information or options received. Only few couples proactively participated in decision-making. The continuation of therapy was often the preferred course of action of the healthcare team and the option of palliative care was not mentioned. However, once the option for palliative care was raised, the parents' wishes and needs regarding the end-of-life care of their child were obtained, respected, and implemented by the team. Conclusion: Although shared decision-making was a familiar concept in Swiss neonatal intensive care units, parental involvement in the decision-making process illustrated a somewhat different and complex picture. Strict adherence to the concept of certainty might impede the process of decision-making, thereby not discussing palliation and missing opportunities to include parental values and preferences. [ABSTRACT FROM AUTHOR]

Aim: Due to scarce available national data, this study assessed current attitudes of neonatal caregivers regarding decisions on life‐sustaining interventions, and their views on parents' aptitude to express their infant's best interest in shared decision‐making. Methods: Self‐administered web‐based quantitative empirical survey. All 552 experienced neonatal physicians and nurses from all Swiss NICUs were eligible. Results: There was a high degree of agreement between physicians and nurses (response rates 79% and 70%, respectively) that the ability for social interactions was a minimal criterion for an acceptable quality of life. A majority stated that the parents' interests are as important as the child's best interest in shared decision‐making. Only a minority considered the parents as the best judges of what is their child's best interest. Significant differences in attitudes and values emerged between neonatal physicians and nurses. The language area was very strongly associated with the attitudes of neonatal caregivers. Conclusion: Despite clear legal requirements and societal expectations for shared decision‐making, survey respondents demonstrated a gap between their expressed commitment to shared decision‐making and their view on parental aptitude to formulate their infant's best interest. National guidelines need to address these barriers to shared decision‐making to promote a more uniform nationwide practice. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Erythropoietin has been shown to be protective against hypoxic-ischemic and r inflammatory injuries in cell culture, animal models of brain injury, and clinical trials of adult humans. The rationale for our study was that early administration of high-dose recombinant human erythropoietin may reduce perinatal brain injury (intraventricular hemorrhage and periventricular leukomalacia) in very preterm infants and improve neurodevelopmental outcome. We investigated whether administration of high-dose recombinant human erythropoietin to very preterm infants shortly after birth and subsequently during the first 2 days is safe in terms of short-term outcome. METHODS. This was a randomized, double-masked, single-center trial with a 2:1 allocation in favor of recombinant human erythropoietin. Preterm infants (gestational age: 240/7 to 316/7 weeks) were given recombinant human erythropoietin or NaCl 0.9% intravenously 3, 12 to 18, and 36 to 42 hours after birth. RESULTS. The percentage of infants who survived without brain injury or retinopathy was 53% in the recombinant human erythropoietin group and 60% in the placebo group. There were no relevant differences regarding short-term outcomes such as intraventricular hemorrhage, retinopathy, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. For 5 infants who were in the recombinant human erythropoietin group and had a gestational age of <260/7 weeks, withdrawal of intensive care was decided (3 of 5 with severe bilateral intraventricular hemorrhage, 2 of 5 with pulmonary insufficiency); no infant of the control group died. Recombinant human erythropoietin treatment did not result in significant differences in blood pressure, cerebral oxygenation, hemoglobin, leukocyte, and platelet count. CONCLUSIONS. No significant adverse effects of early high-dose recombinant human erythropoietin treatment in very preterm infants were identified. These results enable us to embark on a large multicenter trial with the aim of determining whether early high-dose administration of recombinant human erythropoietin to very preterm infants improves neurodevelopmental outcome at 24 months' and 5 years' corrected age. [ABSTRACT FROM AUTHOR]

