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Objective To compare therapeutic hypothermia (TH) treatment of term and near-term neonates with hypoxic-ischemic encephalopathy (HIE) between neonatal units. Study design Population-based, retrospective analysis of TH initiation and maintenance, and of diagnostic imaging. The comparison between units was based on crude data analysis, indirect standardization, and adjusted logistic regression. Results TH was provided to 570 neonates with HIE between 2011 and 2018 in 10 Swiss units. We excluded 121 off-protocol cooled neonates to avoid selection bias. Of the remaining 449 neonates, the outcome was favorable to international benchmarks, but there were large unit-to-unit variations in baseline perinatal data and TH management. A total of 5% neonates did not reach target temperature within 7 h (3–10% between units), and 29% experienced over- or undercooling (0–38%). Conclusion Although the neonates had favorable short-term outcomes, areas for improvement remain for Swiss units in both process and outcome measures.

Objective To assess patent ductus arteriosus treatment variation between Swiss perinatal centers and to determine its effect on outcome in a population-based setting. Study design This was a retrospective cohort study of infants born less than 28 weeks of gestation between 2012 and 2017. Outcomes between surgically ligated and pharmacologically treated infants as well as infants born in centers performing ≤10% ligation (“low” group) and >10% (“high” group) were compared using logistic regression and 1:1 propensity score matching. Matching was based on case-mix and preligation confounders: intraventricular hemorrhages grades 3-4, necrotizing enterocolitis, sepsis, and ≥28 days’ oxygen supply. Results Of 1389 infants, 722 (52%) had pharmacologic treatment and 156 (11.2%) received surgical ligation. Compared with infants who received pharmacologic treatment, ligated infants had greater odds for major morbidities (OR 2.09, 95% CI 1.44-3.04) and 2-year neurodevelopmental impairment (OR 1.81, 95% CI 1.15-2.84). Mortality was comparable after restricting the cohort to infants surviving at least until day 10 to avoid survival bias. In the “low” group, 34 (4.9%) of 696 infants were ligated compared with 122 (17.6%) of 693 infants in the “high” group. Infants in the “high” group had greater odds for major morbidities (OR 1.49, 95% CI 1.11-2.0). Conclusions Our analysis identified a burden on infants receiving surgical ligation vs pharmacologic treatment in a population-based setting where there was no agreed-on common procedure. These results may guide a revision of patent ductus arteriosus treatment practice in Switzerland.

Impaired neurodevelopment is increasingly recognized as a major health issue in children born prematurely. Creative music therapy (CMT) intends to prevent and or reduce neurobehavioral deficits in pre-term infants using musical stimulation and socio-emotional co-regulation. We conducted a randomized, clinical pilot CMT trial to test feasibility and to examine long-term neurodevelopmental outcomes in pre-term infants (NCT02434224: https://clinicaltrials.gov/ct2/show/NCT02434224). Eighty-two pre-term infants were randomized either to CMT or standard care. A specially trained music therapist provided family-integrating CMT via infant-directed singing during hospitalization. Fifty-six infants underwent follow-up at 2 years of corrected age. No significant beneficial nor adverse effects of CMT were identified in routine clinical neurodevelopmental measures (Bayley-III Scales of Infant and Toddler Development and the standardized neurological examination). Longer term follow-up (5 years) and larger future studies are recommended to elucidate possible long-term effects of music in relation to more sensitive outcomes including executive function, detailed language processing and social-emotional development.

Background: The COVID-19 pandemic is a global issue which affects the entire population&rsquo, s mental health. This study evaluates how restrictions to curtail this pandemic change parenting self-efficacy, depressive symptoms, couple satisfaction and health-related quality of life in parents after delivery of a newborn. Methods: In this prospective single center evaluation of parental self-efficacy and quality of life, four validated questionnaires were used to repeatedly assess parenting self-efficacy (Tool to measure Parental Self-Efficacy, TOPSE), depressive symptoms (Edinburgh Postnatal Depression Scale, EPDS), couple satisfaction (Couple Satisfaction Index, CSI) and health-related quality of life (short form 12, SF12). Fifty-three parents of 50 infants answered a total number of 63 questionnaires during the lockdown period to limit the spread of COVID-19. These questionnaires were matched with 63 questionnaires of 58 other parents that had answered them before or after strong pandemic related measures. Results: Parents experienced lower parenting self-efficacy during the strict pandemic measures as compared to before and after (p = 0.04). In terms of age, socioeconomic, marital status and duration of hospitalization we detected no significant difference between both groups. On univariate linear regression, TOPSE scores were associated with gestational age (p = 0.044, parameter estimate: 1.67, 95% CI: 0.048 to 3.301), birth weight (p = 0.035, parameter estimate: 0.008, 95% CI: 0.001 to 0.015), number of newborns&rsquo, siblings (p = 0.0554, parameter estimate: 7.49, 95% CI: &minus, 0.174 to 15.145) and distance of home from hospital (p = 0.043, parameter estimate: &minus, 0.38, 95% CI: &minus, 0.745 to &minus, 0.011). Interestingly, there was a positive correlation between quality of life and TOPSE scores, suggesting that those who experience a higher self-efficacy also have a higher quality of life. Conclusions: When implementing a lock-down period psychological effects such as lower experience of parental self-efficacy have to be considered.

