Blood loss in the first days of life has been associated with increased morbidity and mortality in very preterm infants. In this systematic review we included randomized controlled trials comparing the effects of interventions to preserve blood volume in the infant from birth, reduce the need for sampling, or limit the blood sampled. Mortality and major neurodevelopmental disabilities were the primary outcomes. Included studies underwent risk of bias-assessment and data extraction by two review authors independently. We used risk ratio or mean difference to evaluate the treatment effect and meta-analysis for pooled results. The certainty of evidence was assessed using GRADE. We included 31 trials enrolling 3,759 infants. Twenty-five trials were pooled in the comparison delayed cord clamping or cord milking vs. immediate cord clamping or no milking. Increasing placental transfusion resulted in lower mortality during the neonatal period (RR 0.51, 95% CI 0.26 to 1.00; participants = 595; trials = 5; I² = 0%, moderate certainty of evidence) and during first hospitalization (RR 0.70, 95% CI 0.51, 0.96; 10 RCTs, participants = 2,476, low certainty of evidence). The certainty of evidence was very low for the other primary outcomes of this review. The six remaining trials compared devices to monitor glucose levels (three trials), blood sampling from the umbilical cord or from the placenta vs. blood sampling from the infant (2 trials), and devices to reintroduce the blood after analysis vs. conventional blood sampling (1 trial); the certainty of evidence was rated as very low for all outcomes in these comparisons. Increasing placental transfusion at birth may reduce mortality in very preterm infants; However, extremely limited evidence is available to assess the effects of other interventions to reduce blood loss after birth. In future trials, infants could be randomized following placental transfusion to different blood saving approaches. Trial registration: PROSPERO CRD42020159882.

Aim: We reviewed the literature on cooling methods during transport of newborn infants with hypoxic‐ischaemic encephalopathy (HIE) born in a non‐tertiary centre and transferred to a neonatal intensive care unit for therapeutic hypothermia.Methods: The electronic databases CENTRAL, MEDLINE, Embase, CINAHL, and Scopus were searched from inception up to 8 March 2022 for studies comparing cooling versus no cooling, active versus passive cooling, and servo‐controlled versus non‐servo‐controlled cooling. Odds ratio and confidence of interval were calculated for dichotomous outcomes and mean difference and confidence interval for continuous outcomes.Results: The final analysis included 14 studies, 1 randomised and 13 non‐randomised, involving 1098 newborn infants. Compared with the other cooling methods, servo‐controlled active cooling was more likely to maintain body temperature within the target range of 33°C–34°C on arrival at a neonatal intensive care unit: odds ratio 13.58, 95% confidence interval 4.32–42.66, risk difference 0.33, 95% confidence interval 0.19–0.46; 224 participants; three studies; I² 0%. The certainty of evidence was low. Only five studies reported mortality rates.Conclusion: Servo‐controlled active cooling may be the preferred method during transport of newborn infants with HIE. A future area of focus should be long‐term neurodevelopmental outcomes after servo‐controlled active cooling.

Heart rate asymmetry (HRA) reflects different contributions of heart rate (HR) decelerations and accelerations to heart rate variability (HRV). In this study, we examined various properties of HRA, including its compensation and HRV, in 48-h electrocardiogram (ECG) recordings in healthy adults. Furthermore, we compared sex differences in parameters used to quantify HRA and HRV. Variance-based and relative HRA and HRV parameters were computed for Holter ECG recordings lasting up to 48 h in 101 healthy volunteers. The median age of the subjects was 39 years, with 47 of them being men. The prevalence of all forms of HRA was statistically different from randomness (p < 0.0001). Specifically, HR decelerations contributed >50% (C1d) to short-term HRA in 98.02% of subjects, while HR decelerations contributed <50% to long-term HRA in 89.11% of recordings and to total HRA in 88.12% of recordings. Additionally, decelerations accounted for <50% of all changing heartbeats (Porta’s index) in 74.26% of subjects, and HRA compensation was present in 88.12% of volunteers. Our findings suggest that various HRA features are present in most healthy adults. While men had more pronounced HRA expression, the prevalence of short-, long-term, and total HRA and its compensation was similar in both sexes. For HRV, values of variance-based indices were higher in men than in women, but no differences were found for relative measures. In conclusion, our study references HRA and HRV for longer ECG recordings of up to 48 h, which have become increasingly important in clinical ECG monitoring. The findings can help understand and compare the characteristics of HRA and HRV in patients with different diseases.

Background: Very preterm infants are at high risk of developing chronic lung disease, which requires respiratory support and might have long-term sequelae. As lung inflammation plays an important role in pathogenesis, antileukotrienes have been explored in both clinical and animal studies. We aimed to assess the benefits and harms of antileukotrienes for the prevention and treatment of respiratory morbidity and mortality in very preterm newborns.Methods: In this systematic review, we included randomized trials and non-randomized studies in humans and animals reporting the effects of antileukotrienes in very preterm infants or other mammals within 10 days of birth. Our pre-specified primary outcomes were all-cause mortality and any harm, and, for the clinical studies, incidence of chronic lung disease. Included studies underwent risk of bias-assessment and data extraction performed by two authors independently. There were no language restrictions.Results: Fifteen studies totally met our inclusion criteria: one randomized trial and four non-randomized studies in humans and 10 animal studies (five in rodents, two in lambs and one in either guinea pigs, rabbits or caprinae). All five clinical studies used montelukast and had a small sample size, ranging from 4 to 77 infants. The randomized trial (n = 60) found no difference in the incidence of chronic lung disease between the groups. Only one clinical study, which enrolled four very preterm infants and had a critical overall risk of bias, reported long-term outcomes. All other studies had unclear or greater overall risk of bias and meta-analyses were therefore deemed unfeasible. Eight of ten animal studies used leukotriene receptor antagonists as antileukotriene (montelukast in three of ten studies) and seven had an experimental study design (i.e. some animals were not exposed to antileukotrienes but no randomization). Three of the ten animal studies assessed different doses. Animal studies found no effect on the outcomes mortality, growth, or lung function related surrogate outcomes.Conclusions: Use of antileukotrienes in very preterm infants to prevent or treat chronic lung disease is not supported by the available evidence. Large randomized trials focusing on outcomes relevant to patients, including long-term outcomes, are needed. Studies should also minimize risk of bias.

Neonatal venous thrombosis is a rare condition that can be iatrogenic or occur due to viral infections or genetic mutations. Thromboembolic complications are also commonly observed as a result of SARS-CoV-2 infections. They can affect pediatric patients, especially the ones suffering from multisystem inflammatory syndrome in children (MIS-C) or multisystem inflammatory syndrome in neonates (MIS-N). The question remains whether the maternal SARS-CoV-2 infection during pregnancy can lead to thromboembolic complications in fetuses and neonates. We report on a patient born with an embolism in the arterial duct, left pulmonary artery, and pulmonary trunk, who presented several characteristic features of MIS-N, suspecting that the cause might have been the maternal SARS-CoV2 infection in late pregnancy. Multiple genetic and laboratory tests were performed. The neonate presented only with a positive result of IgG antibodies against SARS-CoV-2. He was treated with low molecular weight heparin. Subsequent echocardiographic tests showed that the embolism dissolved. More research is necessary to evaluate the possible neonatal complications of maternal SARS-CoV-2 infection.