Aims: To document, and explain, the pulmonary paradox whereby despite relative lung immaturity, preterm infants exposed to amniotic infection (AI) have better postnatal pulmonary function than those exposed to preeclampsia (PE). Methods: Lung maturation was characterized in 65 preterm perinatal deaths wAI (ns40) and PE (n=25)x and postnatal respiratory function in 100 preterm survivors wAI (ns50) and PE (n=50)x. Results: At autopsy, lung architecture was in advance of gestational age in 5% of AI infants versus 40% of PE infants (P<0.001). In survivors, the groups were similar in age and Apgar scores. At birth, 40% of the AI group required continuous positive airway pressure or mechanical ventilation versus 24% of the PE group (NS). However, 24 hours later, only 1 AI infant had deteriorated compared to 40% of PE infants (P<0.05). Conclusions: Accelerated morphologic lung maturation in preterm PE infants does not translate into improved postnatal respiratory function. Most likely, this is due to a relative lack of surfactant, ascribable to low stimulant cytokine and high TNF-α levels. An intrauterine history supplemented by an antenatal cytokine profile could identify an increased exogeneous surfactant need in preterm infants exposed to PE. [ABSTRACT FROM AUTHOR]

Aim: Studies have provided insights into the different attitudes and values of healthcare professionals and parents towards extreme prematurity. This study explored societal attitudes and values in Switzerland with regard to this patient group.Methods: A nationwide trilingual telephone survey was conducted in the French-, German- and Italian-speaking regions of Switzerland to explore the general population's attitudes and values with regard to extreme prematurity. Swiss residents of 18 years or older were recruited from the official telephone registry using quota sampling and a logistic regression model assessed the influence of socio-demographic factors on end-of-life decision-making.Results: Of the 5112 people contacted, 1210 (23.7%) participated. Of these 5% were the parents of a premature infant and 26% knew parents with a premature infant. Most participants (77.8%) highlighted their strong preference for shared decision-making, and 64.6% said that if there was dissent then the parents should have the final word. Overall, our logistic regression model showed that regional differences were the most significant factors influencing decision-making.Conclusion: The majority of the Swiss population clearly favoured shared decision-making. The context of sociocultural demographics, especially the linguistic region in which the decision-making took place, strongly influenced attitudes towards extreme prematurity and decision-making. [ABSTRACT FROM AUTHOR]

Background: The European Society for Neonatology (ESN) developed a curriculum for subspecialist training in Europe recommending standards for national neonatal training programmes. We speculate whether these official recommendations are widely accepted or used in practice. Objectives: To characterize the variation in national neonatal training programmes, to enhance transparency, and to compare them to the ESN Curriculum. Methods: We constructed a database based on the backbone of the ESN Curriculum: (1) training - knowledge, (2) training - skills, (3) key competencies, (4) personal development, and (5) recording of progress. National neonatal representatives from all 30 member states of the Union of European Medical Specialties (UEMS) provided data on national training programmes. Results: Although only one country (3%) based its neonatology training entirely on the ESN Curriculum, we found high levels of uniformity among the UEMS member countries regarding knowledge, skills, and key competencies needed to practice neonatology at a tertiary care level. Discrepancy was encountered on ethical and legal issues and on personal development of the trainees. Mentoring and professional evaluation was generally not implemented in the participating countries. Conclusions: There is an awareness and readiness to focus on educational demands for neonatal trainees. Further discussions about the overall educational goals of neonatal training and the essence of practicing neonatology in each country are needed. The ESN will undertake this process to provide an updated and effective syllabus aimed to harmonize care and outcomes for babies and their families across Europe. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Unlabelled: 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 +/- 4 units (approx. 56 micromol/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 +/- 62 microtmol/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 75 Lmol/l). Skin pigmentation and ambient light both adversely affected noninvasive 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 (>250 Lmol/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 ( < 230 micromol/l) for the Minolta JM-102, or with a cut-off of 190 microlmol/l for the Bili-Check. If these respective thresholds are exceeded, serum bilirubin concentrations should be measured. [ABSTRACT FROM AUTHOR]

This study reports 5-year neurodevelopmental outcomes for Swiss children born before 32 weeks' gestation and randomized at birth to receive early high-dose recombinant human erythropoietin (rhEpo) vs placebo. [ABSTRACT FROM AUTHOR]