It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open datasets of segmented fetal brains. Here we introduce a publicly available dataset of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the dataset for the development of automatic algorithms., Scientific Data, 8 (1), ISSN:2052-4463

Background. The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes., Methods. We conducted a multicenter, population-based, prospective study including previously healthy children aged >= 28 days and, Results. There were 176 children presenting with 185 sepsis episodes who underwent WES (median age, 52 months; interquartile range, 15.4-126.4). There were 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants that were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories, as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants., Conclusions. Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected variants of uncertain significance in PID genes in 1 out of 5 children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.

Although recombinant human erythropoietin (rhEpo) has been shown to be neuroprotective in experimental and clinical studies,1,2 prophylactic early high-dose rhEpo did not improve neurodevelopment among 2-year-olds who had been born very preterm in a randomized clinical trial.3 We report the prespecified secondary neurodevelopmental outcomes of the trial cohort at early school age.

Introduction: The only causal therapy is fetoscopic laser surgery (FLS). The aims of this study were to analyze the long-term outcome of monochorionic twins treated by FLS, including their school career, need for therapy and special aid equipment, and free-time activities, and compare their outcome to matched dichorionic twins. Material and Methods: Among the 57 women treated at a single fetal treatment center between 2008 and 2017 with FLS because of twin-to-twin transfusion syndrome, 25 women with 42 children were included in the FLS group. The control group consisted of 16 dichorionic twin pairs matched for birth year, gestational age (GA), birth weight, and sex. The long-term outcome was assessed by a parental questionnaire and a standardized neurodevelopmental examination for children born before 32 gestational weeks or with a birth weight lower than 1500 g. They were also registered into the Swiss Neonatal Network database. The primary outcome was event-free survival, defined as normal neurology, behavior, vision, and hearing. The secondary outcomes were school career, need for therapy and special aid equipment, and free-time activities. Results: An event-free survival was found in 32 children (76%) in the laser and in 24 children (75%) in the control group (p = 0.91). Neurological anomalies were found in 5 children (12%) in the laser group and 3 children (9%) in the control group (p = 1.00). Multiple logistic regression analysis showed that GA at delivery was the only predictive factor for event-free survival. There were no significant differences regarding school career, therapies, or special aid equipment between the 2 groups. We found that children without FLS were involved in more free-time activities and needed fewer breaks during physical activity than children with FLS during pregnancy. Conclusion: The outcome of monochorionic twins treated with FLS is comparable to the outcome of dichorionic twins. Long-term neurodevelopment in the cohort was mainly dependent on GA at birth.

The recent introduction of newborn screening for severe primary T and B cell deficiencies in Switzerland allows rapid identification of patients with severe combined immunodeficiency (SCID). Outcomes for SCID are greatly improved by early diagnosis and treatment with allogeneic haematopoietic stem cell transplantation or, in selected cases, gene therapy. National centralised newborn screening is performed in Switzerland since January 2019 using a combined T cell receptor excision circles (TREC) / κ-deleting recombination excision circles (KREC) assay, also revealing infants with non-SCID severe T and B cell disorders, who are often diagnosed with a substantial delay. Here, we outline the screening procedure currently performed in Switzerland and give recommendations for diagnostic evaluations and precautionary measures against infection in children with abnormal screening test results.

Introduction The thalamus is a key hub for regulating cortical connectivity. Dysmaturation of thalamocortical networks that accompany white matter injury has been hypothesized as neuroanatomical correlate of late life neurocognitive impairment following preterm birth. Our objective was to find a link between thalamocortical connectivity measures at term equivalent age and two‐year neurodevelopmental outcome in preterm infants. Methods Diffusion tensor MRI data of 58 preterm infants (postmenstrual age at birth, mean (SD), 29.71 (1.47) weeks) were used in the study. We utilized probabilistic diffusion tractography to trace connections between the cortex and thalami. Possible associations between connectivity strength, the length of the probabilistic fiber pathways, and developmental scores (Bayley Scales of Infant Development, Second Edition) were analyzed using multivariate linear regression models. Results We found strong correlation between mental developmental index and two complementary measures of thalamocortical networks: Connectivity strength projected to a cortical skeleton and pathway length emerging from thalamic voxels (partial correlation, R = .552 and R = .535, respectively, threshold‐free cluster enhancement, corrected p‐value, Our purpose was to find a link between thalamocortical connectivity measures at term equivalent age and two‐year neurodevelopmental outcome in 58 infants following preterm birth. Using probabilistic diffusion tractography, we found that injury or dysmaturation of tracts emerging from ventral‐specific and various nonspecific thalamus projecting to late‐maturing cortical regions is predictive of mental, but not psychomotor developmental outcomes

