Asymmetric Properties of the Heart Rate Microstructure in Healthy Adults during 48 h ECG Recordings

Heart rate asymmetry reflects the different contributions of heart rate (HR) decelerations and accelerations to heart rate variability (HRV). We examined the contribution of monotonic runs of HR accelerations and decelerations to the asymmetric properties of the HR microstructure in the 48 h electrocardiograms (ECGs) of healthy adults (n = 101, 47 males, average age of 39 years) and analysed sex differences in the HR microstructure. The HR microstructure was asymmetric for runs of most lengths, except for sequences of two consecutive decelerations (DR2s) or accelerations (AR2s). Women had a higher prevalence of AR2s than men but fewer runs in the range of 4 to 11 consecutive accelerations (AR4–AR11s) and 5 to 11 consecutive decelerations (DR5–DR11s). The longest runs consisted of 47 consecutive accelerations (AR47s) and 27 consecutive decelerations (DR27s). More DR3s than AR3s and more DR4s than AR4s reveal a crossing of HR microstructure asymmetry. In conclusion, more acceleration than deceleration runs demonstrate that the HR microstructure was asymmetric in the 48 h ECGs. This phenomenon was present in both sexes but was more pronounced in men. For shorter runs of 3 and 4 consecutive heartbeats, there was a crossing of HR microstructure asymmetry, with more deceleration than acceleration runs

Interventions for the Management of Pain and Sedation in Newborns Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy : A Systematic Review

Background Newborn infants undergoing therapeutic hypothermia (TH) are exposed to multiple painful and stressful procedures. The aim of this systematic review was to assess benefits and harms of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing TH for hypoxic-ischemic encephalopathy. Methods We included randomized and observational studies reporting any intervention (either drugs or non-pharmacological interventions) to manage pain and sedation in newborn infants (> 33 weeks' gestational age) undergoing TH. We included any dose, duration and route of administration. We also included any type and duration of non-pharmacological interventions. Our prespecified primary outcomes were analgesia and sedation assessed using validated pain scales in the neonatal population; circulatory instability; mortality to discharge; and neurodevelopmental disability. A systematic literature search was conducted in the PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, and Web of Science databases, with no language restrictions. Included studies underwent risk-of-bias assessment (Cochrane risk-of-bias tool and ROBINS-I) and data extraction performed by two authors independently. The plan had been to use effect measures such as mean difference for continuous outcomes and risk ratio for dichotomous outcomes, however the included studies are presented in a narrative synthesis due to their paucity and heterogeneity. Results Ten studies involving 3551 infants were included-one trial and nine observational studies. Most studies examined the use of phenobarbital or other antiepileptic drugs with primary outcomes related to seizure activity. The single trial that was included compared pentoxifylline with placebo. Among the primary outcomes, six studies reported circulatory instability and five reported mortality to discharge without relevant differences; two studies reported on neurodevelopmental disability and one study reported on pain scale. Three studies were ongoing. Conclusions We found limited evidence to establish the benefits and harms of the interventions for the management of pain and sedation in newborn infants undergoing TH. Long-term outcomes were not reported. Given the very low certainty of evidence-due to imprecision of the estimates, inconsistency and limitations in study design (all nine observational studies with overall serious risk of bias)-for all outcomes, clinical trials are required to determine the most effective interventions in this population. Systematic Review Registration PROSPERO registration number: CRD42020205755

Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia

Antileukotrienes for the prevention and treatment of chronic lung disease in very preterm newborns : a systematic review

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

Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia

Background: Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life. Objectives: To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge. Search methods: We searched CENTRAL, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial register ISRCTN in August 2021. We also checked the reference lists of relevant articles to identify additional studies. Selection criteria: We included randomized controlled trials (RCT), quasi-RCTs and cluster-randomized trials comparing drugs used for the management of pain or sedation, or both, during therapeutic hypothermia: any opioids (e.g. morphine, fentanyl), alpha-2 agonists (e.g. clonidine, dexmedetomidine), N-Methyl-D-aspartate (NMDA) receptor antagonist (e.g. ketamine), other analgesics (e.g. paracetamol), and sedatives (e.g. benzodiazepines such as midazolam) versus another drug, placebo, no intervention, or non-pharmacological interventions. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge. Data collection and analysis: Two review authors independently assessed studies identified by the search strategy for inclusion. We planned to use the GRADE approach to assess the certainty of evidence. We planned to assess the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We planned to evaluate treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. Main results: We did not find any completed studies for inclusion. Amongst the four excluded studies, topiramate and atropine were used in two and one trial, respectively; one study used dexmedetomidine and was initially reported in 2019 to be a randomized trial. However, it was an observational study (correction in 2021). We identified one ongoing study comparing dexmedetomidine to morphine. Authors' conclusions: We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia

Cooling strategies during neonatal transport for hypoxic-ischaemic encephalopathy

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

Interventions to minimize blood loss in very preterm infants-A systematic review and meta-analysis.

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

Prenatal and Neonatal Pulmonary Thrombosis as a Potential Complication of SARS-CoV-2 Infection in Late Pregnancy

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