Importance: Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies.Objective: To determine whether prophylactic early high-dose recombinant human erythropoietin (rhEPO) in preterm infants improves neurodevelopmental outcome at 2 years' corrected age.Design, Setting, and Participants: Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multicenter trial in Switzerland between 2005 and 2012. Neurodevelopmental assessments at age 2 years were completed in 2014.Interventions: Participants were randomly assigned to receive either rhEPO (3000 IU/kg) or placebo (isotonic saline, 0.9%) intravenously within 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth.Main Outcomes and Measures: Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 2 years corrected age. The minimal clinically important difference between groups was 5 points (0.3 SD). Secondary outcomes were motor development (assessed with the Psychomotor Development Index), cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.Results: Among 448 preterm infants randomized (mean gestational age, 29.0 [range, 26.0-30.9] weeks; 264 [59%] female; mean birth weight, 1210 [range, 490-2290] g), 228 were randomized to rhEPO and 220 to placebo. Neurodevelopmental outcome data were available for 365 (81%) at a mean age of 23.6 months. In an intention-to-treat analysis, mean MDI was not statistically significantly different between the rhEPO group (93.5 [SD, 16.0] [95% CI, 91.2 to 95.8]) and the placebo group (94.5 [SD, 17.8] [95% CI, 90.8 to 98.5]) (difference, -1.0 [95% CI, -4.5 to 2.5]; P = .56). No differences were found between groups in the secondary outcomes.Conclusions and Relevance: Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Follow-up for cognitive and physical problems that may not become evident until later in life is required.Trial Registration: clinicaltrials.gov Identifier: NCT00413946. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive prenatal testing (NIPT) is increasingly being used in prenatal aneuploidy screening. The objective of this study was to assess the positive predictive value in our cohort of 68 cases with positive NIPT result. In addition, we wondered if the use of NIPT in cases with ultrasound abnormalities is appropriate, given the limited number of chromosomes investigated.Design: We performed confirmative invasive testing using karyotyping, fluorescence in situ hybridization (FISH) and/or high-resolution chromosomal microarray analysis.Results: In line with the published data, the positive NIPT result was confirmed in 64.7% of cases. Inconclusive and negative NIPT results followed by cytogenetically pathologic findings were encountered in three and in five cases, respectively. Four of the five fetuses with negative NIPT but pathologic cytogenetic findings were born with several malformations and diagnosed right after birth with severe genetic conditions. Of note, in all of those four cases, NIPT was offered despite the finding of major fetal ultrasound abnormalities and despite the fact that the family would not have opposed invasive testing or pregnancy termination.Conclusion: More education of health care providers and caution in counseling and interpretation of test results are needed in order to meet the challenges that this new test, which enriches our diagnostic options in prenatal testing, poses. [ABSTRACT FROM AUTHOR]