Purpose: Twin-to-twin transfusion syndrome (TTTS) complicates 10–15% of all monochorionic twin pregnancies. Selective laser coagulation of placental anastomoses is the only causal therapy. ...

Objective\ud To validate and test a German version of the revised Parent Report of Children's Abilities questionnaire (PARCA-R).\ud \ud Methods\ud Multicentre cross-sectional study. Parents of infants born

Mycoplasma pneumoniae is a significant cause of pneumonia in school-aged children and young adults. We report a case of neonatal M. pneumoniae pneumonia in a preterm child manifesting in the first hours of life. Vertical transmission was demonstrated by the detection of M. pneumoniae in inflamed placental tissue indicating chorioamnionitis.

Background In utero intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus. Purpose To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM-MRI. Study type Retrospective, cross-sectional study. Subjects Fifty-five datasets from 33 singleton pregnancies were acquired (17-36 gestational weeks). Field strength/sequence In utero diffusion-weighted echo-planar imaging at 1.5T and 3.0T with b-factors ranging from 0 to 900 s/mm2 in 16 steps. Assessment Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free-form nonlinear deformation algorithm was used to correct for the frame-by-frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound-based assessment of the umbilical artery resistance index. Statistical tests Pearson product-moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age-related changes were assessed using linear regression analysis (LR). Results Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = -0.457). The f of the liver decreased sharply during gestation (LR, R = -0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = -0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver. Data conclusion Gestational age-associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

AimTo analyse the association between early aEEG and cognitive outcome at early school-age in very preterm infants.MethodsProspective cohort study including infants with gestational age (GA) ResultsAmong 118 monitored preterm children, 89 were assessed at median(IQR) corrected age of 68.6 months (65.5-71.2) [48% female, median(IQR) GA 29.9(28.2,30.9) weeks, mean(SD) birth weight 1235(363) grams]. Mean(SD) IQ was 97.8(12.7). IQConclusionIn this cohort of very preterm infants, early short-term aEEG was not predictive of later cognitive outcome. Further research is needed to explore how aEEG could help to inform long-term prognosis in this population group.Key notesPreterm born infants are at high risk for neurodevelopmental impairment.Early amplitude integrated electroencephalography characteristics are univariately associated with cognitive outcome at 5 years of age in preterm born children.However, socioeconomic factors and neonatal morbidity were stronger predictors of long-term neurodevelopmental outcome than early aEEG measures.

AIM We investigated the association between early amplitude-integrated electroencephalography (aEEG) and cognitive outcome in very preterm infants at early school-age. METHODS This prospective cohort study, conducted in the Department of Neonatology, University Hospital Zurich, Switzerland, from 2009-2012, comprised infants born at less than 32 weeks of gestation, who underwent continuous aEEG recording during the first four days of life. Cognitive outcome was assessed with the Kaufman-Assessment Battery for Children at five years. Univariate and multivariate logistic regressions were calculated between aEEG parameters and normal cognitive outcome, defined as an intelligence quotient (IQ) of at least 85. RESULTS The 118 (52.5% male) infants were born at a mean gestational age of 29.9 weeks and a mean birth weight of 1,235 ±363 grams. We followed up 89 children at the age of five and they had a mean IQ of 97.8 ±12.7 with 21.3% under 85 - and 2.2% had cerebral palsy. Univariate analyses found associations between aEEG measures and normal cognitive outcome, but these were no longer significant after adjustment for confounders. Socioeconomic status and neonatal morbidity were independent predictors of cognitive outcome. CONCLUSION Early short-term aEEG did not predict later cognitive outcome in our cohort of very preterm infants. This article is protected by copyright. All rights reserved.

