Effects of hemodynamic alterations and oxygen saturation on cerebral perfusion in congenital heart disease.

BACKGROUND: Patients with severe congenital heart disease (CHD) are at risk for neurodevelopmental impairment. An abnormal cerebral blood supply caused by the altered cardiac physiology may limit optimal brain development. The aim of this study was to evaluate the effect of a systemic-to-pulmonary shunt, aortic arch obstruction and arterial oxygen saturation on cerebral perfusion in patients with severe CHD. METHODS: Patients with severe CHD requiring cardiac surgery within the first six weeks of life, who underwent pre- and/or postoperative brain magnetic resonance imaging (MRI), and healthy controls with one postnatal scan were included. Cerebral perfusion in deep and cortical gray matter was assessed by pseudocontinuous arterial spin labeling MRI. RESULTS: We included 59 CHD and 23 healthy control scans. The presence of a systemic-to-pulmonary shunt was associated with decreased perfusion in cortical (p = 0.003), but not in deep gray matter (p = 0.031). No evidence for an effect of aortic arch obstruction and arterial oxygen saturation on cerebral perfusion was found. After adjusting for hemodynamic and oxygen saturation parameters, deep (p = 0.018) and cortical (p = 0.012) gray matter perfusion was increased in patients with CHD compared to controls. CONCLUSION: We detected regional differences in compensation to the cerebral steal effect in patients with severe CHD. IMPACT: Patients with severe congenital heart disease (CHD) have altered postnatal brain hemodynamics. A systemic-to-pulmonary shunt was associated with decreased perfusion in cortical gray matter but preserved perfusion in deep gray matter, pointing towards regional differences in compensation to the cerebral steal effect. No effects of aortic arch obstruction and arterial oxygenation on cerebral perfusion were seen. Cerebral perfusion was increased in patients with CHD compared to healthy controls after adjusting for hemodynamic alterations and oxygen saturation. To improve neuroprotection and neurodevelopmental outcomes, it is important to increase our understanding of the factors influencing cerebral perfusion in neonates with severe CHD.

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

OBJECTIVES: Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction. DESIGN: We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015. SETTING: Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland. PATIENTS: Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores, measured at blood culture sampling, to predict 30-day mortality. We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Percentage with organ dysfunction ranged from 32.7% (IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy for identification of 30-day mortality was area under the curve (AUC) 0.87 (95% CI, 0.82-0.92) for IPSCC, 0.83 (0.76-0.89) for PELOD-2, 0.85 (0.78-0.92) for pSOFA, and 0.85 (0.78-0.91) for PODIUM. When restricting scores to neurologic, respiratory, and cardiovascular dysfunction, the adjusted AUC was 0.89 (0.84-0.94) for IPSCC, 0.85 (0.79-0.91) for PELOD-2, 0.87 (0.81-0.93) for pSOFA, and 0.88 (0.83-0.93) for PODIUM. CONCLUSIONS: IPSCC, PELOD-2, pSOFA, and PODIUM performed similarly to predict 30-day mortality. Simplified scores restricted to neurologic, respiratory, and cardiovascular dysfunction yielded comparable performance.

Characterization of dynamic patterns of human fetal to neonatal brain asymmetry with deformation-based morphometry.

Introduction: Despite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of inter-hemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans. Methods: Super-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformation-based morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants' age and sex and using threshold-free cluster enhancement. Results: Fetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole, and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical gray matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints. Discussion: While these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development.

Behavioural outcomes of children born with intrauterine growth restriction: protocol for a systematic review and meta-analysis.

INTRODUCTION: Intrauterine growth restriction (IUGR) is a pregnancy condition, which is associated with poor perinatal outcomes and long-term neurodevelopmental impairment. Several studies also investigated the impact of IUGR on child behaviour (eg, internalising and externalising behaviour, social competencies). However, so far, no systematic review or meta-analysis has been conducted that summarises these effects while considering relevant third variables such as type of IUGR diagnosis and control group, or concurrent cognitive abilities. The objective of this study is to summarise the current evidence regarding the relationship between IUGR and behavioural outcomes from early childhood to young adulthood. Additionally, to explore how third variables such as type of control group, or cognitive abilities, relate to this association. METHODS: Search strategy: The following electronic databases will be searched-Web of Science, Medline Ovid, PsycInfo, Cochrane Library, Scopus and Embase. INCLUSION CRITERIA: observational (eg, cohort studies and case-control studies) and intervention studies (if standard care is used and norm values are reported for the control group) will be included if they quantitatively compare children with and without IUGR from the age of 2 to 18 years. The main outcomes are internalising and externalising behaviour, and social competencies. ETHICS AND DISSEMINATION: No ethics approval was necessary for this protocol. Dissemination of findings will be done by publishing the results in peer-reviewed journals. The results of this systematic review will provide guidance for practice and counselling for clinicians and therapists facing patients affected by IUGR and their families. PROSPERO REGISTRATION NUMBER: CRD42022347467.

