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Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of “European Guidelines for the Management of RDS” by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

STUDY QUESTION: Do 8- to 9-year-old singletons conceived after frozen embryo transfer (FET) or fresh embryo transfer (Fresh-ET) have increased arterial stiffness compared to naturally conceived (NC) children? SUMMARY ANSWER: The process of FET or Fresh-ET is not associated with altered cardiovascular function in 8- to 9-year-old singletons, including arterial stiffness, as compared to NC children. WHAT IS KNOWN ALREADY: ART has been suggested to influence cardiovascular risk factors (i.e. endothelial dysfunction, increased arterial blood pressure and insulin resistance). It is not known if ART procedures alter arterial stiffness in singletons. STUDY DESIGN, SIZE, DURATION: A cohort study was carried out, including 8- to 9-year-old singletons conceived after FET, Fresh-ET and NC children (50 children in each group). This study was conducted between November 2018 and August 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 150 singletons were identified through the Danish IVF Registry and the Medical Birth Registry. They underwent cardiac magnetic resonance imaging (CMR) and anthropometric measurements. Parental data were collected using questionnaires. NC children were matched by sex and birth year with FET/Fresh-ET children. Exclusion criteria were congenital heart disease, maternal gestational diabetes or maternal diabetes mellitus. Our primary outcome was arterial stiffness, which is assessed from noninvasive arterial blood pressure and aortic ascendens distensibility. The secondary outcome was the pulse wave velocity of total aorta and exploratory outcomes were left ventricular ejection fraction, mean arterial pressure, cardiac output and total peripheral resistance. Measurements and analyses were performed blinded to the child group. MAIN RESULTS AND THE ROLE OF CHANCE: Aortic ascendens distensibility of children conceived after FET and Fresh-ET did not differ from NC children (mean (SD): FET 11.1 (3.6) 10-3 mmHg-1, Fresh-ET 11.8 (3.0) 10-3 mmHg-1, NC

Objectives A new device that combines, for the first time, two photonic technologies (time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy) was provided and tested within the BabyLux project. Aim was to validate the expected changes in cerebral oxygenation and blood flow. Methods A pulse oximeter and the BabyLux device were held in place (right hand/wrist and frontoparietal region, respectively) for 10 min after birth in healthy term infants delivered by elective caesarean section. Pulse oximeter saturation (SpO 2), cerebral tissue oxygen saturation (StO 2) and blood flow index (BFI) were measured over time. Tissue oxygen extraction (TOE) and cerebral metabolic rate of oxygen index (CMRO 2 I) were calculated. Results Thirty infants were enrolled in two centres. After validity check of data, 23% of infants were excluded from TOE and CMRO 2 I calculation due to missing data. As expected, SpO 2 (estimate 3.05 %/min; 95% CI 2.78 to 3.31 %/min) and StO 2 (estimate 3.95 %/min; 95% CI 3.63 to 4.27 %/min) increased in the first 10 min after birth, whereas BFI (estimate-2.84×10-9 cm 2/s/min; 95% CI-2.50×10-9 to-3.24×10-9 cm 2/s/min) and TOE (estimate-0.78 %/min; 95% CI-1.12 to-0.45 %/min) decreased. Surprisingly, CMRO 2 I decreased (estimate-7.94×10-8/min; 95% CI-6.26×10-8 to-9.62×10-8/min). Conclusions Brain oxygenation and BFI during transition were successfully and simultaneously obtained by the BabyLux device; no adverse effects were recorded, and the BabyLux device did not limit the standard care. The preliminary results from clinical application of the BabyLux device are encouraging in terms of safety and feasibility; they are consistent with previous reports on brain oxygenation during transition, although the interpretation of the decreasing CMRO 2 I remains open. Trial registration number NCT02815618.

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. Impact: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways.Copyright © 2021, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

OBJECTIVE: To study the effect of antenatal magnesium sulphate (MgSO4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis.DESIGN: Double-blind, randomised, placebo-controlled, multi-centre trial.SETTING: Fourteen Danish obstetric departments.POPULATION: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children.METHODS: Women were randomised to receive either a loading dose of 5 g MgSO4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire.MAIN OUTCOME MEASURE: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP.RESULTS: The crude rates of moderate to severe CP in the MgSO4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65).CONCLUSIONS: Antenatal MgSO4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis.TWEETABLE ABSTRACT: Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation.

As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of “European Guidelines for the Management of RDS” by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

AIM: The aim of the study was to investigate whether amplitude-integrated electroencephalography (aEEG) and cerebral magnetic resonance imaging (MRI) in preterm piglets would provide measures of cerebral functional, microstructural and anatomical maturation, which might reflect the signs of functional brain immaturity, documented in preterm piglets.METHODS: During July-October 2013 at the NEOMUNE Centre, Copenhagen University, Denmark, 31 preterm (90% gestation) and 10 term piglets underwent aEEG on days 1, 2, 4 and 11, and MRI on day 25. Physical activity levels were recorded.RESULTS: Preterm showed delayed neonatal arousal and physical activity, relative to term piglets. Preterm piglets had lower growth rates and brain volume than term piglets, but aEEG patterns were similar. MRI mean diffusivity was also similar, but fractional anisotropy (FA) was lower in preterm piglets (p < 0.001).CONCLUSION: Functional brain maturation, as assessed by aEEG, was relatively advanced in preterm piglets. Conversely, the low FA in the preterm piglets suggests that the white matter microstructure remains less mature in preterm compared to term piglets at postnatal day 25. The results might be utilised to define whether and how preterm piglets may contribute to preclinical models for brain development in preterm infants.

OBJECTIVES: The aim of this study was to estimate the prevalence of specific neurodevelopmental disorders in children prenatally believed to have isolated mild ventriculomegaly in the second trimester of pregnancy to optimize the counselling process.METHODS: This was a nationwide register based study including all singleton pregnancies which had a first and second trimester scan in the period 1 January 2008 to 1 October 2014, identified through the Danish Fetal Medicine Database and from local clinical databases. All fetuses prenatally believed to have isolated mild ventriculomegaly (measurement of the atrium of the lateral ventricles between 10.0-15.0 mm) diagnosed prenatally between 18-22 weeks of gestation were followed-up through national patient registers until the age of 2 to 7 years. We obtained information about the diagnoses of intellectual disability, cerebral palsy, autism spectrum disorders, epilepsy and impaired psychomotor development from national registers. Results Among a cohort 292,046 of fetuses, 133 cases were found to have apparent isolated mild at the second trimester scan for fetal malformations. In eleven cases, long-term follow-up was not possible due to termination of pregnancy, spontaneous miscarriage, neonatal death and loss to follow-up. Among 122 live born children followed up for between 2-7 years, 15 children were identified with additional abnormalities while 107 children were postnatally confirmed with isolated mild ventriculomegaly. Of the 107 children, a neurodevelopmental disorder diagnosis was registered in 6 (5.6%) cases corresponding to an OR of 2.64 (95% CI 1.16-6.02) compared to the reference population. The diagnoses were autism spectrum disorders, epilepsy and impaired psychomotor development. None of the children were diagnosed with intellectual disability or cerebral palsy.CONCLUSIONS: Our results show that a diagnosis of confirmed isolated mild ventriculomegaly was associated with an increased risk of neurodevelopmental