Objective: In order to provide aid for prenatal counseling in fetal isolated ventriculomegaly (IVM) on ultrasound, we recorded the latest long-term clinical and imaging outcomes of children with a mean age of 7.2 years (range 2.1-14.6). Methods: In 72 fetuses with IVM, diagnosed between 1999 and 2011, the measurement quality of atrial diameter was reviewed in the axial plane. We assessed the association of characteristics of IVM with outcome parameters in the cohort and in subgroups. Prognostic values of significant associations were reported by receiver operating characteristic curve analysis. Results: Cerebral anomalies were diagnosed postnatally in 42% and genetic disorders in 12% of 45 live births. Significant associations of outcome parameters were found between the degree of IVM and genetic disorders (p = 0.017) with an area under the curve (AUC) of 0.866, and between progression of IVM and motor impairment (p = 0.024) with an AUC of 0.789. No significant correlation was found with the other assessed outcome parameters. Furthermore, our subgroup analysis clearly showed that, if cerebral or genetic anomalies are not found postnatally, a favorable outcome may be expected. Discussion: Diameter and progression in IVM are not significantly associated with most outcome parameters. Cerebral anomalies and genetic disorders may contribute to an unfavorable outcome.

Objective To assess the contribution of the severity of bronchopulmonary dysplasia (BPD) and the time point of its diagnosis to the prediction of neurodevelopmental impairment (NDI) at corrected age of 2 years in preterm infants. Design Retrospective cohort study. Setting Level-III perinatal centre. Patients and outcome measures Infants born in 2000–2013 with gestational age 21% for ≥28 days and its severity classified as mild, FiO2=21%; moderate, FiO2 21% for ≥28 days nor mild or moderate BPD at either 36 or 40 weeks’ PMA was associated with NDI, but severe BPD was (at 36 weeks’ PMA 5.6 (2.0 to 16.0) and at 40 weeks’ PMA 16.6 (4.6 to 59.9)). Infants with severe BPD at both 36 and 40 weeks’ PMA had lower mental (mean difference −11.4 (−18.5 to −4.3), −25.7(−35.9 to −15.5), respectively) and motor (−7.8 (−14.9 to −0.6), −20.1(−30.7 to −9.5), respectively), developmental scores than infants without BPD. Conclusion In this cohort, severe BPD was a better independent predictor of NDI at 2 years than mild or moderate BPD. BPD diagnosed at 40 weeks’ PMA might allow better identification of infants at highest risk for NDI.

Aim: This study aimed at exploring the type, degree, and duration of work-related burden on neonatal physicians and nurses working in tertiary level neonatal intensive care units, its impact on their private life, and at assessing which coping strategies were found helpful. Methods: Transversal descriptive study using an anonymous questionnaire. Results: Fifty-two neonatal physicians and 60 nurses took part in this survey (response rate 77%). Altogether, 78% stated that the difficult medical and ethical dilemmas represent a burden to them. 87% experienced this work burden as momentary, and 12% as long-lasting. In 40% of the respondents, their private life was affected. Exhaustion was the most frequently cited stress symptom (physicians 25%, nurses 15%). Close to 90% of the caregivers were offered a platform for team debriefings and discussions or pastoral assistance by their hospital, but most of the respondents found relief from stress through discussions with family members and friends (20%), and through their hobbies (15%), or both (43%). Conclusion: Working in a NICU environment represents a burden for the majority of neonatal health care providers. Exhaustion was the most frequent symptom. Social contacts with family and friends and hobbies are the coping strategies found most helpful. Staff meetings, debriefing platforms and pastoral assistance help alleviate work-related stress. Keywords: Coping; Coping behavior; Exhaustion; Work-related stress; NICU

To assess neurodevelopmental outcome during toddlerhood in very low birthweight (VLBW) infants with absent or reverse end-diastolic flow (AREDF) in the umbilical artery (UA) during pregnancy.Retrospective cohort study with matched control group.Tertiary perinatal centre.We compared longitudinally collected data on neonatal and neurodevelopmental outcomes among 41 infants born in our institution from 1997 to 2010 with birth weight1500 g and UA AREDF and 41 infants with prenatally normal UA Doppler parameters matched for gestational age, birth weight, sex and year of birth. We evaluated neurodevelopmental outcome at a median (range) corrected age of 23.3 (10.1-29.6) months using the Bayley scales of infant development, 2nd edition (BSID-II), and neurological examination.The mental development index in UA AREDF children (median (range) 84 (49-116)) was significantly lower than in controls (median (range) 91 (62-140)), including after adjustment for confounders. Intergroup differences in psychomotor development index (PDI; BSID-II) and the rate of cerebral palsy or minor neuromotor dysfunction were non-significant.VLBW infants with UA AREDF have a higher risk of poorer mental development during toddlerhood than controls matched for gestational age, birth weight, sex and year of birth. UA AREDF may be considered a prenatal predictor of poorer mental development in this population. Long-term follow-up studies with larger cohorts are needed to better evaluate the impact of this prenatal factor on later neurodevelopment.