Creative music therapy for long-term neurodevelopment in extremely preterm infants: Results of a feasibility trial.

AIM: We tested the feasibility of a future randomised clinical trial (RCT) in which Creative Music Therapy (CMT), a family-integrating individualised approach in neonatal care, could improve neurodevelopment in extremely preterm infants (EPTs). METHODS: In this feasibility trial, 12 EPTs received CMT, while the remaining 19 received standard neonatal care. Socio-demographic data and perinatal complications were compared between groups as risk factors. Bayley Scales of Infant and Toddler Development at 2-year follow-up (FU2) and KABC-II-Kaufman Assessment Battery for Children at 5-year follow-up (FU5) were analysed using the Mann-Whitney U-tests. RESULTS: Twenty-seven (87.1%) and 18 (58.1%) EPTs attended the FU2 and FU5 examination, respectively. The rate of neurodevelopmental risk factors at birth of the two groups was quite similar. While there was no difference in the FU2 outcomes between groups, there were higher values in the CMT group's Fluid-Crystallised Index of the KABC-II. CONCLUSION: Our results indicate neither a beneficial nor a detrimental effect of CMT on neurodevelopment at 2 years but a trend of improved cognitive outcomes at 5 years more similar to cognitive scores of term-born infants than of standard treatment EPTs. The findings favour an RCT but must be interpreted cautiously due to the reduced sample size and non-randomised design.

Trends in Outcomes of Major Intracerebral Haemorrhage in a National Cohort of Very Preterm Born Infants in Switzerland.

BACKGROUND: Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. AIM: To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). METHODS: In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24-29 weeks gestational age (GA) in Switzerland in 2002-2014, with G3-IVH and/or PVHI. RESULTS: Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002-2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. CONCLUSION: In 2002-2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results.

Lactation-associated macrophages exist in murine mammary tissue and human milk.

Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multiparameter flow cytometry and single-cell RNA sequencing, we identified a lactation-induced CD11c+CX3CR1+Dectin-1+ macrophage population (liMac) that was distinct from the two resident F4/80hi and F4/80lo macrophage subsets present pregestationally. LiMacs were predominantly monocyte-derived and expanded by proliferation in situ concomitant with nursing. LiMacs developed independently of IL-34, but required CSF-1 signaling and were partly microbiota-dependent. Locally, they resided adjacent to the basal cells of the alveoli and extravasated into the milk. We found several macrophage subsets in human milk that resembled liMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.

Sensitivity of ICD coding for sepsis in children-a population-based study.

Background: International Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease. Aim: To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome. Methods: Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals. Results: We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50). Agreement of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p < 0.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data. Conclusions: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-023-00006-1.

Impact of low-grade intraventricular hemorrhage on neurodevelopmental outcome in very preterm infants at two years of age.

BACKGROUND: High-grade intraventricular hemorrhage (IVH) in very preterm infants is a known risk factor for adverse neurodevelopmental outcome. Prognosis is less clear for low-grade (grades I/II) IVH however, with conflicting study results in recent years. OBJECTIVE: To evaluate the impact of low-grade IVH on neurodevelopmental outcome at 2 years corrected age in preterm infants born below 32 weeks gestation at the University hospital of Zurich between 2009 and 2014. METHODS: Among 843 live-born preterm infants born during the observation period, 509 were included in our study. Exclusion criteria were death, high-grade IVH, cystic periventricular leukomalacia and congenital malformations. Infants were grouped into those with or without low-grade IVH according to cranial ultrasound. Neurodevelopmental impairment (NDI) was defined as cognitive or motor developmental score > 2 standard deviations below the mean and/or CP grades 2-5 and/or moderate/severe vision loss and/or hearing problem corrected with hearing aids. Multivariate linear regression was used to assess effect of low-grade IVH on endpoints while adjusting for other risk factors. RESULTS: 87 preterm infants had low-grade IVH (42 grade I, 45 grade II) on cranial ultrasound. These were compared to 422 preterm infants without IVH. Follow-up rate was 82.4 %. Preterm infants with low-grade IVH had higher rates of NDI (21.8 vs 13.3 %, p = 0.047). Infants with IVH grade II had significantly higher rates for CP (8.9 % vs 3.6 %, p = 0.003), visual impairment (20.5 % vs 8.3 %, p = 0.009) and NDI (33.3 % vs 13.3 %, p < 0.001). CONCLUSION: In our study, low-grade IVH - and especially IVH grade II - is associated with adverse neurodevelopmental outcome at 2 years of corrected age.