Background: Since the introduction of randomized controlled trials (RCT) in clinical research, there has been discussion of whether enrolled patients have worse or better outcomes than comparable non-participants. Objective: To investigate whether very preterm infants randomized to a placebo group in an RCT have equivalent neurodevelopmental outcomes to infants who were eligible but not randomized (eligible NR). Methods: In the course of an RCT investigating the neuroprotective effect of early high-dose erythropoietin on the neurodevelopment of very preterm infants, the outcome data of 72 infants randomized to placebo were retrospectively compared with those of 108 eligible NR infants. Our primary outcome measures were the mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development II at 24 months of corrected age. The outcomes of the two groups were considered equivalent if the confidence intervals (CIs) of their mean differences fitted within our ±5-point margin of equivalence. Results: Except for a higher socioeconomic status of the trial participants, both groups were balanced for most perinatal variables. The mean difference (90% CI) between the eligible NR and the placebo group was -2.1 (-6.1 and 1.9) points for the MDI and -0.8 (-4.2 and 2.5) points for the PDI. After adjusting for the socioeconomic status, maternal age and child age at follow-up, the mean difference for the MDI was -0.5 (-4.3 and 3.4) points. Conclusions: Our results indicate that the participation of very preterm infants in an RCT is associated with equivalent long-term outcomes compared to non-participating infants. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: High-dose recombinant human erythropoietin (rEpo) has first been administered in clinical trials for neuroprotection in very preterm neonates at high risk of brain injury and in (near-) term neonates with hypoxic-ischemic encephalopathy. However, recent trials in adults raised concerns about the safety of high-dose rEpo for neuro- and cardioprotection. Objectives: To evaluate the putative accumulation or renal leakage of Epo as a function of developmental stage after repetitive early short-term infusion of high-dose rEpo (3 × 3,000 U/kg within 42 h after birth; NCT00413946) for neuroprotection in very preterm infants. Methods: Epo concentrations were measured using the ELISA technique in the first two consecutive urine specimens after each rEpo infusion. Results: Renal Epo excretion was significantly higher in preterm infants with gestational ages <29 weeks than in more mature infants and reached up to 23% of the administered rEpo within 8 h after each infusion. The urinary Epo concentration did not increase after three repetitive infusions of high-dose rEpo. The ratio of urinary Epo to total protein concentrations was the same in infants with gestational ages <29 weeks and in those with gestational ages ≥29 weeks. Conclusions: Our data suggest that the higher renal Epo excretion in more immature infants may be attributed to a higher glomerular filtration leakage due to the lower maturation of the kidneys and argue against saturation kinetics after multiple doses of 3,000 U/kg rEpo. This information should be considered in future trials on the use of rEpo for neuroprotection in neonates. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To assess health-related quality of life of young adults born very preterm compared with a term control group. Methods: A cohort of preterm infants <1250 g and a term control group, both born between 1983 and 1985, were surveyed as adults at the median age of 23 years. Questionnaires including the Short Form 36 Health Survey (SF 36) and a modified lifestyle questionnaire assessed quality of life, health attitudes, height and weight, chronic diseases, medication and drug consumption. Results: Fifty-two preterms and 75 controls matched for age and sex participated in the study. There were no significant differences in the quality of life as assessed by SF 36. Former preterms were significantly smaller than their term controls but not so for body mass index. The overall consumption of illicit drugs was significantly lower in former preterms. Moreover, former preterms went significantly less often in for sports. There was a trend for higher prevalence of chronic diseases in male compared to female preterms, but their use of medication was significantly lower. Conclusion: Adults born very preterm show no significant differences in their quality of life when compared to controls in early adulthood. However, based on their lifestyle and health disadvantages, male preterm subjects constitute a risk group when entering early adulthood with a clear need for continued attention. [ABSTRACT FROM AUTHOR]

Fetal hemoglobin, HbF (&agr;2&ggr;2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (&agr;2&bgr;2), becomes predominant. Several studies have indicated that expression of the HbF subunit c-globin might be regulated post-transcriptionally. This could be confered by ∼22-nucleotide long microRNAs that associate with argonaute proteins to specifically target c-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that &ggr;-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 c-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased c-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of c-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of c-globin. Based on these results we conclude that microRNA-96 directly suppresses &ggr;-globin expression and thus contributes to HbF regulation. [ABSTRACT FROM AUTHOR]

Background: The increase in neonatal survival in recent decades has been followed by an increase in later disabilities. This has given rise to many new ethical issues. In different countries, efforts are being made to define ethical guidelines regarding withholding or withdrawing intensive care and end-of-life decisions in critically ill newborn infants. These guidelines have to be differentiated from ethical decision-making models which structure the process of decision making for an individual child. Such a framework has been in existence in our clinic for 10 years. Aim: The aims of this study were to evaluate how end-of-life decisions are taken in our perinatal centre and to analyse whether these decisions are consistent with our framework for structured ethical decision making. Methods: 199 consecutive neonatal deaths over 5 y were evaluated. Results: In 157 cases (79%), end-of-life decisions were taken according to our ethical framework; in the remaining 42 cases (21%), the baby died before this could be done. In 92% of cases, parents were involved in the decision and, in all cases but one, agreed with the decision. A patient's life was never intentionally and actively terminated. Conclusion: In contrast to earlier years, in-hospital death in our clinic is nowadays usually preceded by structured and documented medical end-of-life decisions. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyze the neonatal impact of a methadone maintenance program in pregnancy, and the social resources of the families involved.Descriptive analysis of neonatal data in live births after 24 weeks of gestation in pregnant women enrolled in a methadone maintenance program. The data of 86 babies were analyzed.Median gestational age was 380/7 (31–41) weeks; 21 babies (24%) were premature. Median birthweight was 2662 (1340–4050) g; 27% of babies were growth retarded (<3rd centile), and 13% had microcephaly (<3rd centile). Sixty-two percent developed abstinence syndrome requiring pharmacological treatment for a median 47 days. Child Protective Services (CPS) were involved in 56% of cases, and 42% of newborns required placement outside the mother's home.Babies born to women on methadone had a fourfold higher incidence of prematurity, a ninefold higher incidence of intrauterine growth retardation (IUGR), and a fourfold higher incidence of microcephaly compared with the normal population. Sixty-two percent required pharmacological treatment for abstinence syndrome and 42% required placement. [ABSTRACT FROM AUTHOR]