BACKGROUND Therapeutic hypothermia following hypoxic ischaemic encephalopathy in term infants was introduced into Switzerland in 2005. Initial documentation of perinatal and resuscitation details was poor and neuromonitoring insufficient. In 2011, a National Asphyxia and Cooling Register was introduced. AIMS To compare management of cooled infants before and after introduction of the register concerning documentation, neuromonitoring, cooling methods and evaluation of temperature variability between cooling methods. STUDY DESIGN Data of cooled infants before the register was in place (first time period: 2005-2010) and afterwards (second time period: 2011-2012) was collected with a case report form. RESULTS 150 infants were cooled during the first time period and 97 during the second time period. Most infants were cooled passively or passively with gel packs during both time periods (82% in 2005-2010 vs 70% in 2011-2012), however more infants were cooled actively during the second time period (18% versus 30%). Overall there was a significant reduction in temperature variability (p < 0.001) comparing the two time periods. A significantly higher proportion of temperature measurements within target temperature range (72% versus 77%, p < 0.001), fewer temperature measurements above (24% versus 7%, p < 0.001) and more temperatures below target range (4% versus 16%, p < 0.001) were recorded during the second time period. Neuromonitoring improved after introduction of the cooling register. CONCLUSION Management of infants with HIE improved since introducing the register. Temperature variability was reduced, more temperature measurements in the target range and fewer temperature measurements above target range were observed. Neuromonitoring has improved, however imaging should be performed more often.

Background: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). Objectives: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). Methods: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. Results and Conclusions: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

Placebo effects emerging from the expectations of relatives, also known as placebo by proxy, have seldom been explored. The aim of this study was to investigate whether in a randomized controlled trial (RCT) there is a clinically relevant difference in long-term outcome between very preterm infants whose parents assume that verum (PAV) had been administered and very preterm infants whose parents assume that placebo (PAP) had been administered. The difference between the PAV and PAP infants with respect to the primary outcome-IQ at 5 years of age-was considered clinically irrelevant if the confidence interval (CI) for the mean difference resided within our pre-specified ±5-point equivalence margins. When adjusted for the effects of verum/placebo, socioeconomic status (SES), head circumference and sepsis, the CI was [-3.04, 5.67] points in favor of the PAV group. Consequently, our study did not show equivalence between the PAV and PAP groups, with respect to the pre-specified margins of equivalence. Therefore, our findings suggest that there is a small, but clinically irrelevant degree to which a preterm infant's response to therapy is affected by its parents' expectations, however, additional large-scale studies are needed to confirm this conjecture.

Background As the survival rate of preterm infants constantly improves, knowledge on the impact of prematurity on long-term health-related quality of life (HRQoL) is important for clinical and parental guidance. We aimed to assess HRQoL in a national cohort of young adolescents born very preterm, and to identify predictors for poorer HRQoL. Patients and methods All surviving Swiss live-born children below 30weeks of gestation during the year 2000 (290 subjects) were contacted at age 12years, together with their parents (262 families). HRQoL of the study children was assessed using both the Kidscreen-27 (KS-27) self- and parent forms. Neonatal data of the cohort were prospectively collected. Results Among the contacted families, 176 returned the complete set of questionnaires for 194 adolescents (67%): 100 (51%) females, mean (range) gestational age was 27.8 (24.1–29.9) weeks, birth weight 1025 (420–1730) grams, mean age at assessment 12.0 (11.0–13.0) years. Included children had similar neonatal and socio-demographic characteristics as non-responders. Average self- and parent-reported HRQoL of former preterms was similar to Swiss KS-27 norms. According to the multivariable models (r 2 =0.2), surgical closure of patent ductus arteriosus, attention deficit/hyperactivity disorder, severe neurodevelopment impairment were negatively associated with both self- and parent-reported HRQoL. Conclusions HRQoL in this population-based cohort of adolescents born very preterm is good. Surgical closure of patent ductus arteriosus, attention deficit/hyperactivity disorder, severe neurodevelopment impairment were identified as predictors of poorer HRQoL using multivariable models, explaining however only a low proportion of variance in HRQoL.

Aim This study assessed predictive values of fidgety movement assessment (FMA) in a large sample of infants born very preterm for developmental abnormalities, in particular for cerebral palsy (CP) at 2 years in an everyday clinical setting. Method This is a multicentre study of infants born preterm with gestational age lower than 32.0 weeks. FMA was performed at 3 months corrected age; neurodevelopment (Bayley Scales of Infant Development, 2nd edition) and neurological abnormalities were assessed at 2 years. Predictive values of FMA for the development of CP were calculated and combined with abnormalities at cerebral ultrasound. Results Five hundred and thirty-five infants (gestational age 28.2wks [standard deviation 1.3wks]) were included. Eighty-one percent showed normal fidgety movements and 19% atypical (82 absent, 21 abnormal) fidgety movements. Absent fidgety movements predicted CP at 2 years with an odds ratio (OR) of 8.9 (95% confidence interval [CI] 4.1–17.0), a combination of atypical fidgety movements and major brain lesion on cerebral ultrasound predicted it with an OR of 17.8 (95% CI 5.2–61.6). Mean mental developmental index of infants with absent fidgety movements was significantly lower (p=0.012) than with normal fidgety movements. Interpretation Detection of infants at risk for later CP through FMA was good, but less robust when performed in a routine clinical setting; prediction improved when combined with neonatal cerebral ultrasound.