Respiratory morbidity in preschool and school-age children born very preterm and its association with parents' health-related quality of life and family functioning.

The purpose of this study is to describe the prevalence and severity of respiratory symptoms in children born very preterm and to assess their association with parents' health-related quality of life (HRQoL) and family functioning. We conducted a cross-sectional study and recruited children born less than 32 weeks' gestation between January 2006 and December 2019, in the greater Zurich area, Switzerland. Between May and December 2021, parents were invited to complete an online survey for their preterm child and for a control term born (≥ 37 weeks' gestation) sibling aged 1 to 18 years. We used a validated questionnaire to assess respiratory symptoms and the Pediatrics Quality of Life Family Impact Module (PedsQL FIM) to assess parents' HRQoL and family functioning. The survey was completed for 616 very preterm children (99 with bronchopulmonary dysplasia (BPD)) and 180 controls. Girls made up 45% (46% in controls) of the sample, and 63% (60% in controls) of participants were aged 6 to 18 years (school-age). Very preterm children reported a higher risk of respiratory symptoms than controls, especially preschoolers and those with moderate-to-severe BPD. Parents of children with "mild" and "moderate-severe" respiratory symptoms had on average -3.9 (95%CI: -6.6 to -1.1) and -8.2 (-11.2 to -5.2) lower PedsQL FIM total score, respectively, than parents of children with no symptoms. The same pattern was observed after stratifying by age categories.  Conclusions: Our study suggests that respiratory morbidity in very preterm children has a negative impact on parents' HRQoL and family functioning, even beyond the first years of life. What is Known: • The burden of respiratory morbidity associated with very premature birth is high and last far beyond the neonatal period. • Respiratory morbidity contributes to lower health-related quality of life (HRQoL) in parents of very preterm children in early infancy. What is New: • Respiratory morbidity in very preterm children has a negative impact on parents' HRQoL and family functioning beyond the first years of life. • Parents of very preterm children with moderate and severe respiratory symptoms are the ones who report lower scores, both for preschool and school-age children.

Infant regulation during the pandemic: Associations with maternal response to the COVID-19 pandemic, well-being, and socio-emotional investment.

In the transition to parenthood, the COVID-19 pandemic poses an additional strain on parental well-being. Confirmed infections or having to quarantine, as well as public health measures negatively affect parents and infants. Contrary to previous studies mainly focusing on the well-being of school-aged children and their parents during lockdown periods, the present study investigated how mothers of infants respond to the COVID-19 pandemic and whether this is related to maternal well-being, maternal socio-emotional investment, and infant regulation. Between April and June 2021, 206 mothers of infants (Mage  = 7.14 months, SDage  = 3.75 months) reported on COVID-19 infections, their response to the COVID-19 pandemic, their well-being, socio-emotional investment, and their infant's regulation. Exploratory factor analyses yielded five dimensions of maternal response to the COVID-19 pandemic: social distancing, worrying about the child, birth anxiety, distancing from the child, and information on COVID-19-related parenting behavior and support. These dimensions were related to mother-reported infant regulatory problems. Path analyses revealed paths via reduced maternal well-being and maternal socio-emotional investment. Maternal perceptions of infant regulatory problems are related to how the mothers respond to the COVID-19 pandemic. Better information about COVID-19-related parenting behavior and support might buffer against these effects.

Effect of Early High-Dose Recombinant Human Erythropoietin on Behavior and Quality of Life in Children Aged 5 Years Born Very Preterm: Secondary Analysis of a Randomized Clinical Trial.

Importance: In light of the promising neuroprotective properties of recombinant human erythropoietin (RHEpo), the Swiss EPO Neuroprotection Trial was started to investigate its effect on neurodevelopment in very preterm infants. The results of the primary and secondary outcome analysis did not show any effect of RHEpo on cognitive performance, neuromotor outcomes, or somatic growth of the study participants at ages 2 or 5 years. Objective: To investigate whether early high-dose RHEpo improves behavioral outcomes and health-related quality of life (HRQoL) at age 5 years. Design, Setting, and Participants: This was a prespecified secondary analysis of the double-blind, placebo-controlled, multicenter Swiss EPO Neuroprotection randomized clinical trial, which was conducted at 5 level-III perinatal centers in Switzerland. Infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were recruited between 2005 and 2012 and followed-up until age 5 years (last follow-up in 2018). Data were analyzed from January 6 to December 31, 2021. Interventions: Infants were assigned to receive either RHEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 42 hours after birth. Main Outcomes and Measures: The prespecified parent-reported measures of behavioral outcomes and health-related quality of life (HRQoL) of their children at the age of 5 years were assessed by two standardized questionnaires: the Strengths and Difficulties Questionnaire (behavioral outcomes) and the KIDSCREEN-27 (HRQoL). Results: Among 448 randomized infants, 228 infants were assigned to the RHEpo group and 220 infants were assigned to the placebo group. Questionnaire data were available for 317 children (71%) at a mean (SD) age of 5.8 (0.4) years (mean [SD] gestational age at birth, 29.3 [1.6] weeks; mean [SD] birth weight 1220 [340] grams; 128 [40%] female infants). At the age 5 years follow-up, the mean (SD) total difficulties score in the RHEpo group (8.41 [5.60] points) was similar to that of the placebo group (7.76 [4.81]) (P = .37). There were no statistically significant differences between the groups in any other outcome measures. Conclusions and Relevance: This secondary analysis of a randomized clinical trial showed no evidence for an effect of early high-dose RHEpo administration on behavioral outcomes or HRQoL in children born very preterm at early school age. Trial Registration: ClinicalTrials.gov Identifier: NCT00413946.