Objective. Blood sampling from an umbilical artery catheter (UAC) placed in a high position (thoracal 6-9) has the potential to produce clinically significant changes in cerebral blood flow and, thereby, in cerebral oxygenation. This may contribute to cerebral impairment in preterm newborn infants. Therefore, we set up a study to determine the effects of different sampling speeds through a UAC on cerebral oxygenation in preterm infants. Methods. Thirty pairs of measurements were conducted on 20 preterm infants (median gestational age: 30.14 weeks; median birth weight: 1170 g). For each infant, 2 blood samplings (both 2.3 mL, including flush volume) through the UAC in high position were taken at 2 different speeds (20 and 40 seconds) in alternating sequence. Cerebral oxygenation was measured noninvasively by near-infrared spectroscopy. Concentration changes in cerebral oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb), along with the tissue oxygenation index (TOI; O2Hb/[O2Hb + HHb] x 100), were recorded while blood was withdrawn and subsequently reinfused. Results. A significant decrease in O2Hb and TOI occurred during blood sampling within 20 seconds (median ΑO2Hb: -1.5 μmol/L; range: -4.1-2.3; median ΑTOI: -0.6%; range: -6.3-2.3), whereas HHb increased (median ΑHHb: 0.4 μmol/L, range: -1.1-change was found in O2Hb, HHb, and TOI when sampling 3.9). No significant time was extended to 40 seconds. Conclusion. Our results show that blood withdrawal over 20 seconds from a UAC in high position significantly decreases cerebral O2Hb and TOI in preterm infants. Prolonging sampling time to 40 seconds can prevent this phenomenon. [ABSTRACT FROM AUTHOR]

Unlabelled: The outcome of very preterm infants varies widely from centre to centre and from country to country. The aim of this study was to evaluate growth, developmental milestones and post-discharge morbidity of infants born before 32 weeks of gestation in Switzerland. A questionnaire was sent to the parents of 456 survivors born in 1996. A total of 309 (68%) parents responded and their infants were matched with 309 control infants born at term. At the corrected age of 24 months, the very preterm infants had significantly lower weight (-1.0 z-scores), lower length (-1.23 z-scores), and lower head circumference (-.64 z-scores). Very preterm infants were reported to eat with a spoon later than those born at term (50% at 7.5 months corrected for prematurity versus 10 months. P<0.001), to drink later out of a cup (50% at 16.5 months versus 13.5 months, P=0.03) and to walk later independently (50% at 14.5 months versus 13.5 months, P=0.04), whereas timing of sitting unsupported was no different (50% at 7.4 months versus 7.2 months, P=0.9). Of very preterm infants, 16% were not able to walk at least three steps unsupported at 18 months after term which puts them at an increased risk for cerebral palsy. Some 35% of very preterm infants had to be readmitted to hospital during the first 24 months compared with 20% of control infants born at term (P<0.05). There was no difference between very preterm and term infants in respect to episodes of fever > 38.5 degrees C, episodes of coughing > 3 days and treatment with antibiotics.Conclusion: these data based on a national survey allow to quantify growth retardation, developmental delay and post-discharge health problems within the first 2 years in preterm infants born before 32(0)/7 weeks. [ABSTRACT FROM AUTHOR]