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.

Aims: To determine the motor and cognitive outcome in a regional cohort of survivors of surgically corrected congenital diaphragmatic hernia. Methods: Thirty-three children (85% of survivors) were examined at a mean age of 8.6 years (3.3–15.7 years), seven had a genetic comorbidity. Outcome was assessed with the Wechsler Preschool and Primary Scale of Intelligence 3rd version and the Wechsler Intelligence Scale 4th version. Motor performance was tested with the Movement Assessment Battery for Children 2nd edition in children younger than 5 years and thereafter with the Zurich Neuromotor Assessment. Results: Children without a genetic comorbidity had a normal cognitive outcome (median IQ 103, 70–121), but fine motor (p = 0.008) and gross motor outcome (p = 0.001) were poorer than the norm. Medical variables were not predictive of adverse outcome, whereas genetic comorbidity was the strongest predictor of low IQ (p

Aim We assessed motor and intellectual outcome in triplets at school age and investigated the predictive value of perinatal and demographic factors. Methods Seventy-one live-born newborn infants (24 triplet pregnancies) were prospectively enrolled at birth. At the age of 6 years, 58 children (31 males, 27 females; mean gestational age 31.2wks [SD 2.2wks]; mean birthweight 1622g [SD 440g]) returned for a neurodevelopmental examination. A comparison group for triplets born before 32 gestational weeks comprising 26 gestational age-, birthweight-, and sex-matched singletons was also recruited (mean gestational age 30.1wk [SD 1.5wk]; mean birthweight 1142g [SD 210g]; 12 males, 14 females). The Zurich Neuromotor Assessment was used to examine motor performance, and intellectual abilities were assessed with the Kaufman Assessment Battery for Children (K-ABC). Results Motor performance and movement quality in these individuals was significantly reduced compared with the test norms for all motor tasks (p

The aim of this study is to describe the effect of sedation and analgesia on postoperative amplitude-integrated EEG (aEEG) in newborns with congenital heart disease (CHD) undergoing heart surgery. This is a consecutive series of 26 newborns with CHD of which 16 patients underwent cardiopulmonary bypass (CPB) surgery and 10 patients did not. aEEG was monitored for at least 12 h preoperatively and started within the first 6 h postoperatively for 48 h. Outcome was assessed at 1 year of age. All 26 patients showed a normal preoperative continuous cerebral activity with sleep-wake cycles (SWC). The postoperative duration to return to normal background activity with SWC was similar for both groups. Independent of group assignment, patients requiring midazolam had a significantly later onset of a normal SWC than those without midazolam (p=0.03). Three patients in the CPB group and two in the non-CPB group showed continuous low voltage or flat trace after administration of fentanyl. These changes did not correlate with neurodevelopmental outcome. Sedation with midazolam has a transient effect on the background activity, whereas fentanyl can induce a severe pathologic background pattern. The significance of these changes on outcome is not yet clear. Thus, more attention should be paid to these effects when interpreting aEEG in this population.

Background Neonates with hypoxic ischaemic encephalopathy (HIE) are routinely treated with therapeutic hypothermia (TH) for 72 h in order to improve neurological outcome. Subcutaneous fat necrosis (SCFN) is an adverse event occurring in neonates with HIE. Methods We analyzed risk factors for SCFN regarding demographic factors, cooling methods and deviation from target temperature range during hypothermia therapy. Data of all neonates registered in the National Asphyxia and Cooling Register in Switzerland between 2011 and 2013 were analyzed. Results 2.8 % of all cooled neonates with HIE developed SCFN. Perinatal and neonatal characteristics did not differ between neonates with and without SCFN. Applied cooling methods did not correlate with the occurrence of SCFN. In neonates with SCFN 83.3 % of all noted temperatures were within the target temperature range versus 77.5 % in neonates without SCFN. Neonates with SCFN showed 3.6 % of all measured temperatures below target temperature range compared to 12.7 % in neonates without SCFN. Conclusion Subcutaneous fat necrosis in the neonate with HIE undergoing TH is a potential adverse event that seems to occur independently from the whole-body cooling method applied and proportion of temperature measurements outside target temperature range. In this cohort, moderate overcooling associated with moderate hypothermia (33.0–34.0 °C) does not seem to be an independent risk factor for SCFN. There is no correlation between the severity of HIE and incidence of SCFN. Electronic supplementary material The online version of this article (doi:10.1186/s12887-015-0395-7) contains supplementary material, which is available to authorized users.