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION: In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN: • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW: • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed.

Similarities and Differences in the Neurodevelopmental Outcome of Children with Congenital Heart Disease and Children Born Very Preterm at School Entry.

OBJECTIVE: To describe the similarities and differences in the neurodevelopmental outcome of children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery compared with children born very preterm (VPT) at school entry. STUDY DESIGN: IQ, motor abilities, behavior, and therapy use were assessed in 155 children with CHD as part of a prospective, single-center, longitudinal study, and in 251 children born VPT as part of a national follow-up register at the same center. Group differences were tested using independent t-tests and χ2-tests. Equivalence testing was used to investigate similarities between the groups. RESULTS: Mild (ie, 70 ≤ IQ < 85) and severe intellectual impairments (ie, IQ < 70) occurred in 17.4% and 4.5% of children with CHD compared with 22.1% and 5.5% in children VPT, respectively. Motor and behavioral functions were impaired in 57.0% and 15.3% of children with CHD compared with 37.8% and 11.5% of children born VPT, respectively. Children with CHD had poorer global motor abilities (d = -0.26) and poorer dynamic balance (d = -0.62) than children born VPT, and children born VPT had poorer fine motor abilities than children with CHD (d = 0.34; all P < .023). Peer problems were statistically similar between the groups (P = .020). Therapies were less frequent in children with CHD compared with children born VPT (23.4% vs 40.3%; P < .001). CONCLUSIONS: Children with CHD undergoing cardiopulmonary bypass surgery and children born VPT share an overall risk for neurodevelopmental impairments that manifest in different domains. Despite this, children with CHD receive fewer therapies, indicating a lack of awareness of the neurodevelopmental burden these children face.

Interventions to improve neurodevelopmental outcomes of children born moderate to late preterm: a systematic review protocol.

Introduction: Prematurity (birth before 37 +0 weeks' gestation) is associated with wide-ranging neurodevelopmental impairment. Prognosis among moderate to late (32 +0 to <37 +0  weeks' gestation) preterm infants (MLPT) is better compared to their counterparts born very preterm (<32 +0  weeks' gestation). However the risk of developmental impairment among MLPT, who make up about 84% of all preterm infants, is 2-3 times higher when compared to infants born at term. Early interventions have aimed to improve outcomes in preterm infants generally, but there are limited data on their need and effect in MLPT specifically. Prioritising research, long-term follow-up and early interventions targeted at ameliorating the impact of preterm birth among MLPT is required. Objectives: To conduct a systematic review of the type of early childhood interventions (from birth until 4 years of age) offered to  MLPT children and to evaluate their impact on neurodevelopmental outcomes (cognitive, neurobehavioural and motor) as assessed in these children during childhood (until 18 years of age). Methods and analysis: A systematic literature search in Web of Science, Medline Ovid, PsycINFO, CINAHL and EMBASE will be conducted. Data on MLPT children receiving developmental interventions until the age of 4 years will be evaluated. Interventions may involve parents or primary caregivers. Primary outcomes are cognitive, neurobehavioural and motor development as measured from birth until the age of 18 years. The Cochrane Risk of Bias Assessment Tool will be used to evaluate the methodological quality of randomised controlled trials (RCTs) included in the review and will be graded as low, high  or unclear risk of bias. The quality of non-RCTs will be evaluated with the Newcastle-Ottawa Scale. The quality of evidence for each outcome will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation Approach. Publication and reporting bias will be assessed using Egger's test and funnel plots respectively.

Creative Music Therapy and Neurodevelopmental Outcomes in Pre-term Infants at 2 Years: A Randomized Controlled Pilot Trial.

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.

An automatic multi-tissue human fetal brain segmentation benchmark using the Fetal Tissue Annotation Dataset.

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.

Outcomes for Infants Born in Perinatal Centers Performing Fewer Surgical Ligations for Patent Ductus Arteriosus: A Swiss Population-Based Study.

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.