Amplitude-integrated electroencephalogram (aEEG) is increasingly used for neuromonitoring in preterms. We aimed to quantify the effects of gestational age (GA), postnatal age (PNA), and other perinatal factors on the development of aEEG early after birth in very preterm newborns with normal cerebral ultrasounds.Continuous aEEG was prospectively performed in 96 newborns (mean GA: 29.5 (range: 24.4-31.9) wk, birth weight 1,260 (580-2,120) g) during the first 96 h of life. aEEG tracings were qualitatively (maturity scores) and quantitatively (amplitudes) evaluated using preestablished criteria.A significant increase in all aEEG measures was observed between day 1 and day 4 and for increasing GA (P0.001). The effect of PNA on aEEG development was 6.4- to 11.3-fold higher than that of GA. In multivariate regression, GA and PNA were associated with increased qualitative and quantitative aEEG measures, whereas small-for-GA status was independently associated with increased maximum aEEG amplitude (P = 0.003). Morphine administration negatively affected all aEEG measures (P.05), and caffeine administration negatively affected qualitative aEEG measures (P = 0.02).During the first few days after birth, aEEG activity in very preterm infants significantly develops and is strongly subjected to the effect of PNA. Perinatal factors may alter the early aEEG tracing and interfere with its interpretation.

Aim The aim of this study was to examine neurodevelopment, psychological adjustment, and health-related quality of life (HRQoL) in adolescents after bypass surgery for congenital heart disease (CHD) during early childhood. Method Fifty-nine adolescents (34 females, 25 males) with CHD were examined at a median age of 13 years 8 months (range 11y 5mo–16y 11mo). Outcome was assessed with the Wechsler Intelligence Scale for Children, (fourth edition); the Beery Test of Visual-Motor Integration; the Rey–Osterrieth Complex Figure Test; the Zurich Neuromotor Assessment; the Strengths and Difficulties Questionnaire; and the KIDSCREEN questionnaires. Results were compared with those of 40 age- and sex-matched healthy comparison individuals. Results Outcome with regard to full-scale IQ, perceptual reasoning, and the working memory scale was poorer in patients with CHD than in the comparison group (all p≤0.001). Visual perception, visuomotor integration (p≤0.001), and executive functions (Rey figure copy: p=0.05) were also affected. Patients with CHD also had lower scores on all motor domains (p

Aim To assess patterns of change for different neuromotor functions in very low birth weight (VLBW) children during school age and to identify factors associated with improvement. Methods In a longitudinal study, we examined 65 prospectively enrolled VLBW children (38 female, 59%) without cerebral palsy at age six and 10 years. Measures included the evaluation of timed motor performance and motor overflow (MO) for the motor components of the Zurich Neuromotor Assessment (pure motor-, adaptive fine- and gross motor tasks, static balance) and a standardized neurological examination. Variables associated with improvement were assessed by multiple regression analyses. Results Between six and 10 years, adaptive fine motor tasks (40% vs. 17% of children scoring below 10th percentile) and MO (77% vs. 55%) improved significantly (both p

BackgroundWhile survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling.MethodsProspective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7and 276/7weeks gestational age during 2000–2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System.ResultsOf 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p 0/7weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p ConclusionsIn this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability.

Background: Maturation of amplitude-integrated electroencephalogram (aEEG) activity is influenced by both gestational age (GA) and postmenstrual age. It is not fully known how this process is influenced by cerebral lesions. Objective: To compare early aEEG developmental changes between preterm newborns with different degrees of cerebral lesions on cranial ultrasound (cUS). Methods: Prospective cohort study on preterm newborns with GA Results: 104 newborns with a mean GA (range) 29.5 (24.4–31.7) weeks, and birth weight 1,220 (580–2,020) g were recruited. Newborns with severe brain lesions started with similar aEEG scores and tendentially lower aEEG amplitudes than newborns without brain lesions, and showed a slower development of the cyclic activity (p < 0.001), but a more rapid increase of the maximum and minimum aEEG amplitudes (p = 0.002 and p = 0.04). Conclusions: Preterm infants with severe cerebral lesions manifest a maturational delay in the aEEG cyclic activity already early after birth, but show a catch-up of aEEG amplitudes to that of newborns without cerebral lesions. Changes in the maturational aEEG pattern may be a marker of severe neurological lesions in the preterm infant.

AIM: To assess self-perceived health status and mental health outcomes of former extremely low-birth-weight (ELBW) infants at young adulthood compared with community norms and to analyse predictors of poor outcome. METHODS: Fifty-five ELBW adults, 18 men (33%), with median (range) gestational age of 28.7 (25.0-34.0) weeks and birth weight of 930 (680-990) grams, born in Switzerland, were included. They self-rated their health status and mental health at a mean (range) age of 23.3 (21.8-25.9) years. Health status was measured by the Medical Outcomes Study Short Form-36 questionnaire and mental health by the Brief Symptom Inventory. RESULTS: The mean scores for both outcome measures were in the normal range. However, the study group self-rated significantly higher physical health status and lower mental health status compared with the community norms, and scores for self-perceived mental health tended to be worse in the former. ELBW adults reported more problems in socio-emotional role functioning compared with the community norms. Female sex was associated with poorer and bronchopulmonary dysplasia with better mental health status. CONCLUSION: Health status and mental health of former ELBW adults were overall satisfying. However, the comparison with the community norms revealed differences, which may be important for parental and patient counselling and developing support strategies.

Our aim was to evaluate the clinical impact of routine amniotic fluid and neonatal surface swab microbiology at Caesarean section. Microbiology data from 1 537 neonates delivered by Caesarean section were analysed in the light of clinical outcome. 1 340 (87%) neonates had non-pathogenic bacteria or negative culture results from both amniotic fluid and surface swab samples. Of the 197 (13%) neonates with pathogenic bacteria, 22 (1.4%) were diagnosed with infection, but only in 6 (0.4%) were the bacteria presumed to be responsible for the infection. Amniotic fluid and surface swab culture had sensitivities of 54% and 35%, and positive predictive values of 14% and 17%, respectively, for detecting a neonate at risk of infection. Amniotic fluid and neonatal surface swab microbiology at Caesarean section contributes little if anything to postnatal management and can be safely dropped from operative routine.

Objectives To assess health-related quality of life (HRQoL) and behavior of triplets compared with matched singletons at adolescent age and to identify medical and sociodemographic predictors of outcome. Study design Fifty-four triplets (19 sets, mean [SD] gestational age 32.0 [2.4] weeks, birth weight 1580 [450] g) and 51 gestational age-, birth weight-, and sex-matched singleton controls self-rated their HRQoL at age 14.5 (0.3) years. Proxy reports about HRQoL and behavior were obtained by parents and teachers. HRQoL was measured with the Kidscreen-52 questionnaire child and parent form, and behavior with the Achenbach Child Behavior Checklist. Results Self- and parent-reported HRQoL values was similar in both groups except for the dimensions "mood and emotions" and "autonomy," which were better ( P = .001, P = .03) in triplets. Parents reported significantly less behavioral problems in triplets compared with controls. Compared with community norms, both HRQoL and behavior measures in triplets were in the normal range. Parent-reported HRQoL was predicted by dichorionicity. Conclusions HRQoL and behavioral outcome in adolescent triplets was good in our study and was, in some aspects, better than in matched singleton controls. Dichorionicity is an important outcome determinant.

OBJECTIVE: Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants. PATIENTS AND METHODS: This was a multicenter Swiss cohort study on infants born between 2000 and 2007 at 2407 to 2767 weeks' gestational age. Neurodevelopmental outcome was assessed with the Bayley Scales of Infant Development–II. Neurodevelopmental impairment (NDI) was defined as a Mental or Psychomotor Developmental Index lower than 70, cerebral palsy (CP), or visual or auditory impairment. RESULTS: Of 541 infants, 136 (25%) had proven sepsis, 169 (31%) had suspected sepsis, and 236 (44%) had no signs of infection. CP occurred in 14 of 136 (10%) infants with proven sepsis compared with 10 of 236 (4%) uninfected infants (odds ratio [OR]: 2.90 [95% confidence interval (CI): 1.22–6.89]; P = .016). NDI occurred in 46 of 134 (34%) infants with proven sepsis compared with 55 of 235 (23%) uninfected infants (OR: 1.85 [95% CI: 1.12–3.05]; P = .016). Multivariable analysis confirmed that proven sepsis independently increased the risk of CP (OR: 3.23 [95% CI: 1.23–8.48]; P = .017) and NDI (OR: 1.69 [95% CI: 0.96–2.98]; P = .067). In contrast, suspected sepsis was not associated with neurodevelopmental outcome (P > .05). The presence of bronchopulmonary dysplasia, pathologic brain ultrasonography, retinopathy, and sepsis predicted the risk of NDI (P < .0001). CONCLUSIONS: Proven sepsis significantly contributes to NDI in extremely preterm infants, independent of other risk factors. Better strategies aimed at reducing the incidence of sepsis in this highly vulnerable population are needed.